Modulatory effects of Moringa oleifera leaf extract on sodium nitrate-induced experimental colitis via regulation of P53, Ki-67 and PCNA biomarkers.

BACKGROUND: Ulcerative colitis is a risk factor for colorectal carcinoma. Different mechanisms are related to colitis like apoptosis and hyperproliferation. Moringa oleifera leaves extract (MO) provides a promising option to overcome the risk. PURPOSE: To examine the colonic changes in a rat model of colitis induced by sodium nitrate (SN) and study the effects of MO. STUDY DESIGN: Eight adult male rats were allocated in each of the three group; control (distilled water), SN (100 mg/kg/day, orally via gastric gavage), and SN + MO (100 mg/kg/day, orally via gastric gavage). METHODS: Body weight was measured after the end of the experiment. Colonic homogenates were tested for levels of oxidative stress indicators. Immunohistochemistry for P53, PCNA and Ki-67 was performed. Fresh colon specimens were used for quantitative real-time PCR for assessment of P53, PCNA and Ki-67 gene expression. RESULTS: SN group revealed a significant decreased weight (p = 0.002). MDA and NO levels were higher with SN administration than with MO co-administration (p= 0.04, 0.01 respectively). GSH level was reduced in SN group (p = 0.02) and significantly increased with MO intake (p = 0.04). SN-induced colonic destructive changes were reversed with MO. P53, PCNA and Ki-67 levels of gene expression were reduced in SN + MO group than SN group (P = 0.007, 0.02, 0.001 respectively). CONCLUSION: MO protected the colonic mucosa against SN-induced changes regulating apoptosis, and cell proliferation.

IFNL1 rs30461 polymorphism as a risk factor for COVID-19 severity: A cross-sectional study.

INTRODUCTION: The molecular basis of the progression of some COVID-19 patients to worse outcomes is not entirely known. Interferons-lambda-1/interleukin-29 (IFN-λ1/IL-29) is a member of the type III IFNs with a strong antiviral activity. Given the scant data on the potential role of IFN-λ1/IL-29 in COVID-19, we investigated the association of IFN-λ1/IL-29 serum level and the IFNL1 single-nucleotide polymorphism (SNP) (rs30461) with severe course of COVID-19. MATERIAL AND METHODS: This cross-sectional study included 400 COVID-19 patients, in which 262 mild COVID-19 patients and 138 severe COVID-19 patients were recruited and compared. The IFN-λ1/IL-29 serum levels were assessed in both the mild and severe COVID-19 groups. All participants were genotyped for the IFNL1 SNP (rs30461) by allelic discrimination RT-PCR using specific Taqman probes and primers. The associations between IFNL1 variants and risk of severe COVID-19 were examined via the logistic regression analysis. RESULTS: The serum IFN-λ1/IL-29 levels showed no statistically significant difference between mild and severe COVID-19 patients (P = 0.993). The genotype and allele frequencies of IFNL1 SNP (rs30461) were significantly different between the mild and severe groups, in which the minor G allele carried a highly significant risk of severe COVID-19 compared with the wild A allele [OR (95 %CI): 2.1 (1.5-2.9), P ≤ 0.001]. In multivariate analysis, the A/G and G/G genotypes of IFNL1 SNP (rs30461) were independent predictors of COVID-19 severity (P < 0.05). CONCLUSION: The study concluded that the IFNL1 SNP (rs30461) may constitute an independent risk factor for COVID-19 severity.

Prognostic impact of toll-like receptors gene polymorphism on outcome of COVID-19 pneumonia: A case-control study.

Toll-like receptor 3 (TLR3) and TLR7 genes are involved in the host immune response against viral infections including SARS-COV-2. This study aimed to investigate the association between the TLR3(rs3775290) and TLR7(rs179008) polymorphisms with the prognosis and susceptibility to COVID-19 pneumonia accompanying SARS-COV-2 infection. This case-control study included 236 individuals: 136 COVID-19 pneumonia patients and 100 age and sex-matched controls. Two polymorphisms (TLR3 rs3775290 and TLR7 rs179008) were genotyped by allelic discrimination through TaqMan real-time PCR. This study also investigated predictors of mortality in COVID-19 pneumonia through logistic regression. The mutant 'T/T' genotypes and the 'T' alleles of TLR3(rs3775290) and TLR7(rs179008) polymorphisms were significantly associated with increased risk of COVID-19 pneumonia. This study did not report association between the mutant 'T/T' genotypes of TLR3(rs3775290) and TLR7(rs179008) and the disease outcome. In multivariate analysis, the independent predictors of mortality in COVID-19 pneumonia were male sex, SPO2 ≤ 82%, INR > 1, LDH ≥ 1000 U/l, and lymphocyte count<900/mm3 (P < 0.05).

Relationship between DYNLT1 and Beclin1 expression and the fertilising potential of human spermatozoa.

This study aimed to evaluate dynein light chain type 1 (DYNLT1) mRNA expression in mature spermatozoa and to investigate its association with Beclin1 expression to help in understanding of pathogenesis of male infertility. It included 60 infertile men divided into idiopathic (n = 20), accessory gland inflammation (n = 20), and varicocele (n = 20) groups, and 20 healthy fertile men as a control group. Semen parameters were evaluated according to the 2010 World Health Organization criteria. Mature spermatozoa were isolated by Sil-select gradient. Relative quantification of DYNLT1 and Beclin1 mRNA expression in whole sperm pellet and mature spermatozoa was done using real-time PCR. Beclin1 protein was assessed in whole sperm pellet and mature spermatozoa by ELISA. Beclin1 mRNA and protein were significantly increased in spermatozoa from infertile patients of different aetiologies in comparison to healthy controls (p < .05). However, DYNLT1 mRNA expression was significantly decreased in infertile groups than controls (p < .05). Mature spermatozoa extracted from all studied subjects showed increased DYNLT1 mRNA and decreased Beclin1 mRNA and protein expression compared with the whole sample. It is concluded that decreased Beclin1 and increased DYNLT1 mRNA expression in mature spermatozoa may provide an insight into the biological processes that are activated or suppressed during sperm maturation.