Association between RAD51, XRCC2 and XRCC3 gene polymorphisms and risk of ovarian cancer: a case control and an in silico study.

Homologous recombination (HR) is one of the important mechanisms in repairing double-strand breaks to maintain genomic integrity and DNA stability from the cytotoxic effects and mutations. Various studies have reported that single nucleotide polymorphisms (SNPs) in the HR-associated genes may have a significant association with ovarian cancer (OCa) risk but the results were inconclusive. In the present study, five polymorphisms of HR-associated genes (RAD51, XRCC2 and XRCC3) were genotyped by allelic discrimination assay in 200 OCa cases and 200 healthy individuals. The association with OCa risk was evaluated by unconditional logistic regression analyses. The results revealed that the mutant allele in both rs1801320 (CC) and rs1801321 (TT) of RAD51 gene was associated with increased risk of OCa (odds ratio [OR] 3.79, 95% confidence interval [CI] 1.21-11.78, p = 0.014 and OR 1.61, 95% CI 1.06-2.45, p = 0.025, respectively). Moreover, a significant association of TT allele (OR 4.68, 95% CI 1.27-17.15, p = 0.011) of rs3218536 of XRCC2 gene with OCa was observed. Stratified analysis results showed that patients with early menarche and stages 3 and 4 were found to be associated with rs1801321 of RAD51 gene and rs1799794 of XRCC3 gene. In silico analysis predicted that the two missense SNPs (rs3218536 and rs1799794) were found to have an impact on the protein structure, stability and function. The present study suggested that RAD51 and XRCC2 gene polymorphisms might have an impact on the OCa risk in the South Indian population. However, studies with a larger sample and on different populations are needed to support the conclusions.

HLA-DRB1 shared epitope alleles in patients with rheumatoid arthritis: relation to autoantibodies and disease severity in a south Indian population.

AIM: To investigate the presence of the 'shared epitope' (SE) in the HLA-DRB1 alleles in patients with RA and to ascertain the frequency of the HLA-DRB1 alleles with autoantibodies (anti-cyclic citrullinated peptide [anti-CCP] rheumatoid factor [RF]) and disease severity. METHODS: A total of 200 RA patients and 200 apparently healthy subjects participated in the study. HLA-DRB1 were genotyped using polymerase chain reaction with sequence-specific primer (PCR-SSP). Anti-CCP and RF in serum were determined by in vitro quantitative enzyme-linked immunosorbent assay (ELISA) method. Erythrocyte sedimentation rate (ESR) was measured by Westergren method. Disease activity was assessed by using the disease activity score-28 (DAS-28). Chi-square test and Student's t-test were used in the statistical analysis. RESULTS: A significant increase in the frequency of HLA-DRB1*01, *04, *10 and *14 were identified in RA patients and showed a strong association with the disease susceptibility. While the frequencies of HLA-DRB1*03, *07, *11 and *13 were significantly lower in RA patients than in controls. The other HLA-DRB1 alleles *08, *09, *12, *15 and *16 showed no significant difference. The frequency of anti-CCP and RF antibodies did not showed significant difference in SE-positive patients compared with SE-negative patients. DAS-28 values of RA patients showed no significant difference between SE-positive and SE-negative groups. CONCLUSION: Our results indicate that HLA-DRB1*01, *04, *10 and *14 alleles are related with RA, while HLA-DRB1*03, *07, *11 and *13 protect against RA in our population. On the other hand, we failed to provide evidence for the association of the autoantibodies and DAS-28 with SE-positive RA patients.

Heat stress and inadequate sanitary facilities at workplaces - an occupational health concern for women?

BACKGROUND: Health concerns unique to women are growing with the large number of women venturing into different trades that expose them to hot working environments and inadequate sanitation facilities, common in many Indian workplaces. OBJECTIVE: The study was carried out to investigate the health implications of exposures to hot work environments and inadequate sanitation facilities at their workplaces for women workers. DESIGN: A cross-sectional study was conducted with 312 women workers in three occupational sectors in 2014-2015. Quantitative data on heat exposures and physiological heat strain indicators such as core body temperature (CBT), sweat rate (SwR), and urine specific gravity (USG) were collected. A structured questionnaire captured workers perceptions about health impacts of heat stress and inadequate sanitary facilities at the workplace. RESULTS: Workplace heat exposures exceeded the threshold limit value for safe manual work for 71% women (Avg. wet bulb globe temperature=30°C±2.3°C) during the study period. Eighty-seven percent of the 200 women who had inadequate/no toilets at their workplaces reported experiencing genitourinary problems periodically. Above normal CBT, SwR, and USG in about 10% women workers indicated heat strain and moderate dehydration that corroborated well with their perceptions. Observed significant associations between high-heat exposures and SwR (t=-2.3879, p=0.0192), inadequate toilet facilities and self-reported adverse heat-related health symptoms (χ (2)=4.03, p=0.0444), and prevalence of genitourinary issues (χ (2)=42.92, p=0.0005×10(-7)) reemphasize that heat is a risk and lack of sanitation facilities is a major health concern for women workers. CONCLUSIONS: The preliminary evidence suggests that health of women workers is at risk due to occupational heat exposures and inadequate sanitation facilities at many Indian workplaces. Intervention through strong labor policies with gender sensitivity is the need of the hour to empower women, avert further health risks, and also enhance productivity for the few million women workers who contribute largely to the country's economy.

Oral candidal carriage, salivary lysozyme levels, and their relationship with CD4 count in HIV-infected patients.

AIM: The aim of the present study was to compare the lysozyme concentration and candidal count in saliva between HIV-seropositive and HIV-negative individuals, and to correlate the relationship between lysozyme concentrations, candidal count, and CD4 count in HIV patients. METHODS: A study was conducted in 90 HIV-seropositive patients (subgroups: 1 [CD4 ≥ 500 cells/µL], 2 [CD4 200-499 cells/µL], and 3 [CD4 ≤ 200 cells/µL] and 30 HIV-negative individuals. A total of 6 mL unstimulated saliva was collected and stored at -80°C. Samples were centrifuged and divided into two portions of 600 µL each. One portion was used for the candidal assay and the other for the lysozyme assay using ready-made kits. Student's independent t-test and Karl Pearson correlation coefficient were used for the statistical analysis. RESULTS: There was a significant increase (P < 0.001) in lysozyme levels and the candidal count in the saliva of HIV-positive individuals compared with the HIV-negative individuals. A significant increase (P < 0.004) in the salivary candidal count was observed in the HIV subgroups 1-3. There was a significant negative correlation (P < 0.01) between the CD4 and candidal counts in subgroup 1 (P < 0.02) and between the lysozyme concentration and CD4 count in subgroup 3. There was no correlation between the lysozyme concentration and oral candidal carriage. CONCLUSIONS: An association exists between the lysozyme concentration and specific immunity. Yeast colonization serves as a marker of immunodeficiency in HIV disease progression.

Association of susceptible genetic markers and autoantibodies in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic autoimmune disorder of unknown aetiology resulting in inflammation of the synovium, cartilage and bone. The disease has a heterogeneous character, consisting of clinical subsets of anti-citrullinated protein antibody (ACPA)-positive and APCA-negative disease. Although, the pathogenesis of RA is incompletely understood, genetic factors play a vital role in susceptibility to RA as the heritability of RA is between 50 and 60%, with the human leukocyte antigen (HLA) locus accounting for at least 30% of overall genetic risk. Non-HLA genes, i.e. tumour necrosis factor-α (TNF-α) within the MHC (major histocompatibility complex) have also been investigated for association with RA. Although, some contradictory results have originated from several studies on TNF-α gene, the data published so far indicate the possible existence of TNF-α gene promoter variants that act as markers for disease severity and response to treatment in RA. The correlation of HLA and non-HLA genes within MHC region is apparently interpreted. A considerable number of confirmed associations with RA and other autoimmune disease susceptibility loci including peptidylarginine deiminase type 4 (PADI4), protein tyrosine phosphatase non-receptor type 22 (PTPN22), signal transducer and activator of transcription (STAT4), cluster of differentiation 244 (CD244) and cytotoxic T lymphocyte-associated antigen 4 (CTLA4), located outside the MHC have been reported recently. In this review, we aim to give an update on recent progress in RA genetics, the importance of the combination of HLA-DRB1 alleles, non-HLA gene polymorphism, its detection and autoantibodies as susceptibility markers for early RA disease.

Activation of intrinsic apoptotic signaling pathway in cancer cells by Cymbopogon citratus polysaccharide fractions.

Essential oils of Cymbopogon citratus were already reported to have wide ranging medical and industrial applications. However, information on polysaccharides from the plant and their anticancer activities are limited. In the present study, polysaccharides from C. citratus were extracted and fractionated by anion exchange and gel filtration chromatography. Two different polysaccharide fractions such as F1 and F2 were obtained, and these fractions were found to have distinct acidic polysaccharides as characterized by their molecular weight and sugar content. NMR spectral analysis revealed the presence of (1→4) linked b-d-Xylofuranose moiety in these polysaccharides. Using these polysaccharide fractions F1 and F2, anti-inflammatory and anticancer activities were evaluated against cancer cells in vitro and the mechanism of action of the polysaccharides in inducing apoptosis in cancer cells via intrinsic pathway was also proposed. Two different reproductive cancer cells such as Siha and LNCap were employed for in vitro studies on cytotoxicity, induction of apoptosis and apoptotic DNA fragmentation, changes in mitochondrial membrane potential, and profiles of gene and protein expression in response to treatment of cells by the polysaccharide fractions. These polysaccharide fractions exhibited potential cytotoxic and apoptotic effects on carcinoma cells, and they induced apoptosis in these cells through the events of up-regulation of caspase 3, down-regulation of bcl-2 family genes followed by cytochrome c release.

Serum biochemical markers in rheumatoid arthritis.

Rheumatoid arthritis (RA) characterized by local and systemic effects of inflammation has a wide range of biochemical markers implicated directly or indirectly to its pathogenesis. In the present study, homocysteine, cortisol, adenosine deaminase (ADA), ferritin, malondialdehyde (MDA) and alpha-tocopherol in serum of RA patients and healthy individuals were estimated to assess if they contribute to the disease process. The markers of disease activity such as erythrocyte sedimentation rate (ESR) and rheumatoid factor (RF) were also measured. The study group included a total of 45 subjects, including 30 RA patients and the rest being healthy individuals. RA group showed a significant increase in the levels of homocysteine, ADA and MDA, and a significant decrease in alpha-tocopherol compared to the healthy individuals. However, cortisol and ferritin levels did not show any significant change. Also, there was no significant correlation between the studied serum markers and markers of disease activity. Our results indicate that these biochemical markers contribute independently to the pathogenesis of RA.

Effect of type II collagen treatment on the antioxidant status in immune tissues of adjuvant induced arthritic rats.

Adjuvant induced arthritis (AIA) is a model widely used to study Rheumatoid arthritis (RA). In the present study, lipid peroxides level in spleen and thymus of AIA rats was observed to be significantly high compared to normal rats. A significant decrease in ascorbic acid (ASA), reduced glutathione (GSH), superoxide dismutase activity (SOD) was also observed in spleen and thymus of AIA rats compared to normal rats. There was also a steady increase in the circulating immune complex level (CIC) throughout the experimental period in serum of AIA rats. In the present investigation, it was decided to study the effect of pre and post treatment with TYPE II collagen on the antioxidant status and the circulating immune complex level in AIA rats. The results from the present work indicates that the pretreatment with TYPE II collagen was effective in bringing significant changes on all the parameters studied in AIA rats. The post treatment with TYPE II collagen was effective in bringing significant changes on the CIC immune complex level and GSH content in the thymus tissue of AIA rats. The present work suggests that the pre treatment with TYPE II collagen was more effective in suppressing the disease than the post treatment.