Flavonoids, a group of natural compounds with phenolic structure, are becoming popular as alternative medicines obtained from plants. These compounds are reported to have various pharmacological properties, including attenuation of inflammatory responses in multiple health issues. Epilepsy is a disorder of the central nervous system implicated with the activation of the inflammatory cascade in the brain. The aim of the present study was to summarize the role of various neuroinflammatory mediators in the onset and progression of epilepsy, and, thereafter, to discuss the flavonoids and their classes, including their biological properties. Further, we highlighted the modulation of anti-inflammatory responses achieved by these substances in different forms of epilepsy, as evident from preclinical studies executed on multiple epilepsy models. Overall, the review summarizes the available evidence of the anti-inflammatory potential of various flavonoids in epilepsy.

Introduction: COVID-19 is caused by a new strain of coronavirus called SARS-coronavirus-2 (SARS-CoV-2), which is a positive sense single strand RNA virus. In humans, it binds to angiotensin converting enzyme 2 (ACE2) with the help a structural protein on its surface called the S-spike. Further, cleavage of the viral spike protein (S) by the proteases like transmembrane serine protease 2 (TMPRSS2) or Cathepsin L (CTSL) is essential to effectuate host cell membrane fusion and virus infectivity. COVID-19 poses intriguing issues with imperative relevance to clinicians. The pathogenesis of GI symptoms, diabetes-associated mortality, and disease recurrence in COVID-19 are of particular relevance because they cannot be sufficiently explained from the existing knowledge of the viral diseases. Tissue specific variations of SARS-CoV-2 cell entry related receptors expression in healthy individuals can help in understanding the pathophysiological basis the aforementioned collection of symptoms. Materials and Methods: The data were downloaded from the Human Protein Atlas available at ( https://www.proteinatlas.org/humanproteome/sars-cov-2 ) and the tissue specific expressions (both mRNA and protein) of ACE2 and TMPRSS2 as yielded from the studies with RNA sequencing and immunohistochemistry (IHC) were analyzed as a function of the various components of the digestive tract. A digestive system specific functional enrichment map of ACE2 gene was created using g:profiler ( https://biit.cs.ut.ee/gprofiler/gost ) utility and the data were visualized using Cytoscape software, version 3.7.2 ( https://cytoscape.org/ ). Results: The correlated expression (transcriptomic and proteomic) of ACE2 (to which SARS-CoV-2 binds through the S-spike) was found to be enriched in the lower gastrointestinal tract (GIT) (highest in small intestine, followed by colon and rectum), and was undetectable in the upper GIT components: mouth cavity (tongue, oral mucosa, and salivary glands), esophagus, and stomach. High expression of ACE2 was noted in the glandular cells as well as in the enterocytes in the lining epithelium (including brush border epithelium). Among other digestive system organs, Gall bladder (GB) showed high expression of ACE2 in glandular cells, while any protein expression was undetectable in liver and pancreas. TMPRSS2 was found enhanced in GIT and exocrine glands of pancreas, and co-localized with ACE2 in enterocytes. Conclusions: Based on the findings of this study and supportive evidence from the literature we propose that a SARS-CoV-2 binding with ACE2 mediates dysregulation of the sodium dependent nutrient transporters and hence may be a plausible basis for the digestive symptoms in COVID-19 patients. ACE2 mediated dysregulation of sodium dependent glucose transporter (SGLT1 or SLC5A1) in the intestinal epithelium also links it to the pathogenesis of diabetes mellitus which can be a possible reason for the associated mortality in COVID-19 patients with diabetes. High expression of ACE2 in mucosal cells of the intestine and GB make these organs potential sites for the virus entry and replication. Continued replication of the virus at these ACE2 enriched sites may be a basis for the disease recurrence reported in some, thought to be cured, patients. Graphical

Purpose: Since immunohistological investigations have given rise to divergent perspectives about continued hippocampal neurogenesis in adult humans, a comprehensive transcriptomic analysis of the neurogenesis signature markers supplemented with insights from gliogenesis and apoptotic markers (in context to the developmental stages across age) may discern important aspects and may well be the appropriate methodology for resolving this conflict. Materials and Methods: RNA expression data for the salient neurogenesis, gliogenesis, and apoptotic marker genes in post-mortem human hippocampal tissue of the Prenatal (n=15), Infant/Early childhood (n= 5), Adolescence (n=4), and Adulthood (n=6) ages were downloaded from Allen Brain Atlas database ( http://www.brainspan.org/rnaseq ). Gene expression data was categorized, median values were computed, and age group specific differential expression was statistically analyzed (the confidence level of 95%, p value ≤ 0.05 is used). Results: A sharp fall in prenatal to infant/early childhood expression was observed for all studied neurogenesis markers, except that for the post-mitotic late maturation (CALB1, CALB2, MAP2, NEUN, STMN2) which showed no significant differences in expression profiles. A continued post childhood decrease across advancing age was observed in the neural stem cells and progenitor markers with insignificant differences across close age groups. Uniquely, the postnatal sharp fall of KI67 and TBR2 continued across advancing age groups, reached near baseline until adolescent age. The immature granule cell, post mitotic early maturation, and late maturation markers showed a maintained or slightly increased (albeit insignificant) post childhood expression. The gliogenesis markers mostly showed a significant downregulation between prenatal and infant /early childhood age groups; this decline was persistent thereafter with insignificant differences between close age groups. A continued postnatal decrease occurred in apoptotic markers with observable, but insignificant, differences between adolescent and adult age. Conclusions: Our findings indicate a possibility of continued but minimal neurogenesis in the adult human hippocampus. A significant part of the newborn cells in the neurogenic niche may be glial cells. (Findings of this study were first presented at the Annual Meeting of Society for Neuroscience (SFN), 3 ^rd -7 ^th November, 2018, San Diego, USA. https://abstractsonline.com/pp8/#!/4649/presentation/37213 ) Graphical Highlights: A varying but continued fall in expression was observed for all studied neurogenesis markers across advancing age groups, except that for the immature granule cells, early and post-mitotic late neuronal maturation markers. A continued postnatal sharp fall of progenitor markers KI67 and TBR2 reached near baseline until adolescent age. Gliogenesis markers showed continued but insignificant fall in expression post infant/early childhood. Apoptotic markers showed continued post infant/early childhood downfall but changes were negligible between adolescent and adult age.

Purpose: The etiology of schizophrenia is extensively debated, and multiple factors have been contended to be involved. A panoramic view of the contributing factors in a genome-wide study can be an effective strategy to provide a comprehensive understanding of its causality. Materials and Methods: GSE53987 dataset downloaded from GEO-database, which comprised mRNA expression data of post-mortem brain tissue across three regions from control and age-matched subjects of schizophrenia (N= Hippocampus (HIP): C-15, T-18, Prefrontal cortex (PFC): C-15, T-19, Associative striatum (STR): C-18, T-18). Bio-conductor-affy-package used to compute mRNA expression, and further t-test applied to investigate differential gene expression. The analysis of the derived genes performed using PANTHER Classification System and NCBI database. Results: A set of 40 genes showed significantly altered (p<0.01) expression across all three brain regions. The analyses unraveled genes implicated in biological processes and events, and molecular pathways relating basic neuronal functions. Conclusions: The deviant expression of genes maintaining basic cell machinery explains compromised neuronal processing in SCZ. Abbreviations: Schizophrenia (SCZ), Hippocampus (HIP), Associative striatum (STR), Prefrontal cortex (PFC)