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Background: As per WHO, Cervical cancer (CaCx) is a global issue, being the fourth common cancer in women with incidence rate of 13.1 per 1 lakh women globally and accounting for 311000 deaths in the year 2018 itself globally. The molecular pathogenesis in Human papillomavirus (HPV) infected cases is inconclusive. The detection of molecular factors leading to progression of CaCx can be important in the diagnosis and management of the disease. p53 a known tumor suppressor gene having a regulative role in cell cycle has been highlighted as key factor in the prevention of cancer but its significance in CaCx cases has been variably documented. The present study therefore targeted to evaluate the significance of p53 profile in CaCx cases in ethnically distinct northeast Indian population. Methods: Blood and Tissue samples (N = 85) of cervical cancer patients were collected and screening for HPV was performed using PCR. Thereafter the differential mRNA expression(qPCR), Immunohistochemistry, Mutation (PCR direct sequencing method) of p53 was studied. Further p53 epigenetic profiling was done by Methylation specific PCR (MS-PCR) and western blotting by using p53 acetylation specific antibodies. Results: Our findings revealed that the downregulation of p53 was associated with the progression of disease and the variation in downregulation based on p53 polymorphism was observed. Further hypermethylation and deacetylation of p53 was also found to be associated with the pathogenesis of CaCx. The downregulated expression and hypermethylation of p53 in lower grade of CaCx, together established its association with the progression of CaCx from lower to severe grade. Conclusion: Therefore, in CaCx patients of northeast Indian population, malfunctioning of p53 is found to have significant role in cervical cancer progression. [ABSTRACT FROM AUTHOR]

Background/Aims Role of specific chemokine-chemokine receptor(s) axis involvement has been increasingly realized in many pathophysiological conditions involving inflammatory states, including sporadic reports in nonalcoholic fatty liver disease (NAFLD) pathogenesis. The present study aimed to evaluate the significance of chemokine RANTES and associated immunomodulation and modulations of key HSC signaling regulators in the susceptibility and severity of NAFLD in non-obese subjects. Methods Clinically characterized NAFLD cases (n=58; NAFL, 45; nonalcoholic steatohepatitis [NASH], 13) with clinical details and fibroscan based liver stiffness measurement (LSM)-score were enrolled along with healthy controls (HC, n=90). Serum RANTES and cytokine panels were evaluated by enzyme-linked immunosorbent assay. Chemokine receptors (CCR5, CCR1), monocyte (sCD14, mCD14) and its activation (CD40, HLA-DR), T-cell activation (CD25) profile were analyzed using various molecular tools. All statistical analysis was performed using SPSS version 13.0 software. Results The serum RANTES levels were significantly higher in NASH cases compared to NAFL cases (p=0.29) and HC subjects (p=0.047). Expression of RANTES (CCL5) ligands CCR5 and CCR1 mRNA and cellular protein expression was increased in NASH cases compared to both HC and NAFL cases. Both significant monocyte and T-cell activation profile was observed in NASH compared to NAFL cases and HC cases, and nonsignificantly increased in NAFL cases compared to HC subjects. A sharp Th1 biased cytokine profile with upregulation of tumor necrosis factor (TNF)-α , interleukin (IL)-12 and IL-2 was observed in NASH cases compared to NAFL cases. The profile of regulators of HSC activations viz., TNF-α, transforming growth factor-β1, PDGF-BB and vascular endothelial growth factor was significantly activated in NAFLD cases, and correlated positively with serum RANTES expression, monocyte activation markers (CD40 and CCR5), higher alanine transaminase, GGTP, and LSM-score. Conclusions RANTES levels possibly contributes to chronic inflammatory microenvironment in NAFL subjects through increased immunomodulation and increased expression of regulators associated with HSC activation in non-obese NAFL cases thereby augmenting progression to NASH. Therefore RANTES-chemokine receptor axis therefore holds both prognostic and therapeutic importance in NAFLD. [ABSTRACT FROM AUTHOR]

Background/Aims Present study focused on alterations in gut-microbiota and its clinical relevance with nonalcoholic fatty liver disease (NAFLD) pathogenesis in tribal cases enrolled from northeast India. Methods Clinically characterized NAFLD cases (n=36) with clinical details and fibroscan based liver stiffness measurement (LSM)-score were enrolled along with healthy controls (n=52). Decidual aspirations based microbiome load and diversity analysis was performed by standard culture and microbial metagenomics methods for NAFLD and representative HC cases. Serum endotoxin levels were estimated using standard kit. Differential sCD14, mCD14, CD40, sTLR2, TLR2, TLR4, NK/NKT expression and cytokine panels were analyzed by enzyme-linked immunosorbent assay /flowcytometry. HepG2 cell line based microbial stimulation studies were performed for specificity of differential monocyte, cytokine and HSC activation. Results Increased total and gram negative bacterial load was observed in NAFLD cases compared to HC. Metagenomic diversity profile data indicated a sharp difference in microbiota between NAFLD and HC subjects. Serum endotoxin and sCD14 levels were higher in NAFLD cases. Monocyte CD14 (p=0.019) and activation marker CD40 (p=0.043) was significantly increased in NAFLD cases. Average TLR4 (p=0.071) and TLR2 expression (p=0.137) on blood cells was also higher in NAFLD cases, while sTLR2 expression was significantly reduced in NAFLD cases (p=0.031) compared to HC. The CD40 and TLR4 levels significantly positively correlated with higher LSM scores. NK cell expression was higher in NAFLD. Distinct up-regulation of NFkBp65, tumor necrosis factor-α, interleukin (IL)-12 combined with significant downregulation of anti-inflammatory cytokine IL-10 and IL-4 was found to be significantly correlating with NAFLD pathogenesis and higher LSM-score (p<0.001). The hepG2 cell line (naïve and oleic acid stimulated) with NAFLD and HC microbial antigen stimulation and coculture study also indicated the increased monocyte activation, inflammatory cytokine expression and HSC activation markers on stimulation with microbes of NAFLD patient's origin. Conclusions Dysbiosis and resulting altered monocytosis and hyper-immunomodulation is specific and detrimental to NAFLD pathogenesis. [ABSTRACT FROM AUTHOR]

The article discusses a study which investigated chemokine receptor 5 (CCR5) polymorphism in chronic hepatitis B patients treated with three different nucleotide analogues. It was found that the use of several antiviral drugs, including adefovir, lamivudine, and telbivudine, brought about biochemical and serological improvement. The treatment also significantly reduced serum hepatitis B virus (HBV) DNA levels.

Aim: To investigate hepatitis virus, genetic and environmental factors, and their interactions in predisposing patients to liver diseases in Northeast India., Methods: A total of 104 jaundice patients and 124 community controls were included. Serological analysis was performed by routine enzyme-linked immunosorbent assay, and nucleic acid testing for hepatitis viruses was done by polymerase chain reaction (PCR), followed by PCR direct sequencing for viral genotyping. Cytochrome P450 2E1 (CYP2E1) polymorphism was studied by PCR-restriction fragment length polymorphism. Nitrite and volatile nitrosamines in indigenous foods consumed routinely by the Northeast Indian ethnic population were estimated by Griess's reagent and GC-MS, respectively., Results: Hepatitis A virus (HAV) infection was predominantly prevalent (36.5%) in our cohort, followed by hepatitis B virus (HBV), hepatitis E virus (HEV) and hepatitis C virus. HBV genotype D and HEV genotype 1 were the most dominant. CYP2E1 c1/c2 genotype frequency was comparatively higher in alcoholic (P < 0.0001, OR = 30.5) and cryptogenic (P = 0.014, OR = 8.714) patients, and was associated with significantly higher hepatitis risk (P = 0.0.007, OR = 6.489). Mutant C allele of Cyp2E1 DraI frequency was comparatively higher in HAV (P = 0.006), alcoholic (P = 0.003) and cryptogenic (P = 0.014) cases, and was associated with overall hepatitis risk (P = 0.026, OR = 5.083). Indigenous foods, Gundruk, Kharoli, betel leaf and nuts were found to have the highest nitrite content., Conclusion: Apart from viral factors, CYP2E1 polymorphism might be associated with increased risk of liver diseases in Northeast India. Indigenous foods that contain nitrite and nitrosamine might be an associated risk factor.