Venom of the desert black snake Walterinnesia aegyptia enhances anti-tumor immunity via its beneficial modulatory effects on pro- and anti-tumorigenic inflammatory mediators in cultured colon cancer cells.

The role of inflammation in colon cancer is understood as a well-accepted factor that has the tendency to release multiple pro- and anti-tumorigenic inflammatory mediators. Inflammation-induced increased expression of anti-tumorigenic inflammatory mediators and decreased expression of pro-tumorigenic inflammatory mediators encourage beneficial inflammatory effects in terms of powerful anti-tumor immunity. The present study aims to screen the beneficial inflammatory effects of Walterinnesia aegyptia venom via determining its modulatory tendency on the expression of 40 pro- and anti-tumorigenic inflammatory mediators (cytokines/growth factors/chemokines) in LoVo human colon cancer cell line. LoVo-cells were treated with varying doses of crude venom of W. aegyptia. Cell viability was checked utilizing flow cytometry, and IC50 of venom was determined. Venom-induced inflammatory effects were evaluated on the expression of 40 different inflammatory mediators (12 anti-tumorigenic cytokines, 11 pro-tumorigenic cytokines, 7 pro-tumorigenic growth factors, 9 pro-tumorigenic chemokines and 1 anti-tumorigenic chemokine) in treated LoVo-cells [utilizing enzyme-linked immunosorbent assay (ELISA)] and compared with controls. Treatment of venom induced significant cytotoxic effects on inflamed LoVo-cells. IC50 treatment of venom caused significant modulations on the expression of 22 inflammatory mediators in treated LoVo-cells. The beneficial modulatory effects of venom were screened via its capability to significantly increase the expression of five powerful anti-tumorigenic mediators (IL-9, IL-12p40, IL-15, IL-1RA and Fractalkine) and decrease the expression of four major pro-tumorigenic mediators (IL-1ß, VEGF, MCP-1 and MCP-3). Walterinnesia aegyptia venom-induced beneficial modulations on the expression of nine crucial pro/anti-tumorigenic inflammatory mediators can be effectively used to enhance powerful anti-tumor immunity against colon cancer.

Influence of KISS1 gene polymorphisms on the risk of polycystic ovary syndrome and its associated variables, in Saudi women.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a complex multifactorial disorder, affecting millions of women worldwide. The role of genetic polymorphisms of the KISS1 gene on the development of PCOS is still obscure. This study was designed to investigate the probable influence of KISS1 gene polymorphisms on PCOS and its associated variables: BMI, waist-hip ratio, kisspeptin, LH, FSH, and LH-FSH ratio. METHODS: The study comprised 104 PCOS women and 109 controls, with age ranging from 19 to 36 years. BMI, waist-hip ratio, and circulating levels of kisspeptin, LH, and FSH were measured. DNA was extracted, and genotyping of the KISS1 gene was carried out by nucleotide sequencing. The PCOS-associated variables were analyzed in different genotypes of single nucleotide polymorphisms (SNPs) of the KISS1 gene. RESULTS: The values of waist-hip ratio (WHR), LH, and LH-FSH ratio were significantly higher in PCOS women than controls. BMI, kisspeptin, and FSH levels exhibited no significant difference between the groups. Six novel SNPs of KISS1 gene were identified. Three: rs372790354G > A, rs12998G > A, and rs35431622A > T were investigated. Among these SNPs, the genotype and allele frequencies of rs372790354 showed significant association with PCOS (GA: p = 0.018, AA: p = 0.022, mutant allele-A: p = 0.021) and the G allele was protective. The values of LH, kisspeptin, and WHR of PCOS women were significantly influenced (p < 0.05) by the AA genotype of rs372790354. The other two SNPs rs12998G > A and rs35431622A > T revealed no significant influence on PCOS and associated variables. Haplotypes were constructed, but there was no significant difference between the patients and controls. CONCLUSION: In conclusion, this is the first study, which reports a significant influence of KISS1 gene polymorphism (rs372790354G > A) on PCOS and its associated variables. However, more extensive research is necessary to confirm these findings.

Genotoxicity and oxidative stress in chromium-exposed tannery workers in North India.

Trivalent chromium (Cr) is an environmental contaminant, which is extensively used in tanning industries throughout the world and causes various forms of health hazards in tannery workers. Therefore, a cross-sectional study design was used to evaluate the DNA damage and oxidative stress condition in tannery workers exposed to Cr in North India. The study population comprised 100 male tanners in the exposed group and 100 healthy males (no history of Cr exposure) in the comparable control group. Baseline characteristics including age, smoking, alcohol consumption habits and duration of exposure were recorded via interviewing the subjects. Blood Cr level (measured by atomic absorption spectrophotometry), DNA damage (measured by comet assay) and oxidative stress parameters (malondialdehyde (MDA), glutathione (GSH) and superoxide dismutase (SOD)) were estimated in both the groups. As a result of statistical analysis, exposed group showed significantly higher level of Cr (p < 0.0001), DNA damage (p < 0.0001), MDA (p < 0.0001), SOD (p < 0.05) and lower level of GSH (p < 0.001) when compared with controls. Smoking, alcohol consumption habits and age had no significant effect (p > 0.05) on DNA damage and oxidative stress parameters in both the groups. In simple and multiple correlation analysis, DNA damage and oxidative stress parameters showed significant correlation with Cr level and duration of exposure in exposed group. The findings of the present study revealed that chronic occupational exposure to trivalent Cr may cause DNA damage and oxidative stress in tannery workers.

Assessment of health risks with reference to oxidative stress and DNA damage in chromium exposed population.

Trivalent chromium [Cr(III)] is widely used in tanning industrial processes. The population living in tanning industrial area is continuously exposed to Cr(III) which appears to be associated with both acute and chronic health problems. Therefore, the aim of this study was to evaluate the health risk with special reference to oxidative stress parameters (malondialdehyde - MDA, glutathione - GSH, and superoxide dismutase - SOD) and DNA damage in 100 Cr-exposed and 100 unexposed populations. The total blood Cr level, SOD level, MDA level and DNA damage were significantly (p<0.05) higher and GSH level was significantly (p<0.05) lower in exposed group as compared to the unexposed group. The altered oxidative stress parameters and DNA damage were found to be slightly higher in female population of both groups. In simple and multiple correlation analyses (adjusted with potential confounders), blood Cr level showed negative significant correlation with GSH level and positive significant correlation with level of MDA, SOD and DNA damage in both groups. The overall prevalence of morbidity was found to be significantly (p<0.05) higher in the exposed group as compared to the unexposed group. In the exposed group, the prevalence of respiratory illness is highest, followed by diabetes, gastrointestinal tract problems and dermal problems respectively. Our results concluded that the Cr(III) exposed population is at high risk for health hazards and the female population is slightly more susceptible to Cr(III) exposure.