Neurotropic mouse hepatitis virus (MHV-A59/RSA59) infection in mice induces acute neuroinflammation due to direct neural cell dystrophy, which proceeds with demyelination with or without axonal loss, the pathological hallmarks of human neurological disease, Multiple sclerosis (MS). Recent studies in the RSA59-induced neuroinflammation model of MS showed a protective role of CNS-infiltrating CD4+ T cells compared to their pathogenic role in the autoimmune model. The current study further investigated the molecular nexus between CD4+T cell-expressed CD40Ligand and microglia/macrophage-expressed CD40 using CD40L-/- mice. Results demonstrate CD40L expression in the CNS is modulated upon RSA59 infection. We show evidence that CD40L-/- mice are more susceptible to RSA59 induced disease due to reduced microglia/macrophage activation and significantly dampened effector CD4+ T recruitment to the CNS on day 10 p.i. Additionally, CD40L-/- mice exhibited severe demyelination mediated by phagocytic microglia/macrophages, axonal loss, and persistent poliomyelitis during chronic infection, indicating CD40-CD40L as host-protective against RSA59-induced demyelination. This suggests a novel target in designing prophylaxis for virus-induced demyelination and axonal degeneration, in contrast to immunosuppression which holds only for autoimmune mechanisms of inflammatory demyelination.

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Background Cervical cancer remains one of the significant causes of mortality in women due to the limitations of current treatment strategies and their associated side effects. Investigation of alternative medicine, including phytomedicine, has shown effective anti-cancer potential with fewer side effects. Azadirachta indica (commonly known as neem) is known for its medicinal properties. The present study investigated the anti-cancer potential of methanolic neem stem bark extract (MNBE) against cervical cancer using HeLa, SiHa, and ME-180 cell lines. Methods Cytotoxic effect of MNBE on cultured cell lines was evaluated by MTT and clonogenic assay. The growth-inhibiting effect of MNBE was further confirmed by performing cell cycle analysis and apoptosis assay using flow cytometry. The anti-migratory effect of MNBE was evaluated by using wound healing and Boyden chamber assay. Real-time PCR was used to determine the mRNA expression, and western blot and flow cytometry was used to determine the protein levels of growth and migration-related genes. Results MNBE significantly suppressed the growth and survival of cervical cancer cells in a dose-dependent manner by inducing cell cycle arrest and apoptosis. In addition, the growth inhibitory effect of MNBE was specific to cervical cancer cells than normal cells. Cell cycle arrest was correlated to transcriptional downregulation of cyclin dependent kinase 1 (CDK1), cyclin A, and cyclin B. Additionally, MNBE treatment resulted in the upregulation of active caspase-3 protein and downregulation of prosurvival genes, Bcl2, and survivin at mRNA level and NFkB-p65 at the protein level. Furthermore, MNBE inhibited the migration of cervical cancer cells accompanied by modulation of migration-related genes, including zona occludens-1 (ZO-1), matrix metalloproteinase 2 (MMP2), focal adhesion kinase (FAK), N-cadherin, snail, and E-cadherin. Conclusion In summary, the present study provides the first evidence of MNBE in restricting cervical cancer cell growth and migration, which warrants further investigation for developing novel anti-cancer drugs.

Aim:Theaimof studywas toassess theroleofhyperbilirubinemiaasapredictorofgangrenousorperforated appendicitis. Introduction: Appendicitis is characterised by means of infection and inflammation of the appendix. It was hypothesized that an association exists between the presence of appendiceal perforation and hyperbilirubinemia.The present study has been designed to evaluate the association between hyperbilirubinemia in cases of acute appendicitis and its complications. Methods: This study was conducted at SMS hospital Jaipur as a prospective observational study. One hundred twenty patients of appendicitis were enrolled from 1 March 2017 to 30 November 2018 according sample size. Patients underwent appendectomy after confirmation of diagnosis by USG and other investigations and biopsy was sent for histopathological examination. Results: Total 120 patients were analysed In our study as per inclusion criteria. Hyperbilirubinemia (>1.2 mg/dL) was found in gangrenous appendicitis and perforated appendicitis (91.67% and 100% respectively) as compared to in acute appendicitis (15.63%) cases (P<0.001). most of the acute (84.37%) and some gangrenous appendicitis (8.33%) patients had normal TSB but all perforated appendicitis patients had hyperbilirubinemia (>1.2 mg/dL). Liver enzymes were normal in most of cases or slightly elevated in some cases.Alvarado Score and CRP were also significantly elevated in complicated appendicitis than acute appendicitis. Conclusion: Our study concluded that isolated hyperbilirubinemia is a predictor of perforated or gangrenous appendicitis.High Alvarado Score and CRP level are also indicating complicated appendicitis.

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