Neurodegenerative Disorders

Spinal Cord Image Denoising Using Dncnn Algorithm

Background: Spinal image denoising plays a vital role in the accurate diagnosis of disc herniation (DH).

Objective: Traditional denoising algorithms perform less due Limited Directional Selectivity problem and do not adequately capture directional information in pixels. Traditional algorithms' edge representation and texture details are insufficient for the earlier detection of DH. Limited Directional Selectivity leads to inaccurate diagnosis and classification of Disc Herniation (DH) stages. The DH stages are (i) Degeneration (ii) Prolapse (iii) Extrusion and (iv) Sequestration. Moreover, detection of DH size below 2mm using MR image is the major problem.

Methods: To solve the above problem, spinal cord MR images fed to the proposed Parrot optimization tuned Denoising Convolutional Neural Network (Po- DnCNN) algorithm for perspective enhancement of nucleus pulposus region in the spinal cord, vertebrae. The perspective enhancement of Spinal cord image led to the accurate classification of stages and earlier detection of DH by using the proposed Hippopotamus optimization- Fast Hybrid Vision Transformer (Ho–FastViT) algorithm. For this study, spinal cord MR images are obtained from the Grand Challenge website – SPIDER dataset.

Results: The proposed Po-DnCNN method and Ho-FastViT results are analysed quantitatively and qualitatively based on the edge, contrast, classification of the stage, and enhancement of the projected nucleus pulposus region in the spinal cord and vertebrae. The predicted DH results using the proposed method are compared with the manual Pfirrman Grade value of the spinal card method.

Conclusion: Proposed method is better than traditional methods for earlier detection of DH. Po-DnCNN and Ho-FastViat methods give high accuracy of about 98% and 97% compared to traditional methods.

A Survey on Diagnosis and Prognosis of Prenatal Asphyxia based on Oxidant Antioxidant Balance: Evidence from a Systematic Review and Meta-analysis

Introduction: The mechanism of occurrence and complications of asphyxia change in the treatment process and the future prognosis of newborns. One of the discussed mechanisms is the disruption of oxidant anti-oxidant balance. Therefore, the current study was conducted aiming to systematically review and meta-analysis in the diagnosis and prognosis of prenatal asphyxia based on oxidant-antioxidant balance.

Methods: A comprehensive electronic search was conducted with PubMed, Cochrane Library, Scopus, and Web of Science databases, up to February 2023 to identify relevant studies examining the association between Prooxidant anti-oxidant balance (PAB) and Malondialdehyde 1 levels with the risk of prenatal asphyxia. Only English studies were incorporated. The search terms used included Asphyxia, Diagnosis, Prognosis, Newborns, Prenatal, Oxidant antioxidant balance, and oxidative stress. A total of 13 studies were retrieved. Data regarding the standard mean difference (SMD) were collected, and a pooled SMD with 95%CI was calculated using a random-effect model to determine the strength of the relationship. Furthermore, the risk of publication bias was assessed through funnel plot and Egger’s linear regression tests. Inclusion criteria was 1) The studies conducted on neonates, diagnosis and outcomes of prenatal asphyxia, oxidants and antioxidants were included. Research conducted on adults or on animals or review articles, and articles which only their abstracts were available were excluded. The quality of the reported studies was also assessed.

Results: Out of 980 searched articles, 13 articles (10 prospective articles and 3 cross-sectional articles) were studied. An increase in antioxidant enzymes (Glutathione peroxidase (GSH-Px), catalase (CAT) and Plasma superoxide dismutase (SOD)) cannot be dealt with excessive oxidants produced in the body (Plasma and cerebrospinal fluid levels of Malondialdehyde (MDA), free radical products (F8-isoprostane and MDA), saturated fatty acids and % CoQ-10). Prooxidant anti-oxidant balance (PAB) levels among neonates who had asphyxia were announced to be two times higher than normal newborns. PAB values in neonates with asphyxia, who had adverse prognosis, were about three times higher than those with favorable prognosis. The sensitivity of PAB in predicting the prognosis of neonates with asphyxia was reported 83- 89% and its specificity was 71- 92%. The pooled SMD analysis revealed a significant association between PAB and MDA levels with the risk of prenatal asphyxia both overall (SMD = 1.447, 95%CI: 0.961-1.934, P < 0.001), as well as separately in subgroups of PAB (SMD = 1.134, 95%CI: 0.623-1.644, P < 0.001) and MDA (SMD = 1.910, 95%CI: 0.916-2.903, P < 0.001).

Conclusion: Our meta-analysis findings revealed the potential of evaluating antioxidant enzymes and oxidant agents, as well as assessing the balance between them (PAB), in diagnosing and predicting the prognosis of neonatal asphyxia. The limitations of the present study included not having access to all related complete articles, lack of quality and usability in reports of some articles, and the different diagnostic methods of prenatal asphyxia in different studies.

A Comprehensive Review of Alternative Therapeutic Approaches for Nausea and Vomiting Relief in Pregnancy

Alternative medication is used for treating the common problems associated with pregnancy. 80% of women suffer from morning sickness during pregnancy. Treatment during pregnancy via using non-pharmacological therapy is quite popular all over the world as it is safe and has no negative effects on the fetus. Nausea and vomiting are one of the most prominent problems faced by pregnant women. Acupressure and Aromatherapy have been used by pregnant ladies nowadays for relieving nausea and vomiting symptoms. Conventional therapies also aid in medication of morning sickness in pregnancy duration that covers drugs like Antiemetics, Corticosteroids, Antihistaminic, IV fluids and Vitamin-B6 supplements. Many scientific studies have demonstrated that few drugs that come under conventional treatment cause severe birth defects and stillbirth. This is the leading reason pregnant women prefer to use herbs instead of using conventional medical treatment. The prospective of this review article is to find out the alternative and conventional therapeutic approaches for alleviating the symptoms of morning sickness during pregnancy.

Anabolic Androgenic Steroids: A Review

A lot of athletes, bodybuilders, and those who want to look better in general use AAS (anabolic androgenic steroids) to achieve their goals. These steroids can be found in nature or synthesised in a lab. These substances are attempts to mimic the anabolic (muscle-building) and androgenic (masculinizing) properties of testosterone. Steroids like testosterone, methandienone, Nandrolone Decanoate (ND), and methenolone are only a few examples of AAS that are commonly abused. Initially exclusive to professional bodybuilders, these substances are increasingly being tried out by amateur and professional athletes alike. The anabolic properties of AAS have led to their usage in medicine for the treatment of conditions like chronic renal disease and osteoporosis in postmenopausal women. Despite being banned by the World Anti-Doping Agency, anabolic steroid (AAS) use is estimated to be between 1% and 3% among the general population of the United States (WADA). Their negative effects on several organs, including the cardiovascular and reproductive systems, have aroused concerns. Therefore, there are serious health risks linked with the inappropriate use of AAS. More education is needed for both the general public and medical professionals on how to recognise symptoms, administer effective care, and prevent AAS-related disorders. The goal of this study is to examine the current state of our understanding regarding the functioning of AAS and their associated deleterious consequences.

Arsenic Exposure and Amyloid Precursor Protein Processing: A Focus on Alzheimer's Disease

Background: Arsenic is present in above permissible safe limits in groundwater, soil, and food, in various areas of the world. This is increasing exposure to humankind and affecting health in various ways. Alternation in cognition is one among them. Epidemiological research has reflected the impact of arsenic exposure on children in the form of diminished cognition.

Aims: Considering this fact, the present study reviewed the impact of arsenic on amyloid precursor protein, which is known to cause one of the commonest cognitive disorders such as Alzheimer’s disease.

Methods: The present study reviews the arsenic role in the generation of amyloid-beta from its precursor that leads to Alzheimer’s disease through the published article from Pubmed and Scopus.

Description: According to the findings, regular, long-term exposure to arsenic beginning in infancy changes numerous arsenic level-regulating regions in the rat brain, which are related to cognitive impairments. Arsenic also affects the BBB clearance route by increasing RAGE expression. Arsenic triggers the proamyloidogenic pathway by increasing APP expression and subsequently, its processing by β-secretase and presenilin. Arsenic also affects mitochondrial dynamics, DNA repair pathway and epigenetic changes. The mechanism behind all these changes is explained in the present review article.

Conclusion: A raised level of arsenic exposure affects the amyloid precursor protein, a factor for the early precipitation of Alzheimer’s disease.

All-trans Retinoic Acid Increased Transglutaminase 2 Expressions in BV-2 Cells and Cultured Astrocytes

Background: Activation of microglia and astrocytes has been observed in Alzheimer’s disease (AD). Transglutaminase 2 (TG2) is reported to be activated in AD and involved in cell proliferation, differentiation, and inflammation. Moreover, amyloid β (Aβ) aggregation is detected as a characteristic pathology in the AD brain, and is known to be a substrate of TG2. All-trans retinoic acid (ATRA) can modify cell proliferation and differentiation, and is reported to have therapeutic effects on AD pathology.

Objective: We aimed to assess the effects of ATRA in microglia and astrocytes on TG2 expression and glial functions.

Methods: After treatment with ATRA, TG2 expression and TG activity were assayed in both murine microglia BV-2 cells and cultured rat brain astrocytes. Endocytosis activity in BV-2 cells and Aβ aggregation by astrocytes conditioned medium were also assessed.

Results: In both BV-2 cells and cultured astrocytes, ATRA increased TG2 expression and TG activity. The increase was blocked by AGN194310, an RA receptor antagonist. ATRA enhanced the endocytosis activity in BV-2 cells, and the addition of AGN194310 reversed it. The addition of cystamine, a competitive TG inhibitor, also reduced ATRA-enhanced endocytosis activity. On the other hand, Aβ aggregation was potentiated by ATRA-treated astrocytes conditioned medium compared to control astrocytes conditioned medium.

Conclusion: These results suggest that ATRA increased TG2 expression and TG activity via RA receptor in microglia and astrocytes. ATRA-enhanced TGs might be involved in phagocytosis and Aβ aggregation. Adequate control of TGs expression and function in microglia and astrocytes can be an important factor in AD pathology.

Physalin B Reduces Tau Phosphorylation and Cell Apoptosis in HEK293 Cells by Activating FoxO1

Background: Physalin B (PB) is one of the main active compounds of Solanaceae plants, with a wide range of biological activities. PB reportedly has the potential to treat Alzheimer’s disease (AD).

Objective: In this study, we investigated the effect of PB on Tau phosphorylation and cell apoptosis using Tau-expressing HEK293 cells (HEK293/Tau) as a cellular model.

Methods: The optimum concentration of PB to treat HEK293/Tau cells was determined using the CCK-8 assay. Additionally, the expression of FoxO1, Tau-5, p-Tau (T231, S262, and S404), ERK, p-ERK, GSK-3β, and p-GSK-3β was detected using western blotting to determine the effect of PB on Tau phosphorylation. The apoptosis rate was detected using flow cytometry, and the expression of Bax and Bcl-2 was detected using western blotting and verified using real-time quantitative polymerase chain reaction (RT-qPCR). Moreover, cells were transfected with FoxO1 siRNA to downregulate FoxO1 expression, and the expression of the above-mentioned proteins was detected to verify the effect of PB on Tau phosphorylation and cell apoptosis.

Results: After 24 h of PB treatment, the phosphorylation levels of Tau at S404, S262, and T231 sites decreased significantly, and the activities of GSK-3β and ERK were inhibited. PB also reduced cell apoptosis by reducing the expression of Bax and increasing the expression of Bcl-2. In addition, PB decreased Tau phosphorylation and cell apoptosis by upregulating FoxO1.

Conclusion: The natural compound PB exhibited a protective effect in the AD cell model by increasing FoxO1 expression and reducing Tau phosphorylation and cell apoptosis.

Nrf2 Mediates Effect of Resveratrol in Ischemia-reperfusion Injury

Ischemia-Reperfusion Injury (IRI) is a paradoxical phenomenon where removing the source of injury can cause additional damage. Ischemia reduces ATP production and intracellular pH, reducing oxidative reactions, increasing lactic acid release, and activating anaerobic metabolism. Reperfusion restores aerobic respiration and increases ROS production, leading to malfunction of transmembrane transport, activation of proteases, DNA dissolution, and protein denaturation, leading to apoptotic cell death. Nrf2 is a transcription factor that regulates cellular inflammation and oxidative responses. It is activated by oxidants and electrophiles and enhances detoxifying enzyme expression, maintaining redox homeostasis. It also activates ARE, which activates several ARE-regulated genes that favor cell survival by exhibiting resistance to oxidants and electrophiles. Nrf2 regulates the antioxidant defense system by producing phase II and antioxidant defense enzymes, including HO-1, NQO-1, gglutamylcysteine synthetase, and rate-limiting enzymes for glutathione synthesis. Nrf2 protects mitochondria from damage and supports mitochondrial function in stress conditions. Resveratrol is a stilbene-based compound with a wide variety of health benefits for humans, including antioxidant, anticarcinogenic, antitumor, and estrogenic/antiestrogenic. Resveratrol protects against IRI through several signaling pathways, including the Nrf2/ARE pathway. Here, we review the studies that investigated the mechanisms of resveratrol protection against IRI through modulation of the Nrf2 signaling pathway.

Targeting Cellular Senescence: A Potential Therapeutic approach for Alzheimer’s Disease

Although Amyloid beta plaque and neurofibrillary tangles are considered the two main hallmarks of Alzheimer’s disease (AD), the mechanism by which they contribute is not clearly understood. Cellular senescence (CS) has been demonstrated to be a key characteristic of AD. Recent research suggests that persistent buildup of senescent cells over time results in protracted activation of inflammatory stress as an organism ages because of the accumulation of irreversible DNA damage and oxidative stress as well as the deterioration of immune system function. Studies on both humans and animals have shown evidence that CS is a crucial factor in AD. The brains of AD patients have been found to have senescent glial cells and neurons, and removal of these senescent cells results in a decrease in Amyloid beta plaque and Neurofibrillary tangles, along with improved cognitive functions. This review summarises recent results and the mechanism by which CS contributes to the development of AD, and how the elimination of senescent cells may be a therapeutic target in the management of AD.

Differential Kat3 Coactivator Usage Regulates Brain Metabolism and Neuronal Differentiation

Introduction: Our previous work has demonstrated significant effects on the oxidative stress response, mitochondrial function, and oxidative phosphorylation in the livers and intestines of p300 S89A knockin (S89AKI) mice. We now show that this mutation is also associated with brain metabolic defects and neuronal differentiation.

Methods: p300 S89A edited P19 cells, and S89AKI mice demonstrated metabolic and neuronal differentiation defects based on proteomic, cell biological and PET imaging studies.

Results: The metabolic and differentiation defects associated with the p300 S89A knockin mutation could be corrected both in vitro and in vivo utilizing the small molecule CBP/beta-catenin antagonist ICG-001.

Conclusion: Rebalancing the equilibrium between CBP/β-catenin versus p300/β-catenin associated transcription, utilizing the small molecule CBP/beta-catenin antagonist ICG-001, enhances mitochondrial oxidative phosphorylation, metabolic function, and neuronal differentiation and may be able to ameliorate the cognitive decline seen in neurodegenerative disorders, including Alzheimer’s Disease.

Evaluation of Neuroprotective effect of Cassia occidentalis L. against Colchicine Induced Memory Impairment in Wistar Rats

Background: Alzheimer’s disease (AD) is a progressive neurological disorder that develops with aging.

Objective: In this research, we have examined the anti - Alzheimer’s effect of ethanolic extract from roots of Cassia occidentalis L. on colchicine-induced Alzheimer’s in Wistar rats.

Methods: Ethanolic extract was obtained and spectroscopic, chromatography analysis was performed. Acute toxicity studies using Organization of Economic Co-operation and Development (OECD) Guidelines 423 were performed to examine and make sure that there were no signs of toxic effects. The induction of AD was done using colchicine which leads to symptoms like neurotoxicity, neuroinflammation, and neurodegeneration. In this experiment, a thorough analysis of body weight, behavioral parameters, locomotor activity, and biochemical evaluation was performed to estimate the medicinal properties of Cassia occidentalis L in treating Alzheimer’s disease.

Results: Pharmacognostic analysis showed the presence of vascular bundles, starch grains, fibers, calcium oxalate crystals, elongated parenchyma, and collenchyma mucilage as shown in the supplementary files. Locomotor activity, Escape latency time, Conditioned avoidance response, and Transfer latency were improved with treatment. Interleukin- 6 (IL - 6) levels were reduced significantly in the Colchicine + 200 Cassia mg/kg group (739.2 ± 0.37 pg/ml) than in the Colchicine Group (850.6 ± 0.40 pg/ml). Tumor necrosis factor (TNF-α) was decreased in the Colchicine + 200 Cassia mg/kg Group (1030.93 ± 0.51 pg/ml) than in the Colchicine Group (1455.06 ± 1.25 pg/ml). A significant decrease in total protein level was observed in the Colchicine Group (2.52 ± 0.10 mg/ml), (3.33 ± 0.90 mg/ml) as compared to Colchicine + 200 Cassia mg/kg Group (5.27 ± 0.09 mg/ml, (5.01 ± 0.10 mg/ml) respectively, in the Hippocampus and Entorhinal cortex. The levels of antioxidant enzymes such as Catalase (CAT), Serum superoxide dismutase (SOD), Reduced glutathione (GSH) and Malondialdehyde (MDA) were measured. When compared to the Colchicine Group (7.33 ± 0.16 nM/ mg, the MDA level was lower in the Colchicine + 100 Cassia mg/kg Group (3.20 ± 0.01 nM/ mg). The level of CAT in Colchicine + 200 Cassia mg/kg Group (7.01 ± 0.03 μmoles of H₂O₂/mg of protein) was seen to be increased when compared to Colchicine Group (3.32 ± 0.17 μmoles of H₂O₂/mg of protein). The level of SOD in Colchicine + 200 Cassia mg/kg Group (7.43 ± 0.02 U mg -1 of protein) was seen to be increased when compared with Colchicine Group (4.55 ± 0.03 U mg -1 of protein). The level of GSH in Colchicine + 200 Cassia mg/kg Group (10.07 ± 0.19 nM/mg -1 of protein) was increased when compared with the Colchicine Group (5.82 ± 0.11nM/mg -1 of protein). Histopathology of the Hippocampus and Entorhinal cortex showed diminished amyloid plaques, and neurodegeneration in the treatment groups.

Conclusion: The present study showed that ethanolic extract from the roots of Cassia occidentalis L. At 100 and 200 mg/kg doses in Wistar rats improved memory damage, by reducing oxidative stress. Levels of the antioxidant enzymes as CAT, and SOD, GSH were increased and MDA was decreased. The cytokine levels in the serum of Wistar rats of IL-6 level and TNF-α level were reduced significantly. Estimation of total protein level was found to be increased. It restored neuronal degeneration in the Hippocampus, and Entorhinal cortex and reduced oxidative stress. This suggests that the ethanolic extract of Cassia occidentalis L. could be an effective therapeutic treatment for neurodegenerative diseases like AD.

Role of Nanomedicine for Targeted Drug Delivery in Livestock: Future Prospective

Nanotechnology has advanced significantly in recent years and is currently used in a wide range of sectors. Only a handful of the many diverse issues covered by nanotechnology include nanoscale gadgets, nanomaterials, nanoparticles, and nanomedicines. Its performance in treating a range of grave conditions, such as cancer, early detection of infections, analysis, bio-imaging, and bio sensing, suggests that it is highly advanced. Nanoscale materials have been employed for medicine delivery, pharmaceutics, and a range of diagnostic techniques due to their various biochemical and physical features. The use of nanoparticles that are based on nanotechnology can significantly improve the drug delivery mechanism. It is believed that nanoparticles capacity to improve the stability and solubility of drugs and shield them from impulsive inactivation during drug transfer makes it possible for them to capture, encapsulate, or bond with the molecules. The use of nanomedicine or nanoparticle-based tactics to combat viruses has emerged as a potentially life-saving tactic. These approaches have the power to protect both humans and animals against viruses. In order to inactivate a virus, nanoparticles have the unique capacity to connect with the virus epitope. Many nanocarriers have the potential to replace current drug delivery methods with focused drug delivery. Small dosages, low toxicity, and targeted flow of drug release at the infected location are all characteristics of nanocarriers or nanomedicine. Due to their distinct physicochemical and biological features, nanomaterial- based drug delivery systems (NBDDS) are frequently employed to enhance the safety and therapeutic efficacy of encapsulated pharmaceuticals. The program’s objective can be supported by the applications that have so far been developed. This idea is therefore essential and sophisticated for the development of civilization. Our research will therefore concentrate on how human use of nanomedicines has changed through time in many domains.

Exploring Potential of Nano-formulations in the Treatment of Alzheimer’s Disease through Nasal Route

Alzheimer's disease, a progressive neurodegenerative disorder, severely impacts cognitive function and daily living. The current treatment provides only symptomatic relief, and thus, disease-modifying therapies targeting underlying causes are needed. Although several potential therapies are in various stages of clinical trials, bringing a new Alzheimer's drug to market remains challenging. Hence, researchers are also exploring monoclonal antibodies, tau protein inhibitors, and anti-inflammatory drugs as treatment options. Conventionally designed dosage forms come with limitations like poor absorption, first-pass metabolism, and low bioavailability. They also cause systemic adverse effects because these designed systems do not provide target-specific drug delivery. Thus, in this review, the authors highlighted the current advancements in the development of intranasal nanoformulations for the treatment of Alzheimer’s disease. This strategy of delivering anti-Alzheimer drugs through the nasal route may help to target the drug exactly to the brain, achieve rapid onset of action, avoid first-pass metabolism, and reduce the side effects and dose required for administration. Delivering drugs to the brain through the nasal route for treating Alzheimer's disease is crucial due to the limited efficacy of existing treatments and the profound impact of the disease on patients and their families. Thus, by exploring innovative approaches such as nose-to-brain drug delivery, it is possible to improve the quality of life for individuals living with Alzheimer's and alleviate its societal burden.

Current Progress and Emerging Role of Essential Oils in Drug Delivery Therapeutics

The utilization of novel drug delivery systems loaded with essential oils has gained significant attention as a promising approach for biomedical applications in recent years. Plants possess essential oils that exhibit various medicinal properties, i.e., anti-oxidant, anti-microbial, anti- inflammatory, anti-cancer, immunomodulatory, etc., due to the presence of various phytoconstituents, including terpenes, phenols, aldehydes, ketones, alcohols, and esters. An understanding of conventional and advanced extraction techniques of essential oils (EOs) from several plant sources is further required before considering or loading EOs into drug delivery systems. Therefore, this article summarizes the various extraction techniques of EOs and their existing limitations. The in-built biological applications of EOs are of prerequisite importance for treating several diseases. Thus, the mechanisms of action of EOs for anti-inflammatory, anti-oxidant, anti-bacterial activities, etc., have been further explored in this article. The encapsulation of essential oils in micro or nanometric systems is an intriguing technique to render adequate stability to the thermosensitive compounds and shield them against environmental factors that might cause chemical degradation. Thus, the article further summarizes the advanced drug delivery approaches loaded with EOs and current challenges in the future outlook of EOs for biomedical applications.

Effectiveness of the Neuroimaging Techniques in the Recognition of Psychiatric Disorders: A Systematic Review and Meta-analysis of RCTs

Background: Neuroimaging has helped us learn about the stages of brain development from infancy to maturity. Neuroimaging helps physicians diagnose mental illnesses and find novel treatments for them. It can distinguish depression from neurodegenerative diseases or brain tumors, and it can reveal structural defects that cause psychosis. Psychosis has been linked to lesions in the frontal or temporal lobes of the brain, as well as the thalamus and hypothalamus, which can be detected using a brain scan for mental illnesses. Neuroimaging uses quantitative and computational methods to explore the central nervous system. It can detect brain injuries and psychological illnesses. Thus, a systematic review and meta-analysis of randomized controlled trials using neuroimaging to detect psychiatric disorders assessed their efficacy and benefits.

Materials and Methods: Appropriate articles were searched from PubMed, MEDLINE, and CENTRAL databases using the appropriate keywords as per the PRISMA guidelines. Randomized controlled trials and open-label studies were included as per the predefined PICOS criteria. Meta-analysis was performed using the RevMan software, and statistical parameters like odds ratio and risk difference were calculated.

Results: Twelve randomized controlled clinical trials with a total of 655 psychiatric patients were included following the criteria from the year 2000 to 2022. We included studies that use different neuroimaging techniques for the detection of organic brain lesions that would help diagnose psychiatric disorders. The primary outcome was detecting brain abnormalities in diverse psychiatric illnesses with neuroimaging versus conventional methods. We found the odds ratio value of 2.29 (95% CI 1.49-3.51). The results were heterogeneous with a Tau² value of 0.38, chi² value of 35.48, df value of 11, I² value of 69%, the z value of 3.78, and p-value less than 0.05. The risk difference is 0.20 (95% CI 0.09 -0.31) with heterogeneity of Tau2 value of 0.03, chi² value of 50, df value of 11, I2 value of 78%, the z value of 3.49, and p-value less than 0.05.

Conclusion: The present meta-analysis strongly recommends the use of neuroimaging techniques for the detection of psychiatric disorders.

Quantification of Iron Deposition in the Brain of Hypertensive Patients using 3D-enhanced Susceptibility-weighted Angiography (ESWAN)

Background: Cerebral microbleeds (CMBs) are commonly present in patients with hypertension, producing iron-containing metabolites. A small amount of regional iron deposition is hardly discernible on conventional magnetic resonance imaging (MRI). Three-dimensional enhanced susceptibilityweighted angiography (ESWAN) provides tissue images with high spatial resolution and signal-noise ratio, and has been widely used to measure brain iron deposition in neurodegenerative diseases and intracranial hemorrhage.

Objective: The study aimed to demonstrate iron deposition in the brain of hypertensive patients using ESWAN.

Methods: Twenty-seven hypertension patients, with or without CMBs, and 16 matched healthy controls (HCs) were enrolled. From the post-processed ESWAN images, phase and magnitude values of the regions of interest (ROIs) were calculated. Two-sample t-test and one-way variance analysis were applied to compare groups. The relationship between ESWAN parameters and clinical variables was assessed using Pearson’s correlation coefficient.

Results: Compared to HCs, the phase value of the hippocampus, head of caudate nucleus (HCN), and substantia nigra (SN) was decreased in hypertension with the CMBs subgroup, while that of HCN and SN was decreased in hypertension without CMBs subgroup. Similarly, the magnitude value of the hippocampus, HCN, thalamus red nucleus, and SN was significantly lower in the hypertension group than HCs. In addition, the phase and magnitude values showed a correlation with clinical variables, including disease duration and blood pressure.

Conclusion: Deep grey matter nuclei displayed greater iron content in hypertension patients. Iron deposition may precede the appearance of CMBs on MRI, serving as a potential marker of microvascular damage.

Advances in Imaging Techniques of the Blood-brain Barrier and Clinical Application

The blood-brain barrier (BBB) is an important structure that maintains the normal function of the central nervous system (CNS). The functional structure of BBB is closely related to diseases of CNS, including degenerative diseases, brain tumours, traumatic brain injury, stroke, etc. Imaging methods were commonly used to monitor the integrity of BBB, such as DCE-MRI, DSC-MRI, and PET, this contributes to understand the process of related diseases and develop appropriate treatment options. In recent years, many studies had shown that the MRI methods (ASL, IVIM, CEST, etc.) could evaluate blood-brain barrier function, which use endogenous contrast agents and become an increasingly great concern. Another image methods (FUS, uWB-eMPs) can open up the normal BBB, allowing macromolecular drugs across the locally opening BBB, which could be beneficial to the treatment of some brain diseases. In this review, we briefly introduce the theory of BBB imaging modalities and its clinical application.

Nano Lipid Carriers: A Novel Approach for Nose to Brain Drug Delivery

Background: A nanostructured lipid carrier (NLC) is a nanoparticulate carrier system consisting of solid lipids, liquid lipids, surfactants, and water. NLCs are second-generation lipid nanocarriers, gained continuous significance in recent times, and possess better physical stability, increased drug loading, improved permeability, and bioavailability. They are considered superior to many other traditional lipid-based nanocarriers such as nanoemulsion, liposomes, and solid lipid nanoparticles (SLN) and have emerged as an alternative to first-generation nanoparticles (SLN). NLCs have significant potential in the pharmaceutical industry due to their extensive beneficial effects, like drug targeting, enhanced bioavailability, and their wide positive benefits.

Objective: The primary aim of this review was to study and explore the Nano lipid carrier, its advantages, patent preferences, and advancement of NLCs use in nose-to-brain drug delivery.

Methods: The objective of this study was to conduct a literature review on the development of NLC for nose-to-brain drug delivery. The review focused on NLC, its significant role in nose-to-brain delivery, and relevant patents. To achieve this goal, different review articles searched, were studied, and summarized from various sources such as research articles, review articles, books, scientific reports, and patents.

Conclusion: This review article discusses the potential benefits of NLCs in brain-targeting drug delivery through the intranasal route and key aspects of NLCs, including their structure composition, formulation technique, and characterization, which are crucial for developing a reliable drug delivery.

Application of Deep Learning in the Diagnosis of Alzheimer’s and Parkinson’s Disease: A Review

Most neurodegenerative diseases such as Alzheimer's and Parkinson's are life-threatening, critical, and incurable affecting mainly the elderly population. Early diagnosis is challenging as disease phenotype is very crucial for predicting, preventing the progression, and effective drug discovery. In the last few years, Deep learning (DL) based neural networks are the state-of-the-art models deployed in industries and academics across different areas like natural language processing, image analysis, speech recognition, audio classification, and many more It has been slowly realized that they have a high potential in medical image analysis and diagnostics and medical management in general. As this field is vast and expanding rapidly, we have put focused on existing DL-based models to detect Alzheimer’s and Parkinson's in particular. This study gives a summary of related medical examinations for these diseases. Frameworks and applications of many deep learning models have been discussed. We have given precise notes on pre-processing techniques used by various studies for MRI image analysis. An overview of the application of DLbased models in different stages of medical image analysis has been conferred. It has been realized from the review that more studies are focused on Alzheimer's compared to Parkinson's disease Additionally, we have tabulated the various public datasets available for these diseases. We have highlighted the potential use of a novel biomarker for the early diagnosis of these disorders. Also, some challenges and issues in implementing deep learning techniques for the detection of these diseases have been addressed. Finally, We concluded with some future research directions regarding deep learning techniques for diagnosis of the above diseases.

Modified Exigent Features Block in JAN Net for Analysing SPECT Scan Images to Diagnose Early-Stage Parkinson’s Disease

Background: The quantitative measure of dopamine transporter (DaT) in the human midbrain is generally used as a biomarker for analyzing Parkinson’s disease (PD).

Introduction: DaT scan images or Single- photon emission computed tomography (SPECT) images are utilized to capture the dopamine content more accurately.

Methods: Only sixteen slices out of ninety-one of SPECT images were chosen on the basis of the high amount of dopamine content and were named Volume rendering image slices (VRIS). This paper proposes a novel Convolutional Neural Network (CNN) called JAN Net which particularly treats the VRIS for identifying PD. The JAN Net preserves the edges and spatial features of the striatum by using a modified exigent feature (M-ExFeat) block, that contains convolutional and additive layer. The different-sized convolutional layer extracts both low- and high-level features of Striatum. The additive layer adds up all the features of different filter sized convolutional layers like 1x1, 3x3, and 5x5. The added output features are used to improve the learnability of neurons in the hidden layer. The network performance is tested for stride 1 and stride 2.

Results: The results are validated using the dataset taken from the Parkinson’s Progression Markers Initiative (PPMI) database. The JAN Net ensures improved performance in terms of accuracy. The training and validation accuracy for stride 2 is 100% with minimum losses. The outcome has been compared with different deep learning architectures and the machine learning techniques like Extreme Learning Machines (ELM), and Artificial Neural Networks (ANN) to highlight the efficacy of the proposed architecture.

Conclusion: Hence, the present work could be of great aid to the experts in neurology to protect the neurons from impairment.

Secondary Degeneration of White Matter Tract following Basal Ganglia Infarction: A Longitudinal Diffusion Tensor Imaging Study

Introduction: We explored the relationship between secondary degeneration of white matter (WM) tracts and motor outcomes after left basal ganglia infarction and investigated alterations in the diffusion indices of WM tracts in distal areas.

Methods: Clinical neurological evaluations were accomplished using the Fugl–Meyer scale (FMS). Then, the fractional anisotropy (FA) of the bilateral superior corona radiata (SCR), cerebral peduncle (CP), corticospinal tracts (CST), and corpus callosum (CC) were measured in all patients and control subjects.

Results: Regional-based analysis revealed decreased FA values in the ipsilesional SCR, CP, and CST of the patients, compared to the control subjects at 5- time points. The relative FA (rFA) values of the SCR, CP, and CST decreased progressively with time, the lowest values recorded at 90 days before increasing slightly at 180 days after stroke. Compared to the contralateral areas, the FA values of the ipsilesional SCR and CST areas were significantly decreased (P=0.023), while those of the CP decreased at 180 days (P=0.008). Compared with the values at 7 days, the rFA values of the ipsilesional SCR and CP areas were significantly reduced at 14, 30, and 90 days, while those in the CST area were significantly reduced at 14, 90, and 180 days. The CP rFA value at 7 days correlated positively with the FM scores at 180 days (r=0.469, P=0.037).

Conclusion: This study provides an objective, comprehensive, and automated protocol for detecting secondary degeneration of WM, which is important in understanding rehabilitation mechanisms after stroke.

CMC and QMS Regulatory Requirements and Challenges for mRNA-based Vaccines

Biopharmaceuticals differ significantly from chemical drugs, and thus their CMC regulatory compliance is distinct from them. The development of biologicals, like mRNA vaccines, holds promise for preventing infectious diseases and generating an antigen-specific immune response. These vaccines are a better option than traditional vaccination methods because of their significant potency and swift and affordable manufacture. The compliance strategy is shaped by evaluating resource allocation and risk tolerance. This review examines the CMC regulatory requirements concerned with the manufacturing of biologics, particularly mRNA vaccines. The many challenges that could arise when producing biological products are also discussed in this paper, like the introduction of adventitious agents that can affect the safety of the product and the molecular designs of mRNA molecules, which may need to be optimized for higher protein expression and improved structural stability. By implementing the Quality by Design approach during the development, a better understanding of the controls and risk management should be utilized to minimize the risk and improve compliance.

Exploring the Efficacy of Herbal Medications in the Treatment of Parkinsonism: A Mini Review

Background: Over 10 million people worldwide are affected by the chronic neurodegenerative condition of Parkinson's disease. Dopaminergic neurons in the Substantia Nigra area of the brain are gradually lost as a result. Herbal medicine, which have its roots in ancient cultures, uses medicinal herbs to treat illnesses and advance general health. There is considerable interest in researching the possibilities of herbal medicine for treating neurodegenerative diseases like Parkinson's disease because they are thought to be safer than synthetic medications.

Objective: The objective of this article is to investigate the potential of herbal medications as a treatment option for Parkinsonism, and to provide a clear understanding of the current state of research on this topic.

Conclusion: This review focuses on herbal treatments and components that have demonstrated promise in Parkinson's disease in vitro and animal models. This information can be used to identify prospective traditional medicine prescription therapies. New therapeutic treatments for Parkinson's disease may result from further study of pharmaceutical components with well-established therapeutic potential.

Osteogenic Differentiation of Adipose Tissue-Derived Mesenchymal Stem Cells on Composite Polymeric Scaffolds: A Review

The mesenchymal stem cells (MSCs) are the fundamental part of bone tissue engineering for the emergence of reconstructive medicine. Bone tissue engineering has recently been considered a promising strategy for treating bone diseases and disorders. The technique needs a scaffold to provide an environment for cell attachment to maintain cell function and a rich source of stem cells combined with appropriate growth factors. MSCs can be isolated from adipose tissue (ASCs), bone marrow (BM-MSCs), or umbilical cord (UC-MSCs). In the present study, the potential of ASCs to stimulate bone formation in composite polymeric scaffolds was discussed and it showed that ASCs have osteogenic ability in vitro. The results also indicated that the ASCs have the potential for rapid growth, easier adipose tissue harvesting with fewer donor site complications and high proliferative capacity. The osteogenic differentiation capacity of ASCs varies due to the culture medium and the addition of factors that can change signaling pathways to increase bone differentiation. Furthermore, gene expression analysis has a significant impact on improving our understanding of the molecular pathways involved in ASCs and, thus, osteogenic differentiation. Adding some drugs, such as dexamethasone, to the biomaterial composite also increases the formation of osteocytes. Combining ASCs with scaffolds synthesized from natural and synthetic polymers seems to be an effective strategy for bone regeneration. Applying exopolysaccharides, such as schizophyllan, chitosan, gelatin, and alginate in composite scaffolds enhances the osteogenesis potential of ASCs in bone tissue regeneration.

Targeting Epigenetic Modifiers: Promising Strategies for Cancer Therapy and Beyond

Epigenetic changes are important for controlling how genes are expressed and how cells work, and their misregulation has been linked to many diseases, including cancer. Targeting epigenetic modifiers has become a promising way to treat cancer, and it may also be useful outside of oncology. This review article goes into detail about the rapidly changing field of epigenetic-based therapies, with a focus on how they are used to treat cancer. We discuss in-depth the main epigenetic changes seen in cancer, such as DNA methylation, changes to histones, and dysregulation of noncoding RNA, as well as their roles in tumour growth, metastasis, and drug resistance. Epigenetic drugs and small molecule inhibitors that target epigenetic enzymes and reader proteins have shown a lot of promise in both preclinical and clinical studies on different types of cancer. We show the most recent evidence that these epigenetic therapies work and look into how they might be used in combination with other treatments. We talk about new research into the therapeutic potential of epigenetic modifiers in diseases other than cancer, such as neurological disorders, autoimmune diseases, and heart conditions. Even though there is a lot of potential for therapy, there are still problems, such as side effects and differences between patients. We talk about the work that is still being done to get around these problems and explain new ways to deliver epigenetic-based interventions that are more precise and effective. For epigenetic-based therapies to be used in clinical settings, it is important to understand how they work and how they interact with other types of treatment. As the field moves forward, we try to figure out where it is going and what it means to target epigenetic modifiers in cancer therapy and other areas of disease. This review looks at the role of epigenetic modulation in shaping the landscape of precision medicine and its possible effects on human health from a broad and forward-looking point of view.

Effect of Per and Poly-Fluoroalkyl Substances on Pregnancy and Child Development

Background: Childhood obesity is significantly influenced by maternal exposure to Per and Poly-Fluoroalkyl Substances (PFAS) during pregnancy. PFAS exposure occurs through the Peroxisome Proliferator-Activated Receptor (PPAR-γ) receptor, leading to increased fat deposition and profound health effects in child growth and development. Despite ongoing investigations, the relationship between maternal serum PFAS concentration and child obesity requires further exploration.

Objective: This study aimed to review the possible effects of Per and poly-fluoroalkyl substances exposure and their mechanism in overweight/obese children from pregnant ladies.

Methods: A detailed literature survey was conducted using online databases, including Science Direct, Google Scholar, Scopus, Cochrane, and PubMed. The study focused on the diverse effects of PFAS on maternal and child health, with particular emphasis on neurological complications.

Results: Child growth development depends upon breastfeeding and placenta health, which is disrupted by PFAS exposure, ultimately destroying the body mass index of the child. Neurotoxicity testing utilized the SH-SY5Y human-derived cell line as an in vitro model, revealing PFAS-induced increases in adipocyte number, reduced cell size, altered lipid conglomeration, increased adiposity, and changes in liver function. in vivo studies in mice and human cell lines indicated PPAR-γ and ER-α activation, leading to adiposity and weight gain through Estrogen signaling and Lipid metabolism. PFAS concentrations positively correlated in maternal sera, analyzed by liquid chromatography/quadrupole mass spectrometry.

Conclusion: PFAS, with a long half-life of 3.5-8.5 years, is commonly found in the serum of pregnant women, crossing the placenta barrier. This exposure disrupts placental homeostasis, negatively impacting mechanisms of action and potentially leading to deterioration in pregnancy and child health. Further research is needed to comprehensively understand the complex interplay between PFAS exposure and its implications for maternal and child well-being.

The Neuroprotective Properties of Thymol and Carvacrol: A Review Study

Over the past few decades, researchers have become interested in natural compounds and their potential to prevent and treat diseases. Phenolic monoterpenoids, thymol and carvacrol, are quickly absorbed into the bloodstream through the gastrointestinal tract. Studies conducted in vitro and in vivo have shown that both thymol and carvacrol have anti-inflammatory, antioxidant, and antiapoptotic properties. Research indicates these compounds can easily cross the blood-brain barrier and offer neuroprotective effects. They are both very safe and have no toxicity in therapeutic doses. This review focuses on the neuroprotective effects of thymol and carvacrol and analyzes their impact on the central nervous system, including their antioxidant and anti-inflammatory effects. The report also highlights their potential influence on neurodegenerative diseases like Parkinson's and Alzheimer's, emotional disorders, and brain and spinal cord ischemia.

Beneficial Effects of Spirulina on Brain Health: A Systematic Review

Background: This review provides a concise overview of existing scientific research concerning the potential advantages of incorporating spirulina, a blue-green algae, into one's diet to promote brain health. The substantial nutritional composition and associated health benefits of algae have drawn significant interest.

Methods: Numerous studies have illuminated the neuroprotective characteristics of spirulina, contributing to its positive influence on brain functionality. Primarily, spirulina boasts antioxidants, like phycocyanin and beta-carotene, that effectively counter oxidative stress and curb inflammation within the brain. This is particularly significant as these factors play roles in the advancement of neurodegenerative conditions like Parkinson's and Alzheimer's disease. Additionally, spirulina has demonstrated the capacity to enhance cognitive capabilities and enrich memory and learning aptitudes.

Results: Animal-based investigations have revealed that introducing spirulina can bolster spatial learning and memory, as well as guard against cognitive decline linked to aging. Research has indicated its potential in shielding against neurotoxins, encompassing heavy metals and specific environmental pollutants. Its potential to neutralize heavy metals and counteract free radicals contributes to these protective effects, potentially thwarting neuronal harm.

Conclusion: In conclusion, the extant scientific literature proposes that spirulina integration can elicit advantageous outcomes for brain health. Its antioxidative, neuroprotective, cognitiveenhancing, and mood-regulating properties present a promising avenue for bolstering brain health and potentially diminishing the susceptibility to neurodegenerative ailments. Nonetheless, further research, notably well-designed human clinical trials, is imperative to ascertain the optimal dosing, duration, and enduring consequences of spirulina supplementation concerning brain health.

In silico Evaluation of the Feasibility of Magnolia officinalis Electron-shuttling Compounds as Parkinson’s Disease Remedy

Background: Parkinson’s Disease is one of the leading neurodegenerative disorders in the world. Currently, there is still no treatment that could completely cure the disease. Traditional Chinese Medicine has been a source for drug candidates, and many studies have elucidated its pharmacokinetic capabilities. Previous studies showed that Magnolia officinalis has anti-inflammatory, antioxidant, and bioenergy generation activities. Furthermore, the electron-shuttling and bioenergy-stimulating capabilities of herbal and brain disorder medicines have been linked to their effectiveness as a remedy.

Objective: This preliminary study aims to evaluate the electron-shuttling compounds of Magnolia officinalis (i.e., acteoside, isoquercitrin, magnatriol B, obovatol, quercitrin, randaiol, and rutin) as potential drug candidates for Parkinson’s Disease.

Methods: The seven electron-shuttling compounds were individually docked to the five Parkinson’s Disease-related proteins, namely aromatic L-amino acid decarboxylase, α-synuclein, monoamine oxidase B, catechol-o-methyltransferase, and A_2A adenosine receptor, using LibDock. ADMET predictions were also made to screen the compounds further.

Results: Molecular docking results showed that all compounds have relatively high LibDock scores against the proteins, with acteoside, isoquercitrin, and rutin having the highest scores. However, considering the ADMET results, only magnatriol B, obovatol, and randaiol had optimal properties as candidates for neurodegenerative drugs.

Conclusion: The electron-shuttling compounds of M. officinalis, magnatriol B, obovatol, and randaiol, have the potential to be a remedy for Parkinson’s Disease due to their high probability of binding to the proteins.

Neurotrophin-3 Rescues Striatal Synaptic Plasticity in Model of Neurodegeneration by PLC Signaling Activation

Background: Neurotrophins are essential factors for neural growth and function; they play a crucial role in neurodegenerative diseases where their expression levels are altered. Our previous research has demonstrated changes in synaptic plasticity and neurotrophin expression levels in a pharmacological model of Huntington's disease (HD) induced by 3-nitropropionic acid (3-NP). In the 3-NP-induced HD model, corticostriatal Long Term Depression (LTD) was impaired, but neurotrophin- 3 (NT-3) restored striatal LTD. This study delves into the NT-3-induced signaling pathways involved in modulating and restoring striatal synaptic plasticity in cerebral slices from 3-NPinduced striatal degeneration in mice in vivo.

Methods: Phospholipase C (PLC), phosphatidylinositol-3-kinase (PI3K), and mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK) pathways activated by NT-3 were analyzed by means of field electrophysiological recordings in brain slices from control and 3-NP treated in the presence of specific inhibitors of the signaling pathways.

Results: Using specific inhibitors, PLC, PI3K, and MEK/ERK signaling pathways contribute to NT-3-mediated plasticity modulation in striatal tissue slices recorded from control animals. However, in the neurodegeneration model induced by 3-NP, the recovery of striatal LTD induced by NT-3 was prevented only by the PLC inhibitor. Moreover, the PLC signaling pathway appeared to trigger downstream activation of the endocannabinoid system, evidenced by AM 251, an inhibitor of the CB1 receptor, also hindered NT-3 plasticity recovery.

Conclusion: Our finding highlights the specific involvement of the PLC pathway in the neuroprotective effects of NT-3 in mitigating synaptic dysfunction under neurodegenerative conditions.

Intranasal Route an Alternative Approach for Systemic Drug Delivery: Recent Strategies and Progression

Intranasal administration has proven to be a viable alternative for local and systemic delivery of varied therapeutic agents. This route has been potentially researched for delivering polar compounds, vaccines, hormones, peptides, proteins, etc. Being non-invasive and painless with a fast onset of action (both local and systemic), intranasal has become an ideal route for medication to children. This route is specifically employed for the delivery of drugs that are unstable in GIT, which gets significantly degraded or metabolized by the first-pass effect. The nasal route's high absorption and permeability profile has led to its exploration as a substitute for parenteral delivery. This paper reviews the feasibility and potentials of intranasal administration, discussing its benefits, drawbacks, market analysis, factors affecting nasal drug delivery system, conventional and novel strategies (polymeric and nano-carrier-based delivery systems) to improve nasal absorption and its clinical management of varied systemic and topical disorders viz. neurodegenerative, pulmonary, microbial, neoplastic, etc.

Fucoxanthin Enhances the Antifibrotic Potential of Placenta-derived Mesenchymal Stem Cells in a CCl4-induced Mouse Model of Liver

Background: The effectiveness of fucoxanthin (Fx) in liver diseases has been reported due to its anti-inflammatory and antifibrotic effects. Mesenchymal stem cells (MSCs)-based therapy has also been proposed as a promising strategy for liver fibrosis treatment. Recent studies have shown that the co-administration of MSCs and drugs demonstrates a pronounced effect on liver fibrosis.

Aim: This study aimed to determine the therapeutic potential of placenta-derived MSCs (PD-MSCs) in combination with Fx to treat liver fibrosis and evaluate their impact on the main links of liver fibrosis pathogenesis.

Methods: After PD-MSCs isolation and identification, outbred ICR/CD1 mice were divided into five groups: Control group, CCl₄ group (CCl₄), Fx group (CCl₄+Fx), PD-MSCs group (CCl₄+MSCs) and cotreatment group (CCl₄+MSCs+Fx). Biochemical histopathological investigations were performed. Semiquantitative analysis of the alpha-smooth muscle actin (α-SMA+), matrix metalloproteinases (MMP-9+, MMP-13+), tissue inhibitor of matrix metalloproteinases-1 (TIMP-1+) areas, and the number of positive cells in them were studied by immunohistochemical staining. Transforming growth factor-beta (TGF-β), hepatic growth factor (HGF), procollagen-1 (COL1α1) in liver homogenate and proinflammatory cytokines in blood serum were determined using an enzyme immunoassay.

Results: Compared to the single treatment with PD-MSCs or Fx, their combined administration significantly reduced liver enzyme activity, the severity of liver fibrosis, the proinflammatory cytokine levels, TGF-β level, α-SMA+, TIMP-1+ areas and the number of positive cells in them, and increased HGF level, MMP-13+, and MMP-9+ areas.

Conclusion: Fx enhanced the therapeutic potential of PD-MSCs in CCl4-induced liver fibrosis, but more investigations are necessary to understand the mutual impact of PD-MSCs and Fx.

Neurobiochemical Disturbances in Psychosis and their Implications for Therapeutic Intervention

Psychosis, marked by the emergence of psychotic symptoms, delves into the intricate dance of neurotransmitter dynamics, prominently featuring dopamine as a key orchestrator. In individuals living with psychotic conditions, the finely tuned balance of dopamine becomes disrupted, setting off a cascade of perceptual distortions and the manifestation of psychotic symptoms. A lot of factors can impact dopamine metabolism, further complicating its effects. From genetic predispositions to environmental stressors and inflammation, the delicate equilibrium is susceptible to various influences. The sensorium, the origin of incoming information, loses its intrinsic valence in this complex interplay. The concept of the “signal-to-noise ratio” encapsulates dopamine's role as a molecular switch in neural networks, influencing the flow of information serving the basic biological functions. This nuanced modulation acts as a cognitive prism, shaping how the world is perceived. However, in psychosis, this balance is disrupted, steering individuals away from a shared reality. Understanding dopamine's centrality requires acknowledging its unique status among neurotransmitters. Unlike strictly excitatory or inhibitory counterparts, dopamine's versatility allows it to toggle between roles and act as a cognitive director in the neural orchestra. Disruptions in dopamine synthesis, exchange, and receptor representation set off a chain reaction, impacting the delivery of biologically crucial information. The essence of psychosis is intricately woven into the delicate biochemical ballet choreographed by dopamine. The disruption of this neurotransmitter not only distorts reality but fundamentally reshapes the cognitive and behavioral field of our experience. Recognizing dopamine's role as a cognitive prism provides vital insights into the multifaceted nature of psychotic conditions, offering avenues for targeted therapeutic interventions aimed at restoring this delicate neurotransmitter balance.

Neuroprotective and Nootropic Evaluation of some Important Medicinal Plants in Dementia: A Review

Dementia is a devitalising decline in neurological acuity, which burdens both high- and lowincome countries due to poor diagnostic systems and high healthcare costs. A growing population and rises in deleterious environmental and genetic anomalies aggravate new and aggressive cases of dementia and neurodegenerative disorders. The unparalleled capability of medicinal plants is constantly explored in treating neurological disorders, and some of these phytocompounds are used for treating diseases. However, some of these metabolites are neurotoxic and disrupt DNA polymerase functions. They possess lifethreatening side effects and are unable to prevent disease progression. Therefore, it is important to focus on discovering novel compounds from new medicinal plants. Our review encompasses some medicinal plant metabolites recently explored in treating this disease. We also summarized the molecular mechanism of action as determined in in-vitro: the toxic dose, nootropic and neuroprotective effects on neurophysiology and neurotransmitter levels, and the antioxidant effects.

Therapeutic and Health Promoting Potential of Terminalia chebula: An Exploratory Literature Review

The plant Terminalia chebula has been used traditionally in many regions of the world for its therapeutic properties, especially in India. Its therapeutic and health-promoting potential has been recognized for centuries, and modern research continues to unveil its numerous benefits. One of the most significant applications of this plant is its antimicrobial and antioxidant potential. The plant contains high levels of phenolic compounds and flavonoids, which scavenge harmful free radicals in the body, reducing oxidative stress and cellular damage. This antioxidant action contributes to its anti-inflammatory effects, making it beneficial for a wide range of conditions, including arthritis, cardiovascular diseases, and neurodegenerative disorders. Furthermore, Terminalia chebula exhibits antimicrobial activity against various bacteria and fungi, including those responsible for common infections. It has been used to treat respiratory infections, urinary tract infections, and skin ailments. Its broad-spectrum antimicrobial effects make it a valuable natural remedy for combating microbial pathogens. Moreover, Terminalia chebula shows potential in managing diabetes and promoting cardiovascular health. Studies have indicated its ability to regulate blood sugar levels, improve insulin sensitivity, and reduce lipid abnormalities. These properties make it a promising adjunct therapy for individuals with diabetes or at risk of heart disease. In conclusion, Terminalia chebula possesses remarkable therapeutic and health-promoting potential. Its antioxidant, anti-inflammatory, antimicrobial, and digestive benefits make it a valuable natural remedy for various ailments. While research on Terminalia chebula is ongoing, its long-standing use in traditional medicine and emerging scientific evidence solidify its status as a potent medicinal plant with diverse applications in promoting overall well-being.

The Role of Resveratrol in Alzheimer's Disease: A Comprehensive Review of Current Research

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive cognitive decline, memory loss, and impaired daily functioning. The etiology of AD is complex and multifactorial, involving various pathological mechanisms such as the accumulation of amyloid-beta plaques, neurofibrillary tangles, neuroinflammation, and oxidative stress. As the global prevalence of AD continues to rise, there is a growing interest in identifying potential therapeutic interventions to prevent or slow down the progression of the disease. Resveratrol, a natural polyphenolic compound found in various plant sources such as grapes, berries, and peanuts, has gained considerable attention due to its potential neuroprotective effects. Numerous preclinical studies utilizing in vitro and animal models have investigated the impact of resveratrol on AD pathology and associated cognitive impairments. This review aims to provide a comprehensive summary of the current research on the role of resveratrol in AD. In conclusion, resveratrol holds promise as a potential therapeutic agent for AD due to its ability to target multiple pathological processes involved in the disease. Further research, including well-designed clinical trials with larger sample sizes, is needed to fully elucidate the efficacy, optimal dosage, and long-term effects of resveratrol in AD patients. Nevertheless, resveratrol remains an intriguing compound with neuroprotective properties and may contribute to the development of novel therapeutic approaches for AD in the future.

A Comprehensive Study of Allium Sativum Linn

Allium Sativum, commonly known as garlic, has been employed for ages for both cuisines and restorative purposes. Many sulfur-containing phytochemical constituents are abundant in garlic and they are responsible for its many pharmacological properties. The most extensively studied compound in garlic is allicin, however, other forms of garlic such as aged garlic, raw garlic, and oil maceration of garlic, have their own unique chemical properties. Garlic has been shown to lower blood pressure, reduce cholesterol levels, improve insulin sensitivity, inhibit cell proliferation, enhance peristalsis motion, modulate acetylcholine, and inhibit lipid oxidation. Apart from all its traditional therapeutic activity, it has much more potential for further study such as cancer treatment with lesser side-effects, improving mitochondrial dysfunction in Huntington’s disease, enhancement psoriasis treatment, affinity to treat glomerular disease, and vast scope in polycystic ovary syndrome and in uterine contraction. This review talks about pharmacology activities, future aspects, phytochemicals, and the privileged aspects of Allium Sativum.

Phytochemicals as Substances that Affect Astrogliosis and their Implications for the Management of Neurodegenerative Diseases

Astrocytes are a multifunctional subset of glial cells that are important in maintaining the health and function of the central nervous system (CNS). Reactive astrocytes may release inflammatory mediators, chemokines, and cytokines, as well as neurotrophic factors. There may be neuroprotective (e.g., cytokines, like IL-6 and TGF-b) and neurotoxic effects (e.g., IL-1β and TNF-a) associated with these molecules. In response to CNS pathologies, astrocytes go to a state called astrogliosis which produces diverse and heterogenic functions specific to the pathology. Astrogliosis has been linked to the progression of many neurodegenerative disorders. Phytochemicals are a large group of compounds derived from natural herbs with health benefits. This review will summarize how several phytochemicals affect neurodegenerative diseases (e.g., Alzheimer’s disease, Huntington’s disease, amyotrophic lateral sclerosis, and Parkinson’s disease) in basic medical and clinical studies and how they might affect astrogliosis in the process.

Organelle Targeted Drug Delivery: Key Challenges, Recent Advancements and Therapeutic Implications

Organelle-specific targeted drug delivery has emerged as a promising approach in the field of drug delivery and therapeutics. This innovative strategy involves the precise delivery of therapeutic agents to specific organelles within cells, such as the nucleus, mitochondria, endoplasmic reticulum, or lysosomes, with the aim of enhancing drug efficacy while minimizing offtarget effects. Despite its tremendous potential, organelle-specific drug delivery faces several key challenges. One major challenge is the development of delivery systems that can accurately navigate the complex intracellular environment and deliver drugs exclusively to the desired organelles. Achieving this level of precision demands advanced nanotechnology and biomaterials engineering. Furthermore, ensuring the safety and biocompatibility of these delivery systems is paramount. Recent advancements in this field include the development of nanocarriers, such as liposomes, nanoparticles, and dendrimers, designed to target specific organelles through ligandreceptor interactions or pH-responsive mechanisms. Additionally, advancements in molecular biology and genetic engineering have enabled the design of genetically encoded organellespecific drug delivery systems. The therapeutic implications of organelle-specific drug delivery are vast. This approach has the potential to revolutionize the treatment of diseases with organelle- specific pathologies, such as neurodegenerative disorders, cancer, and mitochondrial diseases. By precisely targeting the organelles involved in disease progression, the efficacy of therapies can be significantly improved while minimizing collateral damage to healthy tissues.

Lifestyle, Environment, and Dietary Measures Impacting Cognitive Impairment: The Evidence Base for Cognitive Subtypes

Cognition includes all phases of valid functions and processes, e.g., sensitivity, judgment, assessment, and decision-making. Thinking is also a cognitive procedure since it involves considering potential opportunities. There are various types of cognition. Hot cognition involves mental procedures where emotion plays a role, while cold cognition includes mental processes that do not include feelings or emotions. Cognitive memories of various types include sensor memory, sensing touch, smell, and sight; short-term memory allows one to recall, e.g., what one had for lunch a few days ago; working memory includes remembering telephone numbers or directions to a destination; and long-term memory comprises of major milestones in life and recalling one’s childhood events. These are further classified as episodic, e.g., the first day in primary school, and semantic memories, such as recalling the capital city of a country and filling out crossword puzzles. Declarative memories include remembering significant past events, such as global information. Cognition is affected by factors, such as nutrition, aging, addiction, environment, mental health, physical activity, smoking, and keeping the brain active. Consumption of plant- based foods plays a prominent role in the prevention of cognitive memory. Playing games and instruments, reading books, and being socially active make life more satisfying, thus assisting in the preservation of mental function and slowing mental decline.

Opportunities and Regulatory Challenges of Functional Foods and Nutraceuticals During COVID-19 Pandemic

The novel Coronavirus has brought global mortality, disruption, and a significant loss of life. A compromised immune system is a known risk factor for all viral influenza infections. Due to the perceived “immune-boosting” properties of nutraceutical products, sales of dietary supplements have grown globally. In recent years, consumers have increasingly demanded nutraceutical products rather than curative synthetic medicines for preventive therapies for the coronavirus disease outbreak of 2019 (COVID-19). Healthy foods and nutraceuticals have become daily diet plans for consumers. Although there has been an increase in demand, there is no such regulation and harmonized process, which stands as a barrier to the approval of these products. Therefore, many misbranded and spurious products are entering the market, which may harm consumers. This article focuses on the role of functional foods and nutraceutical in the management of COVID-19 also focuses on the different nutraceutical regulations in each country and compare the similarities and differences of the following countries: India, the USA (United States of America), the EU (European Union), and China. The comparative study of nutraceutical regulations in India, the USA, Europe, and China shows that there is a difference regarding the nutraceutical regulations; however, despite the differences, it is observed that it has the same underlying objective, i.e., ensuring the safety of the consumers by maintaining the product quality.

Curcumin and Curcumin Derivatives for Therapeutic Applications: In vitro and In vivo Studies

Curcumin is a naturally derived phytochemical compound obtained from the turmeric plant Curcuma longa L. (Zingiberaceae family), which is a popular spice and food color and has been actively researched for decades. It has been shown to have a variety of pharmacological properties both in vitro and in vivo. Several investigations have shown that curcumin's metabolites contribute to its pharmacological effectiveness. Curcumin has potent anti-inflammatory and anti-tumor activity when used alone or in conjunction with conventional treatments. There are various unique and diverse pharmacological effects of curcumin against various disease conditions like diabetes, inflammation, cancer, malaria, and Alzheimer's. The in vitro and in vivo mechanisms by which curcumin exerts its pharmacological effects are reviewed. Based on data from the clinical and experimental evaluation of curcumin in animal models and human subjects, the review summarizes the pharmacological effect of curcumin and its derivatives concerning anti-tumor property, their mechanism of action, and their cellular target. The current research focuses on identifying curcumin's function in the immune system's cascade and determining the ideal effective dose (ED50). Through in-vitro and in-vivo experiments, the current study aims to comprehend and establish the role of curcumin in the healing of disease conditions.

Impact of Bioactive Compounds in the Management of Various Inflammatory Diseases

Inflammation is an individual’s physiological response to a sequence of physical, chemical, or infectious stressors acting mainly to provide localized protection. Although inflammation is a protective and thus beneficial process, its excess or prolonged action can be harmful to the body. An increasing number of the population worldwide are changing their lifestyles, which leads to a rise in inflammatory diseases, such as atherosclerosis, angina pectoris, myocardial infarction, ulcerative colitis, cancer, and many more. Their treatment is based majorly on the pharmacological approach. However, natural products or bioactive compounds are of great significance in inflammation therapy because they show minimum side effects and maximum bioavailability. Therefore, it is critical to investigate bioactive substances that can modify target functions associated with oxidative stress defense and might be used to achieve various health benefits. This review accentuates the essence of bioactive chemicals used in the treatment of inflammation and other inflammatory illnesses. These bioactive compounds can be of any origin, such as plants, animals, bacteria, fungi, marine invertebrates, etc. Bioactive compounds derived from plant sources, such as glycyrrhizin, lignans, lycopene, resveratrol, indoles, and phenolic and polyphenolic compounds, work mainly by reducing oxidative stress and thereby preventing various inflammatory disorders. A large diversity of these anti-inflammatory bioactive compounds has also been discovered in marine environments, giving rise to an increase in the interest of various scientists in marine invertebrates and microbes. The vast diversity of microbes found in the marine environment represents an enormous supply to extract novel compounds, such as from bacteria, cyanobacteria, fungi, algae, microalgae, tiny invertebrates, etc. In the present review, an attempt has been made to summarize such novel bioactive compounds that help prevent inflammatory responses via different mechanisms of action.

Pharmacological Mechanism of Herbal Interventions for Bipolar Disorder

Bipolar disorder is a neuropsychiatric disease characterized by an abundance of undesired ideas and thoughts associated with recurrent episodes of mania or hypomania and depression. Alterations in the circuits, including the prefrontal cortex, striatum, and limbic system, regulate mood and cause variation in several crucial neurotransmitters, including serotonin, dopamine, GABA, and glutamate. Imbalances in dopamine levels have been implicated in the manic phase, while variance in serotonin is linked to depressive episodes. The precise pathophysiology of bipolar disorder is still unknown. Though different treatments are available, like lithium, risperidone, valproic acid, etc., which are widely used, they come with certain limitations, including narrow therapeutic index, hypothyroidism, weight gain, extrapyramidal symptoms, etc. The interest in herbal- based treatments for bipolar disorder arises from the desire for alternative, potentially more natural, and holistic approaches with fewer side effects. The current review focuses on the potential effects of herbal drugs and their derivatives to alleviate the symptoms of bipolar disorder.

Role of Artificial Intelligence in Diabetic Wound Screening and Early Detection

The morbidity and death rates linked to diabetes mellitus are substantially increased by foot ulcers, a prevalent consequence of the disease. Proper wound management is essential for controlling foot ulcers. This includes monitoring the ulcers' healing progress through clinical reviews, changing dressings as needed, treating infections with the right medications, and ensuring that the ulcer is offloaded correctly. Taking pictures of the ulcer was a dependable way to track how diabetic foot ulcers were healing in the past. Images of foot ulcers have recently experienced a tremendous change due to the emergence of digital cameras in cell phones. Artificial intelligence (AI) and other recent developments in digital health technology present a great chance to improve the efficiency of diabetes care, which might reduce the growth in healthcare costs associated with diabetes. Patients with diabetes can alleviate the burden on clinics and patients' transportation demands by electronically sharing photos of their ulcers, which diabetes care providers can remotely monitor. Improved remote monitoring of diabetic foot ulcers using smartphone apps is now possible with the help of a new generation of AI-powered solutions. This clinical update review aims to gather information on this trending topic so that medical professionals can be current on all the latest advancements in the field.

Role of miRNAs in Brain Development

Non-coding RNAs that are small in size, called microRNAs (miRNAs), exert a consequence in neutralizing gene activity after transcription. The nervous system is a massively expressed organ, and an expanding body of research reveals the vital functions that miRNAs play in the brain's growth and neural activity. The significant benefit of miRNAs on the development of the central nervous system is currently shown through new scientific methods that concentrate on targeting and eradicating vital miRNA biogenesis pathways the elements involving Dicer and DGCR8. Modulation of miRNA has been associated with numerous essential cellular processes on neural progenitors, like differentiation, proliferation, and destiny determination. Current research discoveries that emphasize the significance of miRNAs in the complex process of brain development are included in this book. The miRNA pathway plays a major role in brain development, its operational dynamics, and even diseases. Recent studies on miRNA-mediated gene regulation within neural discrepancy, the circadian period and synaptic remodeling are signs of this. We also discussed how these discoveries may affect our comprehension of the fundamental processes behind brain diseases, highlighting the novel therapeutic opportunities miRNAs provide for treating various human illnesses.

Urinary miRNAs: Technical Updates

Due to its non-invasive nature and easy accessibility, urine serves as a convenient biological fluid for research purposes. Furthermore, urine samples are uncomplicated to preserve and relatively inexpensive.

MicroRNAs (miRNAs), small molecules that regulate gene expression post-transcriptionally, play vital roles in numerous cellular processes, including apoptosis, cell differentiation, development, and proliferation. Their dysregulated expression in urine has been proposed as a potential biomarker for various human diseases, including bladder cancer. To draw reliable conclusions about the roles of urinary miRNAs in human diseases, it is essential to have dependable and reproducible methods for miRNA extraction and profiling.

In this review, we address the technical challenges associated with studying urinary miRNAs and provide an update on the current technologies used for urinary miRNA isolation, quality control assessment, and miRNA profiling, highlighting both their advantages and limitations.

Naringenin Nanoformulations for Neurodegenerative Diseases

Glioblastoma (GBM) is a grade-IV astrocytoma, which is the most common and aggressive type of brain tumor, spreads rapidly and has a life-threatening catastrophic effect. GBM mostly occurs in adults with an average survival time of 15 to 18 months, and the overall mortality rate is 5%. Significant invasion and drug resistance activity cause the poor diagnosis of GBM. Naringenin (NRG) is a plant secondary metabolite byproduct of the flavanone subgroup. NRG can cross the blood-brain barrier and deliver drugs into the central nervous system when conjugated with appropriate nanocarriers to overcome the challenges associated with gliomas through naringenin-loaded nanoformulations. Here, we discuss several nanocarriers employed that are as delivery systems, such as polymeric nanoparticles, micelles, liposomes, solid lipid nanoparticles (SLNs), nanosuspensions, and nanoemulsions. These naringenin-loaded nanoformulations have been tested in various in vitro and in vivo models as a potential treatment for brain disorders. This review nanoformulations of NRG can a possible therapeutic alternative for the treatment of neurological diseases are discussed.

Curcumin in Cancer Prevention: Insights from Clinical Trials and Strategies to Enhance Bioavailability

Cancer remains a leading cause of death worldwide, and current cancer drugs often have high costs and undesirable side effects. Additionally, the development of drug resistance can reduce their effectiveness over time. Natural products have gained attention as potential sources for the treatment and prevention of various diseases. Curcumin, an extract from turmeric (Curcuma longa), is a natural phenolic compound with diverse pharmacological properties, including antioxidant, anti-inflammatory, antiviral, antibacterial, antifungal, antiprotozoal, antidiabetic, antivenom, antiulcer, anticarcinogenic, antimutagenic, anticoagulant, and antifertility activities. Given the increasing interest in curcumin for cancer prevention, this review aims to comprehensively examine clinical trials investigating the use of curcumin in different types of cancer. Additionally, effective techniques and approaches to enhance the bioavailability of curcumin are discussed and summarized. This review article provides insights into the properties of curcumin and its potential as a future anticancer drug.

Bile Acid Nanoparticles - An Emerging Approach for Site Specific Drug Targeting

Bile acids, a group of steroidal acids present in the bile act as biological surfactants and ligands for bile acid transporter proteins for signalling molecules to perform various paracrine and endocrine functions. The enterohepatic circulation of bile acids can be exploited to develop attractive drug delivery approaches with improved targetability of facial amphiphiles and enhanced drug bioavailability by improving absorption and metabolic stability. The effectiveness, safety and targetability of nanoparticles conjugated with bile acids and salts have been discussed in the present review. Various modifications of bile acids promoting absorption and oral bioavailability of drugs for treatment of various disease conditions such as cancer, diabetes and psychosis has also been discussed. Additionally, neuroprotective effect of bile acids and salts has demonstrated utility in various neurodegenerative disorders. Nanoparticles based on bile acids and salts represent an area of emergent interest due to their unique and modifiable properties for improving effectiveness of drugs.

Nanorevolution Unleashing the Power of Nanotechnology

Nanotechnology, the manipulation of matter at the nanoscale, has been an extraordinary scientific frontier that has revolutionized various fields, with one of the most promising applications being in the realm of medicine. Nanomedicine, an interdisciplinary field at the intersection of nanotechnology and medicine, holds tremendous potential to transform the landscape of healthcare, diagnosis, and treatment. This abstract delves into the burgeoning advancements of nanotechnology in nanomedicine, highlighting its significance, potential benefits, and ethical considerations.

The primary focus of nanomedicine is to engineer and utilize nanoscale materials, such as nanoparticles and nanostructures, to improve the effectiveness and precision of medical interventions. Nano-sized drug delivery systems can target specific cells or tissues, enhancing therapeutic outcomes and reducing side effects. These nanocarriers can penetrate biological barriers and accumulate at disease sites, enabling more efficient drug delivery and increasing the bioavailability of therapeutic agents. Furthermore, nanotechnology has opened new horizons in medical imaging. Nanoparticles can be engineered to be responsive to certain diseases or conditions, providing valuable information for early detection and precise diagnosis. Novel contrast agents based on nanomaterials have the potential to revolutionize imaging techniques, offering higher sensitivity and specificity, ultimately leading to improved patient outcomes.

Beyond diagnostics and drug delivery, nanotechnology is fostering breakthroughs in regenerative medicine. Nanomaterials can act as scaffolds, guiding tissue repair and promoting cellular regeneration. By harnessing the unique properties of nanoscale materials, tissue engineering, and organ transplantation may witness unparalleled advancements, bringing hope to countless patients awaiting life-saving treatments. However, the unprecedented potential of nanomedicine also raises ethical concerns that demand careful consideration. As nanotechnology progresses, concerns about the safety of nanomaterials, potential toxicity, and long-term effects must be addressed to ensure responsible and sustainable development.

The Common Denominators of Parkinson’s Disease Pathogenesis and Methamphetamine Abuse

The pervasiveness and mortality associated with methamphetamine abuse have doubled during the past decade, suggesting a possible worldwide substance use crisis. Epitomizing the pathophysiology and toxicology of methamphetamine abuse proclaims severe signs and symptoms of neurotoxic and neurobehavioral manifestations in both humans and animals. Most importantly, chronic use of this drug enhances the probability of developing neurodegenerative diseases manifolds. Parkinson's disease is one such neurological disorder, which significantly and evidently not only shares a number of toxic pathogenic mechanisms induced by methamphetamine exposure but is also interlinked both structurally and genetically. Methamphetamine-induced neurodegeneration involves altered dopamine homeostasis that promotes the aggregation of α-synuclein protofibrils in the dopaminergic neurons and drives these neurons to make them more vulnerable to degeneration, as recognized in Parkinson’s disease. Moreover, the pathologic mechanisms such as mitochondrial dysfunction, oxidative stress, neuroinflammation and decreased neurogenesis detected in methamphetamine abusers dramatically resemble to what is observed in Parkinson’s disease cases. Therefore, the present review comprehensively cumulates a holistic illustration of various genetic and molecular mechanisms putting across the notion of how methamphetamine administration and intoxication might lead to Parkinson’s disease-like pathology and Parkinsonism.

A Systematic Review on the Potential Applications of Theranostic Nanoparticles in Diabetes and its Associated Complication Diabetic Neuropathy

Background: Diabetes neuropathy is a frequent ailment that has a substantial impact on patients by increasing the risk of falls and causing discomfort. The lower extremities are where diabetic neuropathy patients first feel pain. This discomfort could seem like a pinprick, an electric shock, or something else.

Objective: Here, we give a comprehensive overview of this quickly developing theranostic application that includes all relevant imaging, diagnostic, therapeutic, and monitoring elements for the management of diabetes and diabetes neuropathy.

Methods: The data for the current study was gathered by searching PubMed and Google Scholar. Several research and review publications from various publishers, including Springer Nature, Bentham Science, PLOS one, MDPI, and ACS Publishing Centre, were evaluated to compile the data.

Result: Recent developments in theranostics have shown promise as alternate management approaches for diabetes and ailments linked to diabetes. Numerous nanotechnology-built biosensors, including multiwalled carbon nanotubes, copper nanowires, zinc oxide tetrapods, and nanoparticle- embedded contact lenses, offer benefits in monitoring diabetic neuropathy.

Conclusion: The potency, usability, and dependability of insulin substitutes have been demonstrated by a variety of innovative methods for the management of diabetes, which includes nanotechnology approaches using Gene-Based Nanoparticles (siRNA), Liposomes, Exosomes/ Extracellular Vesicles, Neuromodulation, and Inhalable Nanoparticles. Over the past few years, the development of various theranostic nanoparticles for Diabetic neuropathy has experienced an unprecedented expansion. Even though much work needs to be done to precisely evaluate the genuine benefits provided by these particles, such as issues with nanotoxicity, theranostic nanoparticles will have a significant impact on the field of nanomedicine.

Nanomedicine as a Better Therapeutic Approach: An Overview

The fields of nanotechnology and nanomedicine have undergone a revolution. There has been a striking rise in authorized nanomedicines since 1980. Apart from functioning as therapeutic agents, they also act as carriers for delivering various active pharmaceuticals to target organs. The ultimate goal of nanomedicine has always been the generation of translational technologies that can improve current therapies. Nanocrystals, nanotubes, liposomes, exosomes, solid lipid nanoparticles, polymeric nanoparticles, and metallic and magnetic nanoparticles are examples of nanostructures that are now in the market as well as in ongoing research. The preparation of these nanomaterials requires consideration of a number of difficulties. Only a few of these nanomaterials were successful in obtaining marketing permission after passing all required toxicological and ethical evaluations and making them affordable to users and, at the same time, profitable to investors. Cancer, central nervous system (CNS) diseases, and cardiovascular (CVS) diseases represented the primary targets of nanotechnology applied to medicine. Therefore, this review article is focused on providing a summary of several nano-based delivery systems, including their limitations and prospects in different therapeutic fields.

Characterization of Intrinsically Disordered Proteins in Healthy and Diseased States by Nuclear Magnetic Resonance

Introduction: Intrinsically Disordered Proteins (IDPs) are active in different cellular procedures like ordered assembly of chromatin and ribosomes, interaction with membrane, protein, and ligand binding, molecular recognition, binding, and transportation via nuclear pores, microfilaments and microtubules process and disassembly, protein functions, RNA chaperone, and nucleic acid binding, modulation of the central dogma, cell cycle, and other cellular activities, post-translational qualification and substitute splicing, and flexible entropic linker and management of signaling pathways.

Methods: The intrinsic disorder is a precise structural characteristic that permits IDPs/IDPRs to be involved in both one-to-many and many-to-one signaling. IDPs/IDPRs also exert some dynamical and structural ordering, being much less constrained in their activities than folded proteins. Nuclear magnetic resonance (NMR) spectroscopy is a major technique for the characterization of IDPs, and it can be used for dynamic and structural studies of IDPs.

Results and Conclusion: This review was carried out to discuss intrinsically disordered proteins and their different goals, as well as the importance and effectiveness of NMR in characterizing intrinsically disordered proteins in healthy and diseased states.

Drug Target to Alleviate Mitochondrial Dysfunctions in Alzheimer’s Disease: Recent Advances and Therapeutic Implications

Alzheimer's disease (AD) is a severe progressive neurodegenerative condition associated with neuronal damage and reduced cognitive function that primarily affects the aged worldwide. While there is increasing evidence suggesting that mitochondrial dysfunction is one of the most significant factors contributing to AD, its accurate pathobiology remains unclear. Mitochondrial bioenergetics and homeostasis are impaired and defected during AD pathogenesis. However, the potential of mutations in nuclear or mitochondrial DNA encoding mitochondrial constituents to cause mitochondrial dysfunction has been considered since it is one of the intracellular processes commonly compromised in early AD stages. Additionally, electron transport chain dysfunction and mitochondrial pathological protein interactions are related to mitochondrial dysfunction in AD. Many mitochondrial parameters decline during aging, causing an imbalance in reactive oxygen species (ROS) production, leading to oxidative stress in age-related AD. Moreover, neuroinflammation is another potential causative factor in AD-associated mitochondrial dysfunction. While several treatments targeting mitochondrial dysfunction have undergone preclinical studies, few have been successful in clinical trials. Therefore, this review discusses the molecular mechanisms and different therapeutic approaches for correcting mitochondrial dysfunction in AD, which have the potential to advance the future development of novel drug-based AD interventions.

Natural Plant Materials as a Source of Neuroprotective Peptides

In many circumstances, some crucial elements of the neuronal defense system fail, slowly leading to neurodegenerative diseases. Activating this natural process by administering exogenous agents to counteract unfavourable changes seems promising. Therefore, looking for neuroprotective therapeutics, we have to focus on compounds that inhibit the primary mechanisms leading to neuronal injuries, e.g., apoptosis, excitotoxicity, oxidative stress, and inflammation. Among many compounds considered neuroprotective agents, protein hydrolysates and peptides derived from natural materials or their synthetic analogues are good candidates. They have several advantages, such as high selectivity and biological activity, a broad range of targets, and high safety profile. This review aims to provide biological activities, the mechanism of action and the functional properties of plant-derived protein hydrolysates and peptides. We focused on their significant role in human health by affecting the nervous system and having neuroprotective and brain-boosting properties, leading to memory and cognitive improving activities. We hope our observation may guide the evaluation of novel peptides with potential neuroprotective effects. Research into neuroprotective peptides may find application in different sectors as ingredients in functional foods or pharmaceuticals to improve human health and prevent diseases.

Aducanumab in Alzheimer’s Disease: A Critical Update

Alzheimer's disease (AD) is a complex neurological disorder that results in cognitive decline. The incidence rates of AD have been increasing, particularly among individuals 60 years of age or older. In June 2021, the US FDA approved aducanumab, the first humanized monoclonal antibody, as a potential therapeutic option for AD. Clinical trials have shown this drug to effectively target the accumulation of Aβ (beta-amyloid) plaques in the brain, and its effectiveness is dependent on the dosage and duration of treatment. Additionally, aducanumab has been associated with improvements in cognitive function. Biogen, the pharmaceutical company responsible for developing and marketing aducanumab, has positioned it as a potential breakthrough for treating cerebral damage in AD. However, the drug has raised concerns due to its high cost, limitations, and potential side effects. AD is a progressive neurological condition that affects memory, cognitive function, and behaviour. It significantly impacts the quality of life of patients and caregivers and strains healthcare systems. Ongoing research focuses on developing disease-modifying therapies that can halt or slow down AD progression. The pathogenesis of AD involves various molecular cascades and signaling pathways. However, the formation of extracellular amyloid plaques is considered a critical mechanism driving the development and progression of the disease. Aducanumab, as a monoclonal antibody, has shown promising results in inhibiting amyloid plaque formation, which is the primary pathological feature of AD. This review explores the signaling pathways and molecular mechanisms through which aducanumab effectively prevents disease pathogenesis in AD.

Anticancer Potential of ACEIs/ARBs Administration in Colorectal Cancer

Background: Colorectal cancer (CC) is the fourth most common type of cancer that causes illness and death. Medicines like ACE inhibitors and ARBs, usually used for heart problems, have shown they might help with the growth and development of CC.

Introduction: An analysis of ACE inhibitors and colon cancer is conducted in this comprehensive review. The main goal is to see how ACEIs/ARBs affect the chances of getting cancer and dying in patients with CC.

Methods: A systematic literature search was conducted to identify relevant studies. Inclusion criteria encompassed studies that evaluated the use of ACEIs/ARBs in patients with CC and reported outcomes related to new cancer incidence and mortality. Data from selected studies were extracted and analyzed using appropriate statistical methods.

Results: The study showed that fewer cancer cases occurred in patients who took ACEIs/ARBs compared to those who did not (RR 0.962, 95% CI 0.934-0.991, p = 0.010). Furthermore, patients with CC who utilized ACEIs/ARBs exhibited a decreased mortality rate compared to non-users (HR 0.833, 95% CI 0.640-1.085, p = 0.175).

Conclusion: This review suggests that using ACEIs/ARBs medicine could help people with CC live longer and lower their chances of dying. These results highlight the potential benefits of utilizing ACE inhibitors in the management of CC, warranting further investigation and consideration in clinical practice.

Therapeutic Potential of Capsaicin in Various Neurodegenerative Diseases with Special Focus on Nrf2 Signaling

Neurodegenerative disease is mainly characterized by the accumulation of misfolded proteins, contributing to mitochondrial impairments, increased production of proinflammatory cytokines and reactive oxygen species, and neuroinflammation resulting in synaptic loss and neuronal loss. These pathophysiological factors are a serious concern in the treatment of neurodegenerative diseases. Based on the symptoms of various neurodegenerative diseases, different treatments are available, but they have serious side effects and fail in clinical trials, too. Therefore, treatments for neurodegenerative diseases are still a challenge at present. Thus, it is important to study an alternative option. Capsaicin is a naturally occurring alkaloid found in capsicum. Besides the TRPV1 receptor activator in nociception, capsaicin showed a protective effect in brain-related disorders. Capsaicin also reduces the aggregation of misfolded proteins, improves mitochondrial function, and decreases ROS generation. Its antioxidant role is due to increased expression of an nrf2-mediated signaling pathway. Nrf2 is a nuclear erythroid 2-related factor, a transcription factor, which has a crucial role in maintaining the normal function of mitochondria and the cellular defense system against oxidative stress. Intriguingly, Nrf2 mediated pathway improved the upregulation of antioxidant genes and inhibition of microglial-induced inflammation, improved mitochondrial resilience and functions, leading to decreased ROS in neurodegenerative conditions, suggesting that Nrf2 activation could be a better therapeutic approach to target pathophysiology of neurodegenerative disease. Therefore, the present review has evaluated the potential role of capsaicin as a pharmacological agent for the treatment and management of various neurodegenerative diseases via the Nrf2-mediated signaling pathway.

Discovery and Development of HDAC Inhibitors: Approaches for the Treatment of Cancer a Mini-review

Histone deacetylase (HDAC) inhibitors have emerged as promising cancer therapeutics due to their ability to induce differentiation, cell cycle arrest, and apoptosis in cancer cells. In the present review, we have described the systemic discovery and development of HDAC inhibitors. Researchers across the globe have identified various small molecules like benzo[d][1,3]dioxol derivatives, belinostat analogs, pyrazine derivatives, quinazolin-4-one-based derivatives, 2,4-imidazolinedione derivatives, acridine hydroxamic acid derivatives, coumarin derivatives, tetrahydroisoquinoline derivatives, thiazole-5-carboxamide, salicylamide derivatives, β-peptoid-capped HDAC inhibitors, quinazoline derivatives, benzimidazole and benzothiazole derivatives, and β- elemene scaffold containing HDAC inhibitors. Most of the scaffolds have shown attractive IC50 (μM) in various cell lines like HDAC1, HDAC2, HDAC6, PI3K, HeLa, MDA-MB-231, MCF-10A, MCF-7, U937, K562 and Bcr-Abl cell lines.

Unlocking the Potential of Drug Delivery Systems: A Comprehensive Review of Formulation Strategies and Technologies in the Field of Pharmaceutics

The creation of innovative drug delivery systems to enhance therapeutic effectiveness, safety, and patient compliance has resulted in considerable developments in pharmaceutics in recent years. The most recent formulation techniques and technologies are reviewed in this article to improve medication distribution and accomplish specific therapeutic goals.

This article thoroughly summarizes the most recent formulation techniques and technologies used to enhance medication delivery and provide specific therapeutic effects. It discusses the variety of medication delivery methods, including nanoparticles, liposomes, micelles, and dendrimers, and explores the application of nanotechnology and biotechnology in drug delivery. Additionally, the paper emphasizes the significance of targeted drug delivery systems and their capacity to cross biological barriers including the blood-brain barrier and tumor microenvironment.

The review also addresses the challenges faced in developing and commercializing drug delivery systems and suggests potential solutions to overcome them. Furthermore, the article emphasizes the role of computational modeling and simulation in designing and optimizing drug delivery systems.

Overall, this review paper offers insightful information for pharmaceutics researchers, scientists, and practitioners that will help in the creation of novel drug delivery systems that improve patient outcomes and quality of life.

Spinacia Oleracea: Exploring the Therapeutic Potential in Persian Medicine and Modern Pharmacology

Background: Spinach is a widely cultivated dark leafy vegetable highly regarded for its medicinal properties in traditional Persian medicine. It is rich in vitamins, minerals, flavonoids, carotenoids, and other bioactive compounds, and this review aims to explore the historical applications of spinach in Persian medicine and juxtapose them with current scientific evidence. Despite its historical significance, there remains a need to comprehensively evaluate and integrate traditional knowledge with modern research on the therapeutic benefits of spinach.

Methods: To achieve this, a comprehensive search was conducted in Persian medicine references and scientific databases to gather information on the traditional uses, chemical composition, and pharmacological effects of spinach. Studies that met the inclusion criteria were meticulously categorized, and relevant data were analyzed to draw insightful comparisons.

Results: Persian medicine describes spinach as a nutrient-rich, laxative, and fast-digesting agent with therapeutic effects on inflammation, lung diseases, back pain, sore throats, jaundice, urinary disorders, joint pain, eye inflammation, insomnia, dementia, and more. Modern studies have substantially corroborated these traditional uses, revealing that spinach possesses antioxidant, anti-inflammatory, anti-cancer, blood sugar-lowering, lipid-lowering, anti-obesity, neurological, ocular, and musculoskeletal effects.

Conclusion: Spinach exhibits a wide range of beneficial effects on various health conditions. Its widespread availability, low cost, and exceptional nutritional richness position it as a promising candidate for further investigation. Future studies should explore the clinical effectiveness of spinach in various diseases, while taking into consideration the principles emphasized in Persian medicine to guide research and inform therapeutic strategies.

Molecular Modeling of Brassicaceae Derivatives for Inhibiting Lipoxygenases: A Promising Therapeutic Strategy

Introduction: Inflammation plays a crucial role in the body's defense mechanisms, but uncontrolled inflammation can lead to chronic and pathological conditions. This study aimed to identify natural compounds as potential replacements for the synthetic drug Zileuton, known for its side effects.

Method: Utilizing the MOE and Molegro modeling methods, several molecules were evaluated, and three compounds, namely 1-Isothiocyanatopent-4-en-2-ol, 7-Isothiocyanatohept-1-ene, and 5- (Isothiocyanatomethyl)-1,2,3-trimethoxybenzene, exhibited superior inhibitory properties. These compounds consistently demonstrated low energy values, indicating high inhibition potency. Notably, 5-(Isothiocyanatomethyl)-1,2,3-trimethoxybenzene emerged as the most promising candidate among all tested compounds.

Results: These findings provide valuable insights for the development of alternative anti-inflammatory agents. Further research is required to assess the efficacy and safety profiles of these compounds in clinical settings.

Conclusion: This study represents a significant advancement in the search for innovative therapeutic strategies to manage inflammation-related disorders.

In-silico, in-vitro and in-vivo Biological Activities of Flavonoids for the Management of Type 2 Diabetes

In spite of the fact that many medicinal plants have been truly utilized for the management of diabetes all through the world, very few of them have been reported scientifically. Recently, a diverse variety of animal models have been established to better understand the pathophysiology of diabetes mellitus, and new medications to treat the condition have been introduced in the market. Flavonoids are naturally occurring substances that can be found in plants and various foods and may have health benefits in the treatment of neuropathic pain. Flavonoids have also been shown to have an anti-inflammatory impact that is significant to neuropathic pain, as indicated by a decrease in several pro-inflammatory mediators such TNF-, NF-B IL-6, and IL-1. Flavonoids appear to be a viable novel therapy option for macrovasular complications in preclinical models; however, human clinical data is still inadequate. Recently, several in silico, in-vitro and in-vivo aproaches were made to evaluate mechanisms associated with the pathogenesis of diabetes in a better way. Screening of natural antidiabetic agents from plant sources can be analysed by utilizing advanced in-vitro techniques and animal models. Natural compounds, mostly derived from plants, have been studied in diabetes models generated by chemical agents in the majority of research. The aim of this work was to review the available in silico, in-vitro and animal models of diabetes for screening of natural antidiabetic agents. This review contributes to the scientist's design of new methodologies for the development of novel therapeutic agents having potential antihyperglycemic activity.

Prospective Approaches of Herbal Novel Delivery System with Special Reference to the Herbal Nanosciences

Medicinal and culinary uses of plants date back centuries. Projects on a global scale are conducting laboratory research to identify plants with therapeutic properties, with the ultimate goal of developing such compounds into medicines with acceptable drug delivery mechanisms and bringing them to market. Non-synthetic medications derived from plant or herbal sources have attracted a lot of interest because of their high tolerability and low likelihood of adverse medication reactions. All diseases, the theory goes, can be cured by something found in nature. Medicines can be taken in a wide variety of forms, including tablets, capsules, powders, semi-liquid extracts, tinctures, decoctions, medicinal teas, solutions, and more. Longer release, patient adherence, and other objectives necessitate adjustments to herbal medications. Researchers into novel drug delivery systems had hitherto overlooked herbal remedies due to a lack of scientific validation and the challenges inherent in processing, standardizing, extracting, and identifying them. Transdisciplinary research and cuttingedge isolation, purification, and identification techniques have led to the development of novel herbal compositions. Bioactive plant extracts and phytoconstituents are used in a wide variety of Nano- Emulsions, microspheres, transferosomes, implants, and ethosomes. Compared to herbal remedies, novel formulations fared better. Among these advantages are increased solubility, bioavailability, toxicity, pharmacological activity, stability, delivery duration, and resistance to physical and chemical degradation. As a result, the pharmacokinetic and pharmacodynamic properties of herbal medications can be enhanced by the use of novel drug delivery systems, making them safer and more effective.

This article aims to provide a concise description of the many new drug delivery techniques that have been created for the administration of herbal medications. The ultimate goal is to increase the efficacy of therapies and to learn more about their significance and worldwide appeal.

Stimuli-sensitive Chitosan-based Nanosystems-immobilized Nucleic Acids for Gene Therapy in Breast Cancer and Hepatocellular Carcinoma

Chitosan-based nanoparticles have emerged as a promising tool in the realm of cancer therapy, particularly for gene delivery. With cancer being a prevalent and devastating disease, finding effective treatment options is of utmost importance. These nanoparticles provide a unique solution by encapsulating specific genes and delivering them directly to cancer cells, offering immense potential for targeted therapy. The biocompatibility and biodegradability of chitosan, a naturally derived polymer, make it an ideal candidate for this purpose. The nanoparticles protect the genetic material during transportation and enhance its cellular uptake, ensuring effective delivery to the site of action. Furthermore, the unique properties of chitosan-based nanoparticles allow for the controlled release of genes, maximizing their therapeutic effect while minimizing adverse effects. By advancing the field of gene therapy through the use of chitosan-based nanoparticles, scientists are making significant strides toward more humane and personalized treatments for cancer patients.

Nanoparticle-based Gene Therapy for Neurodegenerative Disorders

Neurological disorders present a formidable challenge in modern medicine due to the intricate obstacles set for the brain and the multipart nature of genetic interventions. This review article delves into the promising realm of nanoparticle-based gene therapy as an innovative approach to addressing the intricacies of neurological disorders. Nanoparticles (NPs) provide a multipurpose podium for the conveyance of therapeutic genes, offering unique properties such as precise targeting, enhanced stability, and the potential to bypass blood-brain barrier (BBB) restrictions. This comprehensive exploration reviews the current state of nanoparticle-mediated gene therapy in neurological disorders, highlighting recent advancements and breakthroughs. The discussion encompasses the synthesis of nanoparticles from various materials and their conjugation to therapeutic genes, emphasizing the flexibility in design that contributes to specific tissue targeting. The abstract also addresses the low immunogenicity of these nanoparticles and their stability in circulation, critical factors for successful gene delivery. While the potential of NP-based gene therapy for neurological disorders is vast, challenges and gaps in knowledge persist. The lack of extensive clinical trials leaves questions about safety and potential side effects unanswered. Therefore, this abstract emphasizes the need for further research to validate the therapeutic applications of NP-mediated gene therapy and to address nanosafety concerns. In conclusion, nanoparticle-based gene therapy emerges as a promising avenue in the pursuit of effective treatments for neurological disorders. This abstract advocates for continued research efforts to bridge existing knowledge gaps, unlocking the full potential of this innovative approach and paving the way for transformative solutions in the realm of neurological health.

Benzimidazole as a Privileged Scaffold in Drug Design and Discovery

Benzimidazole is a privileged drug design and discovery scaffold with various pharmacological activities, including antimicrobial, anticancer, antitubercular, anti-inflammatory, antidiabetic, antihypertensive, antimalarial, and many more. This scaffold can be observed in the structure of numerous FDA-approved drugs and employed in medicinal chemistry to develop novel bioactive compounds through rational drug design. Its broad pharmacological significance is due to physicochemical attributes, including H-bond donor-acceptor efficiency, π-π stacking interactions, and hydrophobic interactions; these characteristics enable benzimidazole derivatives to bind with macromolecules efficiently. This article emphasizes mechanisms, SAR, and docking studies to unveil benzimidazole's various active hybrids accountable for diversified activities. It will assist researchers in strategically designing various novel benzimidazole-endowed hybrids to develop clinically active therapeutic candidates.

Intestinal Barrier Function and Neurodegenerative Disease

Neurodegenerative diseases are caused by the loss of neurons and/or their myelin sheaths, which deteriorate over time and become dysfunctional. Alzheimer's disease, Parkinson's disease, and multiple sclerosis are among the most prominent neurodegenerative diseases that affect millions of older adults worldwide. Despite extensive research over several decades, controversies still surround the etiology of neurodegenerative diseases, and many of them remain incurable. Meanwhile, an increasing number of new mechanistic studies related to the microbiota-gut-brain axis have emerged, among which the relationship between the function of the intestinal barrier and neurodegenerative diseases has received widespread attention. As one of the first lines of defense between the body and the external environment, the impaired function of the intestinal barrier is closely related to the development of neurodegenerative pathologies. Among them, the microbiota-gut-brain axis disorder characterized by intestinal barrier disruption mainly includes impaired function of the intestinal microbial barrier, chemical barrier, mechanical barrier, and immune barrier. This review focuses on the structure and molecular mechanisms of the various layers of the intestinal barrier as well as their relationship with neurodegenerative lesions. In recent years, intestinal barrier repair therapies have provided new ideas for the studied disease treatment modalities. We believe that a better understanding of the role of the intestinal barrier in neurodegenerative diseases would provide new insights for the development of viable therapeutic strategies for patients.

The Essential Role of Astrocytes in Neurodegeneration and Neuroprotection

Astrocytes are glial cells that perform several fundamental physiological functions within the brain. They can control neuronal activity and levels of ions and neurotransmitters, and release several factors that modulate the brain environment. Over the past few decades, our knowledge of astrocytes and their functions has rapidly evolved. Neurodegenerative diseases are characterized by selective degeneration of neurons, increased glial activation, and glial dysfunction. Given the significant role played by astrocytes, there is growing interest in their potential therapeutic role. However, defining their contribution to neurodegeneration is more complex than was previously thought. This review summarizes the main functions of astrocytes and their involvement in neurodegenerative diseases, highlighting their neurotoxic and neuroprotective ability.

Natural Compounds as Inhibitors of Aβ Peptide and Tau Aggregation

Neurodegenerative conditions like Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS) encompass disorders characterized by the degeneration of neurons in specific circumstances. The quest for novel agents to influence these diseases, particularly AD, has unearthed various natural compounds displaying multifaceted activities and diverse pharmacological mechanisms. Given the ongoing extensive study of pathways associated with the accumulation of neurofibrillary aggregates and amyloid plaques, this paper aims to comprehensively review around 130 studies exploring natural products. These studies focus on inhibiting the formation of amyloid plaques and tau protein tangles, with the objective of potentially alleviating or delaying AD.

Application of Nanocomposites and Nanoparticles in Treating Neurodegenerative Disorders

Neurodegenerative diseases represent a formidable global health challenge, affecting millions and imposing substantial burdens on healthcare systems worldwide. Conditions, like Alzheimer's, Parkinson's, and Huntington's diseases, among others, share common characteristics, such as neuronal loss, misfolded protein aggregation, and nervous system dysfunction. One of the major obstacles in treating these diseases is the presence of the blood-brain barrier, limiting the delivery of therapeutic agents to the central nervous system. Nanotechnology offers promising solutions to overcome these challenges. In Alzheimer's disease, NPs loaded with various compounds have shown remarkable promise in preventing amyloid-beta (Aβ) aggregation and reducing neurotoxicity. Parkinson's disease benefits from improved dopamine delivery and neuroprotection. Huntington's disease poses its own set of challenges, but nanotechnology continues to offer innovative solutions. The promising developments in nanoparticle-based interventions for neurodegenerative diseases, like amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS), have offered new avenues for effective treatment. Nanotechnology represents a promising frontier in biomedical research, offering tailored solutions to the complex challenges posed by neurodegenerative diseases. While much progress has been made, ongoing research is essential to optimize nanomaterial designs, improve targeting, and ensure biocompatibility and safety. Nanomaterials possess unique properties that make them excellent candidates for targeted drug delivery and neuroprotection. They can effectively bypass the blood-brain barrier, opening doors to precise drug delivery strategies. This review explores the extensive research on nanoparticles (NPs) and nanocomposites in diagnosing and treating neurodegenerative disorders. These nanomaterials exhibit exceptional abilities to target neurodegenerative processes and halt disease progression.

Exerkines: A Crosstalk between Lactate Production, Exercise and Mental Health

Muscle skeletal striated cells secrete a wide range of proteins called myokines or “exerkines”, which in turn perform autocrine, paracrine, or endocrine functions. For being able to act in the communication between skeletal muscle, adipose tissue, and mainly the brain, exerkines play a prominent role and potential influence on health promotion. Furthermore, we detected in the literature that one of these potential therapeutic substances derived from muscle contraction is a molecule derived from glycolytic metabolism that in the past was largely marginalized, the lactate. Currently, studies are dedicated to examining the target structures for exerkines that may contribute to the maintenance and restoration of mental health. Thus, lactate appears to be recognized as a critical mediator of exercise-related changes and their health benefits, particularly in their role in communication and coordination between organs. It is inferred that the BDNF expression mechanism can be induced by lactate, which in turn derives from the activation of SIRT pathways 1 and 2 and activates the PGC1-α cascade. The behavior of lactate concentration is intensity-dependent, directly related to the type of fast-twitch fibers (type IIb) and the recruitment of these fibers would potentiate the responses in the brain. In this sense, high-intensity exercise would establish itself as an important strategy to be considered. Despite this understanding, there is still much to be done. However, lactate appears to be a highly promising exerkine for future research initiatives and a potential biomarker to reduce illness and promote mental health.

Role of Imaging Genetics in Alzheimer’s Disease: A Systematic Review and Current Update

Background: Alzheimer’s disease is a neurodegenerative disorder characterized by severe cognitive, behavioral, and psychological symptoms, such as dementia, cognitive decline, apathy, and depression. There are no accurate methods to diagnose the disease or proper therapeutic interventions to treat AD. Therefore, there is a need for novel diagnostic methods and markers to identify AD efficiently before its onset. Recently, there has been a rise in the use of imaging techniques like Magnetic Resonance Imaging (MRI) and functional Magnetic Resonance Imaging (fMRI) as diagnostic approaches in detecting the structural and functional changes in the brain, which help in the early and accurate diagnosis of AD. In addition, these changes in the brain have been reported to be affected by variations in genes involved in different pathways involved in the pathophysiology of AD.

Methodology: A literature review was carried out to identify studies that reported the association of genetic variants with structural and functional changes in the brain in AD patients. Databases like PubMed, Google Scholar, and Web of Science were accessed to retrieve relevant studies. Keywords like ‘fMRI’, ‘Alzheimer’s’, ‘SNP’, and ‘imaging’ were used, and the studies were screened using different inclusion and exclusion criteria.

Results: 15 studies that found an association of genetic variations with structural and functional changes in the brain were retrieved from the literature. Based on this, 33 genes were identified to play a role in the development of disease. These genes were mainly involved in neurogenesis, cell proliferation, neural differentiation, inflammation and apoptosis. Few genes like FAS, TOM40, APOE, TRIB3 and SIRT1 were found to have a high association with AD. In addition, other genes that could be potential candidates were also identified.

Conclusion: Imaging genetics is a powerful tool in diagnosing and predicting AD and has the potential to identify genetic biomarkers and endophenotypes associated with the development of the disorder.

Designing and Formulation of Nanocarriers for “Alzheimer’s and Parkinson’s” Early Detection and Therapy

The potential of nanotechnology in advancing the diagnosis and treatment of neurodegenerative diseases is explored in this comprehensive literature review. The findings of these studies suggest that nanotechnology has the capacity to improve existing therapeutic approaches, create novel and safe compounds, and develop more precise imaging techniques and diagnostic methods for neurodegenerative diseases. With the emergence of the nanomedicine era, a new and innovative approach of diagnosing and treating these conditions has been introduced. Notably, the researchers' development of a nanocarrier drug delivery tool demonstrates immense potential compared to conventional therapy, as it maximizes therapeutic efficacy and minimizes undesirable as side effects.

LRRK2; Communicative Role in the Treatment of Parkinson’s Disease and Ulcerative Colitis Overlapping

Background: Involvement of gastrointestinal inflammation in Parkinson’s disease (PD) pathogenesis and movement have progressively emerged. Inflammation is involved in the etiology of both PD and inflammatory bowel disease (IBD). Transformations in leucine-rich recurrent kinase 2 (LRRK2) are among the best hereditary supporters of IBD and PD. Elevated levels of LRRK2 have been reported in stimulated colonic tissue from IBD patients and peripheral invulnerable cells from irregular PD patients; thus, it is thought that LRRK2 directs inflammatory cycles.

Objective: Since its revelation, LRRK2 has been seriously linked in neurons, albeit various lines of proof affirmed that LRRK2 is profoundly communicated in invulnerable cells. Subsequently, LRRK2 might sit at a junction by which stomach inflammation and higher LRRK2 levels in IBD might be a biomarker of expanded risk for inconsistent PD or potentially may address a manageable helpful objective in incendiary sicknesses that increment the risk of PD. Here, we discuss how PD and IBD share covering aggregates, especially regarding LRRK2 and present inhibitors, which could be a helpful objective in ongoing treatments.

Method: English data were obtained from Google Scholar, PubMed, Scopus, and Cochrane library studies published between 1990-December 2022.

Result: Inhibitors of the LRRK2 pathway can be considered as the novel treatment approaches for IBD and PD treatment.

Conclusion: Common mediators and pathways are involved in the pathophysiology of IBD and PD, which are majorly correlated with inflammatory situations. Such diseases could be used for further clinical investigations.

Georgian Medicinal Plants as Rich Natural Sources of Antioxidant Derivatives: A Review on the Current Knowledge and Future Perspectives

The study of antioxidants is of pivotal importance in biomedicine as these molecules could be involved in biological pathways associated with disease. The identification of new antioxidants together with the acquisition of a deeper knowledge on their biology, could lead to the use of these compounds as drugs for innovative treatments. Plants are an important reservoir of phytodrugs that in many cases can be isolated with good extraction yields directly from the vegetal source and are often endowed with a low toxicity profile. Georgia, a country situated on the Black Sea coast in the Caucasus region at the intersection of Western Asia and Eastern Europe, is renowned for its unique woodland habitats and immense biological diversity due to the great variety of climate zones and landscapes. Many wild plants in the area are used as remedies for a number of illnesses in the local traditional medicine. However, the scientific knowledge of these sources of natural drugs and of their molecular components is still far from exhaustive. Therefore, with the present work we reviewed the scientific literature on some of the main Georgian medicinal plants and found that several species are a valuable source of hydrophilic and hydrophobic antioxidants, endowed in some cases with a high ROS-scavenging ability. The analysis of the literature also demonstrated that most of the medicinal extracts and compounds isolated from these plants are beneficial in suppressing multiple diseases in vitro. This review will provide information for scientists looking to develop secure plant-based pharmaceuticals as well as a rationale for using Georgian medicinal plants for the treatment of a range of diseases.

The Combined Effect of Curcumin and Crocin on the Reduction of Inflammatory Responses in Arthritic Rats

Background: The present study evaluated the anti-arthritic impact of combined crocin and curcumin on Adjuvant Induced Arthritis (AIA) in rats.

Methods: The arthritis model was induced in rats by injecting Complete Freund’s adjuvant (CFA) into the right hind paw and was subsequently treated with crocin and curcumin. Evaluation of anti- arthritic activity was carried out using paw swelling, hematological parameters, biochemical parameters, inflammatory cytokines, and histopathology of rats.

Results: The results showed increased paw swelling, increased serum markers levels, including CRP, RF, ALP, ALT, and AST, and inflammatory cytokines (ILlβ and TNFα) along with histology changes (cartilage and bone degradation) in arthritic rats when compared to the normal group. Crocin, curcumin and crocin + curcumin administration at different doses (especially combination at 40 mg/kg and 30 mg/kg, respectively), as well as MTX, revealed a suitable therapeutic effect on AIA rats. Moreover, both phytochemicals and their combination at different doses showed effective anti- arthritic effects owing to their anti-inflammatory effects.

Conclusion: Crocin and curcumin, either alone or in combination, can be a suitable treatment modality for rheumatoid arthritis.

Therapeutical Approach to Arterial Hypertension - Current State of the Art

Arterial hypertension (AH) is recognized as the most common illness within the group of cardiovascular diseases and the most massive chronic non-infectious disease in the world. The number of hypertensive patients worldwide has reached 1.28 billion, contributing to an increase in cardiovascular diseases and premature death globally. The high prevalence of hypertension emphasizes the importance of effectively treating this condition. Elevated blood pressure often leads to lethal complications (heart failure, stroke, renal disorders, etc.) if left untreated. Considering an increase in AH prevalence in the future, a successful therapeutical approach to this disease and its complications is essential. The goal of AH treatment is to maintain normotensive blood pressure through various approaches, including lifestyle changes, a well-balanced diet, increased physical activity, psychoeducation, and, when necessary, pharmacotherapy. The evolving pharmacotherapeutic landscape reflects the progress made in our understanding of hypertension and emphasizes the need for continuous innovation to meet the challenges posed by this prevalent global health concern. The journey toward more effective and tailored treatments for hypertension is ongoing, and the introduction of new medications plays a pivotal role in shaping the future of antihypertensive pharmacotherapy.

Decades Long Involvement of THP-1 Cells as a Model for Macrophage Research: A Comprehensive Review

Over the years, researchers have endeavored to identify dependable and reproducible in vitro models for examining macrophage behavior under controlled conditions. The THP-1 cell line has become a significant and widely employed tool in macrophage research within these models. Originating from the peripheral blood of individuals with acute monocytic leukemia, this human monocytic cell line can undergo transformation into macrophage-like cells, closely mirroring primary human macrophages when exposed to stimulants. Macrophages play a vital role in the innate immune system, actively regulating inflammation, responding to infections, and maintaining tissue homeostasis. A comprehensive understanding of macrophage biology and function is crucial for gaining insights into immunological responses, tissue healing, and the pathogenesis of diseases such as viral infections, autoimmune disorders, and neoplastic conditions. This review aims to thoroughly evaluate and emphasize the extensive history of THP-1 cells as a model for macrophage research. Additionally, it will delve into the significance of THP-1 cells in advancing our comprehension of macrophage biology and their invaluable contributions to diverse scientific domains.

Role of Circular RNAs in Prostate Cancer

Objectives: This study aims to summarize the current literature to demonstrate the importance of circular RNAs (circRNAs) in multiple aspects of prostate cancer (PCa) occurrence, progression, and treatment resistance and explore the potential role in therapeutic strategies aimed at targeting this molecule in PCa.

Methods: The relevant literature from PubMed and Medline databases is reviewed in this article.

Results: Non-coding RNA has been proven to play a vital role in regulating tumor progression. Among them, circular RNA plays a more unique role due to its nonlinear structure. Lots of circRNAs were found to be differentially expressed in PCa and regulate cell signaling pathways by regulating particular gene expressions. Recent studies have demonstrated that circRNAs are associated with the chemoresistance of urinary tumors, suggesting that circRNAs might be a novel therapeutic target and a marker for therapeutic response and prognosis assessment.

Conclusion: The potential crosstalk of circRNAs modifications in PCa development, therapy, and regulation of tumor metabolism is portrayed in this review. However, more preclinical and clinical trials of this targeted strategy are necessary for the treatment of urinary tumors.

N-Methyl-D-Aspartate (NMDA) Receptor Antagonists and their Pharmacological Implication: A Medicinal Chemistry-oriented Perspective Outline

N-methyl-D-aspartate (NMDA) receptors, i.e., inotropic glutamate receptors, are important in synaptic plasticity, brain growth, memory, and learning. The activation of NMDA is done by neurotransmitter glutamate and co-agonist (glycine or D-serine) binding. However, the over-activation of NMDA elevates the intracellular calcium influx, which causes various neurological diseases and disorders. Therefore, to prevent excitotoxicity and neuronal death, inhibition of NMDA must be done using its antagonist. This review delineates the structure of subunits of NMDA and the conformational changes induced after the binding of agonists (glycine and D-serine) and antagonists (ifenprodil, etc.). Additionally, reported NMDA antagonists from different sources, such as synthetic, semisynthetic, and natural resources, are explained by their mechanism of action and pharmacological role. The comprehensive report also addresses the chemical spacing of NMDA inhibitors and in-vivo and in-vitro models to test NMDA antagonists. Since the Blood-Brain Barrier (BBB) is the primary membrane that prevents the penetration of a wide variety of drug molecules, we also elaborate on the medicinal chemistry approach to improve the effectiveness of their antagonists.

Therapeutic Effect of Resveratrol and its Novel Formulations on Lung Cancer: Focus on Biological Aspects and Underlying Pathways

Lung cancer is a leading cause of mortality and morbidity worldwide. Due to significant advances in therapeutic strategies, patients' survival and life quality have been improved, however there is still an urgent requirement for developing more effective therapeutic methods. Resveratrol, a natural polyphenol with numerous biological potentials, has been widely studied. It has shown therapeutic potetial in various diseases including neurodegenerative diseases, cardiovascular disorders, and cancers through the regulation of key cellular signaling such as apoptosis, as well as molecular pathways such as microRNA modulation. It has been reported that resveratrol acts as an anticancer agent against lung cancer in vivo and in vitro. Resveratrol could combat against lung cancer by modulating various molecular targets and signaling pathways involved in oxidative stress, inflammation, apoptosis and autoghagy and also microRNAs expression. Moreover, novel delivery systems and analogs have recently been introduced to promote the anticancer impacts of resveratrol. In this article, we review current evidence on the anticancer effects of resveratrol and its novel formulations in the treatment of lung cancer with a focus on underlying mechanisms.

Current Understanding of Androgen Signaling in Prostatitis and its Treatment: A Review

Chronic prostatitis is a highly prevalent condition that significantly impacts the quality of life and fertility of men. Because of its heterogeneous nature, there is no definitive treatment, which requires ongoing research into its etiology. Additionally, the association between prostatitis and an elevated risk of prostate cancer highlights the importance of comprehending androgen involvement in prostatitis. This paper examines the current understanding of androgen signaling in prostatitis and explores contemporary therapeutic approaches. It was reviewed Medline articles comprehensively, using keywords such as nonbacterial prostatitis, prostatitis infertility, androgen role in prostatitis, and chronic pelvic pain. Several cellular targets are linked to androgen signaling. Notably, the major tyrosine phosphatase activity (cPAcP) in normal human prostate is influenced by androgen signaling, and its serum levels inversely correlate with prostate cancer progression. Androgens also regulate membrane-associated zinc and pyruvate transporters transduction in prostate cells, suggesting promising avenues for novel drug development aimed at inhibiting these molecules to reduce cancer tumor growth. Various therapies for prostatitis have been evaluated, including antibiotics, anti-inflammatory medications (including bioflavonoids), neuromodulators, alpha-blockers, 5α-reductase inhibitors, and androgen receptor antagonists. These therapies have demonstrated varying degrees of success in ameliorating symptoms.In conclusion, aging decreases circulating T and intraprostatic DHT, altering the proper functioning of the prostate, reducing the ability of androgens to maintain normal Zn²⁺ levels, and diminishing the secretion of citrate, PAcP, and other proteins into the prostatic fluid. The Zn²⁺-transporter decreases or is absent in prostate cancer, so the pyruvate transporter activates. Consequently, the cell ATP increases, inducing tumor growth.

Chitosan-Based Nanocarriers for Pulmonary and Intranasal Drug Delivery Systems: A Comprehensive Overview of their Applications

The optimization of respiratory health is important, and one avenue for achieving this is through the application of both Pulmonary Drug Delivery System (PDDS) and Intranasal Delivery (IND). PDDS offers immediate delivery of medication to the respiratory system, providing advantages, such as sustained regional drug concentration, tunable drug release, extended duration of action, and enhanced patient compliance. IND, renowned for its non-invasive nature and swift onset of action, presents a promising path for advancement. Modern PDDS and IND utilize various polymers, among which chitosan (CS) stands out. CS is a biocompatible and biodegradable polysaccharide with unique physicochemical properties, making it well-suited for medical and pharmaceutical applications. The multiple positively charged amino groups present in CS facilitate its interaction with negatively charged mucous membranes, allowing CS to adsorb easily onto the mucosal surface. In addition, CS-based nanocarriers have been an important topic of research. Polymeric Nanoparticles (NPs), liposomes, dendrimers, microspheres, nanoemulsions, Solid Lipid Nanoparticles (SLNs), carbon nanotubes, and modified effective targeting systems compete as important ways of increasing pulmonary drug delivery with chitosan. This review covers the latest findings on CS-based nanocarriers and their applications.

Magnetomorph: The Future of Targeted Drug Delivery

Recent Advances in the Treatment Strategies of Friedreich’s Ataxia: A Review of Potential Drug Candidates and their Underlying Mechanisms

Background: Friedreich's Ataxia (FRDA) is a rare hereditary neurodegenerative disorder characterized by progressive ataxia, cardiomyopathy, and diabetes. The disease is caused by a deficiency of frataxin, a mitochondrial protein involved in iron-sulfur cluster synthesis and iron metabolism.

Objective: This review aims to summarize recent advances in the development of treatment strategies for FRDA, with a focus on potential drug candidates and their mechanisms of action.

Methods: A comprehensive literature search was conducted using various authentic scientific databases to identify studies published in the last decade that investigated potential treatment strategies for FRDA. The search terms used included “Friedreich's ataxia”, “treatment”, “drug candidates”, and “mechanisms of action”.

Results: To date, only one drug got approval from US-FDA in the year 2023; however, significant developments were achieved in FRDA-related research focusing on diverse therapeutic interventions that could potentially alleviate the symptoms of this disease. Several promising drug candidates have been identified for the treatment of FRDA, which target various aspects of frataxin deficiency and aim to restore frataxin levels, reduce oxidative stress, and improve mitochondrial function. Clinical trials have shown varying degrees of success, with some drugs demonstrating significant improvements in neurological function and quality of life in FRDA patients.

Conclusion: While there has been significant progress in the development of treatment strategies for FRDA, further research is needed to optimize these approaches and identify the most effective and safe treatment options for patients. The integration of multiple therapeutic strategies may be necessary to achieve the best outcomes in FRDA management.

Revolutionizing Neurological Disorder Treatment: Integrating Innovations in Pharmaceutical Interventions and Advanced Therapeutic Technologies

Neurological disorders impose a significant burden on individuals, leading to disabilities and a reduced quality of life. However, recent years have witnessed remarkable advancements in pharmaceutical interventions aimed at treating these disorders. This review article aims to provide an overview of the latest innovations and breakthroughs in neurological disorder treatment, with a specific focus on key therapeutic areas such as Alzheimer's disease, Parkinson's disease, multiple sclerosis, epilepsy, and stroke. This review explores emerging trends in drug development, including the identification of novel therapeutic targets, the development of innovative drug delivery systems, and the application of personalized medicine approaches. Furthermore, it highlights the integration of advanced therapeutic technologies such as gene therapy, optogenetics, and neurostimulation techniques. These technologies hold promise for precise modulation of neural circuits, restoration of neuronal function, and even disease modification. While these advancements offer hopeful prospects for more effective and tailored treatments, challenges such as the need for improved diagnostic tools, identification of new targets for intervention, and optimization of drug delivery methods will remain. By addressing these challenges and continuing to invest in research and collaboration, we can revolutionize the treatment of neurological disorders and significantly enhance the lives of those affected by these conditions.

Advances in the Synthesis and Bioactivity of Polysaccharide Selenium Nanoparticles: A Review

Selenium, an essential trace element of the human body, is pivotal in human health and disease prevention. Nevertheless, the narrow therapeutic index of selenium, where the toxic and therapeutic doses are close, limits its clinical utility. Significantly, nanoscale selenium synthesized by different methods using polysaccharides as stabilizers has low toxicity properties and exhibits excellent bioactivity. Its biological activities, such as anti-tumor, anti-inflammatory, antioxidant, antibacterial, and immune function enhancement, are improved compared with traditional organic and inorganic selenium compounds, conferring greater potential for application in biomedicine. Therefore, this review evaluates the advancements in various synthesis methodologies for polysaccharide selenium nanoparticles (Se NPs) and their biological activities. It aims to provide a comprehensive theoretical basis and research directions for the future development of highly efficient, minimally toxic, and biocompatible polysaccharide-Se NPs and the application of polysaccharide-Se NPs in biomedicine.

In silico Approaches for Exploring the Pharmacological Activities of Benzimidazole Derivatives: A Comprehensive Review

Background: This article reviews computational research on benzimidazole derivatives. Cytotoxicity for all compounds against cancer cell lines was measured and the results revealed that many compounds exhibited high inhibitions. This research examines the varied pharmacological properties like anticancer, antibacterial, antioxidant, anti-inflammatory and anticonvulsant activities of benzimidazole derivatives. The suggested method summarises In silico research for each activity. This review examines benzimidazole derivative structure-activity relationships and pharmacological effects. In silico investigations can anticipate structural alterations and their effects on these derivative’s pharmacological characteristics and efficacy through many computational methods. Molecular docking, molecular dynamics simulations and virtual screening help anticipate pharmacological effects and optimize chemical design. These trials will improve lead optimization, target selection, and ADMET property prediction in drug development. In silico benzimidazole derivative studies will be assessed for gaps and future research. Prospective studies might include empirical verification, pharmacodynamic analysis, and computational methodology improvement.

Objectives: This review discusses benzimidazole derivative In silico research to understand their specific pharmacological effects. This will help scientists design new drugs and guide future research.

Methods: Latest, authentic and published reports on various benzimidazole derivatives and their activities are being thoroughly studied and analyzed.

Result: The overview of benzimidazole derivatives is more comprehensive, highlighting their structural diversity, synthetic strategies, mechanisms of action, and the computational tools used to study them.

Conclusion: In silico studies help to understand the structure-activity relationship (SAR) of benzimidazole derivatives. Through meticulous alterations of substituents, ring modifications, and linker groups, this study identified the structural factors influencing the pharmacological activity of benzimidazole derivatives. These findings enable the rational design and optimization of more potent and selective compounds.

A Narrative Review on the Potential of Black Seeds (Nigella Sativa) in the Management of West Nile Virus Infection

West Nile virus (WNV) infection is a mosquito-borne illness that is endemic to Africa, Asia, the Middle East, Australia, and Europe. WNV-infected individuals can only be managed with symptomatic therapy and supportive care at this point of time. Thus, we have analyzed the possible beneficial effects of black seeds (N. sativa) in this literature review. To find relevant articles, various online databases, such as the Web of Science, Medline, PMC, PubMed, Embase, EBSCO, Google Scholar, Science Direct, and reference lists were searched. The antiviral, analgesic, anti-inflammatory, antioxidant, and immunomodulatory effects of black seeds (N. sativa) have been established by numerous clinical, animal, in vivo, in vitro, and in silico studies. It has been found that black seeds (N. sativa) have the potential to be included as adjuvant therapy in addition to symptomatic treatment and supportive care in the early stages of WNV infection once randomized controlled clinical trials (RCTs) affirm the safety and efficacy of black seeds (N. sativa) in WNV infection management as they have been considered the gold standard of treatment in clinical studies.

Nuclear Factor Kappa B: A Nobel Therapeutic Target of Flavonoids Against Parkinson's Disease

Parkinson's disease (PD), the most common brain-related neurodegenerative disorder, is comprised of several pathophysiological mechanisms, such as mitochondrial dysfunction, neuroinflammation, aggregation of misfolded alpha-synuclein, and synaptic loss in the substantia nigra pars compacta region of the midbrain. Misfolded alpha-synuclein, originating from damaged neurons, triggers a series of signaling pathways in both glial and neuronal cells. Activation of such events results in the production and expression of several proinflammatory cytokines via the activation of the nuclear factor κB (NF-κB) signaling pathway. Consequently, this cascade of events worsens the neurodegenerative processes, particularly in conditions, such as PD and synucleinopathies. Microglia, astrocytes, and neurons are just a few of the many cells and tissues that express the NF-κB family of inducible types of transcription factors. The dual role of NF-κB activation can be crucial for neuronal survival, although the classical NF-κB pathway is important for controlling the generation of inflammatory mediators during neuroinflammation. Modulating NF-κB-associated pathways through the selective action of several agents holds promise for mitigating dopaminergic neuronal degeneration and PD. Several naturally occurring compounds in medicinal plants can be an effective treatment option in attenuating PD-associated dopaminergic neuronal loss via selectively modifying the NF-κB-mediated signaling pathways. Recently, flavonoids have gained notable attention from researchers because of their remarkable anti-neuroinflammatory activity and significant antioxidant properties in numerous neurodegenerative disorders, including PD. Several subclasses of flavonoids, including flavones, flavonols, isoflavones, and anthocyanins, have been evaluated for neuroprotective effects against in vitro and in vivo models of PD. In this aspect, the present review highlights the pathological role of NF-κB in the progression of PD and investigates the therapeutic potential of natural flavonoids targeting the NF-κB signaling pathway for the prevention and management of PD-like manifestations with a comprehensive list for further reference. Available facts strongly support that bioactive flavonoids could be considered in food and/or as lead pharmacophores for the treatment of neuroinflammation-mediated PD. Furthermore, natural flavonoids having potent pharmacological properties could be helpful in enhancing the economy of countries that cultivate medicinal plants yielding bioactive flavonoids on a large scale.

Potential Role of Oxidative Stress in the Pathophysiology of Neurodegenerative Disorders

Neurodegeneration causes premature death in the peripheral and central nervous system. Neurodegeneration leads to the accumulation of oxidative stress, inflammatory responses, and the generation of free radicals responsible for nervous disorders like amyotrophic lateral sclerosis, Alzheimer's disease, Parkinson's disease, and Huntington's disorders. Therefore, focus must be diverted towards treating and managing these disorders, as it is very challenging. Furthermore, effective therapies are also lacking, so the growing interest of the global market must be inclined towards developing newer therapeutic approaches that can intercept the progression of neurodegeneration. Emerging evidences of research findings suggest that antioxidant therapy has significant potential in modulating disease phenotypes. This makes them promising candidates for further investigation. This review focuses on the role of oxidative stress and reactive oxygen species in the pathological mechanisms of various neurodegenerative diseases, amyotrophic lateral sclerosis, Alzheimer's disease, Parkinson's disease, and Huntington's disorders and their neuroprotection. Additionally, it highlights the potential of antioxidant-based therapeutics in mitigating disease severity in humans and improving patient compliance. Ongoing extensive global research further sheds light on exploring new therapeutic targets for a deeper understanding of disease mechanisms in the field of medicine and biology targeting neurogenerative disorders.

Curcumin- β-Cyclodextrin Molecular Inclusion Complex: A Water- Soluble Complex in Fast-dissolving Tablets for the Treatment of Neurodegenerative Disorders

Background: Orally disintegrating tablets (ODTs) have become an excellent choice for delivering drugs as their palatability is greatly improved. In this work, β-cyclodextrin has been used to improve the solubility of curcumin by encapsulating it into the hydrophobic cavity for the treatment of neurodegenerative disorders.

Objectives: The current study aimed to present the design, formulation, and optimisation of fastdissolving oral tablets of curcumin- β-cyclodextrin molecular inclusion complex using a 3²-factorial design.

Methods: The drug-excipient compatibility was studied by FTIR spectroscopy. The inclusion complex of curcumin-β-cyclodextrin was prepared using solvent casting and confirmed using XRD studies. Powder blends were evaluated for flow properties. Tablets prepared by direct compression were evaluated for post-compression parameters. Further, the effect of formulation variables, such as sodium starch glycolate (X1) and Neusilin^® ULF2 (X2), on various responses, including disintegration time and dissolution at 2 hours, was studied using statistical models.

Results: Post-compression parameters, i.e., hardness (4.4-5 kg/cm²), thickness (3.82-3.93 mm), weight variation (±7.5%), friability (< 1%), wetting time (51-85 seconds) and drug content (96.28- 99.32%) were all found to be within the permissible limits and the disintegration time of tablets with super-disintegrants ranged between 45-58 seconds. The in-vitro dissolution profile of tablets showed that higher SSG and Neuslin^® ULF2 levels promoted drug release. For statistical analysis, the 2FI model was chosen. Optimised variables for formulation have been determined and validated with the experimental findings based on the significant desirability factor.

Conclusion: The current study reveals the validated curcumin-β-cyclodextrin inclusion complex fastdissolving tablets with SSG and Neusilin^® ULF2 to be an ideal choice for effectively treating neurodegenerative disorders.

Regulation of Gut Microbiota by Herbal Medicines

Preserving host health and homeostasis is largely dependent on the human gut microbiome, a varied and ever-changing population of bacteria living in the gastrointestinal tract. This article aims to explore the multifaceted functions of the gut microbiome and shed light on the evolving field of research investigating the impact of herbal medicines on both the composition and functionality of the gut microbiome. Through a comprehensive overview, we aim to provide insights into the intricate relationship between herbal remedies and the gut microbiome, fostering a better understanding of their potential implications for human health.The gut microbiota is composed of trillions of microorganisms, predominantly bacteria, but also viruses, fungi, and archaea. It functions as a complex ecosystem that interacts with the host in various ways. It aids in nutrient metabolism, modulates the immune system, provides protection against pathogens, and influences host physiology. Moreover, it has been linked to a range of health outcomes, including digestion, metabolic health, and even mental well-being. Recent research has shed light on the potential of herbal medicines to modulate the gut microbiome. Herbal medicines, derived from plants and often used in traditional medicine systems, contain a diverse array of phytochemicals, which can directly or indirectly impact gut microbial composition. These phytochemicals can either act as prebiotics, promoting the growth of beneficial bacteria, or possess antimicrobial properties, targeting harmful pathogens. Several studies have demonstrated the effects of specific herbal medicines on the gut microbiome. For example, extracts from herbs have been shown to enhance the abundance of beneficial bacteria, such as Bifidobacterium and Lactobacillus, while reducing potentially harmful microbes. Moreover, herbal medicines have exhibited promising antimicrobial effects against certain pathogenic bacteria. The modulation of the gut microbiome by herbal medicines has potential therapeutic implications. Research suggests herbal interventions could be harnessed to alleviate gastrointestinal disorders, support immune function, and even impact metabolic health. However, it is important to note that individual responses to herbal treatments can vary due to genetics, diet, and baseline microbiome composition.

In conclusion, the gut microbiome is a critical player in maintaining human health, and its modulation by herbal medicines is a burgeoning area of research. Understanding the complex interactions between herbal compounds and gut microbiota will pave the way for innovative approaches to personalized healthcare and the development of herbal-based therapeutics aimed at promoting gut health and overall well-being.

Role of BDNF Signaling in the Neuroprotective and Memory-enhancing Effects of Flavonoids in Alzheimer’s Disease

Background: Foods rich in flavonoids are associated with a reduced risk of various chronic diseases, including Alzheimer's disease (AD). In fact, growing evidence suggests that consuming flavonoid- rich foods can beneficially affect normal cognitive function. Animal models have shown that many flavonoids prevent the development of AD-like pathology and improve cognitive deficits.

Objective: Identifying the molecular causes underlying the memory-enhancing effect of flavonoid-rich foods makes it possible to provide the best diet to prevent cognitive decline associated with aging and Alzheimer's disease. Based on the most recent scientific literature, this review article critically examines the therapeutic role of dietary flavonoids in ameliorating and preventing the progression of AD and enhancement of memory with a focus on the role of the BDNF signaling pathway.

Methods: The databases of PubMed, Web of Science, Google Scholar, and Scopus were searched up to March 2023 and limited to English language. Search strategies were using the following keywords in titles and abstracts: (Flavonoid-rich foods OR Flavonoids OR Polyphenols); AND (Brain-Derived Neurotrophic Factor OR BDNF OR CREB OR) AND (Alzheimer's disease OR memory OR cognition OR).

Results: Flavonoid-rich foods including green tea, berries, curcumin and pomegranate exert their beneficial effects on memory decline associated with aging and Alzheimer's disease mostly through the direct interaction with BDNF signaling pathway.

Conclusion: The neuroprotective effects of flavonoid-rich foods through the CREB-BDNF mechanism have the potential to prevent or limit memory decline due to aging and Alzheimer's disease, so their consumption throughout life may prevent age-related cognitive impairment.

Phosphodiesterase 2 and Its Isoform A as Therapeutic Targets in the Central Nervous System Disorders

Cyclic adenosine monophosphates (cAMP) and cyclic guanosine monophosphate (cGMP) are two essential second messengers, which are hydrolyzed by phosphodiesterase's (PDEs), such as PDE-2. Pharmacological inhibition of PDE-2 (PDE2A) in the central nervous system improves cAMP and cGMP signaling, which controls downstream proteins related to neuropsychiatric, neurodegenerative, and neurodevelopmental disorders. Considering that there are no specific treatments for these disorders, PDE-2 inhibitors' development has gained more attention in the recent decade. There is high demand for developing new-generation drugs targeting PDE2 for treating diseases in the central nervous and peripheral systems. This review summarizes the relationship between PDE-2 with neuropsychiatric, neurodegenerative, and neurodevelopmental disorders as well as its possible treatment, mainly involving inhibitors of PDE2.

Artificial Intelligence in The Management of Neurodegenerative Disorders

Neurodegenerative disorders are characterized by a gradual but irreversible loss of neurological function. The ability to detect and treat these conditions successfully is crucial for ensuring the best possible quality of life for people who suffer from them. The development of effective new methods for managing and treating neurodegenerative illnesses has been made possible by recent developments in computer technology. In this overview, we take a look at the prospects for applying computational approaches, such as drug design, AI, ML, and DL, to the treatment of neurodegenerative diseases. To review the current state of the field, this article discusses the potential of computational methods for early disease detection, quantifying disease progression, and understanding the underlying biological mechanisms of neurodegenerative diseases, as well as the challenges associated with these approaches and potential future directions. Moreover, it delves into the creation of computational models for the individualization of care for neurodegenerative diseases. The article concludes with suggestions for future studies and clinical applications, highlighting the advantages and disadvantages of using computational techniques in the treatment of neurodegenerative diseases.

Pyrazoline and Analogs: Substrate-based Synthetic Strategies

Among the many reports published on strategies applicable to synthesizing pyrazolines and its analogs, The 1,3-dipolar cycloaddition offers a remarkably wide range of utility. Many 1,3-dipolar cycloaddition reactions used for the synthesis of pyrazolines provide better selectivity, eco-friendly, and less expensive chemical processes. In the presented study, we have reviewed various recently adopted strategies for the synthesis of pyrazoline, which followed the 1,3-dipolar cycloaddition reactions mechanism and classified them based on starting materials such as nitrile imines, diazo compounds, different zwitter ions, chalcones, and isoprene units. The manuscript also focused on the synthesis of pyrazolines starting from Seyferth−Gilbert reagents (SGR) and Psilostachyin (PSH) reagents. We hope this work will help those engaged or have plans to research pyrazoline or its analogs, as synthetic protocols based on starting material are rarely available for pyrazolines. Thus, this article holds a valuable complement to the development of newer pyrazoline and its derivatives.