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

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

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

Methods: To investigate IMPDH2 expression in HB tissues and prognostic significance in HB patients, gene expression profiling interactive analysis (GEPIA) has been adopted. Immunohistochemistry has also helped to validate the protein expression of IMPDH2 in HB tissues. The effect of IMPDH2 overexpression or depletion on the proliferation of Hepatoblastoma cells in vitro has been evaluated by CCK8 assays and colony formation assays. Xenograft tumor growth of mice has been detected. Luciferase reporter assays have been conducted to determine the interaction of IMPDH2 and JunB, which was further asserted by pharmacological inhibition of JunB.

Results: IMPDH2 was highly expressed in HB tissues. Experimentally, the proliferation and colony formation of HuH6 cells were increased by IMPDH2 overexpression. Conversely, genetic inactivation of IMPDH2 impaired the proliferative efficiency and colony-forming rate of HepG2 cells. Besides, the luciferase reporter assay validated IMPDH2 overexpression to be associated with enhanced JunB transcriptional activity, while its activity was diminished in the case of IMPDH2 depletion. JunB inhibitor neutralized the IMPDH2-mediated increased phosphorylation of JunB.

Conclusion: Our findings, thus, suggest that IMPDH2 exhibits its oncogenic role in HB partially via JunB-dependent proliferation.

Methods: Here, using scRNA-sequencing and ATAC-seq on primary chronic myelogenous leukemia (CML) patient samples, combined with bioinformatics analyses, we further examine the heterogeneity of a previously characterized in vitro imatinib-selected CD34-CD38- CML LSC population. We utilized a series of functional analyses, including single-cell metabolomic and Seahorse analyses, to validate the existence of the deepest quiescent leukemia initiators (LI) subset.

Results: Current study revealed heterogeneity of therapy resistant LSC in CML patients and their existence of two functionally distinct states. The most deeply quiescent LI suppress the expression of MC-1, yet are highly dependent on fatty acid oxidation (FAO) for their metabolic requirements and ATAC-seq demonstrated increased chromatin accessibility in this population, all consistent with an extremely primitive, quiescent stemness transcriptional signature. Importantly, the specific CREB binding protein (CBP)/β-catenin antagonist ICG-001 initiates the differentiation of LSC, including LI, decreases chromatin accessibility with differentiation and increasing expression of MC-1, CD34, CD38 and BCR-ABL1, thereby resensitizing them to imatinib.

Conclusion: We investigated the biological aspects related to LSC heterogeneity in CML patients and demonstrated the ability of specific small molecule CBP/β-catenin antagonists to safely eliminate deeply quiescent therapy resistant CSC. These observations may represent an attractive generalizable therapeutic strategy that could help develop better protocols to eradicate the quiescent LSC population.

Objective: The objective of this study was to examine the impact of paeoniflorin (PF) on anxiety and visceral hypersensitivity in maternal separation-induced IBS-like rats.

Methods: The IBS-like rat model was established through the implementation of Maternal Separation (MS) and subsequently subjected to various doses of PF administered via oral gavage for 14 days. Anxiety-like behavior was evaluated using the Open Field Test (OFT) and Elevated Plus Maze (EPM) test. The assessment of visceral sensitivity involved the utilization of the Abdominal Withdrawal Reflex (AWR) score and electromyographic (EMG) responses of the external oblique muscle in response to colorectal distention. The levels of adrenocorticotropic hormone (ACTH), corticosterone (CORT), and corticotrophin-releasing hormone (CRH) were examined by ELISA. Quantitative real-time PCR (qRT-PCR) and immunofluorescence were employed to detect the expressions of CRH receptors 1 (CRHR1) and 2 (CRHR2). Glucocorticoid receptors (GR), mineralocorticoid receptor (MR), brain-derived neurotrophic factor (BDNF), tyrosine receptor kinase B (TrkB), and phospholipase C γ1 (PLCγ1) were examined by Western blot.

Results and Discussion: The results showed that MS induced anxiety-like behavior and visceral hypersensitivity, while PF treatment attenuated these changes. Furthermore, the HPA axis hyperactivity in MS rats was attenuated by PF treatment, indicated by reduced serum ACTH, CORT, and CRH levels and recovered hippocampal CRHR1 and GR expressions. In addition, PF inhibited BDNF/TrkB signaling by downregulating the protein levels of BDNF, TrkB, and phospho-PLCγ1 in the colon.

Conclusion: These findings suggest that PF alleviated anxiety and visceral hypersensitivity in MS-induced IBS-like rats, which may be the modulation of HPA axis activity and BDNF/TrkB/PLCγ1 signaling pathway.

Background: GBM is the most malignant primary brain cancer with a poor prognosis. Previous studies have suggested that GBM vessels undergo dynamic remodeling modulated by tumor vasodilation and vasoconstriction instead of tumor angiogenesis.

Objective: Here, we have first investigated the expression and function of UTS2, a potent vasoconstrictor, in GBM.

Methods: The mRNA expression profiles and clinical information of GBM patients were obtained from the TCGA database. The clinical relevance of UTS2 was explored by the Mann-Whitney U test and Cox hazard regression survival test. We further explored the role of UTS2 in GBM cell proliferation, migration, and tumor immune microenvironment. Moreover, we established the in vivo mice model to validate its oncogenic effects on GBM progression.

Results: Although we did not find significant correlations between UTS2 expression and patients’ clinical characteristics, UTS2 was identified as a valid independent prognostic indicator according to multivariate survival analysis. Knockdown of UTS2 resulted in decreased GBM cell proliferation and migration. In addition, functional enrichment analysis implied UTS2 to be involved in the regulation of the immune microenvironment. In vivo studies showed that UTS2 knockdown suppressed GBM xenograft growth, highlighting the tumor-promoting effects of UTS2 on GBM.

Conclusion: Our study identified that UTS2 could predict the prognosis of GBM patients and provided evidence regarding its oncogenic effects both in vitro and in vivo.

Methods: Seventy-one patients with rectal adenocarcinoma confirmed by pathology after surgical resection were collected retrospectively. According to pathology, they were divided into a poorly differentiated group (n=23) and a moderately differentiated group (n=48). The IVIM-DWI parameters and TA characteristics of the two groups were compared, and a prediction model was constructed by multivariate logistic regression analysis. ROC curves were plotted for each individual and combined parameter.

Results: There were statistically significant differences in D and D* values between the two groups (P < 0.05). The three texture parameters SmallAreaEmphasis, Median, and Maximum had statistically significant differences between groups (P = 0.01, 0.004, 0.009, respectively). The logistic regression prediction model showed that D*, the median, and the maximum value were significant independent predictors, and the AUC of the regression prediction model was 0.860, which was significantly higher than other single parameters.

Conclusion: 3.0T MRI IVIM-DWI parameters combined with TA can provide valuable information for predicting the histological grades of rectal adenocarcinoma one week before the operation.

Case Reports: Three hospitalised patients aged 23 to 86 years underwent venous air embolism (VAE) in the right heart system after performing CTPA. One of the patients died from a complication of venous thromboembolic disease (PE, coronary sinus thrombosis, mesenteric venous thrombosis).

Conclusion: CTPA is a procedure that a priori seems innocuous, but it can be a potential cause of death or serious consequences for patients undergoing radiological procedures where the administration of contrast and the use of an injector could be counterproductive. Radiologists and physicians responsible for the patient should be aware of vascular gas embolism after contrast injection in patients undergoing CTPA.

Objective: Here, we present a fetus with DSM by multiple imaging methods to help better understand the imaging characteristics of this malformation.

Case Presentation: A 22-year-old primipara was referred to our hospital at 25 weeks of gestation following the detection of a fetal intracranial mass without any symptoms. A prenatal ultrasound performed in our hospital at 25 ^{+ 2} gestational weeks showed a large anechoic mass with liquid dark space, while no blood flow was detected. After the initial evaluation, this primipara received a prenatal MRI in our hospital. This examination at 25 ^{+ 5} gestational weeks delineated a fan-shaped mass in the torcular herophili, which was iso-to hyperintense on T1WI and hypointense on T2WI. At the lower part of this lesion, a quasi-circular hyperintense on T1WI and a signal slightly hyperintense on T2WI could be seen. Meanwhile, the adjacent brain parenchyma was compressed by the mass.

Conclusion: We reviewed the current literature to obtain a better understanding of the mechanisms, imaging characteristics, and survival status of DSM. Although the primipara of the present study regretfully opted for elective termination of pregnancy, the reevaluation of DSM survival deserves more attention because of the better survival data from recent studies.

Methods: A partial taxonomy of the GBM problems tackled with ML methods was formulated with 15 subcategories grouped into four categories: extraction of characteristics from tumoral regions, differentiation, characterization, and problems based on genetics.

Results: The dominant techniques in solving these problems are: Radiomics for feature extraction, Least Absolute Shrinkage and Selection Operator for feature selection, Support Vector Machines and Random Forest for classification, and Convolutional Neural Networks for characterization. A noticeable trend is that the application of Deep Learning on GBM problems is growing exponentially. The main limitations of ML methods are their interpretability and generalization.

Conclusion: The diagnosis, treatment, and characterization of GBM have advanced with the aid of ML methods and MRI data, and this improvement is expected to continue. ML methods are effective in solving GBM-related problems with different precisions, Overall Survival being the hardest problem to solve with accuracies ranging from 57%-71%, and GBM differentiation the one with the highest accuracy ranging from 80%-97%.

Case Report: A 24-year-old male patient presented with a speech disorder and numbness in his hands and tongue, which developed after flu-like symptoms. An appearance compatible with COVID-19 pneumonia was detected in thorax computed tomography. Delta variant (L452R) was positive in the COVID reverse-transcriptase polymerase chain reaction test (RT-PCR). Cranial radiological imaging revealed intracranial cytotoxic edema, which was thought to be related to COVID-19. Apparent diffusion coefficient (ADC) measurement values in the magnetic resonance imaging (MRI) taken on admission were 228 mm2/sec in the splenium and 151 mm2/sec in the genu. During the follow-up visits of the patient, epileptic seizures developed due to intracranial cytotoxic edema. ADC measurement values in the MRI taken on the 5th day of the patient's symptoms were 232 mm2/sec in the splenium and 153 mm2/sec in the genu. ADC measurement values in the MRI taken on the 15th day were 832 mm2/sec in the splenium and 887 mm2/sec in the genu. He was discharged from the hospital on the 15th day of his complaint with a clinical and radiological complete recovery.

Conclusion: Abnormal neuroimaging findings caused by COVID-19 are quite common. Although not specific to COVID-19, cerebral cytotoxic edema is one of these neuroimaging findings. ADC measurement values are significant for planning follow-up and treatment options. Changes in ADC values in repeated measurements can guide clinicians about the development of suspected cytotoxic lesions. Therefore, clinicians should approach cases of COVID-19 with CNS involvement without extensive systemic involvement with caution.

Objective: Nearby the specific therapeutic action, ASMs, like other types of pharmacotherapy, can produce various side effects. In this review, we shall analyze the different pharmaceutical classes of ASMs, their mechanism of action, and their interaction with the respiratory system.

Methods: This manuscript is based on a retrospective review of English publications indexed by Pubmed, UpToDate and datasheets published by the European Medicines Agency and the Food and Drug Administration (FDA), using various terms reminiscent of ASMs and pulmonary function.

Results: ASMs act on organism homeostasis in different ways, acting on lung function directly and indirectly and playing a protective or damaging role. A damaging direct lung involvement ranged from infections, hypersensitivity reactions, and respiratory depression to other structured pulmonary diseases. Meanwhile, a damaging indirect effect, might be constituted by pulmonary artery hypertension. On the other hand, a protective effect might be the expression of developmental processing, decreasing airway remodelling in asthma patients, vascular remodelling in pulmonary hypertension and, nonetheless, anti-inflammatory and immunomodulatory actions.

Conclusion: An adequate awareness of ASMs effects on the respiratory system seems essential for better managing frail individuals or/and those predisposed to respiratory disorders to improve our patients' clinical outcomes.

Methods: Here in the present work, we have collected scientific information on cornin and presented it with respect to its medicinal importance and pharmacological activities with their analytical aspects. Scientific information on cornin has been collected from numerous scientific databases such as PubMed, Science Direct, Google, and Scopus to know the biological potential of cornin in medicine. Further, pharmacological activity scientific data of cornin has been presented in this work with proper citations.

Results: The scientific data of the present paper described the biological significance of cornin in medicine. The further detailed pharmacological activity of cornin signified its therapeutic effectiveness on cerebral ischemia, angiogenesis, autophagy, myocardial injury, cerebral injury, oxidative injury, lipid peroxidation, proliferation, and cytochrome p450. Analytical data signified the separation, isolation, and identification techniques of cornin in medicine.

Conclusion: The scientific information of the present work will be beneficial for all scientific people to explore the therapeutic effectiveness of cornin in medicine.

Objective: In the present pilot study, we aimed to disclose the presence of serum BDNF in infants hospitalized with bronchiolitis at discharge as a disease severity indicator.

Methods and Results: Serum BDNF, measured at hospital discharge, was significantly lower in severe bronchiolitis (expressed as O₂-supplemented infants). Furthermore, no changes were disclosed for the Tropomyosin receptor kinase B, the main BDNF receptor and neurofilament light chain, a biomarker of neuronal degeneration.

Conclusion: Low serum BDNF in infants with severe bronchiolitis could be associated with a higher utilization by lung cells or with an altered production by lung cells. Therefore, further research is required to study if a decreased production or increased consumption of this biomarker is at the base of the above-mentioned findings.

Objective: This study aimed to investigate the effects of HSV-G47Δ oncolytic virus on telomerase and telomere length alterations in U251GBMCSCs (U251-Glioblastoma cancer stem cells) under hypoxia and normoxia conditions.

Methods: U251-CSCs were exposed to the HSV-G47Δ virus in optimized MOI (Multiplicity of infection= 1/14 hours). An absolute telomere length and gene expression of telomerase subunits were determined using an absolute human telomere length quantification PCR assay. Furthermore, a bioinformatics pathway analysis was carried out to evaluate physical and genetic interactions between dysregulated genes with other potential genes and pathways.

Results: Data revealed that U251CSCs had longer telomeres when exposed to HSV-G47Δ in normoxic conditions but had significantly shorter telomeres in hypoxic conditions. Furthermore, hTERC, DKC1, and TEP1 genes were significantly dysregulated in hypoxic and normoxic microenvironments. The analysis revealed that the expression of TERF2 was significantly reduced in both microenvironments, and two critical genes from the MRN complex, MER11 and RAD50, were significantly upregulated in normoxic conditions. RAD50 showed a significant downregulation pattern in the hypoxic niche. Our results suggested that repair complex in the telomeric structure could be targeted by HSV-G47Δ in both microenvironments.

Conclusion: In the glioblastoma treatment strategy, telomerase and telomere complex could be potential targets for HSV-G47Δ in both microenvironments.

Objectives: This systematic review was to explore whether berberine (BBR) has any anti-seizure or anti-epileptic effects and also reviewed this possible mechanism.

Methods: The EMBASE, Scopus, Cochrane Library, PubMed, and Web of Science databases were searched before Sep 2023. All types of studies that investigated the effects of BBR on epilepsy or chemical-induced seizures were eligible for inclusion. Two authors independently evaluated and reviewed titles/abstracts to identify publications for potential eligibility, and a third team member resolved discrepancies. Data were extracted in an Excel form, and the outcomes were discussed.

Results: BBR showed its neuroprotective properties by reducing oxidative stress, neuroinflammation, and anti-apoptosis effects. It also increases brain-derived neurotrophic factor (BDNF) release and reduces transforming growth factor-beta (TGF-β1) and hypoxia-inducible factor 1α (HIF-1α). BBR by increasing scavenging reactive oxygen species (ROS), nuclear factor erythroid 2–related factor 2 (Nrf2), endogenous antioxidant enzymes, heme oxygenase-1 (HO-1), and inhibition of lipid peroxidation insert its antioxidant activity. Moreover, BBR showed antiinflammatory activity by reducing Interleukin (IL)-1β, IL-6, and tumor necrosis factor-alpha (TNF-α) levels and through inhibiting cyclooxygenase-2 (COX-2), and including nuclear factor κB (NF-κB). In addition, it modulated c-fos expression and neuronal excitability in the brain.

Conclusion: BBR indicated promising anti-seizure effects with remarkable antioxidant, antiinflammatory, anti-apoptotic, and neuroprotective activity. Future studies should be based on well-designed clinical trial studies that are integrated with new methods related to increasing bioavailability.

Understanding of the disease has improved through registries, classifying it into five distinct groups with similar histology, pathophysiology, and therapeutic approaches. These groups include PAH, with heritable and idiopathic causes, as well as various clinical subsets involving connective tissue disease, HIV, portopulmonary hypertension, congenital heart disease, and schistosomiasis. Long-term responders to calcium channel blockers, PAH with venous/capillaries involvement, and persistent PH of newborns are categorized under Group 1, now re-classified as IPAH.

A comprehensive workup for suspected patients includes various tests like electrocardiogram, pulmonary function testing, autoimmune workup, HIV testing, echocardiogram, right heart catheterization, and cardiopulmonary exercise testing.

This review emphasizes the disease's definition and epidemiology, delving into each subset and providing updated workup guidelines. The subsequent article will focus on risk stratification and treatment strategies.

Materials and Methods: This cross-sectional study was carried out in a tertiary neonatal intensive care unit of a maternal and neonatal hospital from September 2018 to August 2019. Premature infants under 34 weeks of age and with birth weight < 1500 grams who did not have significant congenital anomalies participated in the study. A brain ultrasound was performed by a sonologist during the first week. The infants were subsequently categorized into two groups: those with and without IVH. A comparative analysis was conducted using the chi-square test and logistic regression. A significance level of p<0.05 was considered statistically significant.

Results: Of the 205 premature infants who completed the study, IVH was reported in 107 cases (52.1%), of which 97.3% of ventricular hemorrhages were grade I and II and 2.7% accounted for severe bleeding (grade III and IV). Gestational age less than 28 weeks, weight less than 1000 g, vaginal delivery, asphyxia and resuscitation, history of intubation and mechanical ventilation, cord blood acidity, dopamine infusion, and history of fever and chorioamnionitis in the mother have been found to be significantly associated with increased risk of IVH (p<0.001). Antenatal corticosteroids decreased the risk (OR=10.63).

Conclusion: In this study, IVH has been found to be common in infants under 1500 g of weight, but the severe form was low in frequency and was observed significantly in high-risk pregnancies.

Methods: This study revealed that high levels of USP31 were discovered in LUSC tissue samples employing the Gene Expression Profiling Interactive Analysis (GEPIA) database, quantitative real- time PCR (qRT-PCR), and Western blot analysis. Cell proliferation was tested via cell counting kit 8 (CCK-8) as well as colony formation, demonstrating that USP31-stable knockdown reduced cell viability.

Results: Immunofluorescence analysis illustrated that USP31 knockdown blocked the occurrence of LUSC autophagy. Meanwhile, USP31 has been shown to stabilize the expression of E2F transcription factor 1 (E2F1) through the proteasome pathway. Furthermore, overexpressed E2F1 effectively eliminated the effect of USP31 knockdown on LUSC cell proliferation and autophagy.

Conclusion: In summary, this investigation proved that USP31 promoted LUSC cell growth and autophagy, at least in part by stabilizing E2F1 expression, which provided a potential therapeutic gene for the treatment of LUSC.

Methods: A co-culture system for ECs and CMs was set up, and subjected to HR. The transcription, expression, and secretion of FGF2 were detected by RT-qPCR, western blot, and ELISA, respectively. siRNAs specifically targeting FGF2 were transfected into ECs. FGF2 receptor- specific inhibitors (AZD4547) were used to treat CMs.

Results: The co-culture with ECs did not affect the proliferation of CMs, while CUR and ECs co-culture had a synergistic effect on promoting the proliferation of CMs in HR. Furthermore, the co-culture with ECs did not affect the apoptosis and autophagy of CMs in HR. However, the co-culture of ECs after CUR treatment inhibited the apoptosis and autophagy of CMs in HR. CUR treatment significantly enhanced FGF2 mRNA, protein, and secretion levels of ECs in HR. In addition, CUR treatment increased FGF2 levels in the CMs medium in the ECs and CMs co-culture system. The reduction of FGF2 levels in the medium and the inhibition of FGF2 receptors significantly inhibited the proliferation of CMs and significantly promoted the apoptosis and autophagy of CMs in HR.

Conclusion: Focusing on the protective effects of CUR and ECs on cardiomyocytes is of great significance for the treatment of clinical myocardial HR injury.

Methods: The systematic review was conducted on PubMed, Lilacs, and Embase, according to PRISMA. For this purpose, three groups of descriptors were used: Adults with T1DM, anaerobic physical exercise, and glycemic control. The search filter was set to human beings older than 18 years of age, longitudinal and cross-sectional studies, with studies published from 2000 to 2023 in English, Spanish, or Portuguese. Titles and abstracts were read independently by two reviewers, and then the articles were selected for this review. The Kappa coefficient was measured to evaluate the selection.

Results: A total of 738 articles were identified, and five were selected to be part of the review after applying the steps of the procedure. Some benefits were observed in fatigue reduction, absence of diabetic ketoacidosis requiring hospitalization, and enhancement of glucose monitoring during exercise. In the anaerobic workouts of the groups with T1DM, glycemic mean values ranged from 124.5-185.0 mg/dl, and glycated hemoglobin records ranged from 6.7-8.1%.

Conclusion: Anaerobic exercise improved the biomarkers of T1DM, especially glycemic control, and the reduction of symptomatic hypoglycemic episodes. Anaerobic exercise can be performed by individuals with T1DM, suggesting an individualized training prescription and encouraging its practice associated with aerobic exercise.

Methods: Autophagic Inducer functions on the activation of Transcriptional factor EB (TFEB) and its mechanism; mTOR Complex Inhibition dependently or independently may repair the malfunction of the entire mechanism. Finding a potential autophagic inducer is still a work in progress, but targeting TFEB and mTOR could redefine LSD treatment. The development of experimentally available TFEB modulators could enhance autophagic flux promote lysosomal function and increase lysosomal biogenesis and can be a promising technique for treating illnesses caused by ALP dysfunction, such as lysosomal storage disorder.

Results: MTORC1 suppression causes TFEB to be transported to the nucleus and transcription of multiple genes involved in the formation of autophagosomes and lysosomes, indicating that MTORC1 has positive effects in treating lysosomal storage diseases such as Pompe disease, Batton disease, Fabry disease, etc. thus modulating autophagy attenuates the above condition.

Conclusion: This review comprises autophagy and lysosome association, and their malfunction leads to various lysosomal diseases. Several natural products are also discussed, which can be possible treatment options.

Objective: Abuse of alcohol does not occur suddenly. People becoming addicted to various alcoholic beverages is a problem that results from months and years of irresponsible drinking. The process of recovering from the issue in turn includes targeted, particular methods for raising awareness of the negative effects of alcohol usage.

Conclusion: Due to the heightened risks for one's bodily and mental health along with the social issues it generates, alcohol consumption results in these costs. We discuss the three areas of the epidemiology of alcohol's impact on health and diseases, the public health approach for treating problems related to alcohol use, and advancements in alcohol science.

Objective: The objective of this study is to develop and validate a new cell model overexpressing sTGFBR3 for studying AD in vitro.

Methods: BV2 cells (a microglial cell derived from C57/BL6 murine) were used as a cell model. Cells were then treated with different concentrations of lipopolysaccharide (LPS) (0, 1, or 0.3 μg/mL) for 12, 24, or 48h and then with or without sodium pervanadate (100 μM) for 30 min. Next, the effect surface optimization method was used to determine optimal experimental conditions. Finally, the optimized model was used to assess the effect of ZQX series compounds and vasicine on cell viability and protein expression. Expression of TGFBR3 and TNF-α was assessed using Western blot. MTT assay was used to assess cell viability, and enzyme- linked immunosorbent assay (ELISA) was employed to evaluate extracellular TGF-β1 and sTGFBR3.

Results: LPS (0.3 μg/mL) treatment for 11 h at a cell density of 60% and pervanadate concentration (100 μM) incubation for 30 min were the optimal experimental conditions for increasing membrane protein TGFBR3 overexpression, as well as extracellular sTGFBR3 and TGF-β1. Applying ZQX-5 and vasicine reversed this process by reducing extracellular TGF-β1, promoting the phosphorylation of Smad2/3, a protein downstream of TGF-β1, and inhibiting the release of the inflammatory factor TNF-α.

Conclusion: This new in vitro model may be a useful cell model for studying Alzheimer's disease in vitro.

Objective: We aim to elucidate the molecular mechanisms linking chronic psychological stress with low-grade neuroinflammation in key brain regions, particularly focusing on the roles of G proteins and serotonin (5-HT) receptors.

Methods: This comprehensive review of the literature employs systematic, narrative, and scoping review methodologies, combined with systemic approaches to general pathology. It synthesizes current research on shared signaling pathways involved in stress responses and neuroinflammation, including calcium-dependent mechanisms, mitogen-activated protein kinases, and key transcription factors like NF-κB and p53. The review also focuses on the role of G protein-coupled neurotransmitter receptors (GPCRs) in immune and pro-inflammatory responses, with a detailed analysis of how 13 of 14 types of human 5-HT receptors contribute to depression and neuroinflammation.

Results: The review reveals a complex interaction between neurotransmitter signals and immunoinflammatory responses in stress-related pathologies. It highlights the role of GPCRs and canonical inflammatory mediators in influencing both pathological and physiological processes in nervous tissue.

Conclusion: The proposed Neuroimmunoinflammatory Stress Model (NIIS Model) suggests that proinflammatory signaling pathways, mediated by metabotropic and ionotropic neurotransmitter receptors, are crucial for maintaining neuronal homeostasis. Chronic mental stress can disrupt this balance, leading to increased pro-inflammatory states in the brain and contributing to neuropsychiatric and psychosomatic disorders, including depression. This model integrates traditional theories on depression pathogenesis, offering a comprehensive understanding of the multifaceted nature of the condition.

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Introduction: Cancer is the deadliest disease globally and is challenging to healthcare systems. Colorectal cancer (CRC) is the third most common cancer in the world, affecting all age groups and is the most common cancer in 23 countries, as per the World Health Organization (WHO).

Methods: In this review, we addressed the nanocarrier-based strategic treatment of colorectal cancer, along with major findings, limitations, and future perspectives. For this, we thoroughly reviewed several literatures downloaded from prime sources, such as google scholar, Web of Science, PubMed, and Publon. To filter the exact data needed, we used keywords alone or in combination. Various relevant articles were obtained from the reference section of the selected papers.

Result and Discussion: It is necessary to have an effective and targeted treatment option to control CRC other than available remedies. Nanotechnology has been widely used to diagnose and treat several cancer types. Advances in nanomedicine and phytonanomedicine have promoted novel identification methods to treat colorectal cancer patients. There are several nanocarriers recommended for clinical purposes. However, to date, only a few clinically approved nanocarriers can load anticancer moieties and selectively bind to cancer cells. Some nanocarriers transport and release treatments to the target colorectal area but provide few benefits.

Conclusion: In this review, various nanoparticles (NPs) with unique properties have been discussed in relation to managing colorectal cancer, along with major outcomes of clinical trials and successful patents published so far.

Methods: The method comprises data collection from various search engines like PubMed, ScienceDirect, and SciFinder to get coverage of relevant literature for accumulating appropriate information regarding pain management, opioids, opioid-induced constipation, and its pharmacological interventions.

Results: The thoughtful custom of exploring several options to manage opioid-induced constipation must allow patients to benefit from opioid analgesia.

Conclusion: This paper reviews the role of opioids in pain management, the underlying mechanisms of their action, opioid-induced constipation, and pharmacological therapies, with experimental studies aiding clinicians to optimise treatment plans.

Objective: Understanding the pathways and mechanisms of mitochondrial dysfunction related to neurodevelopmental disorders such as ADHD, Pelizaeus- Merzbacher Disease (PMD), mental retardation, Autism spectrum disorder, Rett's syndrome, and Fragile X syndrome is important. In this review, we discussed the possible factors associated with mitochondria that influence the clinical presentation of NDDs, better understanding of the mechanisms behind these pathways will hopefully be helpful for the diagnosis and treatment approaches.

Conclusion: Mitochondria are simply another subcellular victim of various neurodegenerative pathways, or are they a common denominator on the path to neurodegeneration? A better understanding of functional and molecular mechanistic pathways can lead to the identification of potential targets, thereby opening perspectives for future treatment.

Methodology: This study conducted an electronic search of articles on websites like PubMed and Google. The current review also used an in silico databases search and bioinformatics analysis and an extensive comprehensive literature search for original research articles and review articles as well as retrieval of current and future medications in clinical trials.

Results: This study indicates that several signaling pathways, such as sonic hedgehog, WNT/β-catenin, unfolded protein response mediated ER stress, notch, neurotrophins and TGF-β and ERK, MAPK, and ERK play a crucial role in the pathogenesis of MDB. Gene and ncRNA/protein are also involved as an axis long ncRNA to sponge micro-RNAs that affect downstream signal proteins expression and translation affection disease pathophysiology, prognosis and present potential target hit for drug repurposing. Current treatment options include surgery, radiation, and chemotherapy; unfortunately, the disease often relapses, and the survival rate is less than 5%. Therefore, there is a need to develop more effective treatments to combat recurrence and improve survival rates.

Conclusion: This review describes various MDB disease hallmarks, including the signaling mechanisms involved in pathophysiology, related-causal genes, epigenetics, downstream genes/epigenes, and possibly the causal disease genes/non-protein coding (nc)RNA/protein axis. Additionally, the challenges associated with MDB treatment are discussed, along with how they are being addressed using nano-technology and nano-biomedicine, with a listing of possible treatment options and future potential treatment modalities.

Methods: To accomplish these objectives, we explored immune cell infiltration and the expression patterns of immune cells and immune function-related genes of AD patients. Furthermore, we utilized the consensus clustering method combined with aggrephagy-related genes (ARGs) for typing AD patients and categorized AD specimens into distinct clusters (C1, C2). A total of 272 candidate genes were meticulously identified through a combination of differential analysis and Weighted Gene Co-Expression Network Analysis (WGCNA). Subsequently, we applied three machine learning algorithms-namely random forest (RF), support vector machine (SVM), and generalized linear model (GLM)-to pinpoint a pathogenic signature comprising five genes associated with AD. To validate the predictive accuracy of these identified genes in discerning AD progression, we constructed nomograms.

Results: Our analyses uncovered that cluster C2 exhibits a higher immune expression than C1. Based on the ROC(0.956). We identified five characteristic genes (PFKFB4, PDK3, KIAA0319L, CEBPD, and PHC2T) associated with AD immune cells and function. The nomograms constructed on the basis of these five diagnostic genes demonstrated effectiveness. In the validation group, the ROC values were found to be 0.760 and 0.838, respectively. These results validate the robustness and reliability of the diagnostic model, affirming its potential for accurate identification of AD.

Conclusion: Our findings not only contribute to a deeper understanding of the molecular mechanisms underlying AD but also offer valuable insights for drug development and clinical analysis. The limitation of our study is the limited sample size, and although AD-related genes were identified and some of the mechanisms elucidated, further experiments are needed to elucidate the more in-depth mechanisms of these characterized genes in the disease.

Objective: This review is carried out to highlight the role of tropomyosin receptor kinase in cancer and the function of TRK inhibitors in the intervention of cancer.

Methods: Literature research has been accomplished using Google Scholar and databases like ScienceDirect, WOS, PubMed, SciFinder, and Scopus.

Results: In this review, we provide an overview of the main molecular and functional properties of TRKs and their inhibitors. It also discusses how these advancements have affected the development and use of novel treatments for malignancies and other conditions caused by activated TRKs. Several therapeutic strategies, including the discovery and development of small-molecule TRK inhibitors belonging to various chemical classes and their activity, as well as selectivity towards the receptors, have been discussed in detail.

Conclusion: This review will help the researchers gain a fundamental understanding of TRKs, how this protein family works, and the ways to create chemical moieties, such as TRK inhibitors, which can serve as tailored therapies for cancer.

On the other hand, undergoing debulking surgery becomes challenging, and therapy with many chemotherapeutic medications has manifested resistance, a condition known as multidrug resistance (MDR). Although there are other therapeutic options for ovarian cancer, this article solely focuses on co-delivery techniques, which work via diverse pathways to overcome cancer cell resistance. Different pathways contribute to MDR development in ovarian cancer; however, usually, pump and non-pump mechanisms are involved. Striking cancerous cells from several angles is important to defeat MDR. Nanocarriers are known to bypass the drug efflux pump found on cellular membranes to hit the pump mechanism.

Nanocarriers aid in the treatment of ovarian cancer by enhancing the delivery of chemotherapeutic drugs to the tumour sites through passive or active targeting, thereby reducing unfavorable side effects on the healthy tissues. Additionally, the enhanced permeability and retention (EPR) mechanism boosts the bioavailability of the tumour site. To address the shortcomings of conventional delivery, the current review attempts to explain the current conventional treatment with special reference to passively and actively targeted drug delivery systems (DDSs) towards specific receptors developed to treat ovarian cancer. In conclusion, tailored nanocarriers would optimize medication delivery into the intracellular compartment before optimizing intra-tumour distribution. Other novel treatment possibilities for ovarian cancer include tumour vaccines, gene therapy, targeting epigenetic alteration, and biologically targeted compounds. These characteristics might enhance the therapeutic efficacy.

Observations: Natural origin, low in vivo toxicity, and pleiotropic functional essence are the foremost fascinations for HST use as an anticancer drug. However, low aqueous solubility accompanied with a prompt degradation by intestinal and hepatocellular enzymes impairs HST physiological absorption.

Motivation: Remedies attempted herein comprise the synthesis of derivatives and nanocarrier (NC)-mediated delivery. As the derivative synthesis aggravates the structural complexity, NC-driven HST delivery has emerged as a sustainable approach for its sustained release. Recent interest in HST has been due to its significant anticancer potential, characterized via inhibited cell division (proliferation), new blood vessel formation (angiogenesis), forceful occupation of neighboring cell’s space (invasion), migration to erstwhile physiological locations (metastasis) and apoptotic induction. The sensitization of chemotherapeutic drugs (CDs) by HST is driven via stoichiometrically regulated synergistic actions.

Purpose and Conclusion: This article sheds light on HST structure-function correlation and pleiotropic anticancer mechanisms, in unaided and NC-administered delivery in singular and with CDs synergy. The discussion could streamline the HST usefulness and long-term anticancer efficacy.

Background: VD is a neurodegenerative disease characterized by cognitive deficits caused by chronic cerebral hypoperfusion. AC has been studied for its potential to cure VD but its efficacy and underlying mechanism are still unclear.

Objective: The mechanism of action of AC on cognitive deficits in the early stages of VD is unclear. Here, the 2-vessel occlusion (2-VO) model in vivo and the hypoxia/reoxygenation (H/R) cell model in vitro was established to investigate the function of AC in VD.

Methods: The spatial learning and memory abilities of rats were detected by the Morris method. The IL-6, tumour necrosis factor-α (TNF-α), malondialdehyde (MDA) and superoxide dismutase (SOD) in cell supernatant was tested by ELISA kits. After behavioural experiments, rats were anaesthetized and sacrificed, and their brains were extracted. One part was immediately fixed in 4% paraformaldehyde for H&E, Nissl, and immunohistochemical analyses, and the other was stored in liquid nitrogen. All data were shown as mean ± SD. Statistical comparison between the two groups was performed by Student’s t-test. A two-way ANOVA test using GraphPad Prism 7 was applied for escape latency analysis and the swimming speed test. The difference was considered statistically significant at p < 0.05.

Results: AC decreased apoptosis, increased autophagy, and alleviated oxidative stress in primary hippocampal neurons. AC regulated autophagy-related proteins in vitro by western blotting. VD mice improved cognitively in the Morris water maze. Spatial probing tests showed that VD animals administered AC had considerably longer swimming times to the platform than VD rats. H&E and Nissl staining showed that AC reduces neuronal damage in VD rats. Western blot and qRT-PCR indicated that AC in VD rats inhibited Bax and promoted LC3-II, Beclin-1, and Bcl-2 in the hippocampus region. AC also improves cognition via the AMPK/mTOR pathway.

Conclusion: This study found that AC may relieve learning and memory deficits as well as neuronal damage in VD rats by changing the expression of apoptosis/autophagy-related genes and activating the AMPK/mTOR signalling pathway in neurons.