Hepatocellular carcinoma (HCC) is primarily a malignancy of the liver, advancing from a damaged, cirrhotic liver to HCC. Globally, HCC is the sixth most prevalent cancer and the third-most prevalent reason for neoplastic disease-related deaths. A diverse array of infiltrating immunocytes regulates the development and progression of HCC, as is the case in many other cancers. An understanding of the various immune components during HCC becomes necessary so that novel therapeutic strategies can be designed to combat the disease. A dysregulated immune system (including changes in the number and/or function of immune cells, cytokine levels, and the expression of inhibitory receptors or their ligands) plays a key role in the development of HCC. Alterations in either the innate or adaptive arm of the immune system and cross-talk between them make the immune system tolerant to tumors, leading to disease progression. In this review, we have discussed the status and roles of various immune effector cells (e.g. , dendritic cells, natural killer cells, macrophages, and T cells), their cytokine profile, and the chemokine-receptor axis in promoting or impeding HCC.

SummarySpinocerebellar ataxia type 12 (SCA12) is an autosomal dominant cerebellar ataxia associated with the expansion of an unstable CAG repeat in the 5 region of the PPP2R2B gene on chromosome 5q31-5q32. We found that it accounts for ∼ 16% (20/124) of all the autosomal dominant ataxia cases diagnosed in AIIMS, a major tertiary referral centre in North India. The length of the expanded allele in this population ranges from 51-69 CAG triplets. Interestingly, all the affected families belong to an endogamous population, which originated in the state of Haryana, India. We identified four novel SNPs and a dinucleotide marker spanning ∼ 137 kb downstream of CAG repeat in the PPP2R2B gene. Analysis of 20 Indian SCA12 families and ethnically matched normal unrelated individuals revealed one haplotype to be significantly associated with the affected alleles (P = 0.000), clearly indicating the presence of a common founder for SCA12 in the Indian population. This haplotype was not shared by the American pedigree with SCA12. Therefore, the SCA12 expansion appears to have originated at least twice.

Background Chronic HIV-1 infection is associated with excessive immune activation as well as immune exhaustion. We investigated the relationship of these two phenotypes and frequency of regulatory T cells (Tregs) in controlled and uncontrolled chronic HIV-1 infection. Methods Immune exhaustion marker PD-1, its ligand PD-L1, CD4+CD25brightFoxP3+ Tregs, HLA-DR and CD38 coexpression as activation markers were investigated in peripheral blood lymphocytes of 44 HIV-1 infected patients and 11 HIV-1 uninfected controls by multi-color flow cytometry. Results Activated and PD-1 expressing T cells were increased and Tregs were decreased in HIV-1 infected patients as compared to controls, and alterations were greatest in viremic patients. The proportion of activated CD8+ T cells exceeded activated CD4+ T cells. Tregs had an inverse correlation with activated T cells and PD-1 expressing T cells. PD-L1 was highly expressed on monocytes and to a lesser extent on T lymphocytes of patients. These abnormalities partially reversed with virologic control following potent antiretroviral therapy (ART). Conclusions Immune exhaustion is a component of aberrant immune activation in chronic HIV-1 infection and is associated with loss of Tregs and ongoing virus replication. These defects are corrected partially with effective virologic control by potent ART.

The goals of our present study were to measure plasma homocysteine levels and determine their association with methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms (C677T and A1298C) in essential hypertensive subjects. Plasma total homocysteine and folic acid levels were measured in essential hypertensive patients (n = 153) before and after oral supplementation with either 5 mg folic acid tablet/day or 5 mg placebo/day for 4 weeks and compared with age and sex matched normotensive controls (n = 133). MTHFR gene polymorphisms (C677T and A1298C) were studied by restriction fragment length polymorphism and correlated with plasma homocysteine levels. Homocysteine levels were significantly higher in hypertensive patients as compared to controls and showed a negative correlation with plasma folate levels. Folic acid supplementation (5 mg/day) for 4 weeks resulted in a significant decrease in plasma homocysteine concentrations in these patients. Patients carrying MTHFR 677T allele (OR = 1.90; 95%CI: 1.14-3.19) or MTHFR 1298C (OR = 2.6, 95%CI: 1.55-4.40) allele were at increased risk of hypertension. The frequency of co-occurrence of MTHFR 677 CT/1298 CC genotypes was significantly higher in the patients compared to controls (P < 0.05) and was associated with increased risk of hypertension (OR = 3.54, 95%CI: 0.37-4.30). Subjects with MTHFR 1298 CC genotype had significantly higher homocysteine levels compared to those with MTHFR 1298 AA genotype (P < 0.05). Our results indicate that MTHFR 677T and 1298C alleles and co-occurrence of MTHFR 677 CT/MTHFR 1298 CC genotypes are associated with increased risk of hypertension and MTHFR 1298 CC genotype is associated with higher homocysteine levels in our subjects.

BackgroundNon communicable diseases (NCDs) have become a major concern for global health. Cardiovascular diseases (CVDs) contribute 48 % towards the deaths due to NCDs in India. Though studies have been conducted in urban and rural areas, data related to tribal communities is limited. The present study aims to examine various CVD related risk factors including hypertension, elevated fasting blood glucose, obesity and metabolic syndrome among a tribal population.MethodsThe present study was an observational, cross- sectional study conducted on Rang Bhotias, a tribal population of India. The participants were adults of age between 20 and 60 years. Prior to blood sample collection, interview schedule was administered which included relevant information like age, lifestyle, socio-economic status, education and occupation In addition to this, various anthropometric and physiological measurements were taken. Logistic regression was used to examine the association of the various health disorders related to CVDs with age, gender and behavioural factors (smoking, alcohol consumption and physical activity).ResultsA total of 288 participants were surveyed for the study including 104 males and 184 females. High BMI (56.6 %), hypertension (43.4 %), metabolic syndrome (39.2 %) and abdominal obesity (33.7 %) were the most prevalent CVD risk factors observed in the population. The multivariate logistic regression analysis, conducted to examine the contribution of risk factors including behavioural risk factors on the studied abnormalities, revealed age to be a significant risk factor for all the abnormalities except elevated fasting blood glucose. Gender and physical inactivity contributed significantly towards development of hypertension. Physical inactivity was also found to be associated with high BMI levels.ConclusionIn the present study, hypertension, high BMI levels, MS and abdominal obesity have been found to be high among the studied population. The status of the population with respect to these abnormalities implicates susceptibility of the community towards various common disorders. The prevention and treatment intervention programs should be implemented taking into consideration age and gender.Electronic supplementary materialThe online version of this article (doi:10.1186/s12889-016-3106-x) contains supplementary material, which is available to authorized users.

Low vitamin B₁₂ increases homocysteine, specifically among T allele carrying case mothers, suggesting T allele is detrimental with B₁₂ deficiency. The study emphasizes the importance of vitamin B₁₂ in the prevention of RPL in North Indian women.

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