Genetic polymorphisms of IL6 gene -174G > C and -597G > A are associated with the risk of COVID-19 severity.

Coronavirus disease-2019 (COVID-19) is pro-inflammatory disorder characterized by acute respiratory distress syndrome. Interleukin-6, a cytokine secreted by macrophages, which mediates an inflammatory response, is frequently increased and associated with the severity in COVID-19 patients. The differential expression of IL6 cytokine in COVID-19 patients may be associated with the presence of single nucleotide polymorphisms (SNPs) in regulatory region of cytokine genes. The aim of this study is to investigate the role of two promoter polymorphisms of the IL6 gene (-597G > A and -174G > C) with the severity of COVID-19. The study included 242 patients, out of which 97 patients with severe symptoms and 145 patients with mild symptoms of COVID-19. Genotyping of two selected SNPs, rs1800795 (-174G > C) and rs1800797 (-597G > A) of promoter region of IL6 gene, was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). In our study, individuals with GC genotypes of IL6 (-174G > C) polymorphism showed significantly higher risk of severity [adjusted odds (OR) 3.86, p <.001] but we did not observe any association of COVID-19 severity with rs1800797 (-597G > A) polymorphism. The COVID-19 severity was significantly higher in individuals having 'C' allele of IL6 (-174G > C) polymorphism (p = .014). Linkage disequilibrium between rs1800795 (-174G > C) and rs1800797 (-597G > A) showed that individuals having AC* haplotype significantly association with COVID-19 severity (p = .034). Our results suggest that 'C' allele of rs1800795 (-174G > C) polymorphism of IL6 may be the risk allele for severity of COVID-19 in North Indian population.

Role of exosomes in lung cancer: A comprehensive insight from immunomodulation to theragnostic applications.

Exosomes are 30 to 150 nm-diameter lipid bilayer-enclosed extracellular vesicles that enable cell-to-cell communication through secretion and uptake. The exosomal cargoes contain RNA, lipids, proteins, and metabolites which can be delivered to recipient cells in vivo. In a healthy lung, exosomes facilitate interaction between adaptive and innate immunity and help maintain normal lung physiology. However, tumor-derived exosomes in lung cancer (LC) can, on the other hand, restrict immune cell proliferation, cause apoptosis in activated CD8+ T effector cells, reduce natural killer cell activity, obstruct monocyte differentiation, and promote proliferation of myeloid-derived suppressor and regulatory T cells. In addition, exosomes in the tumor microenvironment may also play a critical role in cancer progression and the development of drug resistance. In this review, we aim to comprehensively examine the current updates on the role of exosomes in lung carcinogenesis and their potential application as a diagnostic, prognostic, and therapeutic tool in lung cancer.

Microbiome dysbiosis and epigenetic modulations in lung cancer: From pathogenesis to therapy.

The lung microbiome plays an essential role in maintaining healthy lung function, including host immune homeostasis. Lung microbial dysbiosis or disruption of the gut-lung axis can contribute to lung carcinogenesis by causing DNA damage, inducing genomic instability, or altering the host's susceptibility to carcinogenic insults. Thus far, most studies have reported the association of microbial composition in lung cancer. Mechanistic studies describing host-microbe interactions in promoting lung carcinogenesis are limited. Considering cancer as a multifaceted disease where epigenetic dysregulation plays a critical role, epigenetic modifying potentials of microbial metabolites and toxins and their roles in lung tumorigenesis are not well studied. The current review explains microbial dysbiosis and epigenetic aberrations in lung cancer and potential therapeutic opportunities.

Oxidative-Stress-Induced Cellular Toxicity and Glycoxidation of Biomolecules by Cosmetic Products under Sunlight Exposure.

Cosmetics, commonly known as 'makeup' are products that can enhance the appearance of the human body. Cosmetic products include hair dyes, shampoos, skincare, sunscreens, kajal, and other makeup products. Cosmetics are generally applied throughout the face and over the neck region. Sunlight has different wavelengths of light, which include UV-A, UV-B, UV-C, and other radiations. Most cosmetic products have absorption maxima (λmax) in the range of visible light and UV-R. The effect of light-induced photosensitization of cosmetic products, which results in the production of free radicals through type-I and type-II photosensitization mechanisms. Free-radicals-mediated DNA damage and oxidative stress are common consequences of cosmetic phototoxicity. Cosmetic phototoxicity may include percutaneous absorption, skin irritation, eye irritation, photosensitization, mutagenicity, and genotoxicity. Oxidative stress induces membrane lipid peroxidation, glycoxidation, and protein covalent modifications, resulting in their dysfunction. Natural antioxidants inhibit oxidative-stress-induced cosmetic toxicity. Sunlight-induced photodegradation and accumulation of cosmetic photoproducts are also a matter of serious concern. India has tropical weather conditions throughout the year and generally, a majority of human activities such as commerce, agriculture, sports, etc. are performed under bright sunlight conditions. Thus, more focused and dedicated research is warranted to explore the effects of cosmetics on oxidative stress, glycoxidation of biomolecules, and photoproducts accumulation for its total human safety.

Role of miRNAs in cervical cancer: A comprehensive novel approach from pathogenesis to therapy.

Human papillomaviruses (HPV) infection is a major causative agent and strongly associated with the development of cervical cancer. Understanding the mechanisms of HPV-induced cervical cancer is extremely useful in therapeutic strategies for primary prevention (HPV vaccines) and secondary prevention (screening and diagnosis of precancerous lesions). However, due to the lack of proper implementation of screening programs in developing countries, cervical cancer is usually diagnosed at advanced stages that result in poor treatment responses. Nearly half of the patients will experience disease recurrence within two years post treatment. Therefore, it is vital to identify new tools for early diagnosis, prognosis, and treatment prediction. MicroRNAs (miRNAs) are small non-coding RNAs, implicated in posttranscriptional regulation of gene expression. Growing evidence has shown that abnormal miRNA expression is associated with cervical cancer progression, metastasis, and influences treatment outcomes. In this review, we provide comprehensive information about miRNA and their potential utility in cervical cancer diagnosis, prognosis, and clinical management to improve patient outcomes.

Impact of I/D polymorphism of angiotensin-converting enzyme 1 (ACE1) gene on the severity of COVID-19 patients.

Severe acute respiratory syndrome corona virus-2 (SARS-CoV-2) has first emerged from China in December 2019 and causes coronavirus induced disease 19 (COVID-19). Since then researchers worldwide have been struggling to detect the possible pathogenesis of this disease. COVID-19 showed a wide range of clinical behavior from asymptomatic to severe acute respiratory disease syndrome. However, the etiology of susceptibility to severe lung injury is not yet fully understood. Angiotensin-converting enzyme1 (ACE1) convert angiotensin I into Angiotensin II that was further metabolized by ACE 2 (ACE2). The binding ACE2 receptor to SARS-CoV-2 facilitate its enter into the host cell. The interaction and imbalance between ACE1 and ACE2 play a crucial role in the pathogenesis of lung injury. Thus, the aim of this study was to investigate the association of ACE1 I/D polymorphism with severity of Covid-19. The study included RT-PCR confirmed 269 cases of Covid-19. All cases were genotyped for ACE1 I/D polymorphism using polymerase chain reaction and followed by statistical analysis (SPSS, version 15.0). We found that ACE1 DD genotype, frequency of D allele, older age (≥46 years), unmarried status, and presence of diabetes and hypertension were significantly higher in severe COVID-19 patient. ACE1 ID genotype was significantly independently associated with high socio-economic COVID-19 patients (OR: 2.48, 95% CI: 1.331-4.609). These data suggest that the ACE1 genotype may impact the incidence and clinical outcome of COVID-19 and serve as a predictive marker for COVID-19 risk and severity.

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.

Circadian rhythm of serum cortisol in female patients with fibromyalgia syndrome.

Fibromyalgia syndrome (FMS) patients have disturbed sleep patterns which may lead to altered circadian rhythm in serum cortisol secretion. The aim of this study was to assess circadian changes, if any, in serum cortisol levels in female patients with FMS. Cortisol levels were estimated every 6 h during 24 h period; in 40 female patients satisfying ACR criteria for FMS (Age 36.4 ± 9.9), and 40 healthy females without FMS (Age 33.8 ± 11.1). A significant difference in the night time serum cortisol level was observed among the patients and control groups (patients, 12.9 ± 9.7 controls 5.8 ± 3.0; p < 0.01). However, no significant difference was found in serum cortisol levels in patients and control groups in the morning (patients, 28.4 ± 13.2 controls, 27.6 ± 14.5; p > 0.05), afternoon (patients, 14.4 ± 5.6 controls, 14.0 ± 6.6; p > 0.05) and evening hours (patients, 10.9 ± 5.8 controls, 8.9 ± 3.6; p > 0.05). It could be concluded that there is an abnormality in circadian secretion of cortisol in female FMS patients.

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.

Y Chromosome microdeletion and altered sperm quality in human males with high concentration of seminal hexachlorocyclohexane (HCH).

Recent studies have shown Y chromosome microdeletions associated with male infertility. The factors responsible for Y chromosome microdeletions in spermatozoa remain unresolved. However, the environmental pollutants are known to damage DNA in differentiating and maturing germ cells in the male reproductive tract. Therefore, the aim of this study was to investigate the effects of seminal hexachlorocyclohexane (HCH) and its isomers, an environmental pollutant, in 50 fertile and 50 infertile males in relation to semen quality and the incidence of Y chromosome microdeletion in azoospermic factor (AZF) region. As compared to control, an increased HCH level and significantly decreased semen quality were observed in the infertile males. A positive significant association was found between sperm count with alpha-HCH and beta-HCH in the infertile males. A negative significant association was observed between sperm counts with gamma-HCH in asthenospermia patients and with beta-HCH and total HCH in oligo-asthenospermic patients. Out of 100 males studied, we found 10 patients with Yq deletion in AZFa and AZFc regions. Subdivision of infertile group revealed a deletion incidence of 61.5% in azoospermic patients, 11.1% in oligospermic patients and 16.6% in oligo-asthenospermic patients. The presence of Yq deletion in azoospermic patients with a significant mean difference of beta-HCH and total HCH in relation to reduced semen quality seem to corroborate with the mutagenic activity of HCH. The results of this study indicated the susceptibility of male germ line to mutagenic potential of HCH which is an acknowledged risk factor leading to spermatogenic failure.