Essential Tremor

Exploring Neurodegenerative Diseases: Bridging the Gap between in vitro and in vivo Models

Neurological disorders are brain conditions characterized by the loss of nerve cells, leading to a decline in function. Standard examples include dementia, tremors, involuntary movements, muscle weakness, and autoimmune attacks. The most common form of dementia is Alzheimer's, affecting over 5 million elderly individuals, while tremors, stiffness, and slow movement are caused by Parkinson's. Involuntary movements and emotional problems are caused by Huntington's, while muscle weakness and eventual demise are caused by Amyotrophic lateral sclerosis. Vision problems, fatigue, and difficulty walking are caused by Multiple sclerosis (MS), an autoimmune disease that attacks the myelin sheath. In vitro models provide cost and complexity reduction, environmental control, and high-throughput. Researchers employ both cell-based (in vitro) and animal- based (in vivo) models to investigate neurodegenerative illnesses and endeavor to formulate novel treatments for diverse conditions. In vitro models provide cost and complexity reduction, environment control, and high-throughput screening of potential therapeutic agents compared to in vivo models. Nevertheless, they possess constraints, including the absence of intricate interactions that transpire in the entire organism and the inability to reproduce the disease progression completely.

Molecular Pathways and Treatment Updates on Huntington’s Disease with Special Preference to Juvenile Phase: A Comprehensive Review

A degenerative brain ailment called Huntington's disease (HTD) causes irritable behavior, emotional distress, cognition, etc. It is also known as Huntington's chorea. Compared to men, women are more likely to get HTD. However, in India, if 3 to 5% of Europeans are affected, it is difficult to estimate the disease's prevalence. The full pathophysiological status, several molecular pathways, and pharmaceutical and non-pharmacological treatments for Huntington's disease are covered in this article. Google, PubMed, Scopus, Bentham, Elsevier, and other significant web resources were used to gather the scientific data. Moreover, this review article may serve as the foundation for future study, particularly on Huntington's illness.

Congenital Abdominal Aortic Aneurysm: Presentation, Etiology, Diagnosis and Management

Aortic aneurysms are common in adults due to atherosclerosis but are rare in children and young adults, often overlooked due to infrequent reporting. Acquired aneurysms are usually linked to factors like umbilical artery ligation, connective tissue diseases, or vasculitides. In contrast, the causes of congenital abdominal aortic aneurysms (AAA) remain unknown due to their extreme rarity. Only a few cases have been reported. Prompt diagnosis is essential when symptoms such as abdominal distention, vomiting, or abdominal pulsatility occur. Diagnosis is typically confirmed through ultrasonography and multi-slice spiral computed tomography angiographies (MCSTA). After detection, a comprehensive investigation is necessary to rule out acquired AAA causes. Managing congenital AAA requires a highly personalized approach, with early surgical repair using grafts as a recommended option. After an extensive analysis of numerous academic sources, we have comprehensively understood the epidemiology, clinical features, and diagnostic and treatment techniques for congenital abdominal aortic aneurysms.

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.

Current Concepts of Pain Pathways: A Brief Review of Anatomy, Physiology, and Medical Imaging

Background: Although the essential components of pain pathways have been identified, a thorough comprehension of the interactions necessary for creating focused treatments is still lacking. Such include more standardised methods for measuring pain in clinical and preclinical studies and more representative study populations.

Objective: This review describes the essential neuroanatomy and neurophysiology of pain nociception and its relation with currently available neuroimaging methods focused on health professionals responsible for treating pain.

Methods: Conduct a PubMed search of pain pathways using pain-related search terms, selecting the most relevant and updated information.

Results: Current reviews of pain highlight the importance of their study in different areas from the cellular level, pain types, neuronal plasticity, ascending, descending, and integration pathways to their clinical evaluation and neuroimaging. Advanced neuroimaging techniques such as fMRI, PET, and MEG are used to better understand the neural mechanisms underlying pain processing and identify potential targets for pain therapy.

Conclusion: The study of pain pathways and neuroimaging methods allows physicians to evaluate and facilitate decision-making related to the pathologies that cause chronic pain. Some identifiable issues include a better understanding of the relationship between pain and mental health, developing more effective interventions for chronic pain's psychological and emotional aspects, and better integrating data from different neuroimaging modalities for the clinical efficacy of new pain therapies.

Analysis of Clinical Pharmacsology Research Publication in Doping and Anti-Doping: A Scientometric Study

The importance of medical professionals like clinical pharmacologists in the field of sport medicine lies in their expertise in doping and anti-doping. There is a need to identify the expertise globally and understand the pattern of research being done in this area. This helps for future collaborative and combined policies, irrespective of any borders. The purpose of this study was to conduct a scientometric examination of bibliographic facts linked to clinical pharmacology in doping and antidoping, and data from PubMed was retrieved between January 2012 and January 2021. This study looked at scientometric approaches such as frequency distribution, percentage analysis, relative growth rate and doubling time, and level of collaboration. During the research period, we acquired a total of 65 articles, and a maximum of 13 (20%) were contributed in the year 2021. The relative growth rate is declining, and the doubling time was increasing between 2014 and 2021. This will be the first scientometric analysis done on the topic to best of our knowledge, and this study will act as a document for further research on the topic.

Neurodevelopmental and Neuropsychiatric Perspectives on Respiratory Control: Understanding Congenital and Developmental Disorders

Breathing is an automatic process generated by the central nervous system, crucial for the homeostasis of several body processes. This vital process is underpinned by an intricate network in which distinct functional and anatomical factors and structures play a role. Transcription factors (i.e., PHOX2B and Pbx proteins), as well as neuromodulators (i.e., serotonin, noradrenaline, GABA, and glycine), have been demonstrated as implicated in the regulation of breathing. Besides, the several intertwined excitatory and inhibitory brainstem neural circuits comprising the so-called central pattern generator (CPG) have recently demonstrated a potential role of cerebellar structures and circuits in coordinating the complex and coordinated respiratory act in eupnea. A disruption affecting one of these components, which may also occur on a genetic basis, may indeed result in complex and heterogeneous disorders, including neurodevelopmental ones (such as Rett and Prader-Willi syndrome), which may also present with neuropsychiatric and breathing manifestations and potentially lead to sudden infant death syndrome (SIDS). Herein, we discuss the main factors and systems involved in respiratory control and modulation, outlining some of the associated neurodevelopmental disorders (NDDs) deriving from an impairment in their expression/ function. Further studies are needed to deepen our knowledge of the complexity underpinning “breathing” and the relation between respiratory implications and congenital and developmental disorders.

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.

Perinatal Exposure to Trace Elements: The Dubious Culprit of Autistic Spectrum Disorder in Children

There is evidence that few trace elements in the environment work as hazardous materials in terms of their exposure in the perinatal period, causing autistic spectrum disorder (ASD) in children, and avoiding these exposures in the environment can reduce the number of new cases. This perspective study provides preliminary evidence to consider a few trace elements as culprits for ASD. More studies with larger cohorts are needed, but meanwhile, as per available evidence, exposure to these hazardous materials must be warranted during pregnancy and early stages of life.

Predictive Analysis of Yi-Gai-San's Multifaceted Mechanisms for Tremor-dominant Parkinson's Disease via Network Pharmacology and Molecular Docking Validation

Introduction: Based on comprehensive network-pharmacology and molecular docking analysis, this study was intended to unveil the multiple mechanisms of Yi- Gai-San (YGS) in treating the tremor-dominant subtype of Parkinson's disease (PD-DT). The compounds of YGS were meticulously analyzed, selected, and standardized with references to their pharmacological attributes. Its components included Gouteng (Uncaria rhynchophylla), Chaihu (Radix Bupleuri), Chuanxiong (Chuanxiong Rhizoma), Danggui (Angelicae sinensis radix), Fuling (Wolfiporia extensa), Baizhu (Atractylodis macrocephalae rhizoma), and Gancao (Licorice, Glycyrrhizae radix).

Methods: We identified 75 active compounds within YGS. From these, we predicted 110 gene targets, which exhibited a direct association with PD-DT. PPI network results highlighted core target proteins, including TP53, SLC6A3, GAPDH, MAOB, AKT, BAX, IL6, BCL2, PKA, and CASP3. These proteins potentially alleviate PD-DT by targeting inflammation, modulating neuronal cell apoptosis, and regulating the dopamine system. Furthermore, GO and KEGG enrichment analyses emphasized that YGS might influence various mechanisms, such as the apoptotic process, mitochondrial autophagy, Age-Rage signaling, and dopaminergic and serotonergic synapses. The core proteins from the PPI analysis were selected for the docking experiment.

Results: The docking results demonstrated that the most stable ligand-receptor conformations were kaempferol with CASP3 (-9.5 kcal/mol), stigmasterol with SLC6A3 (-10.5 kcal/mol), shinpterocarpin with BCL2L1 (-9.6 kcal/mol), hirsutine with MAOB (-9.7 kcal/mol), hederagenin with PRKACA (-9.8 kcal/mol), and yatein with GAPDH (-9.8 kcal/mol). These results provide us with research objectives for future endeavors in extracting single compounds for drug manufacturing or in-depth studies on drug mechanisms.

Conclusion: From these computational findings, we suggested that YGS might mitigate PD-DT via “multi-compounds, multi-targets, and multi-pathways.”

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.

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.

Neuroprotective Properties of Antiepileptics: What are the Implications for Psychiatric Disorders?

Since the discovery of the first antiepileptic compound, increasing attention has been paid to antiepileptic drugs (AEDs), and recently, with the understanding of the molecular mechanism underlying cells death, a new interest has revolved around a potential neuroprotective effect of AEDs. While many neurobiological studies in this field have focused on the protection of neurons, growing data are reporting how exposure to AEDs can also affect glial cells and the plastic response underlying recovery; however, demonstrating the neuroprotective abilities of AEDs remains a changeling task. The present work aims to summarize and review the literature available on the neuroprotective properties of the most commonly used AEDs. Results highlighted how further studies should investigate the link between AEDs and neuroprotective properties; while many studies are available on valproate, results for other AEDs are very limited and the majority of the research has been carried out on animal models. Moreover, a better understanding of the biological basis underlying neuro-regenerative defects may pave the way for the investigation of further therapeutic targets and eventually lead to an improvement in the actual treatment strategies.

Traditional Chinese Medicine as the Preventive and Therapeutic Remedy for COVID-19

The coronavirus disease 2019 (COVID-19) pandemic still has tremendous impacts on the global socio-economy and quality of living. The traditional Chinese Medicines (TCM) approach showed encouraging results during previous outbreaks of Severe Acute Respiratory Syndrome-related Coronavirus (SARS-CoV) and the Middle East Respiratory Syndrome Coronavirus (MERS-CoV). With limited treatment availability, TCM herbs and formulations could be useful to reduce COVID-19 symptoms and potential sources for discovering novel therapeutic targets. We reviewed 12 TCM herbs and formulations recommended for COVID-19 management by the National Health Commission and as National Administration of Traditional Chinese Medicine of the People's Republic of China. This article explored the Chinese national authorities' guidelines from 2003 to 2020, the scientific data in public databases for the recommended TCM remedies, and their potential mechanistic actions in COVID-19 management. Several TCM herbs and formulations could potentially benefit COVID-19 management. The recommended TCM oral preparations list includes Huoxiang zhengqi, Jinhua Qinggan, Lianhua Qingwen, and Shufeng jiedu; the recommended injection preparations comprise Xiyanping Xuebijing, Re-Du-Ning, Tanreqing, Xingnaojing, Shenfu, Shengmai, and Shenmai. TCM remedies are viable options for symptom alleviation and management of COVID-19. The current SARS-CoV-2 pandemic presents an opportunity to find novel therapeutic targets from TCM-active ingredients. Despite the recommendations in Chinese National guidelines, these remedies warrant further assessments in well-designed clinical trials to ascertain their efficacy in the treatment of COVID-19.

Revisiting the Mitochondrial Function and Communication in Neurodegenerative Diseases

Neurodegenerative disorders are distinguished by the progressive loss of anatomically or physiologically relevant neural systems. Atypical mitochondrial morphology and metabolic malfunction are found in many neurodegenerative disorders. Alteration in mitochondrial function can occur as a result of aberrant mitochondrial DNA, altered nuclear enzymes that interact with mitochondria actively or passively, or due to unexplained reasons. Mitochondria are intimately linked to the Endoplasmic reticulum (ER), and ER-mitochondrial communication governs several of the physiological functions and procedures that are disrupted in neurodegenerative disorders. Numerous researchers have associated these disorders with ER-mitochondrial interaction disturbance. In addition, aberrant mitochondrial DNA mutation and increased ROS production resulting in ionic imbalance and leading to functional and structural alterations in the brain as well as cellular damage may have an essential role in disease progression via mitochondrial malfunction. In this review, we explored the evidence highlighting the role of mitochondrial alterations in neurodegenerative pathways in most serious ailments, including Alzheimer’s disease (AD), Parkinson’s disease (PD), and Huntington’s disease (HD).

An Update on Parkinson’s Disease and its Neurodegenerative Counterparts

Introduction: Neurodegenerative disorders are a group of diseases that cause nerve cell degeneration in the brain, resulting in a variety of symptoms and are not treatable with drugs. Parkinson's disease (PD), prion disease, motor neuron disease (MND), Huntington's disease (HD), spinal cerebral dyskinesia (SCA), spinal muscle atrophy (SMA), multiple system atrophy, Alzheimer's disease (AD), spinocerebellar ataxia (SCA) (ALS), pantothenate kinase-related neurodegeneration, and TDP-43 protein disorder are examples of neurodegenerative diseases. Dementia is caused by the loss of brain and spinal cord nerve cells in neurodegenerative diseases.

Background: Even though environmental and genetic predispositions have also been involved in the process, redox metal abuse plays a crucial role in neurodegeneration since the preponderance of symptoms originates from abnormal metal metabolism.

Method: Hence, this review investigates several neurodegenerative diseases that may occur symptoms similar to Parkinson's disease to understand the differences and similarities between Parkinson's disease and other neurodegenerative disorders based on reviewing previously published papers.

Results: Based on the findings, the aggregation of alpha-synuclein occurs in Parkinson’s disease, multiple system atrophy, and dementia with Lewy bodies. Other neurodegenerative diseases occur with different protein aggregation or mutations.

Conclusion: We can conclude that Parkinson's disease, Multiple system atrophy, and Dementia with Lewy bodies are closely related. Therefore, researchers must distinguish among the three diseases to avoid misdiagnosis of Multiple System Atrophy and Dementia with Lewy bodies with Parkinson's disease symptoms.

An Update on Pharmacological and Phytochemical Aspects of Costus pictus D. Don - A Promising Anti-diabetic Plant

Background: The genus Costus is the largest genus in the family Costaceae and encompasses about 150 known species. Among these, Costus pictus D. Don (Synonym: Costus mexicanus) is a traditional medicinal herb used to treat diabetes and other ailments. Currently, available treatment options in modern medicine have several adverse effects. Herbal medicines are gaining importance as they are cost-effective and display improved therapeutic effects with fewer side effects. Scientists have been seeking therapeutic compounds in plants, and various in vitro and in vivo studies report Costus pictus D. Don as a potential source in treating various diseases. Phytochemicals with various pharmacological properties of Costus pictus D. Don, viz. anti-cancer, anti-oxidant, diuretic, analgesic, and anti-microbial have been worked out and reported in the literature.

Objective: The aim of the review is to categorize and summarize the available information on phytochemicals and pharmacological properties of Costus pictus D. Don and suggest outlooks for future research.

Methods: This review combined scientific data regarding the use of Costus pictus D. Don plant for the management of diabetes and other ailments. A systematic search was performed on Costus pictus plant with anti-diabetic, anti-cancer, anti-microbial, anti-oxidant, and other pharmacological properties using several search engines such as Google Scholar, PubMed, Science Direct, Sci-Finder, other online journals and books for detailed analysis.

Results: Research data compilation and critical review of the information would be beneficial for further exploration of its pharmacological and phytochemical aspects and, consequently, new drug development. Bioactivity-guided fractionation, isolation, and purification of new chemical entities from the plant as well as pharmacological evaluation of the same will lead to the search for safe and effective novel drugs for better healthcare.

Conclusion: This review critically summarizes the reports on natural compounds, and different extract of Costus pictus D. Don with their potent anti-diabetic activity along with other pharmacological activity. Since this review has been presented in a very interactive manner showing the geographical region of availability, parts of plant used, mechanism of action and phytoconstituents in different extracts of Costus pictus responsible for particular action, it will be of great importance to the interested readers to focus on the development of the new drug leads for the treatment of diseases.

Drugs to Treat Neuroinflammation in Neurodegenerative Disorders

Neuroinflammation is associated with disorders of the nervous system, and it is induced in response to many factors, including pathogen infection, brain injury, toxic substances, and autoimmune diseases. Astrocytes and microglia have critical roles in neuroinflammation. Microglia are innate immune cells in the central nervous system (CNS), which are activated in reaction to neuroinflammation-inducing factors. Astrocytes can have pro- or anti-inflammatory responses, which depend on the type of stimuli presented by the inflamed milieu. Microglia respond and propagate peripheral inflammatory signals within the CNS that cause low-grade inflammation in the brain. The resulting alteration in neuronal activities leads to physiological and behavioral impairment. Consequently, activation, synthesis, and discharge of various pro-inflammatory cytokines and growth factors occur. These events lead to many neurodegenerative conditions, such as Alzheimer's disease, Parkinson's disease, and multiple sclerosis discussed in this study. After understanding neuroinflammation mechanisms and the involvement of neurotransmitters, this study covers various drugs used to treat and manage these neurodegenerative illnesses. The study can be helpful in discovering new drug molecules for treating neurodegenerative disorders.

Exploring the Efficient Natural Products for the Therapy of Parkinson’s Disease via Drosophila Melanogaster (Fruit Fly) Models

Parkinson's disease (PD) is a severe neurodegenerative disorder, partly attributed to mutations, environmental toxins, oxidative stress, abnormal protein aggregation, and mitochondrial dysfunction. However, the precise pathogenesis of PD and its treatment strategy still require investigation. Fortunately, natural products have demonstrated potential as therapeutic agents for alleviating PD symptoms due to their neuroprotective properties. To identify promising lead compounds from herbal medicines' natural products for PD management and understand their modes of action, suitable animal models are necessary. Drosophila melanogaster (fruit fly) serves as an essential model for studying genetic and cellular pathways in complex biological processes. Diverse Drosophila PD models have been extensively utilized in PD research, particularly for discovering neuroprotective natural products. This review emphasizes the research progress of natural products in PD using the fruit fly PD model, offering valuable insights into utilizing invertebrate models for developing novel anti-PD drugs.

Spinal Muscular Atrophy Treatment: The MTOR Regulatory Intervention

Spinal muscular atrophy (SMA) is a hereditary disorder affecting neurons and muscles, resulting in muscle weakness and atrophy. Most SMA cases are diagnosed during infancy or early childhood, the most common inherited cause of infant mortality without treatment. Still, SMA might appear at older ages with milder symptoms. SMA patients demonstrate progressive muscle waste, movement problems, tremors, dysphagia, bone and joint deformations, and breathing difficulties. The mammalian target of rapamycin (mTOR), the mechanistic target of rapamycin, is a member of the phosphatidylinositol 3-kinase-related kinase family of protein kinases encoded by the mTOR gene in humans. The mTOR phosphorylation, deregulation, and autophagy have shown dissimilarity amongst SMA cell types. Therefore, exploring the underlying molecular process in SMA therapy could provide novel insights and pave the way for finding new treatment options. This paper provides new insight into the possible modulatory effect of mTOR/ autophagy in SMA management.

Role of Omega-3PUFA: A Nutraceutical for Brain Functioning and Treatment of Mental Disorders

Concerning the past few years in terms of health and nature, the globe has witnessed an upsurge in the use of nutraceuticals and nutritional and natural products in therapeutics. The major reason for this step is the conventional pharmacological treatment using synthetic drugs that do not meet the status of health and therapeutic requirements for various pathological conditions. Nutraceuticals promise prominent health and therapeutic benefits with no adverse or side effects, providing extra health benefits besides their action in any defined pathological condition. Nutraceuticals are extensive biological therapies that include herbs, vitamins, fatty acids, prebiotics, and probiotics used to promote and maintain health to prevent and cure pathological conditions, malignant processes, syndromes, and symptoms. Nutraceuticals have multidirectional therapeutic benefits and are claimed to be effective products in aiding human health. The addition of omega-3 for the treatment of mental and mood disorders was found to have safer, more valuable, and better therapeutic results in comparison to the use of synthetic drugs. Omega-3 is available in the regular diet through soybeans, walnuts, codfish, and salmon fish, and its constituents have been found to play a promising role in brain development, including brain aging and neurodegenerative disorders, in the pathology of mental and mood disorders, and treatment of the same. Supplementation with Omega-3 PUFA provides a promising effect in better brain development, treatment, prevention and cure of mental and mood disorders. This review endeavours to display and assert the clinical relevance of omega-3 PUFA in brain development, pathology, and treatment of mental and mood disorders.

Immediate Reaction to Propranolol: An Extremely Rare but Important Condition. A Case Report

Introduction: Beta-blockers involve a group of drugs widely used nowadays. Propranolol was the first beta-blocker available in the market. It is the most prescribed first-generation betablocker and is commonly used. Beta-blocker allergy is extremely unusual. Only an isolated case of an urticaria reaction to propranolol has been published in 1975.

Case Presentation: We present a 44-year-old man. In 2016, he was treated with a daily dose of 5 mg of propranolol prescribed for a diagnosis of essential tremor. On the third day of medical treatment, he experienced an episode of generalized urticaria directly related to the administration of propranolol. He continued with his habitual treatment and he had no other urticaria episodes. A drug provocation test was carried out with gradually increasing doses of the culprit drug. Thirty minutes after a total cumulative dose of 5 mg, the patient had several hives on the chest, abdominal region and arms. Two weeks later, a new drug provocation test was performed to bisoprolol as an alternative beta-blocker, with good tolerance.

Conclusion: We describe a new case of urticaria secondary to propranolol, presenting as an immediate hypersensitivity reaction. Bisoprolol has been succesfully proved to be a safe option. Bisoprolol is a second-generation beta-blocker, it is available and commercialized worldwide, which makes it a good alternative.

Therapeutic Approach of Phytomedicine for Dementia: A Review

Dementia is a brain disorder with progressive neurological disease. It destroys essential brain cells, impairing memory, thinking, and behavior in a severe way to impact health, enduring interests, and social life. Memory, cognition, orientation, learning capacity, language, and judgments gradually get impaired. Dementia results from anatomical and functional abnormalities, cerebral ischemia, energy deficits, calcium excess, glutamate-mediated excitotoxicity, and oxidative stress. Vascular dementia (VaD), which accounts for 10-15% of dementia cases, is the second most frequent form of dementia after Alzheimer's disease (AD). There are currently no approved pharmaceutical treatments for VaD, and traditional anti-AD therapies only offer modest, temporary relief from the symptoms of VaD. Since herbal remedies have a multicomponent and multitarget approach, they may provide effective treatments for VaD. Herbal remedies have been used for centuries to address dementia-like symptoms. This author describes some preliminary research that supports using herbal drugs in managing vascular dementia and dementia.

NLS-3 (Levophacetoperane or (R,R) Phacetoperane): A Reverse Ester of Methylphenidate: A Literature Review

Background: NLS-3 or (R, R) enantiomer of phacetoperane (levophacetoperane) is the reverse ester of methylphenidate, a well-documented psychostimulant marketed for the treatment of attention-deficit/hyperactivity disorder (ADHD) since the end of 1950s. Launched in Canada and Europe by Specia Rhône-Poulenc and Rhodia, marketed as Lidepran® (8228 R.P.), for the treatment of obesity and depression, phacetoperane became an increasingly popular psychiatric medication from 1959 to 1967. Previous data supported that the stimulant effect of phacetoperane differed from those of other medications acting on the catecholamine system (e.g., methylphenidate, amphetamine), with an advantage of benefit/risk balance. Method: The goal of this study is to characterize the binding profile of NLS-3 using in vitro and in vivo assays and hypothesize potential therapeutic uses considering all available data. Results: A complete binding profile assay confirmed the potential benefit of phacetoperane with a higher benefit/risk compared to other stimulants. NLS-3 synthesis resulted from phenylketone, which is also used for the synthesis of methylphenidate. It differs from that used by Rhône-Poulenc SA laboratories, allowing the possibility of individualizing several enantiomers not synthesized previously. The present review also confirmed extensive clinical use of the compound in almost one thousand children and adolescents in large dose ranges with fewer side effects versus comparative treatments. Furthermore, levophacetoperane was found to be generally well-tolerated by the subjects. Conclusion: NLS-3 could be a safer and more potent alternative to stimulants for patients with ADHD.

Natural Anticancer Agents: Their Therapeutic Potential, Challenges and Promising Outcomes

Cancer, the second leading cause of death worldwide, is a major health problem. Chemotherapy, radiation therapy and surgery are current treatments for cancer. Most anticancer drugs have severe toxic effects and are required to be administered in cycles to reduce toxicity and prevent resistance. Plant-based drugs have shown a potential for treatment of cancer, and various plant secondary metabolites have shown promising antitumor activity against several cancer cell lines, such as leukemia, colon cancer, prostate cancer, breast cancer and lung cancer. Vincristine, etoposide, topotecan and paclitaxel, which are of natural origin, are successfully used in clinical practice, and this has generated interest in natural compounds as anticancer agents. Some phytoconstituents like curcumin, piperine, allicin, quercetin and resveratrol have been extensively researched and reviewed. In the current study, we have reviewed several plants like Athyrium hohenackerianum, Aristolochia baetica, Boswellia serrata, Panax ginseng, Berberis vulgaris, Tanacetum parthenium, Glycine max, Combretum fragrans, Persea americana, Raphanus sativus, Camellia sinensis, and Nigella sativa for their source, key phytoconstituents, and anticancer activity along with their toxicity profile. Few phytoconstituents like boswellic acid, sulforaphane and ginsenoside showed excellent anticancer activity compared to standard drugs and are potential clinical candidates.

A Review on History, Chemical Constituents, Phytochemistry, Pharmacological Activities, and Recent Patents of Valerian

Background: Valerian officinalis is a variant of herbaceous flowering plants in the Caprifoliaceae family, members of which can be generally called valerians. Valerian is derived from Valerius, the Latin term “valere”, which means health or well-being. It is used as a sedative and anxiolytic in many countries. The beneficial effects of valerian have always been controversial due to inconsistent clinical trial results. Valerian contains more than 150 chemical constituents. Valerian exhibits sedative, anxiolytic, and antispasmodic activities, and is used to treat various diseases.

Objective: The main aim of this study was to gather knowledge on this herbal plant, its chemical constituents, and how they can be used to treat the most common diseases, such as depression, anxiety, headache, insomnia, etc.

Result: Studies show that valerian is used to treat cardiac arrhythmia, sleep disorders, depression, and headaches, as this plant possesses sedative, anxiolytic, and antispasmodic activities.

Conclusion: This review has explored the different types of studies conducted on valerian, and with their help, we can learn more about its activities and medicinal uses. Additionally, this review paper includes the recent patents on this herbal plant.

Understanding the Molecular Aspects of Vitamins in Parkinson’s Disease: Present-day Concepts and Perspectives

Parkinson’s disease (PD) is designated as a convoluted nerve cell devastating disorder that encompasses the profound declination of dopaminergic (DArgic) nerve cells of the mesencephalon region. The condition is sketched by four eminent motor manifestations, namely, slow movement, muscle tension, shaking, and disrupted balance, but the pathology behind these manifestations is still vague. Modern-day medicinal treatment emphasizes curbing the manifestations via introducing a gold standard (levodopa) instead of forestalling the DArgic nerve cell destruction. Therefore, the invention and utilization of novel neuroprotective candidates are of paramount importance in overcoming PD. Vitamins are organic molecules engaged in the modulation of evolution, procreation, biotransformation, and other operations of the body. Numerous studies employing varying experimental models have promulgated a prominent linkage between vitamins and PD. Vitamins, owing to their antioxidant and gene expression modulation abilities, might be efficacious in PD therapy. Recent corroborations depict that adequate augmentation of vitamins might de-escalate the manifestations and emergence of PD; however, the safety of daily vitamin intake must be considered. By assembling the comprehensive information obtained from existing publications via searching various renowned medical portals, the investigators render in-depth insights into the physiological association amongst vitamins (D, E, B3, and C) and PD and concerned pathological processes and their safeguarding actions in varied PD models. Furthermore, the manuscript delineates the remedial aptitude of vitamins in PD therapy. Conclusively, augmentation of vitamins (owing to their antioxidant and gene expression regulation capabilities) might appear as a novel and terribly efficacious ancillary therapeutic approach for PD.

Clinical Application and Synthesis Methods of Deuterated Drugs

Many drugs have adverse absorption, distribution, metabolism, and excretory (ADME) properties that prevent their widespread use or limit their use in some indications. In addition to preparation techniques and prodrug strategies, deuterium modification is a viable method for improving ADME properties. Deuterated drugs have attracted increasing attention from the pharmaceutical industry in recent years. To date, two deuterated drugs have been approved by the FDA. In 2017, austedo was approved by the FDA as a new drug for Huntington's disease in the United States, the first deuterium drug to be marketed worldwide. Recently (June 9, 2021), donafinil has been listed in China; this result has caused major pharmaceutical companies and the pharmaceutical industry to pay attention to deuterium technology again. In addition, BMS-986165, RT001, ALK-001, HC-1119, AVP-786 and other drugs are in phase III clinical studies, and some solid deuterium compounds have entered phase I and II clinical trials. The deuterium strategy has been widely used in pharmaceutical research and has become a hot spot in pharmaceutical research in recent years. In this paper, the research and development of deuterated drugs are reviewed, and the influence of deuterium modification on drugs, the advantages of deuterium strategies and the synthesis strategies of deuterated drugs are mainly introduced. Hoping to provide references for clinical application, the discovery of new deuterium chemical entities and research and development of new deuterated drugs.

Additional Role of Midbrain F-18 FP-CIT Uptake on PET in Evaluation of Essential Tremor and Parkinsonism

Background: Parkinsonism is a term used for the collection of clinical features that cause movement disorders similar to those in Parkinson’s disease. Accurate differentiation of these disorders is critical for the treatment and prognosis of any disease. Fluorine-18 N-(3-fluoropropyl)-2β- carboxymethoxy-3β-(4-iodophenyl) nortropane (F-18 FP-CIT) has been used in the evaluation of parkinsonism by its uptake in the dopamine active transporter (DAT) of the striatum. Its uptake in other areas of the brain, such as serotonin transporter (SERT) in the midbrain or thalamus, is also recognised.

Objective: To investigate whether midbrain SERT uptake of F-18 FP-CIT on positron emission tomography (PET) could be applied to the differentiation of parkinsonism in combination with striatal DAT uptake.

Methods: This retrospective study included clinically diagnosed three essential tremors (ET), 53 parkinsonism patients (21 idiopathic Parkinson’s disease (IPD), 6 multiple system atrophy – cerebellar type (MSA-C), 7 multiple system atrophy - parkinsonian type (MSA-P), 8 vascular parkinsonism (VP), and 11 drug-induced parkinsonism (DIP)), and 16 healthy controls. The patient group consisted of 29 men and 27 women (age mean ± SD years, 69.9 ± 8.5 and 69.2 ± 8.9, respectively), and the healthy controls consisted of 8 men and 8 women (age mean ± SD years, 64.5 ± 8.2 and 64.3 ± 7.6, respectively). Mean standardized uptake values (SUVs) and activity volumes were measured from the visualized FP-CIT uptake of the midbrain (substantia nigra and dorsal raphe nucleus) as well as the striatum (caudate nucleus and putamen). The mean SUVs of the occipital region were measured as the background activity. The semiquantitative binding ratio (BR) was calculated using the following formula: BR = (SUVmean of the region of interest − SUVmean of background)/SUVmean of the background. SUV, volume, and BR in each type of parkinsonism were compared with those in healthy controls using both nonparametric and parametric methods. The correlation between the visual score of the qualitative analysis and the BR was examined.

Results: Except for the dorsal raphe nucleus in VP, the midbrain BRs in all parkinsonism showed a statistically significant decrease compared to those in healthy controls. Both midbrain and striatal BRs were significantly decreased only in patients with IPD or MSA-P; a greater decrease of substantia nigra BR was identified in MSA-P than in IPD (p < 0.05). The striatal BRs in MSA-C, VP, and DIP showed no significant difference from those in healthy controls. Finally, four patterns of uptake were identified: 1) decreased striatal and midbrain uptake for IPD and MSA-P, 2) normal striatal uptake and decreased midbrain uptake (both substantia nigra and dorsal raphe nucleus) for MSA-C and DIP, 3) normal striatal uptake and decreased substantia nigra uptake (without decreased dorsal raphe nucleus uptake) for VP, and 4) normal striatal and midbrain uptake for ET.

Conclusion: The possible differential diagnoses were split into two groups when only striatal uptake was considered but they were divided into four groups after adding midbrain uptake. Although additional midbrain F-18 FP-CIT uptake still could not make a final definitive diagnosis, it could provide another piece of information and specific diagnostic guidelines for the differentiation of parkinsonism.

Medicinal Prospects of Targeting Tyrosinase: A Feature Review

Tyrosinase is a bifunctional polyphenol oxidase (PPO), catalyzing two oxidative reactions: monophenols to o-quinones (monophenolase activity) and o-diphenols to oquinones (diphenolase activity). As tyrosinase is the rate-limiting enzyme for the melanogenesis process, it is an attractive target for melanogenesis inhibition. Aiming at skin whitening, anticancer, Parkinson’s disease (PD) treatment, antibacterial, fruit and vegetable preservation and other anti-pigmentation effect, medicinal chemists have exploited diverse tyrosinase inhibitors through various approaches. In addition to discovering inhibitors with novel scaffolds, good activity and high safety, researchers also focused on developing strategies for synergistic effects of multiple inhibitors and simultaneously regulating multiple targets to treat cancer or neurodegenerative diseases. This review focused on multiple natural and synthetic tyrosinase inhibitors, which could contribute to preventing fruit and vegetable browning, skin whitening, antibacterial, anticancer, Parkinson's Disease, etc.

Neurological Complications in Systemic Inflammatory Diseases

Systemic inflammatory diseases could produce neurologic complications, and they are frequently incorporated in the differential diagnosis of neurological symptoms. There are wellestablished criteria to meet the diagnosis of neurologic manifestations of these systemic diseases.

Methods: However, the range of clinical presentations varies in each condition, and the prevalence of these complications differs between studies. Hence, in many cases, an etiological relationship is not clearly defined.

Results and Conclusion: For these reasons, it is challenging to make an accurate diagnosis. We analyzed the spectrum of neurological manifestations in a cohort of patients with systemic lupus erythematosus, rheumatoid arthritis, Behçet disease and sarcoidosis in order to improve our current knowledge of these complications.

An Approach to Psychiatric Illness in Rheumatology Clinics

Rheumatologists encounter patients with psychiatric illnesses daily in their practice; however, formal training in rheumatology does not sufficiently equip rheumatologists with guidance for managing common psychiatric illnesses. This study reviews common clinical situations involving psychiatric symptoms, their relationship with rheumatologic conditions, and their effects on clinical presentation and management. We illustrate key principles in a case-based format and reflect on the management of psychiatric components. Based on these discussions and a brief review of the epidemiology of psychiatric illnesses, we emphasize the prevalence and significance of these problems in daily practice.

Pharmacological Activities of the Genus Passiflora (Passifloraceae): A Patent Review

Background: Passiflora L. is a genus belonging to the Passifloraceae family, with many species widely used in folk medicine and several pharmacological activities described in the scientific literature, being a major target for the development of new therapeutic products. Studies have identified several bioactive compounds in their composition as responsible for these activities, mainly C-glycoside flavonoids.

Objective: The aim of this study was to carry out a review of patents related to the genus and its application in several pharmacological activities, important for the development of new drugs and formulations.

Methods: The search was carried out in 5 specialized databases, INPI, EPO, WIPO, Latipat and Derwent, using the term ‘Passiflora’ combined with ‘A61K and A61P', subclasses of section A of the International Patent Classification (IPC), which are destined to medical, dental or hygienic purposes, and therapeutic activity of chemical compounds or medicinal preparation, respectively.

Results: 1,198 patents citing the genus in the title or abstract have been found, 508 being duplicates. After exclusion and inclusion criteria, 23 patents written in English, Portuguese and Spanish were selected, which demonstrated biological assays in vivo with species of Passiflora as the only active constituent or incorporated in formulations with other compounds.

Conclusion: The findings of this search showed growing interest in research and industrial areas in the pharmaceutical development with species of Passiflora, suggesting that the different bioactive compounds present in the genus can be considered as an important tool for the development of new effective and safe products with pharmacological potential.

Comparing the Effects of Pregabalin and Clonidine on Postoperative Pain in Tonsillectomy: A Randomized, Double-blind, Prospective Clinical Trial

Background: Tonsillectomy is one of the most common surgical procedures. This study compared the effect of Pregabalin and Clonidine on postoperative pain in adult patients undergoing elective tonsillectomy.

Methods: This randomized, double-blind, prospective clinical trial was conducted among 92 patients aged 20 to 50. The clonidine group (C) was given 150 μg of clonidine tablet 90 minutes before surgery, and the pregabalin group (P) was given 300 mg of pregabalin tablet 90 minutes before surgery. The results were analyzed by SPSS 25, and statistical analysis consisted of chisquare, T-test, and χ² tests, and a p-value less than 0.05 was considered significant.

Results: The mean pain score and analgesic consumption scores in the pregabalin group were lower than in the clonidine group. According to the t-test, there was a significant difference between the two groups regarding pain score and analgesic consumption (p <0.05). Hemodynamic variation in both groups had no significant differences (p >0.05).

Conclusion: The present study showed that pregabalin reduced postoperative pain and analgesic consumption more effectively than clonidine.

Hepatic Encephalopathy by Manganese Deposition: A Case Report and a Review of Literature

Background: Hepatic encephalopathy is defined as a spectrum of neuropsychiatric disorders in patients with liver dysfunction, usually cirrhosis, after exclusion of brain disease. This study reports the role of manganese in brain alterations and clinical manifestations of hepatic encephalopathy.

Case presentation: Male patient, 67 years old, suffering from alcoholic liver cirrhosis and two previous episodes of hepatic encephalopathy, developed drowsiness, asterixis, amnesia, disorientation in time and space, and psychomotor retardation. Brain MRI without contrast showed initial signs of cerebral atrophy, a hyperintense signal of globi pallidi and bilateral substantia nigra. The hyperintense signal of globi pallidi is the result of manganese deposition in the brain.

Conclusion: The case report presented supports the data reported in the literature, indicating that the increase in plasma manganese levels in subjects with liver dysfunction is correlated with the onset of extrapyramidal symptoms.

A Detailed Review of Various Herbal Treatment Options for Potentially Curing or Ameliorating Pain in Diabetic Neuropathy

Diabetes mellitus (DM) is a group of metabolic disorders associated with hyperglycemia due to deficient insulin secretion, insulin action, or both. In 2008, out of 36 million deaths due to non-communicable diseases, 1.3 million deaths alone were causative of DM, suggesting it to be a significant public health problem, reaching epidemic proportions globally. Diabetic Neuropathy is a common complication of DM. The pathophysiology of DN involves the interplay of metabolic and vascular factors, with the principal factor being hyperglycemia. Since DN is a prevalent, disabling condition associated with nerve injury, efficient treatments include glycaemic control and pain management. The ancient scriptures like Charak Samhita and modern pharmacology have corroborated the vast medicinal potential of herbal plants for achieving a more holistic treatment for several ailments. One of the primary objectives of the current review was to provide collective data on the available pharmacological evidence of selective herbal plants for future clinical translation. Also, the herbal extracts used in the studies need to be standardised according to standard protocols. This is important for understanding the complex effect of specific phytoconstituents at the biomolecular level and determining the clinical dose to make results more repeatable.

An Insight into the Molecular Mechanism of Mitochondrial Toxicant-induced Neuronal Apoptosis in Parkinson’s Disease

Parkinson’s disease (PD) is one of the most common progressive neurodegenerative disorders affecting approximately 1% of the world’s population at the age of 50 and above. Majority of PD cases are sporadic and show symptoms after the age of 60 and above. At that time, most of the dopaminergic neurons in the region of substantia nigra pars compacta have been degenerated. Although in past decades, discoveries of genetic mutations linked to PD have significantly impacted our current understanding of the pathogenesis of this devastating disorder, it is likely that the environment also plays a critical role in the etiology of sporadic PD. Recent epidemiological and experimental studies indicate that exposure to environmental agents, including a number of agricultural and industrial chemicals, may contribute to the pathogenesis of several neurodegenerative disorders, including PD. Furthermore, there is a strong correlation between mitochondrial dysfunction and several forms of neurodegenerative disorders, including Alzheimer’s disease (AD), Huntington’s disease (HD), Amyotrophic lateral sclerosis (ALS) and PD. Interestingly, substantia nigra of patients with PD has been shown to have a mild deficiency in mitochondrial respiratory electron transport chain NADH dehydrogenase (Complex I) activity. This review discusses the role of mitochondrial toxicants in the selective degeneration of dopaminergic neurons targeting the electron transport system that leads to Parkinsonism.

Epidemiology, Pathophysiology, and Pharmacological Status of Asthma

In India, asthma is a prevalent respiratory condition marked by frequent blowouts and a distinctive spread pattern. Respiratory diseases are the main cause of death globally. In India, asthma is more common, particularly in the North Indian states of Delhi and Uttar Pradesh. Our primary objective in this review is to study asthma medication therapy and its associated complications. The epidemiology, etiology, pathophysiology, mechanism of airway inflammation, classification, and diagnosis of asthma are all illustrated in the current work. Additionally, we have gathered state-bystate information on asthma for the last five years in Northern India. Asthma diagnosis and management are also discussed in accordance with the guidelines of many agencies, including NICE, BTS, SIGN, and WHO.

Assessment of the Impact of Herbal Drugs Used in Neurodegenerative Disorders: A Preclinical Review

The use of herbal drugs may offer great potential opportunities in preventing and controlling neurodegenerative disorders, such as Alzheimer’s disease, Parkinson’s disease and Huntington’s disease. Herbal drugs contain multiple pharmacologically active constituents. The relative amounts and nature of these constituents vary due to diverse factors, such as plant source and plant parts, extraction methods, local environmental conditions, storage conditions, adulterations, and accidental or intentional contamination. After administration, they are put through the processes of absorption, distribution, metabolism, and excretion of the same as modern medicines. When handled by the body, they can show a combined effect and interact with modern drugs due to various factors, including similar transport protein interaction, metabolizing cytochrome P450 enzyme, and different transporter mechanisms. Herbal medicine can either induce or inhibit CYP450 enzymes. When herbs are combined with the drugs, either they mimic or oppose the effect of drugs. Many studies worldwide indicate the favorable properties of plant extracts or their bioactive compounds against neurodegenerative disorders, but several clinical concerns have appeared regarding the use of these combinations, which could be due to lack of evidence and scientific support for their effectiveness and safety of the patient.

Stem Cells Treatment for Wilson Disease

Wilson Disease (WD) is a copper excretion disorder, mainly caused by mutations in the ATP7B gene. Pharmacological therapies and liver transplantation are currently the main treatment methods for WD, but they face problems such as drug treatment compliance, adverse reactions, and shortage of liver donors. Stem cell therapy of WD may correct abnormal copper metabolism permanently, which is the focus of current research. In this review, we summarized the latest research on stem cells treatment for WD, as well as current challenges and future expectations.

Comparing the Effects of a Herbal Drug based on Echium Amoenum With Fluvoxamine in the Treatment of Adolescents with Obsessive-compulsive Disorder

Background: Obsessive-compulsive disorder (OCD) is a severe and debilitating neuropsychiatric condition. Although selective serotonin reuptake inhibitors, tricyclic antidepressants, and cognitive- behavioral therapy are the first-line medication and treatment for OCD, an estimated 30% of patients are treatment-resistant, and complete functional recovery is rare. Natural products as adjuvant or alternative therapies should be examined to find safer and more effective ways to manage OCD.

Objectives: To investigate the potential benefits of a combined herbal drug based on Echium amoenum in treating OCD.

Methods: Design and Setting: In the psychiatric clinics of Mashhad University of Medical Sciences, 40 patients who met the criteria for the obsessive-compulsive disorder based on DSM-5 were studied in a parallel, double-blind, randomized clinical trial.

Intervention: Subjects were randomly assigned to receive Echium amoenum-Melissa officinalis syrup and fluvoxamine or placebo syrup and fluvoxamine for 8 weeks.

Outcome Measures: The efficacy of treatment and recurrence of disease were surveyed and compared according to the Yale-Brown Obsessive Compulsive Scale at weeks 0, 4, and 8.

Results: Evaluation at the 4th and 8th week showed no significant differences between the two groups (p-value = 0.11, p-value = 0.445, respectively). At the 8th week of treatment, patients in the intervention group showed a remarkable reduction in scores on the Yale-Brown Obsessive-Compulsive Scale questionnaire (p- value= 0.003), and patients in the control group didn’t ((p- value= 0.180). This study showed that the E.amoneum-M.officinalis syrup was not significantly more efficacious than the fluvoxamine tablet, but the intervention group showed a significant improving trend (p-value= 0.001).

Conclusion: While monotherapy is usually the gold standard methodology, combination or augmentation therapy may also be of merit. Consequently, studies with larger sample sizes and the inclusion of para-clinical assessments such as serologic tests can further shed light on the mechanism of action of the E. amoneum- M. officinalis syrup and deepen our understanding of its effects.

Nanotechnological Advances in the Treatment of Epilepsy

Epilepsy is known as one of the major challenges for medical science. The sudden appearance of a seizure has been a significant health emergency as it may lead to further complications. Although key advancements have been achieved in terms of pharmacological approaches for epilepsy, many issues remain uncertain. Lipid carriers have been at the forefront, especially in neurodegenerative diseases, such as epilepsy, Alzheimer’s, dementia, etc. The blood-brain barrier still appears to be a major impediment in the successful treatment of epileptic seizures. This is mainly due to the limited bioavailability of most anti-convulsant drugs. The present review encompasses the issues underlying the current approach for epilepsy drug treatment and highlights the newer, novel, and more precise drug delivery system to manage seizures. The advantage of using a lipidbased delivery system is its superior absorption in the brain cells. Ample evidence shows that reducing the particle size also infuses the drug easily through the blood-brain barrier. The application of liposomes, polymeric nanoparticles, metallic nanoparticles, and solid lipid nanoparticles for the treatment and management of epilepsy has been highlighted in the present review. This review provides an overview of the current status of the treatment and recent advances in the treatment of epilepsy.

iTRAQ-Based Quantitative Proteomics Analysis Reveals the Invasion Mechanism of Spiroplasma eriocheiris in 3T6 Cells

Background: Spiroplasma eriocheiris is a novel pathogen of freshwater crustaceans and is closely related to S. mirum. They have no cell wall and a helical morphology. They have the ability to infect mammals with an unclear mechanism.

Objective: In this study, our aim was to investigate the profile of protein expression in 3T6 cells infected with S. eriocheiris.

Methods: The proteome of 3T6 cells infected by S. eriocheiris was systematically investigated by iTRAQ.

Results: We identified and quantified 4915 proteins, 67 differentially proteins were found, including 30 up-regulated proteins and 37 down-regulated proteins. GO term analysis shows that dysregulation of adhesion protein , interferon and cytoskeletal regulation are associated with apoptosis. Adhesion protein Vcam1 and Interferon-induced protein GBP2, Ifit1, TAPBP, CD63 ,Arhgef2 were up-regulated. A key cytoskeletal regulatory protein, ARHGEF17 was down-regulated. KEGG pathway analysis showed the NF-kappa B signaling pathway, the MAPK signaling pathway , the Jak-STAT signaling pathway and NOD-like receptor signaling are closely related to apoptosis in vivo.

Conclusion: Analysis of the signaling pathways involved in invasion may provide new insights for understanding the infection mechanisms of S. eriocheiris.

A Comprehensive Review on Preclinical Evidence-based Neuroprotective Potential of Bacopa monnieri against Parkinson's Disease

Parkinson's disease is a chronic and gradually progressive neurodegenerative disorder triggered due to the loss of dopamine-releasing neurons in the region of substantia nigra pars compacta characterized by the motor symptoms, such as tremor, bradykinesia, akinesia, and postural instability. Proteinopathies, mitochondrial dysfunction induced dopaminergic neuronal deterioration, and gene mutations are the hallmarks of Parkinson's disease. The bioactive components of Brahmi, such as Bacoside A, Bacoside B, and Bacosaponins, belong to various chemical families. Brahmi's neuroprotective role includes reducing neuronal oxidative stress, dopaminergic neuronal degeneration, mitochondrial dysfunction, inflammation, inhibition of α-synuclein aggregation, and improvement of cognitive and learning behaviour. Researchers found that Bacopa monnieri significantly increased brain levels of glutathione, vitamin C, vitamin E, and vitamin A in rats exposed to cigarette smoke. Brahmi has a potent antioxidant property and neuroprotective effects against PD that help reduce oxidative stress and neuroinflammation and enhance dopamine levels. The review collates all the preclinical studies that prove the beneficial neuroprotective effect of Brahmi for treating PD.

Role of Cannabinoids in Various Diseases: A Review

Background: The plant, Cannabis sativa, is heavily explored and researched with many industrial and pharmaceutical applications. The medicinal and therapeutic role of Cannabis sativa has been summarized in the paper, citing its mechanism of action and influence on the human body. Diseases like metabolic disorders, infectious diseases, and psychological disorders pose negative and long-term drastic effects on the body like neurodegeneration and other chronic system failures. Several existing studies have proved its effectiveness against such diseases.

Objectives: This review aims to provide an overview of the role of cannabinoids in various diseases like metabolic disorders, infectious diseases, and psychological disorders.

Methods: Various e-resources like Pubmed, Science Direct, and Google Scholar were thoroughly searched and read to make an informative, comprehensive manuscript. Here we tried to summarize the therapeutic aspect of Cannabis sativa and its bioactive compound cannabinoids with respect to various diseases.

Results: This review highlights the various constituents which are present in Cannabis sativa, the endocannabinoid system, and the role of cannabinoids in various diseases.

Conclusion: Recent research on Cannabis has suggested its role in neurodegenerative diseases, inflammation, sleep disorders, pediatric diseases, and their analgesic nature. Therefore, the authors majorly focus on the therapeutic aspect of Cannabis sativa in various diseases. The focus is also on the endocannabinoid system (ECS) and its role in fighting or preventing bacterial, parasitic, fungal, and viral infections.

An Overview of Acute Flaccid Myelitis

Acute Flaccid Myelitis is defined by the presence of Acute Flaccid Paralysis (AFP) and a spinal cord lesion on magnetic resonance imaging that is primarily limited to the grey matter. AFM is a difficult situation to deal with when you have a neurologic illness. According to the Centers for Disease Control and Prevention (CDC), a large number of cases were discovered in the United States in 2014, with 90% of cases occurring in children. Although the exact cause of AFM is unknown, mounting evidence suggests a link between AFM and enterovirus D68 (EV-D68). In 2014, an outbreak of AFM was discovered in the United States. The condition was initially linked to polioviruses; however, it was later found that the viruses were caused by non-polioviruses Enteroviruses D-68 (EV-D68). The number of cases has increased since 2014, and the disease has been declared pandemic in the United States. The sudden onset of muscle weakness, usually in an arm or leg, as well as pain throughout the body, the change in patient's facial expression (facial weakness), and shortness of breath, ingesting, and speaking are all common symptoms in patients suffering from neurologic disease. This article includes graphic and histogram representations of reported AFM incidents and criteria for causality, epidemiology, various diagnostic approaches, signs and symptoms, and various investigational guidelines. It also includes key statements about recent clinical findings related to AFM disease.

Polyphenols and Stem Cells for Neuroregeneration in Parkinson’s Disease and Amyotrophic Lateral Sclerosis

Parkinson’s disease (PD) and Amyotrophic lateral sclerosis (ALS) are neurological disorders pathologically characterized by chronic degeneration of dopaminergic neurons and motor neurons, respectively. There is still no cure or effective treatment against the disease progression and most of the treatments are symptomatic. The present review offers an overview of the different factors involved in the pathogenesis of these diseases. Subsequently, we focused on the recent advanced studies of dietary polyphenols and stem cell therapies, which have made it possible to slow down the progression of neurodegeneration. To date, stem cells and different polyphenols have been used for the directional induction of neural stem cells into dopaminergic neurons and motor neurons. We have also discussed their involvement in the modulation of different signal transduction pathways and growth factor levels in various in vivo and in vitro studies. Likewise stem cells, polyphenols also exhibit the potential of neuroprotection by their anti-apoptotic, anti-inflammatory, and anti-oxidant properties regulating the growth factors levels and molecular signaling events. Overall this review provides a detailed insight into recent strategies that promise the use of polyphenol with stem cell therapy for the possible treatment of PD and ALS.

Association of Oxidative Stress with Neurological Disorders

Backgorund: Oxidative stress is one of the main contributing factors involved in cerebral biochemical impairment. The higher susceptibility of the central nervous system to reactive oxygen species mediated damage could be attributed to several factors. For example, neurons use a greater quantity of oxygen, many parts of the brain have higher concentraton of iron, and neuronal mitochondria produce huge content of hydrogen peroxide. In addition, neuronal membranes have polyunsaturated fatty acids, which are predominantly vulnerable to oxidative stress (OS). OS is the imbalance between reactive oxygen species generation and cellular antioxidant potential. This may lead to various pathological conditions and diseases, especially neurodegenerative diseases such as, Parkinson’s, Alzheimer’s, and Huntington’s diseases.

Objectives: In this study, we explored the involvement of OS in neurodegenerative diseases.

Methods: We used different search terms like “oxidative stress and neurological disorders” “free radicals and neurodegenerative disorders” “oxidative stress, free radicals, and neurological disorders” and “association of oxidative stress with the name of disorders taken from the list of neurological disorders. We tried to summarize the source, biological effects, and physiologic functions of ROS.

Results: Finally, it was noted that more than 190 neurological disorders are associated with oxidative stress.

Conclusion: More elaborated studies in the future will certainly help in understanding the exact mechanism involved in neurological diseases and provide insight into revelation of therapeutic targets.

Anti-inflammatory Effects of Mesenchymal Stem Cells and their Secretomes in Pneumonia

Mesenchymal stem cells (MSCs) are multipotent progenitor cells that play crucial roles in the microenvironment of injured tissues. The potential therapeutics of MSCs have attracted extensive attention for several diseases such as acute respiratory distress syndrome (ARDS) and novel coronavirus disease 2019 (COVID-19) pneumonia. MSC-extracellular vesicles have been isolated from MSC-conditioned media (MSC-CM) with similar functional effects as parent MSCs. The therapeutic role of MSCs can be achieved through the balance between the inflammatory and regenerative microenvironments. Clinical settings of MSCs and their extracellular vesicles remain promising for many diseases, such as ARDS and pneumonia. However, their clinical applications remain limited due to the cost of growing and storage facilities of MSCs with a lack of standardized MSC-CM. This review highlights the proposed role of MSCs in pulmonary diseases and discusses the recent advances of MSC application for pneumonia and other lung disorders.

Tremor and Rigidity in Patients with Parkinson’s Disease: Emphasis on Epidemiology, Pathophysiology and Contributing Factors

Parkinson's disease (PD) is the second most prominent neurodegenerative movement disorder after Alzheimer’s disease, involving 2-3% of the population aged above 65 years. This is mainly triggered by the depletion of dopaminergic neurons located in substantia nigra pars compacta (SNpc) in the region of basal ganglia. At present, diagnosis for symptoms of PD is clinical, contextual, unspecified and therapeutically incomprehensive. Analysis of various causes of PD is essential for an accurate examination of the disease. Among the different causes, such as tremors and rigidity, unresponsiveness to the current treatment approach contributes to mortality. In the present review article, we describe various key factors of pathogenesis and physiology associated with tremors and rigidity necessary for the treatment of PI (postural instability) in patients with PD. Additionally, several reports showing early tremor and rigidity causes, particularly age, cortex lesions, basal ganglia lesions, genetic abnormalities, weakened reflexes, nutrition, fear of fall, and altered biomechanics, have been explored. By summarizing the factors that contribute to the disease, histopathological studies can assess rigidity and tremor in PD. With a clear understanding of the contributing factors, various prospective studies can be done to assess the incidence of rigidity and tremors.

The Treatment of Painful Diabetic Neuropathy

Painful diabetic peripheral neuropathy (painful-DPN) is a highly prevalent and disabling condition, affecting up to one-third of patients with diabetes. This condition can have a profound impact resulting in a poor quality of life, disruption of employment, impaired sleep, and poor mental health with an excess of depression and anxiety. The management of painful-DPN poses a great challenge. Unfortunately, currently there are no Food and Drug Administration (USA) approved disease-modifying treatments for diabetic peripheral neuropathy (DPN) as trials of putative pathogenetic treatments have failed at phase 3 clinical trial stage. Therefore, the focus of managing painful- DPN other than improving glycaemic control and cardiovascular risk factor modification is treating symptoms. The recommended treatments based on expert international consensus for painful- DPN have remained essentially unchanged for the last decade. Both the serotonin re-uptake inhibitor (SNRI) duloxetine and α2δ ligand pregabalin have the most robust evidence for treating painful-DPN. The weak opioids (e.g. tapentadol and tramadol, both of which have an SNRI effect), tricyclic antidepressants such as amitriptyline and α2δ ligand gabapentin are also widely recommended and prescribed agents. Opioids (except tramadol and tapentadol), should be prescribed with caution in view of the lack of definitive data surrounding efficacy, concerns surrounding addiction and adverse events. Recently, emerging therapies have gained local licenses, including the α2δ ligand mirogabalin (Japan) and the high dose 8% capsaicin patch (FDA and Europe). The management of refractory painful-DPN is difficult; specialist pain services may offer off-label therapies (e.g. botulinum toxin, intravenous lidocaine and spinal cord stimulation), although there is limited clinical trial evidence supporting their use. Additionally, despite combination therapy being commonly used clinically, there is little evidence supporting this practise. There is a need for further clinical trials to assess novel therapeutic agents, optimal combination therapy and existing agents to determine which are the most effective for the treatment of painful-DPN. This article reviews the evidence for the treatment of painful-DPN, including emerging treatment strategies such as novel compounds and stratification of patients according to individual characteristics (e.g. pain phenotype, neuroimaging and genotype) to improve treatment responses.

Scientific and Technological Prospecting of 1H-1,2,3-Triazoles

The use of 1H-1,2,3-triazoles has become an important scaffold for applications in different technological sectors. Therefore, we sought to carry out technological monitoring to understand the international scenario involving 1H-1,2,3-triazoles from the patents filed, in addition to evaluating the relationship between the growth in the number of patents and the improvement of strategies for obtaining these compounds via a metal-catalyzed azide-alkyne cycloaddition reaction. Technological monitoring was performed with the support of the PatentInspiration ® platform, using the keywords \"1,2,3-triazol\", \"1,2,3-triazole\", and \"1,2,3- triazolyl\". A total of 960 registered patents were found, most for the years 2014 and 2019. The main filers were prestigious multinational companies, such as Syngenta, Merck, Sandoz, Pfizer, and Bayer. The United States, China, Japan, and Germany lead patent registrations, mainly addressing innovations in chemistry and metallurgy, human needs, and new technologies. These results help to understand the state of innovation for this topic, pointing out the characteristics of the main discoveries concerning 1H-1,2,3-triazole derivatives.

Formulating the Structural Aspects of Various Benzimidazole Cognates

Background: Benzimidazole derivatives are widely used in clinical practice as potential beneficial specialists. Recently, the neuroprotective effect of derivatives of benzimidazole moiety has also shown positive outcomes.

Objectives: To develop favourable molecules for various neurodegenerative disorders using the versatile chemical behaviour of the benzimidazole scaffold.

Methods: About 25 articles were collected that discussed various benzimidazole derivatives and categorized them under various subheadings based on the targets such as BACE 1, JNK, MAO, choline esterase enzyme, oxidative stress, mitochondrial dysfunction in which they act. The structural aspects of various benzimidazole derivatives were also studied.

Conclusion: To manage various neurodegenerative disorders, a multitargeted approach will be the most hopeful stratagem. Some benzimidazole derivatives can be considered for future studies, which are mentioned in the discussed articles.

Novel Pulmonary Delivery of Antiviral Drugs for Treating COVID-19 in Patients with Parkinson’s Disease

The COVID-19 pandemic has caused a significant burden on public health worldwide. Currently, there are limited medications for the treatment of COVID-19 in patients with Parkinson’s disorder (PD). Several antiviral drugs and other pharmacotherapies have shown promising results and are used by various delivery methods. Among the antiviral drugs, amantadine alone was reported to provide therapeutic benefit against COVID-19 in patients with PD. Here, we propose novel strategies for pulmonary drug delivery technology of antiviral drug, amantadine. As such pulmonary delivery of this drug or in combination with the additional antiviral drugs could be a more effective strategy for the treatment of COVID-19-related complications in patients with PD. Furthermore, the important benefits and limitations of this novel delivery technology will be discussed.

Beneficial Extracardiac Effects of Cardiovascular Medications

Cardiovascular diseases are the most common cause of death worldwide, with cardiovascular medications being amongst the most common medications prescribed. These medications have diverse effects on the heart, vascular system, as well as other tissues and organ systems. The extra cardiovascular effects have been found to be of use in the treatment of non-cardiovascular diseases and pathologies. Minoxidil is used to manage systemic hypertension with its well-known side effect of hirsutism used to treat alopecia and baldness. Sildenafil was originally investigated as a treatment option for systemic hypertension; however, its side effect of penile erection led to it being widely used for erectile dysfunction. Alpha-1 blockers such as terazosin are indicated to treat systemic hypertension but are more commonly used for benign prostatic hyperplasia and post-traumatic stress disorder. Beta blockers are the mainstay treatment for congestive heart failure and systemic hypertension but have been found useful to help in patients with intention tremors as well as prophylaxis of migraines. Similarly, calcium channel blockers are indicated in medical expulsion therapy for ureteric calculi in addition to their cardiovascular indications. Thiazides are commonly used for treating systemic hypertension and as diuretics. Thiazides can cause hypocalciuria and hypercalcemia. This side effect has led to thiazides being used to treat idiopathic hypercalciuria and associated nephrolithiasis. Spironolactone is commonly utilized in treating heart failure and as a diuretic for edema. It’s well described anti-androgen side effects have been used for acne vulgaris and hirsutism in polycystic ovarian syndrome. This review article discusses how the various extracardiovascular effects of commonly used cardiovascular medications are put to use in managing non-cardiovascular conditions.

The Impact of Traditional Chinese Medicine on Mitophagy in Disease Models

Mitophagy plays an important role in maintaining mitochondrial quality and cell homeostasis through the degradation of damaged, aged, and dysfunctional mitochondria and misfolded proteins. Many human diseases, particularly neurodegenerative diseases, are related to disorders of mitochondrial phagocytosis. Exploring the regulatory mechanisms of mitophagy is of great significance for revealing the molecular mechanisms underlying the related diseases. Herein, we summarize the major mechanisms of mitophagy, the relationship of mitophagy with human diseases, and the role of traditional Chinese medicine (TCM) in mitophagy. These discussions enhance our knowledge of mitophagy and its potential therapeutic targets using TCM.

Selected Natural and Synthetic Agents Effective against Parkinson’s Disease with Diverse Mechanisms

Similar to other neurodegenerative diseases, Parkinson’s disease (PD) has been extensively investigated with respect to its neuropathological background and possible treatment options. Since the symptomatic outcomes are generally related to dopamine deficiency, the current treatment strategies towards PD mainly employ dopaminergic agonists as well as the compounds acting on dopamine metabolism. These drugs do not provide disease modifying properties; therefore alternative drug discovery studies focus on targets involved in the progressive neurodegenerative character of PD. This study has aimed to present the pathophysiology of PD concomitant to the representation of drugs and promising molecules displaying activity against the validated and non-validated targets of PD.

Exploring the Role of Stem Cell Therapy in Treating Neurodegenerative Diseases: Challenges and Current Perspectives

Several human neurological disorders, such as Parkinson’s disease, Alzheimer’s disease, amyotrophic lateral sclerosis, Huntington’s disease, spinal cord injury, multiple sclerosis, and brain stroke, are caused by the injury to neurons or glial cells. The recent years have witnessed the successful generation of neurons and glia cells driving efforts to develop stem-cell-based therapies for patients to combat a broad spectrum of human neurological diseases. The inadequacy of suitable cell types for cell replacement therapy in patients suffering from neurological disorders has hampered the development of this promising therapeutic approach. Attempts are thus being made to reconstruct viable neurons and glial cells from different stem cells, such as embryonic stem cells, mesenchymal stem cells, and neural stem cells. Dedicated research to cultivate stem cell-based brain transplantation therapies has been carried out. We aim at compiling the breakthroughs in the field of stem cell-based therapy for the treatment of neurodegenerative maladies, emphasizing the shortcomings faced, victories achieved, and the future prospects of the therapy in clinical settings.

Drug-Induced Peripheral Neuropathy: Diagnosis and Management

Peripheral neuropathy comes in all shapes and forms and is a disorder which is found in the peripheral nervous system. It can have an acute or chronic onset depending on the multitude of pathophysiologic mechanisms involving different parts of nerve fibers. A systematic approach is highly beneficial when it comes to cost-effective diagnosis. More than 30 causes of peripheral neuropathy exist ranging from systemic and auto-immune diseases, vitamin deficiencies, viral infections, diabetes, etc. One of the major causes of peripheral neuropathy is drug-induced disease, which can be split into peripheral neuropathy caused by chemotherapy or by other medications. This review deals with the latest causes of drug-induced peripheral neuropathy, the population involved, the findings on physical examination and various workups needed and how to manage each case.

A Systematic Review of Subacute Thyroiditis Related to COVID-19

Background: The novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which belongs to the family Coronaviridae, is the cause of COVID-19 infection. Its outbreak was declared a pandemic on March 11, 2020. COVID-19 does not involve the respiratory system solely, but other systems were also noted to be affected, including the endocrine, cardiovascular, and gastrointestinal systems. Several case reports and series have been published regarding SAT related to COVID-19 infection, yet management and clinical outcomes of the disease have not been discussed in detail.

Methods: This is a systematic review of cases that have been reported to have subacute thyroiditis induced by COVID-19 infection. A systematic search was conducted throughout multiple databases, including PubMed, Google Scholar, and MeSH network.

Results: The total number of reported subacute thyroiditis cases attributed to COVID-19 is 24. There was a female predominance (18 females and 6 males) with a female to male ratio of 3:1. Ages ranged from 18 to 69 years (mean = 38.67). Twenty-four symptoms related to thyroiditis were reported, the most common of which being neck pain (95.83%, n=23), palpitations (79.17%, n=19), and fever (66.67%, n=16). The outcome was complete resolution in 70% of cases.

Conclusion: The endocrine complications of COVID-19 and their management have been disregarded by most as they are rare. Our knowledge of COVID-19 and its complications is growing rapidly. More favourable outcomes were linked with the use of corticosteroid therapy. Until larger studies can be conducted, the management of SAT caused by COVID-19 remains to be based on each individual case. However, the treatment regimen should include corticosteroid therapy.

Novel Self-micro Emulsifying Drug Delivery System for Safe Intramuscular Delivery with Improved Pharmacodynamics and Pharmacokinetics

Background: Diclofenac Sodium (DS) injection is widely used in the management of acute or chronic pain and inflammatory diseases. It incorporates 20% w/v Transcutol-P as a solubilizer to make the stable injectable formulation. However, the use of Transcutol-P in high concentration leads to adverse effects such as severe nephrotoxicity, etc. Some advancements have resulted in the formulation of an aqueous-based injectable but that too used benzyl alcohol which is reported to be toxic for human use.

Objective: This study aimed to develop an injectable Self-Micro Emulsifying Drug Delivery System (SMEDDS) as a novel carrier of DS for prompt release with better safety and efficacy.

Methods: A solubility study was performed with different surfactants and co-surfactants. The conventional stirring method was employed for the formulation of SMEDDS. Detailed in vitro characterization was done for different quality control parameters. In vivo studies were performed using Wistar rats for pharmacokinetic evaluation, toxicological analysis, and analgesic activity.

Results: The optimized formulation exhibited good physical stability, ideal globule size (156±0.4 nm), quick release, better therapeutics, and safety, increase in LD50 (221.9 mg/kg) to that of the commercial counterpart (109.9 mg/kg). Furthermore, pre-treatment with optimized formulation reduced the carrageenan-induced rat paw oedema by 88±1.2% after 4 h, compared to 77±1.6% inhibition with commercial DS formulation. Moreover, optimized formulation significantly (p<0.05) inhibited the pain sensation in the acetic-acid induced writhing test in mice compared to its commercial equivalent with a better pharmacokinetic profile.

Conclusion: The above findings confirmed that liquid SMEDDS can be a successful carrier for the safe and effective delivery of DS.

Peptide Based Therapy for Neurological Disorders

Peptides are small molecules composed of amino acids linked together by peptide bonds. The targeted action of these peptides along with their magnificent ability to reach locations in the body that are complicated to access, is being considered of tremendous potential in disease modifying therapies. Synthetic as well as natural peptides like Carnosine are currently under research for the treatment of Neurodegenerative Disorders (NDDs). Peptide based vaccines are currently under immense research for diseases like dementia. Toxicity of peptide-based drugs towards eukaryotic cells due to their increased haemolytic activity is of major concern and this is being tackled by introducing modifications into the peptide structure. Some crucial peptide inhibitors currently in use for neurodegenerative disorders include Aβ (16-20) KLVFF for Alzheimer’s disease, NAPVSIPQ (NAP) for Parkinson’s disease, towards eukaryotic cells Vasoactive Intestinal Peptides (VIP) for Huntington’s disease, Polyglutamine Binding Peptide-1(QBP1) for Dentatorubral- pallidoluysian atrophy (DRPLA). Certain peptides are involved in inhibition of Mitochondrial Permeability Transition (MPT) that plays a prominent part in the materialization of neurodegenerative diseases, one such example of peptides being Ba-V which is obtained from Bothrops atrox snake venom. New therapeutic peptides are being identified using bioinformatics tools like High Throughput Screening (HTS). These tools are being used to explore the selectivity, stability, extent of immune response and toxic side effects of peptides. Apart from neurodegenerative diseases, the potential of bioactive peptides is also being tested against cancer, diabetes and microbes. This review focuses on the recent advances in peptide therapeutics and novel peptides discovered for the treatment of NDs.

Analytical Methods for the Identification of Pigments in Tattoo Inks and Some of Their Physiological Side Effects: A Review

In this review, numerous analytical methods to distinguish pigments in tattoo, paint, and ink items are discussed. The selection of a method was dependent upon the purpose, e.g., quantification or identification of pigments. The introductory part of this review focuses on describing the importance of setting up a pigment-associated safety profile. The formation of different degradation chemical substances as well as impurity trends can be indicated through the chemical investigation of pigments in tattoo products. It is noteworthy that pigment recognition in tattoo inks can work as a preliminary method to identify the pigments in a patient's tattoo before being removed by laser therapy. Contrary to the study of banned pigments, the identification process usually requires only a few indication substances for positive dyes. In general, tattoo pigments are almost insoluble in aqueous solutions, and many organic solvents and various pigment analyses have been conducted. It is proposed that in the future, laboratories concerned with tattoo substance analysis should have access to extensive pigment specifications and spectroscopic databases. The most important and recent physiological side effects of tattooing have been discussed in this review.

Dysregulation of SIRT-1 Signaling in Multiple Sclerosis and Neuroimmune Disorders: A Systematic Review of SIRTUIN Activators as Potential Immunomodulators and their Influences on other Dysfunctions

Immune dysregulation, neuronal inflammation, and oligodendrocyte degradation are key causes for autoimmune disorders like multiple sclerosis (MS) and various other immune dysregulated neurodegenerative complications responsible for CNS-mediated immune responses. Sirtuin (SIRT-1) is a nicotinamide adenosine dinucleotide (NAD)-dependent transcriptional protein that deacetylases and removes acetyl groups from its transcription factors like P53, FOXO, NF-Κb, PGC-1α. SIRT-1 mediates a wide range of physiological functions, including gene transcription, metabolism, neuronal apoptosis, and glucose production. SIRT-1 dysregulation targets transcription factors, and other molecular alterations such as gene expression modification influence neuronal plasticity, inhibit Th17 cells, and interleukin-1β can aggravate brain diseases. Preclinical and clinical findings show that the upregulation of SIRT-1 reduces autoimmunity, neurodegeneration, and neuroexcitation. Even though drugs are being developed for symptomatic therapies in clinical trials, there are particular pharmacological implications for improving post-operative conditions in neurodegenerative patients where intensive care is required. Understanding the SIRT-1 signaling and identifying immune-mediated neuron deterioration can detect major therapeutic interventions that could prevent neuro complications. Thus, in the current review, we have addressed the manifestations of disease by the downregulation of SIRT-1 that could potentially cause MS and other neurodegenerative disorders and provided data on existing available and effective drug therapies and disease management strategies.

Beta Blockers and Chronic Obstructive Pulmonary Disease (COPD): Sum of Evidence

Approximately half a century has passed since the discovery of beta-blockers. Then, their prime therapeutic purpose was to treat angina and cardiac arrhythmias; nowadays, beta-blockers’ usage and effectiveness are extended to treat other cardiovascular diseases, such as hypertension, congestive heart failure, and coronary artery disease. Safety concerns were raised about beta- blockers and their use for chronic obstructive pulmonary disease (COPD) patients with concurrent cardiovascular disease. After thorough research of the literature, this review summarizes the evidence proving that beta-blockers not only might be well tolerated in COPD patients, but they might also have a beneficial effect in this group of patients.

Engineered Probiotic and Prebiotic Nutraceutical Supplementations in Combating Non-communicable Disorders: A Review

Nutritional supplementations are a form of nutrition sources that may help in improving the health complexities of a person throughout his or her life span. Being also categorized as food supplementations, nutraceuticals are products that are extracted from edible sources with medical benefits as well as primary nutritional values. Nutraceuticals can be considered as functional foods. There are evidences that nutraceutical supplementations can alter the commensal gut microbiota and help to prevent or fight against chronic non-communicable degenerative diseases in adults, including neurological disorders (Autism Spectrum Disorder [ASD], Parkinson’s disease [PD], Multiple sclerosis [MS]) and metabolic disorders (Type-II diabetes, obesity and non-alcoholic fatty liver disease). They can even lessen the complexities of preterm babies like extra-uterine growth restriction, necrotizing enterocolitis, infant eczema and allergy (during pregnancy) as well as bronchopulmonary dysplasia. Molecular perception of inflammatory and apoptotic modulators regulating the pathogenesis of these health risks, their control and management by probiotics and prebiotics could further emphasize the scientific overview of their utility. In this study, the pivotal role of nutraceutical supplementations in regulating or modulating molecular pathways in the above non-communicable diseases is briefly described. This work also gives an overall introduction of the sophisticated genome-editing techniques and advanced delivery systems in therapeutic activities applicable under these health risks.

Potential of Antibiotics for the Treatment and Management of Parkinson's Disease: An Overview

Evidence has emerged over the last 2 decades to ascertain the proof of concepts viz. mitochondrial dysfunction, inflammation-derived oxidative damage and cytokine-induced toxicity that play a significant role in Parkinson's disease (PD). The available pharmacotherapies for PD are mainly symptomatic and typically indicate L-DOPA to restrain dopamine deficiency and its consequences. In the 21st century, the role of antibiotics has emerged at the forefront of medicines in health and human illness. There are several experimental and pre-clinical evidences that support the potential use of antibiotics as a neuroprotective agent. The astonishing effects of antibiotics and their neuroprotective properties against neurodegeneration and neuro-inflammation would be phenomenal for the development of effective therapy against PD. Antibiotics are also testified as useful in not only preventing the formation of alpha-synuclein but also acting on mitochondrial dysfunction and neuro-inflammation. Thus, the possible therapy with antibiotics in PD would impact both pathways leading to neuronal cell death in substantia nigra and pars compacta in the midbrain. Moreover, the antibiotic-based pharmacotherapy will open a scientific research avenue to add more to the evidence-based and rational use of antibiotics for the treatment and management of PD and other neurodegenerative disorders.

Modulation of Huntington’s Disease in Drosophila

Huntington’s disease (HD) is a progressive neurodegenerative disorder which deteriorates the physical and mental abilities of the patients. It is an autosomal dominant disorder and is mainly caused by the expansion of a repeating CAG triplet. A number of animal models ranging from worms, fruit flies, mice and rat, pig, sheep and monkeys are available, which have been helpful in understanding various pathways involved during the progression of the disease. Drosophila is one of the most commonly used model organisms for biomedical science, due to low cost maintenance, short life span and easy implications of genetic tools. The present review provides a brief description of HD and the studies carried out for HD to date, taking Drosophila as a model.

Evaluating the Risks of Systemic Maternal Ivermectin Exposure During Pregnancy in Human and Vertebrate Animals: A Scoping Review

Background: Ivermectin is widely used for the treatment of neglected tropical diseases associated with adverse maternal and fetal outcomes when the infection complicates the pregnancy. However, the United States FDA classification and current distribution protocols limit ivermectin treatment in pregnant women because antepartum safety has not been well-established.

Objective: We conducted a scoping review to address the question of what is known from both human and vertebrate animal studies about the safety of systemic ivermectin exposure during pregnancy.

Methods: We searched PubMed for adverse outcomes related to systemic ivermectin exposure in human and vertebrate animal pregnancies, including English-language primary articles from 1900 - 2019.

Results: We identified 23 primary articles for evaluation, including 10 human studies and 13 vertebrate animal studies of interest. One prospective randomized, controlled trial investigating the safety of systemic ivermectin exposure during pregnancy and four retrospective human studies did not identify a significant association with adverse birth outcome metrics. Out of the three human case reports, two reported uncomplicated prenatal courses and one reported stillbirth and maternal death. A retrospective cross-sectional study concluded a positive association between onchocerciasis and spontaneous abortion, mitigated by ivermectin mass drug administration. While adverse pregnancy outcomes were observed at high doses in mice, rats, and rabbits, there was overall a lack of evidence to support concerns that therapeutic doses of ivermectin (0.2 mg/kg) cause adverse pregnancy outcomes.

Conclusion: Further research is warranted to address safety concerns regarding the use of ivermectin in pregnant women in treating and preventing neglected helminth infections that threaten maternal-child health.

Management of Acute Aluminum Phosphide Poisoning: Has Anything Changed?

Due to its easy availability, rapid and severe toxicity, and no specific antidote, aluminum phosphide has emerged as a lethal toxin, commonly used for suicidal intent in agricultural communities. Despite various advances in medicine, this compound’s toxicity is poorly understood, and it still has a very high case fatality rate with no definitive treatment options available. This review aims to understand the mechanism of toxicity, clinical toxidrome of acute aluminum phosphide poisoning, and the available therapeutic options, including recent advances. A literature review was performed searching PubMed, EMBASE Ovid, and Cochrane Library, using the following search items: (“aluminum phosphide poisoning” OR “aluminum phosphide poisoning toxicity” OR “aluminum phosphide ingestion”) AND (“management” OR “therapy” OR “treatment”). Selected articles were discussed amongst all the authors to shape this review. High case fatality rate and lack of any specific antidote are persisting challenges. Therapeutic measures need to be implemented from all fronts – reducing easy access to the poison, developing less toxic alternatives for use as a pesticide, and more studies directed at developing an effective reversal agent for phosphine. The advent of promising agents like glucose-insulin-potassium infusion and lipid emulsion is a new ray of hope in the complete recovery in this fatal poisoning. The need of the hour is to find an agent that rapidly and effectively reverses aluminum phosphide's toxic effects. Large multicenter controlled trials are required to establish the role of glucose-insulin-potassium and lipid emulsion.

Immunosuppressant Drugs and Covid-19: Associated Risks, Drug-Drug Interactions and Contraindications

Immunosuppressant drugs like Etanercept, Mycophenolate mofetil, Sirolimus, Cyclosporine, and Rituximab can weaken the immune system and make patients susceptible to SARS nCoV-2 virus. These drugs make immunocompromised persons more vulnerable to complications associated with COVID-19. Moreover, it can also increase mortality and morbidity, as a weakened immune system can lead to a longer duration of infection. This study discusses the guidelines on immunosuppressant drugs and their associated risk factors with COVID-19, issued by the U.S CDC (Centers for Disease Control and Prevention), WHO (World Health Organization), U.S FDA (Food and Drug Administration), and other accredited global health organizations. Moreover, it also includes information about pharmaceutical properties, mechanism of action, COVID-19 associated risk factors, adverse drug reactions, contraindications, and drug-drug interactions. Our study will help government partners and international health organizations to understand COVID-19 health risks associated with immunosuppressants. Increased public awareness about effective drug therapy for autoimmune diseases, cancer treatment, immunocompromised, and organ transplant patients will help lower the mortality and morbidity associated with the disease amid the COVID-19 pandemic.

Drosophila melanogaster a Versatile Model of Parkinson’s Disease

Parkinson’s Disease (PD) is one of the most prevalent, recurrent and life-threatening neurodegenerative diseases. However, the precise mechanism underlying this disease is not yet clearly understood. For understanding the pathogenesis of PD, it is essential to identify the symptoms along with the novel biological markers and to develop strategies that could lead towards the development of effective therapy. PD is associated with Lewy bodies (LBs) formation and the loss of dopaminergic neurons in the substantia nigra pars compacta of mid brain region. For the improvement in treatment strategies, as well as understanding the pathophysiology of the PD in a number of animal models have been introduced that can recapitulate the pathophysiology, motor and nonmotor symptoms of PD. In contrast to mammalian models like rodents, mice and monkey, Drosophila is easy to handle as well as its maintenance cost is low. Due to the anatomical differences in the brain and other major organs of human and fly, the issues of standardizing the methods or experiments to analyze behavioral aspects (walking, writhing, eating and sleeping) are difficult in flies. The present review highlights the studies carried out for PD since 2000, using Drosophila melanogaster.

Parkinson’s Disease: Is there a Role for Dietary and Herbal Supplements?

Parkinson’s Disease (PD) is characterised by degeneration of the neurons of the nigrostriatal dopaminergic pathway of the brain. The pharmacological cornerstone of PD management is mainly the use of dopamine precursors, dopamine receptor agonists, and agents that inhibit the biochemical degradation of dopamine. While these drugs initially provide relief to the symptoms and improve the quality of life of the patients, progression of the underlying pathological processes, such as oxidative stress and neuroinflammation (which have been strongly associated with PD and other neurodegenerative disorders), eventually reduce their benefits, making further benefits achievable, only at high doses due to which the magnitude and frequency of side-effects are amplified. Also, while it is becoming obvious that mainstream pharmacological agents may not always provide the much-needed answer, the question remains what succour can nature provide through dietary supplements, nutraceuticals and herbal remedies? This narrative review examines current literature for evidence of the possible roles (if any) of nutraceuticals, dietary supplements and herbal remedies in the prevention or management of PD by examining how these compounds could modulate key factors and pathways that are crucial to the pathogenesis and/or progression of PD. The likely limitations of this approach and its possible future roles in PD prevention and management are also considered.

Neurodegenerative Diseases and Flavonoids: Special Reference to Kaempferol

Neurodegenerative diseases like Alzheimer's disease, Parkinson's disease, Huntington’s disease, Multiple Sclerosis and Ischemic stroke have become a major health problem worldwide. Pre-clinical studies have demonstrated the beneficial effects of flavonoids on neurodegenerative diseases and suggest them to be used as therapeutic agents. Kaempferol is found in many plants such as tea, beans, broccoli, strawberries, and neuroprotective effects against the development of many neurodegenerative diseases such as Parkinson, Alzheimer's disease and Huntington's disease. The present study summarizes the neuroprotective effects of kaempferol in various models of neurodegenerative diseases. Kaempferol delays the initiation as well as the progression of neurodegenerative disorders by acting as a scavenger of free radicals and preserving the activity of various antioxidant enzymes. Kaempferol can cross the Blood-Brain Barrier (BBB), and therefore results in an enhanced protective effect. The multi-target property of kaempferol makes it a potential dietary supplement in preventing and treating neurodegenerative diseases.

Critical Care Management of an Obese Asthmatic Patient: A Review

Obesity and asthma are two conditions that are considered a global health problem. There has been an increased number of obese patients and different factors contribute to the development of this disease, such as changes in lifestyle, poor physical activity, and genetics. Obesity, as a co-morbidity, could contribute to the aggravation of asthma or the progress and exacerbation. This could lead to asthma-related hospitalizations and ICU admissions. Understanding the pathophysiology of those two diseases is helpful in the decision-making process of the management. The main goal of the therapy is reducing the exacerbation symptoms and or the ICU length-stay, which could depend on the type of mechanical ventilation used on the patient.

COVID-19: Our Current Knowledge of Epidemiology, Pathology, Therapeutic Approaches, and Diagnostic Methods

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) firstly emerged in Wuhan, China at the end of 2019. After going through the experimental process, the virus was named the novel coronavirus (2019-nCoV) by the World Health Organization (WHO) in February 2020 which has created a global pandemic. The coronavirus disease 2019 (COVID-19) infection is challenging the people who are especially suffering from chronic health problems such as asthma, diabetes, and heart disease or immune system deteriorating disorders, including cancers, Alzheimer's, etc. Other predisposing/risk factors consist of smoking and age (elderly people are at higher risk). The 2019-nCoV attacks epithelial cells in all organs, particularly epithelial cells in the lungs, resulting in viral pneumonia. The 2019-nCoV starts its invasion with the attachment and entry into the respiratory tract epithelial cells via Angiotensin-Converting Enzyme 2 (ACE2) receptors on the epithelial cells. The critical problem with 2019-nCoV is its ability in human to human asymptomatic transmission which causes the rapid and hidden spread of the virus among the population. Also, there are several reports of highly variable and tightly case-dependent clinical manifestations caused by SARS-CoV2, which made the virus more enigmatic. The clinical symptoms are varied from common manifestations which occurred in flu and cold, such as cough, fever, body-ache, trembling, and runny nose to severe conditions, like the Acute Respiratory Distress Syndrome (ARDS) or even uncommon/unusual symptoms such as anosmia, skin color change, and stroke. In fact, besides serious injuries in the respiratory system, COVID-19 invades and damages various organs, including the kidney, liver, gastrointestinal, and nervous system. Accordingly, to cut the transmission chain of disease and control the infection spread. One of the major solutions seems to be early detection of the carriers, particularly the asymptomatic people, with sensitive and accurate diagnostic techniques. Moreover, developing novel and appropriate therapeutic approaches will contribute to the suitable management of the pandemic. Therefore, there is an urgent necessity to make comprehensive investigations and study reviews about COVID-19, offering the latest findings of novel therapies, drugs, epidemiology, and routes of virus transmission and pathogenesis. In this review, we discuss new therapeutic outcomes and cover and the most significant aspects of COVID-19, including the epidemiology, biological features, organs failure, and diagnostic techniques.

Polypharmacy in Chronic Neurological Diseases: Multiple Sclerosis, Dementia and Parkinson’s Disease

Polypharmacy is an important aspect of medication management and particularly affects elderly and chronically ill people. Patients with dementia, Parkinson’s disease (PD), or multiple sclerosis (MS) are at high risk of multi medication due to their complex symptomatology. Our aim was to provide an overview of different definitions of polypharmacy and to present the current state of research on polypharmacy in patients with dementia, PD, or MS. The most common definition of polypharmacy in the literature is the concomitant use of ≥5 medications (quantitative definition approach). Polypharmacy rates of up to >50% have been reported for patients with dementia, PD, or MS, although MS patients are on average significantly younger than those with dementia or PD. The main predictor of polypharmacy is the complex symptom profile of these neurological disorders. Potentially inappropriate medication (PIM), drug-drug interactions, poor treatment adherence, severe disease course, cognitive impairment, hospitalisation, poor quality of life, frailty, and mortality have been associated with polypharmacy in patients with dementia, PD, or MS. For patients with polypharmacy, either the avoidance of PIM (selective deprescribing) or the substitution of PIM with more suitable drugs (appropriate polypharmacy) is recommended to achieve a more effective therapeutic management.

Harnessing the Potential of Long Non-coding RNAs to Manage Metabolic Diseases

Long non-coding RNAs (lncRNAs) are functionally versatile molecules that regulate gene expression at all levels of biological organization. RNA modulation, at the moment, has emerged as a powerful therapeutic technique to treat human diseases. Lately, lncRNAs have been acknowledged as key players in human metabolism and, indeed, implicated in the etiology of many common diseases other than cancers, where they can perhaps serve as reliable markers to determine disease status or assess outcomes of an intervention. Here, in this review, we cite examples of such lncRNAs, discuss their mechanistic role in human diseases and their genetic association, quote potential biomarkers found in human blood, summarize the methods for therapeutic targeting lncRNAs and examine the progress of lncRNA based drugs in clinical trials. Thus, we propose that lncRNAs serve as both a biomarker and an effective therapeutic target with promising clinical utility to manage human metabolic diseases.

Patients Stratification Strategies to Optimize the Effectiveness of Scavenging Biogenic Aldehydes: Towards a Neuroprotective Approach for Parkinson's Disease

Parkinson’s disease (PD) is a clinically heterogeneous disorder with a multi-factorial pathology. Various molecular mechanisms are involved in the pathogenesis of PD, converging to oxidative stress and proteinopathy. The accumulation of reactive aldehydes (i.e., the dopamine metabolite DOPAL, lipid-peroxidation products, and advanced glycation end-products) has been reported in PD patients’ brains. Aldehydes easily react with primary amines such as lysine residues, which are involved in several regulatory processes in cells. Therefore, aldehyde adducts lead to severe consequences, including neuronal proteostasis, mitochondrial dysfunction, and cell death. In this review, we analyzed the scavenging role of amines toward toxic aldehydes in the brain. Interestingly, small molecules like metformin, rasagiline, hydralazine are already clinically available and used in the therapy for PD and other diseases. Hence, we propose to reevaluate this class of drugs as a disease-modifiers for PD, and we suggest that improved analysis of their pharmacology and bioavailability in the brain, together with a more precise patients stratification, should be considered before planning future clinical trials.

Machine Learning Approaches in Parkinson’s Disease

Background: Parkinson’s disease is the second most frequent neurodegenerative disorder. Its diagnosis is challenging and mainly relies on clinical aspects. At present, no biomarker is available to obtain a diagnosis of certainty in vivo.

Objective: The present review aims at describing machine learning algorithms as they have been variably applied to different aspects of Parkinson’s disease diagnosis and characterization.

Methods: A systematic search was conducted on PubMed in December 2019, resulting in 230 publications obtained with the following search query: “Machine Learning” “AND” “Parkinson Disease”.

Results: The obtained publications were divided into 6 categories, based on different application fields: “Gait Analysis - Motor Evaluation”, “Upper Limb Motor and Tremor Evaluation”, “Handwriting and typing evaluation”, “Speech and Phonation evaluation”, “Neuroimaging and Nuclear Medicine evaluation”, “Metabolomics application”, after excluding the papers of general topic. As a result, a total of 166 articles were analyzed after elimination of papers written in languages other than English or not directly related to the selected topics.

Conclusion: Machine learning algorithms are computer-based statistical approaches that can be trained and are able to find common patterns from big amounts of data. The machine learning approaches can help clinicians in classifying patients according to several variables at the same time.

Learning from Metabolic Networks: Current Trends and Future Directions for Precision Medicine

Background: Systems biology and network modeling represent, nowadays, the hallmark approaches for the development of predictive and targeted-treatment based precision medicine. The study of health and disease as properties of the human body system allows the understanding of the genotype-phenotype relationship through the definition of molecular interactions and dependencies. In this scenario, metabolism plays a central role as its interactions are well characterized and it is considered an important indicator of the genotype- phenotype associations. In metabolic systems biology, the genome-scale metabolic models are the primary scaffolds to integrate multi-omics data as well as cell-, tissue-, condition- specific information. Modeling the metabolism has both investigative and predictive values. Several methods have been proposed to model systems, which involve steady-state or kinetic approaches, and to extract knowledge through machine and deep learning.

Methods: This review collects, analyzes, and compares the suitable data and computational approaches for the exploration of metabolic networks as tools for the development of precision medicine. To this extent, we organized it into three main sections: "Data and Databases", "Methods and Tools", and "Metabolic Networks for medicine". In the first one, we have collected the most used data and relative databases to build and annotate metabolic models. In the second section, we have reported the state-of-the-art methods and relative tools to reconstruct, simulate, and interpret metabolic systems. Finally, we have reported the most recent and innovative studies that exploited metabolic networks to study several pathological conditions, not only those directly related to metabolism.

Conclusion: We think that this review can be a guide to researchers of different disciplines, from computer science to biology and medicine, in exploring the power, challenges and future promises of the metabolism as predictor and target of the so-called P4 medicine (predictive, preventive, personalized and participatory).

GSK-3 Inhibitors: A New Class of Drugs for Alzheimer’s Disease Treatment

Alzheimer’s disease (AD), a chronic neurodegenerative disease, is the most common form of dementia that causes cognitive function impairment, including memory, thinking, and behavioral changes that ultimately lead to death. The overactivation of GSK-3, an enzyme from the proline/serine K_i ^{NS family, has been associated with hyper-phosphorylation of tau proteins. The self- -assembly of hyper-phosphorylated tau proteins to form tangles of straight and helical filaments is known to be involved in AD. Therefore, GSK-3 has been considered a potential target of novel drug discovery for AD treatment. Research on the development of GSK-3 inhibitors has received enormous attention from the vast scientific community because they are targeted for AD and other diseases, including type 2 diabetes, cancers, stroke, Parkinson’s disease and bipolar disorder. Various drugs of both synthetic and natural origins have been designed to inhibit GSK-3 activity. However, there is a need to develop novel drug candidates that can selectively inhibit GSK-3. Hence, this review summarizes the potential of GSK-3 inhibitors for AD therapy and discusses the structure- activity relationship of current drug molecules and the potential problems associated with them.}

An Insight Into Mitochondrial Dysfunction and its Implications in Neurological Diseases

In the last few years, a massive increase in research has been observed that focuses on investigating the role of mitochondria in the pathogenesis of several neurodegenerative disorders. Mitochondria are vital cell organelles having important roles in different cellular processes, including energy production, calcium signaling, Reactive Oxygen Species (ROS) generation, apoptosis, etc. Therefore, healthy mitochondria are necessary for cell survival and functioning. It would seem feasible that mitochondrial dysfunction will have implications in various pathological conditions. A large body of evidence indicates the role of the mitochondrion as a potential key player in the loss or dysfunction of neurons in various neurodegenerative disorders. In this review, we provide an insight into mitochondrial dysfunction and its involvement in the pathology of several neurological diseases such as Alzheimer’s disease, Parkinson’s disease, Amyotrophic Lateral Sclerosis, Hypoxic- Ischemic Brain Injury, and many more.

Mitochondrial Dysfunction in Huntington’s Disease: Pathogenesis and Therapeutic Opportunities

Huntington’s disease (HD) is a prototypical neurodegenerative disease, preferentially disrupting the neurons of the striatum and cortex. Progressive motor dysfunctions, psychiatric disturbances, behavioral impairments, and cognitive decline are the clinical symptoms of HD progression. The disease occurs due to expanded CAG repeats in exon 1 of huntingtin protein (mHtt), causing its aggregation. Multiple cellular and molecular pathways are involved in HD pathology. Mitochondria, as vital organelles have an important role in most neurodegenerative diseases like HD. Over the years, the role of mitochondria in neurons has highly diverged; they not only contribute as a cell power source, but also as dynamic organelles that fragment and then fuse to attain a maximal bioenergetics performance, regulating intracellular calcium homeostasis, reactive oxygen species (ROS) generation, antioxidant activity and involved in apoptotic pathways. Indeed, these events are observed to be affected in HD, resulting in neuronal dysfunction in pre-symptomatic stages. MHtt causes critical transcriptional abnormality by altering the expression of a master co-regulator, peroxisome proliferator-activated receptor-gamma coactivator-1α (PGC-1α), leading to increased susceptibility to oxidative stress and neuronal degeneration. Moreover, mHtt influences multiple cellular signaling events, which end with mitochondrial biogenesis. Here, we resume recent findings that pose mitochondria as an important regulatory organelle in HD and how mHtt affects mitochondrial function, trafficking and homeostasis and makes neurons prone to degeneration. Besides, we also uncover the mitochondrial-based potential targets and therapeutic approaches with imminent or currently ongoing clinical trials.

Extracellular Vesicles in the Treatment of Parkinson’s Disease: A Review

Background: Parkinson’s disease (PD) is one of the most common neurological disorders that can severely affect the ability to perform daily activities. The clinical presentation of PD includes motor and nonmotor symptoms. The motor symptoms generally involve movement conditions like tremors, rigidity, slowness, and impaired balance. In contrast, the nonmotor symptoms are often not apparent but can affect various organ systems, such as the urinary and gastrointestinal systems, and mental health. Gene mutations and toxic environmental factors have contributed significantly to PD; nevertheless, its cause and underlying mechanism remain unknown. Currently, treatments such as dopamine agonists, RNA molecules, and antioxidants can, to some extent, alleviate the motor symptoms triggered by PD. However, these medicines cannot effectively halt ongoing dopaminergic damage, mainly because the blood-brain barrier (BBB) lowers the efficiency of drug delivery. Recently, extracellular vesicles (EVs), a novel drug delivery platform, have been widely used in various neurological diseases, including stroke and brain tumors, because of their excellent biocompatibility, their ability to penetrate the BBB without toxicity, and their target specificity. EVs thus provide a promising therapeutic for treating PD.

Objective: This review focuses on novel therapies based on EVs in practice. Herein, we briefly introduce the biogenesis, composition, isolation, and characterization of EVs, and we discuss strategies for loading therapeutic agents onto EVs and recent applications for PD treatment. Moreover, we discuss perspectives on the direction of preclinical and clinical studies regarding novel and effective therapies.

Methods: A literature search regarding PD treatment based on extracellular vesicles was performed in PubMed (updated in June 2020). Treatment, therapy, drug delivery, extracellular vesicles, and their combinations were the search queries. Both systematic reviews and original publications were included. Searched results were selected and compared based on relevance. Articles published in the last five years were given top priority.

Conclusion: PD is a heterogeneous disease that can be treated by using pharmacologic approaches (e.g. dopamine agonists and levodopa) and nonpharmacologic approaches (e.g. music), based on symptoms and progression level in patients. Even though current treatments have demonstrated effectiveness, clinical challenges remain because the BBB reduces the medication received and lowers the efficacy of drug delivery, which impairs the treatment’s effect. Therefore, EVs, as an emerging delivery platform, are highly promising for PD treatment since they can readily cross the BBB with high therapeutic efficiency through the loading or functionalization process. However, defining a safe source of EVs, reliably purifying and isolating EVs with high yield, and improving the efficacy of therapeutic loading in EVs remain challenging in this field. Therefore, future investigations should focus on generating large-scale exosomal carriers and designing new effective drugs encapsulated in EVs for better efficacy.

Preliminary Studies on Optimization of Anti-Parkinson Drug Loaded Lipid Nanoparticles Enriched Hydrogel Formulations for Management of Parkinson’s Disease

Introduction: Ropinirole (RP), is a selective dopamine agonist that is used alone or with other medications to treat the symptoms of Parkinson’s disease (PD). RP has low bioavailability of only about 50% due to the first-pass metabolism, and it requires frequent dosing during oral administration.

Aim: The objective of the current research was to develop RP-loaded solid lipid nanoparticles (RP- SLNs), nanostructured lipid carriers (RP-NLCs), and their corresponding hydrogels (RP-SLN-C and RP-NLC-C) that could enhance RP therapeutic outcomes during PD treatment.

Methods: RP nanoparticles were prepared by homogenization followed by probe sonication and optimized based on particle size, polydispersity index (PDI), zeta potential (ZP), % assay, % entrapment efficiency, and in vitro release studies. Optimized formulations were converted into hydrogel formulations using Carbopol 934 as a gelling polymer and optimized based on rheological and release characteristics. Optimized formulations were further evaluated using differential scanning calorimetry (DSC), powder X-ray diffractometry (PXRD), scanning electron microscopy (SEM), freeze-drying, and stability study at refrigerated and room temperatures.

Results: The optimized RP-SLN formulation showed particle size and entrapment efficiency of 213.5±3.8 nm and 77.9±3.1% compared to 190.6±3.7 nm and 85.7±1.7% for optimized RP-NLC formulation. PXRD supplemented and confirmed DSC results, RP was entrapped in a molecularly dispersed state inside the core of the lipid nanocarrier. Furthermore, RP-loaded lipid nanocarriers revealed a spherical shape in SEM images. In vitro release studies demonstrated sustained release profiles for RP from SLNs, NLCs, and their hydrogels over 24 h. Optimized SLN, NLC, and nanocarrier- loaded hydrogel formulations were stable over three months at 4ºC and 25ºC storage conditions.

Conclusion: Overall, the results demonstrated that lipid nanocarriers and their corresponding hydrogel formulations can be considered as a topical drug delivery vehicle for RP during the treatment of PD.

Renin-Angiotensin System in Central Nervous System Diseases and its Interaction with COVID-19

Background: The Renin-Angiotensin System (RAS) comprises a complex molecular cascade with two counter-regulatory axes, the classical and the alternative. Angiotensin II and Angiotensin-(1-7), the main peptides of the RAS, exert opposite effects in multiple organs and systems, including the cardiovascular, renal, pulmonary, and immune systems. Strong evidence supports the hypothesis of a local RAS in the Central Nervous System (CNS) and its modulatory roles in neuroendocrinology and neurotransmission.

Objective: In this narrative review, we provide a comprehensive approach to experimental and clinical data regarding RAS molecule expression and their possible roles in the physiology and physiopathology of CNS diseases.

Methods: This non-systematic review summarizes evidence on RAS implications in CNS diseases and their possible relationships with COVID-19.

Results: We divided the possible RAS mechanisms in distinct conditions during the lifespan, approaching from congenital infections to neurodegenerative alterations, passing through mood disorders and cerebrovascular diseases. We also gathered current evidence about the possible effects of RAS in Covid-19, particularly in cases with neurological manifestations.

Conclusion: Although there are limitations and controversies, the analysis of RAS mechanisms in the CNS certainly represents an interesting field of research. However, further investigation is necessary to support the noteworthy interactions and provide a better comprehension of the cross-talk between RAS and the CNS. Investigations in this research field may shed light on the novel therapeutic targets.

Melatonin and its Relationships with Diabetes and Obesity: A Literature Review

Background: Obesity is an important clinical entity, causing many public health issues. Around two billion people in the world are overweight and obese. Almost 40% of American adults are obese and Brazil has about 18 million obese people. Nowadays, 415 million people have diabetes, around 1 in every 11 adults. These numbers will rise to 650 million people within 20 years. Melatonin shows a positive profile on the regulation of the metabolism of the human body.

Objective: This study aimed to carry out a broad narrative review of the metabolic profile and associations between melatonin, diabetes and obesity.

Methods: Article reviews, systematic reviews, prospective studies, retrospective studies, randomized, double-blind, and placebo-controlled trials in humans recently published were selected and analyzed. A total of 368 articles were collated and submitted to the eligibility analysis. Subsequently, 215 studies were selected to compose the content part of the paper, and 153 studies composed the narrative review.

Results: Studies suggest a possible role of melatonin in metabolic diseases such as obesity, T2DM and metabolic syndrome. Intervention studies using this hormone in metabolic diseases are still unclear regarding the possible benefit of it. There is so far no consensus about the possible role of melatonin as an adjuvant in the treatment of metabolic diseases. More studies are necessary to define possible risks and benefits of melatonin as a therapeutic agent.

123I-Ioflupane SPECT and 18F-FDG PET Combined Use in the Characterization of Movement and Cognitive Associated Disorders in Neurodegenerative Diseases

Background: Both movement (MD) and cognitive (CD) disorders can occur associated in some neurodegenerative diseases, such as Parkinson’s disease (PD) and Alzheimer’s disease (AD).

Objective: We further investigated the usefulness of 123I-Ioflupane SPECT and 18F-FDG PET combined use in patients with these disorders in the early stage.

Methods: We retrospectively enrolled twenty-five consecutive patients with MD and CD clinical symptoms of recent appearance. All patients had undergone neurologic examination, neuropsychological tests, and magnetic resonance imaging. 123I-Ioflupane SPECT was performed in all cases, followed by 18F-FDG PET two weeks later. In the two procedures, both qualitative (QL) and quantitative (QN) image analyses were determined.

Results: In patients with both 123I-Ioflupane SPECT and 18F-FDG PET pathologic data, associated dopaminergic and cognitive impairments were confirmed in 56% of cases. Pathologic SPECT with normal PET in 16% of cases could diagnose MD and exclude an associated CD, despite clinical symptoms. On the contrary, normal SPECT with pathologic PET in 28% of cases could exclude basal ganglia damage while confirming CD. QN 123I-Ioflupane SPECT analysis showed better performance than QL since QN correctly characterized two cases of MD with normal QL. Moreover, correct classification of normal metabolism was made only by QN analysis of 18F-FDG PET in four cases, despite suspect areas of hypometabolism at QL.

Conclusion: The combined use of these imaging procedures proved a reliable diagnostic tool to accurately identify and characterize MD and CD in early stage. QN analysis was effective in supporting QL evaluation, and its routine use is suggested, especially with inconclusive QL.

Exploring the Mechanism of Lingzhu San in Treating Febrile Seizures by Using Network Pharmacology

Objective: Lingzhu San (LZS) is a traditional Chinese medicine (TCM) prescription that can be effective in treating febrile seizures (FS) and there are few research works conducted on its mechanisms. In order to better guide the clinical use of LZS, we used the research ideas and methods of network pharmacology to find the potential core compounds, targets and pathways of LZS in the complex TCM system for the treatment of FS, and predict the mechanism.

Materials and Methods: Databases such as BATMAN, TCMSP, TCMID, and SWISS TARGET are used to mine the active compounds and targets of LZS, and the target information of FS is obtained through GENECARDS and OMIM. Using Venny2.1.0 and Cytoscape software, the potential core compounds and targets of FS were obtained. The R language and ClusterProfiler software package are adopted to enrich and analyze the KEGG and GO pathways of the core targets and the biological processes and potential mechanisms of the core targets are also revealed.

Results: 187 active compounds and 2113 target proteins of LZS were collected. And 38 potential core compounds, 35 core targets and 775 metabolic and functional pathways were screened, which were involved in mediating FS. Finally, the role of the core compounds, targets and pivotal pathways of LZS in regulating FS in the pathogenesis and the therapeutic mechanism of FS were discussed and clarified.

Conclusion: In this paper, the multi-compounds, multi-targets and multi-pathways mechanism of LZS in the treatment of FS were preliminarily screened through the analysis of network pharmacology data, which are consistent with the principle of multi-compounds’ compatibility with TCM prescriptions and a unified treatment of diseases from multiple aspects, and it provides a new way for TCM to treat complex diseases caused by multiple factors.

Significance of MRI Guided Focused Ultrasound Thalamotomy for Parkinson’s Disease: A Review

Background: Magnetic-Resonance guided Focused Ultrasound (FUS) thalamotomy is a new and less invasive surgical technique for treating Parkinson’s disease (PD). During therapy, the required part of the cerebral (as STN, Internal Globus Pallidus, and Ventral Intermediate Nucleus) is ablated with less possibility of infection and brain hemorrhage as it normally happens in invasive procedures.

Introduction: New advancement in the technique enables it for transcranial transportation of US. Nowadays, US coupling with MRI confirms the accurate energy transferring and monitoring. So, MRI guided FUS lesioning is discovered for various psychiatric and brain disorders.

Methods: A technical overview of non-invasive MRI-FUS thalamotomy to treat various tremors is described here. Research, review articles, and book chapters are extracted from online resources using related search strings from the year 1994-2020.

Results: MRgFUS is concluded a non-invasive, satisfactory, and safe technique to reduce the tremor.

Conlusion: MRgFUS is comparatively a new method that is being explored as a non-invasive cerebral ablation to solve the problems of movement disorder.

SIRT1 Promotes Neuronal Fortification in Neurodegenerative Diseases through Attenuation of Pathological Hallmarks and Enhancement of Cellular Lifespan

Neurodegeneration is a complex neurological phenomenon characterized by disturbed coherence in neuronal efflux. Progressive neuronal loss and brain damage due to various age-related pathological hallmarks perturb the behavioral balance and quality of life. Sirtuins have been widely investigated for their neuroprotective role, with SIRT1 being the most contemplated member of the family. SIRT1 exhibits significant capabilities to enhance neurogenesis and cellular lifespan by regulating various pathways, which makes it an exciting therapeutic target to inhibit neurodegenerative disease progression. SIRT1 mediated neuronal fortification involves modulation of molecular co-factors and biochemical pathways responsible for the induction and sustenance of pro-inflammatory and pro-oxidative environment in the cellular milieu. In this review, we present the major role played by SIRT1 in maintaining cellular strength through the regulation of genomic stability, neuronal growth, energy metabolism, oxidative stress, inhibiting mechanisms and anti-inflammatory responses. The therapeutic significance of SIRT1 has been put into perspective through a comprehensive discussion about its ameliorating potential against neurodegenerative stimuli in a variety of diseases that characteristically impair cognition, memory and motor coordination. This review enhances the acquaintance concerned with the neuroprotective potential of SIRT1 and thus promotes the development of novel SIRT1 regulating therapeutic agents and strategies.

C-terminus of Hsp70 Interacting Protein (CHIP) and Neurodegeneration: Lessons from the Bench and Bedside

Neurodegenerative diseases are characterized by the increasing dysfunction and death of neurons, resulting in progressive impairment of a person’s mobility and/or cognition. Protein misfolding and aggregation are commonly hypothesized to cause neurotoxicity and, eventually, neuronal degeneration that are associated with these diseases. Emerging experimental evidence, as well as recent findings from human studies, reveal that the C-terminus of Hsp70 Interacting Protein (CHIP), or STIP1 Homology and U-box containing Protein 1 (STUB1), is a quality control protein involved in neurodegeneration. Here, we review evidence that CHIP interacts with and plays a role in regulating proteins implicated in the pathogenesis of Parkinson’s disease, Alzheimer’s disease, amyotrophic lateral sclerosis, and polyglutamine diseases, including Huntington’s disease and spinocerebellar ataxias. We also review clinical findings identifying mutations in STUB1 as a cause of both autosomal recessive and autosomal dominant forms of cerebellar ataxia. We propose that CHIP modulation may have therapeutic potential for the treatment of multiple neurodegenerative diseases.

Nanotechnology Driven Approaches for the Management of Parkinson’s Disease: Current Status and Future Perspectives

Parkinson’s disease (PD) is believed to be one of the commonly found adult-onset movement disorder occurring due to neurodegeneration and striatal dopamine deficiency. Although clinical diagnosis depends on the occurrence of bradykinesia and other cardinal motor features, PD is linked with many non-motor symptoms that are responsible for overall disability. Among several factors, genetic and environment-related factors are thought to be the major ones accountable for PD. Comprehensive research has shown that a number of drugs are effective in providing symptomatic relief to the patients suffering from PD. But some drug molecules suffer from significant drawbacks such as poor bioavailability and instability, therefore, they sometimes fail to deliver the expected results. Hence, to resolve these issues, new promising novel drug delivery systems have been developed. Liposomes, solid lipid nanoparticles, nanoemulsion, self-emulsifying drug delivery system (SEDDS), niosomes are some of the novel drug delivery system (NDDS) carriers that have been explored for enhancing the CNS concentration of levodopa, apomorphine, resveratrol, and other numerous drugs. This paper elucidates various drugs that have been studied for their potential contribution to the treatment and management of PD and also reviews and acknowledges the efforts of several scientists who successfully established various NDDS approaches for these drugs for the management of PD.

Recent Patents, Regulatory Issues, and Toxicity of Nanoparticles in Neuronal Disorders

Background: Form last few decades, nanoparticles have witnessed breakthroughs in the treatment of neurological disorders due to their unique physiochemical properties, which make them an effective drug delivery system. However, there is not much information available on the toxicity of nanoparticles in neuronal disorders. The toxic effect of nanoparticles on brain disorders and their regulatory issues are the primary concerns of the healthcare industry.

Methods: A strategical literature search was performed on various bibliographic databases such as Scopus, PubMed, SciFinder, Google Scholar, Medline, Google Patent, Derwent Innovation, and Orbit Intelligence for retrieval of peer-reviewed articles and patents on regulatory issues and toxicity of nanoparticles in neuronal disorders for last decade. The relevant hits of articles and patents were analyzed, and citation search for the relevant documents was carried out.

Results: The literature documents have been summarized regarding the existing regulatory issues and toxicity of nanoparticles on neuronal disorders with a focus on the detailed mechanism of the developmental toxicity of nanoparticles. The focus of this report is to emphasize the negative effects of nanoparticle on neuronal disorders, which may partially contribute to the management of toxicity of nanoparticles.

Conclusion: Although nanoparticles have unique physical and chemical properties that explain the broad range of application for the central nervous system, they can also manifest neurotoxic effects due to cell necrosis, generation of free radicals, immune responses and neuroinflammation. Thus, this review highlights risk assessment, safety regulations and regulatory guidelines of nanoparticles, which may reduce adverse reactions in humans and animals.

Efficacy and Cardiovascular Safety of DPP-4 Inhibitors

Dipeptidyl peptidase-4 (DPP-4) inhibitors or gliptins belong to the class of incretin mimetics. These drugs have been available on the market for the management of type 2 diabetes mellitus (T2DM) for over a decade. Sitagliptin, linagliptin, vildagliptin, saxagliptin and alogliptin are widely available globally, whilst anagliptin, gemigliptin and teneliptin are used mainly in the Asian countries. The glycemic control conferred by DPP-4 inhibitors varies among individual molecules with an average reduction of glycated hemoglobin (HbA1c) ranging between –0.5 to –1.0% with monotherapy. Additive effects on HbA1c reduction may result from combination therapy with other antidiabetics. Weak evidence from various studies suggests that DPP-4 inhibitors may be useful in treating nonalcoholic fatty liver disease (NAFLD) and polycystic ovary syndrome (PCOS). DPP-4 inhibitors safety is not established in pregnancy, and there is only meagre evidence of its use in T2DM among children. In line with the United States Food and Drug Administration (US FDA) recommendations, sitagliptin, linagliptin, saxagliptin and alogliptin have undergone rigorous cardiovascular outcome trials (CVOTs) in recent years, and the safety data for vildagliptin is available through retrospective analysis of various studies in meta-analysis. Small clinical trial, and meta-analysis based data are available for the CV safety of other DPP-4 inhibitors. In general, the CVOTs and other safety data do not reveal serious warning signals except for saxagliptin (higher risk of hospitalization from heart failure [hHF]), although there is no robust data on the risk of hHF among patients with moderate to severe HF at baseline treated with other DPP-4 inhibitors. This review critically appraises the efficacy and cardiovascular safety of DPP-4 inhibitors to empower clinicians to use this class of antidiabetic medications judiciously.

Nanomedicine against Alzheimer’s and Parkinson’s Disease

Alzheimer’s and Parkinson’s are the two most rampant neurodegenerative disorders worldwide. Existing treatments have a limited effect on the pathophysiology but are unable to fully arrest the progression of the disease. This is due to the inability of these therapeutic molecules to efficiently cross the blood-brain barrier. We discuss how nanotechnology has enabled researchers to develop novel and efficient nano-therapeutics against these diseases. The development of nanotized drug delivery systems has permitted an efficient, site-targeted, and controlled release of drugs in the brain, thereby presenting a revolutionary therapeutic approach. Nanoparticles are also being thoroughly studied and exploited for their role in the efficient and precise diagnosis of neurodegenerative conditions. We summarize the role of different nano-carriers and RNAi-conjugated nanoparticle-based therapeutics for their efficacy in pre-clinical studies. We also discuss the challenges underlying the use of nanomedicine with a focus on their route of administration, concentration, metabolism, and any toxic effects for successful therapeutics in these diseases.

Targeting COVID-19 in Parkinson’s Patients: Drugs Repurposed

The last couple of months have witnessed the world in a state of virtual standstill. The SARS-CoV-2 virus has overtaken the globe to economic and social lockdown. Many patients with COVID-19 have compromised immunity, especially in an aged population suffering from Parkinson's disease (PD).

Alteration in dopaminergic neurons and deficiency of dopamine in PD patients are the most common symptoms affecting 1% population above the age of 60 years. The compromised immune system and inflammatory manifestation in PD patients make them an easy target. The most common drugs under trial for COVID-19 are remdesivir, favipiravir, chloroquine and hydroxychloroquine, azithromycin along with adjunct drugs like amantadine with some monoclonal antibodies.

Presently, clinically US FDA approved drugs in PD include Levodopa, catechol-O-methyl transferase (COMT) inhibitors, (Entacapone and Tolcapone), dopamine agonists (Bromocriptine, Ropinirole, Pramipexole, and Rotigotine), monoamine oxidase B (MAO-B) inhibitors (Selegiline and Rasagiline), amantadine and antimuscarinic drugs. The drugs have established mechanisms of action on PD patients with known pharmacodynamics and pharmacokinetic properties along with dose and adverse effects.

Conclusion and relevance of this review focus on the drugs that can be tried on PD patients with SAR CoV-2 infection, in particular, amantadine that has been approved by all the developed countries as a common drug possessing both antiviral properties by downregulation of CTSL, lysosomal pathway disturbance and change in pH necessary to uncoat the viral proteins and anti- Parkinson properties. To deal with the significant prognostic adverse effect of SARS-CoV-2 on PD, the present-day treatment options, clinical presentation and various mechanisms are the need of the hour.

Perspectives on Drug Repurposing

Complex common diseases are a significant burden for our societies and demand not only preventive measures but also more effective, safer, and more affordable treatments. The whole process of the current model of drug discovery and development implies a high investment by the pharmaceutical industry, which ultimately impact in high drug prices. In this sense, drug repurposing would help meet the needs of patients to access useful and novel treatments. Unlike the traditional approach, drug repurposing enters both the preclinical evaluation and clinical trials of the compound of interest faster, budgeting research and development costs, and limiting potential biosafety risks. The participation of government, society, and private investors is needed to secure the funds for experimental design and clinical development of repurposing candidates to have affordable, effective, and safe repurposed drugs. Moreover, extensive advertising of repurposing as a concept in the health community, could reduce prescribing bias when enough clinical evidence exists, which will support the employment of cheaper and more accessible repurposed compounds for common conditions.

Tetrahydrobioterin (BH4) Pathway: From Metabolism to Neuropsychiatry

Tetrahydrobipterin (BH4) is a pivotal enzymatic cofactor required for the synthesis of serotonin, dopamine and nitric oxide. BH4 is essential for numerous physiological processes at periphery and central levels, such as vascularization, inflammation, glucose homeostasis, regulation of oxidative stress and neurotransmission. BH4 de novo synthesis involves the sequential activation of three enzymes, the major controlling point being GTP cyclohydrolase I (GCH1). Complementary salvage and recycling pathways ensure that BH4 levels are tightly kept within a physiological range in the body. Even if the way of transport of BH4 and its ability to enter the brain after peripheral administration is still controversial, data showed increased levels in the brain after BH4 treatment. Available evidence shows that GCH1 expression and BH4 synthesis are stimulated by immunological factors, notably pro-inflammatory cytokines. Once produced, BH4 can act as an anti- inflammatory molecule and scavenger of free radicals protecting against oxidative stress. At the same time, BH4 is prone to autoxidation, leading to the release of superoxide radicals contributing to inflammatory processes, and to the production of BH2, an inactive form of BH4, reducing its bioavailability. Alterations in BH4 levels have been documented in many pathological situations, including Alzheimer's disease, Parkinson's disease and depression, in which increased oxidative stress, inflammation and alterations in monoaminergic function are described. This review aims at providing an update of the knowledge about metabolism and the role of BH4 in brain function, from preclinical to clinical studies, addressing some therapeutic implications.