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 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.

Association of GSTM1 and GSTT1 gene polymorphisms with COVID-19 susceptibility and its outcome.

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has become a global health issue and develops into a broad range of illnesses from asymptomatic to fatal respiratory diseases. SARS-CoV-2 infection is associated with oxidative stress that triggers cytokine production, inflammation, and other pathophysiological processes. Glutathione-S-transferase (GST) is an important enzyme that catalyzes the conjugation of glutathione (GSH) with electrophiles to protect the cell from oxidative damage and participates in the antioxidant defense mechanism in the lungs. Thus, in this study, we investigated the role of GSTM1 and GSTT1 gene polymorphism with COVID-19 susceptibility, as well as its outcome. The study included 269 RT-PCR confirmed COVID-19 patients with mild (n = 149) and severe (n = 120) conditions. All subjects were genotyped for GSTM1 and GSTT1 by multiplex polymerase chain reaction (mPCR) followed by statistical analysis. The frequency of GSTM1-/- , GSTT1-/- and GSTM1-/- /GSTT1-/- was higher in severe COVID-19 patients as compared to mild patients but we did not observe a significant association. In the Cox hazard model, death was significantly 2.28-fold higher in patients with the GSTT1-/- genotype (p = 0.047). In combination, patients having GSTM1+/+ and GSTT1-/- genotypes showed a poor survival rate (p = 0.02). Our results suggested that COVID-19 patients with the GSTT1-/- genotype showed higher mortality.

Antiproliferative Activity of Cissus quadrangularis L. Extract Against Human Cervical Cancer Cells: In Vitro and In Silico Analysis.

BACKGROUND: Cervical cancer is the second leading cause of cancer in women, which necessitates safe and potential therapeutic agents. OBJECTIVE: This study was designed to investigate the antiproliferative effect of ethanolic extract of Cissus quadrangularis L. (CQ) against human cervical adenocarcinoma HeLa cell line and in silico analysis of selected active agents against apoptosis executioner enzyme caspase-3. METHODS: Cell viability was analyzed in HeLa cells at different concentrations (25-300 µg/ml) of CQ extract. Reactive oxygen species (ROS) generation, cellular apoptosis, cell cycle analysis and caspases-3 activation were evaluated. In silico, structure-based virtual screening analysis was carried out using AutoDock Vina and iGEMDOCK. RESULTS: Cell viability of HeLa cells was reduced significantly (p < 0.05) in a dose-dependent manner, however, CQ extract showed non-toxic to normal kidney epithelial NRK-52E cells. CQ extract induced the intracellular ROS level, nuclear condensation and reduced the mitochondrial membrane potential (MMP) with the induction of annexin V-FITC positive cells. CQ extract arrested cells in G0/G1 and G2/M checkpoints and activated caspase-3 activity significantly in HeLa cells. The molecular docking study showed a strong binding affinity of CQ phytocomponents against the caspase-3 (PDB ID: 1GFW) protein of human apoptosis. PASS analyses of selected active components using Lipinski's Rule of five showed promising results. Further, drug-likeness and toxicity assessment using OSIRIS Data Warrior V5.2.1 software exhibited the feasibility of phytocomponents as drug candidates with no predicted toxicity. CONCLUSION: This study suggested that active constituents in CQ extract can be considered as potential chemotherapeutic candidates in the management of cervical cancer.

Plateau Iris and Severity of Primary Angle Closure Glaucoma.

PURPOSE: To compare the distribution of plateau iris in eyes across varying severity of primary angle closure glaucoma (PACG) using standardized ultrasound biomicroscopy (UBM) criteria. DESIGN: Cross-sectional study. METHODS: UBM was performed on 210 patients with PACG who had previously undergone laser peripheral iridotomy. Plateau iris was defined as the presence of all the following UBM criteria in ≥2 quadrants of the angle: anteriorly directed ciliary body, absent ciliary sulcus, iris angulation, flat iris plane, and iridotrabecular contact. Disease severity was based on the visual field mean deviation (MD) and classified as early-to-moderate (MD ≥ -12 dB), advanced (-12.01 dB to -20 dB), and severe (MD < -20 dB). RESULTS: Of 210 subjects recruited, 23 were excluded because of poor quality UBM images. The remaining 187 patients were categorized as having early-to-moderate (n = 103), advanced (n = 38), and severe PACG (n = 46). Of these subjects, 48.1% were male, and 90.9% were of Chinese ethnicity. The overall proportion of plateau iris was 36.9%, with 32.0% (33/103) in early-to-moderate, 34.2% (13/38) in advanced, and 50% (23/46) in severe PACG (P = .03, comparing severe PACG with early-to-moderate groups). Among the severe PACG group, those with plateau iris configuration had significantly smaller anterior chamber area (P = .03) and volume (P = .01) compared with those without plateau iris. CONCLUSION: The higher proportion of plateau iris configuration in eyes with severe PACG compared with early-to-moderate PACG suggest that this may be a contributory factor for disease severity.

Characteristics of the Corneal Endothelium Across the Primary Angle Closure Disease Spectrum.

Purpose: To evaluate the corneal endothelial characteristics across the primary angle closure (PAC) disease spectrum amongst patients diagnosed as PAC suspects (PACS), PAC, PAC glaucoma (PACG), and previous acute PAC (APAC). Methods: We analyzed a total of 529 subjects (51 PACS, 170 PAC, 234 PACG, and 74 with previous APAC). All subjects had undergone laser peripheral iridotomy prior to study recruitment. Corneal endothelial parameters were measured using a noncontact specular microscope and the following parameters were obtained: mean central endothelial cell density (ECD; cells/mm2), coefficient of variation (CV) in cell area, and percentage of hexagonal cells. Results: The mean age of the subjects was 65.1 ± 8.2 years, and 55.2% were females. The mean central ECD was 2582.0 ± 472.8 cells/mm2 in PACS, 2566.0 ± 408.3 cells/mm2 in PAC, 2523.8 ± 406.8 cells/mm2 in PACG, and 2504.0 ± 558.1 cells/mm2 in APAC, with no significant differences in ECD across the subgroups (P = 0.61). The CV was lowest in PACS (34.38 ± 6.05 µm2/cell), and highest in APAC (37.61 ± 7.98 µm2/cell), but the differences were not significant (P = 0.07). Likewise, the percentage of hexagonality was not significantly different between the groups. A subgroup analysis on the eyes with previous APAC with their fellow eye also showed no significant differences in the corneal endothelial characteristics. Conclusions: The corneal ECD and morphological characteristics such as CV and hexagonality are not significantly different across the PAC disease spectrum. This may reflect the lack of a sustained and/or dramatic IOP insult and/or an insignificant deleterious effect from medications, age, and chronicity on corneal endothelial parameters.

Ultrasound Biomicroscopic Diagnosis of Angle-closure Mechanisms in Vietnamese Subjects With Unilateral Angle-closure Glaucoma.

OBJECTIVE: To identify the mechanisms of angle closure in the fellow eyes of Vietnamese subjects with unilateral primary angle-closure glaucoma (PACG) using ultrasound biomicroscopy (UBM) before and after prophylactic laser peripheral iridotomy (LPI). DESIGN: This is a prospective observational study. PARTICIPANTS: Patients diagnosed with PACG in one eye and primary angle-closure suspect (PACS) in the other eye were included in this study, conducted from January 2014 to October 2014 at Vietnam National Institute of Ophthalmology. MATERIALS AND METHODS: A total of 112 PACS fellow eyes of 112 patients presenting with unilateral PACG were evaluated. All subjects underwent standard ophthalmic clinical examination and UBM imaging a week before and after LPI. On the basis of UBM images, the angle-closure mechanism was defined according to the classification of Svend Vedel Kessing and John Thygesen as pupillary block (PB), plateau iris (PI), and mixed pattern. RESULTS: The proportion of PACS subjects who showed PB was 86.6%, while 13.4% showed a PI configuration before LPI. After LPI the pre-LPI PB group was reclassified, with 55.4% showing pure PB, and 31.3% showing mixed mechanisms (PB and PI). The proportion of patients with PI remained unchanged (13.4%) even after LPI. After the LPI, the angle opening significantly increased in the PB subgroup (14.01±2.43 degrees, P<0.01) and reclassified mixed group (6.34±1.71 degrees, P<0.01) but remained almost unchanged in the PI group (1.81±0.98 degrees, P>0.05). CONCLUSION: On the basis of the UBM criteria, PI was found in 13.4% of PACS fellow eyes of Vietnamese subjects with PACG. The clinical and UBM features of patients showing PI before LPI remained almost unchanged after the procedure. The proportion of patients showing PB pre-LPI reduced from 86.6% to 55.4% showing the important role of mixed mechanisms in PACG.