Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection provides a critical host-immunological challenge. Aim: We explore the effect of host-genetic variation in interferon-lambda-3 rs12979860, Tolloid Like–1 (TLL1) rs17047200 and Discoidin domain receptor 1(DDR1) rs4618569 on host response to respiratory viral infections and disease severity that may probe the mechanistic approach of allelic variation in virus-induced inflammatory responses. Methods: 141 COVID-19 positive patients and 100 healthy controls were tested for interferon-lambda-3 rs12979860, TLL1 rs17047200 and DDR1 rs4618569 polymorphism by TaqMan probe-based genotyping. Different genotypes were assessed regarding the COVID-19 severity and prognosis. Results: There were statistically significant differences between the studied cases and control group with regard to the presence of comorbidities, total leucocytic count, lymphocytic count, CRP, serum LDH, ferritin and D-dimer (p < 0.01). The CC genotype of rs12979860 cytokine, the AA genotype of TLL1 rs17047200 and the AA genotype of the rs4618569 variant of DDR1 showed a higher incidence of COVID-19 compared to the others. There were significant differences between the rs4618569 variant of DDR and the outcome of the disease, with the highest mortality in AG genotype 29 (60.4%) in comparison to 16 (33.3%) and 3 (6.2%) in the AA and GG genotypes, respectively (p = 0.007*), suggesting that the A allele is associated with a poor outcome in the disease. Conclusion: Among people who carry C and A alleles of SNPs IFN-λ rs12979860 and TLL1 rs17047200, respectively, the AG genotype of the DDR1 rs4618569 variant is correlated with a COVID-19 poor outcome. In those patients, the use of anti-IFN-λ 3, TLL1 and DDR1 therapy may be promising for personalized translational clinical practice.

Introduction: Type 2 diabetes mellitus (T2DM) is a major global health concern. It usually develops gradually and is frequently preceded by undetectable pre-diabetes mellitus (pre-DM) stage. The purpose of this study was to identify a novel set of seven candidate genes associated with the pathogenesis of insulin resistance (IR) and pre-DM, followed by their experimental validation in patients’ serum samples.Methods: We used the bioinformatics tools and through a two-step process, we first identified and verified two mRNA candidate genes linked to insulin resistance molecular pathogenesis. Second, we identified a non-coding RNAs related to the selected mRNAs and implicated in the insulin resistance molecular pathways followed by pilot study for the RNA panel differential expression in 66 patients with T2DM, 49 individuals with prediabetes and 45 matched controls using real time PCR.Results: The levels of expression of TMEM173 and CHUK mRNAs, hsa-miR (-611, -5192, and -1976) miRNAs gradually increased from the healthy control group to the prediabetic group, reaching their maximum levels in the T2DM group (p <10-3), whereas the levels of expression of RP4-605O3.4 and AC074117.2 lncRNAs declined gradually from the healthy control group to the prediabetic group, reaching their lowest levels in the T2DM group (p <10-3). TMEM173, CHUK mRNAs, hsa_miR (-611 & -1976) and RP4-605O3.4 lncRNA were useful in distinguishing insulin resistant from insulin sensitive groups. miR_611 together with RP4-605O3.4 exhibited significant difference in good versus poor glycemic control groups.Discussion: The presented study provides an insight about this RNA based STING/NOD/IR associated panel that could be used for PreDM-T2DM diagnosis and also as a therapeutic target based on the differences of its expression level in the pre-DM and T2DM stages.

Background: Type 2 diabetes mellitus is one of the leading causes of morbidity and mortality worldwide and is derived from an accumulation of genetic and epigenetic changes. In this study, we aimed to construct Insilco, a competing endogenous RNA (ceRNA) network linked to the pathogenesis of insulin resistance followed by its experimental validation in patients’, matched control and cell line samples, as well as to evaluate the efficacy of CRISPR/Cas9 as a potential therapeutic strategy to modulate the expression of this deregulated network. By applying bioinformatics tools through a two-step process, we identified and verified a ceRNA network panel of mRNAs, miRNAs and lncRNA related to insulin resistance, Then validated the expression in clinical samples (123 patients and 106 controls) and some of matched cell line samples using real time PCR. Next, two guide RNAs were designed to target the sequence flanking LncRNA/miRNAs interaction by CRISPER/Cas9 in cell culture. Gene editing tool efficacy was assessed by measuring the network downstream proteins GLUT4 and mTOR via immunofluorescence. Results: LncRNA-RP11-773H22.4, together with RET, IGF1R and mTOR mRNAs, showed significant upregulation in T2DM compared with matched controls, while miRNA (i.e., miR-3163 and miR-1) and mRNA (i.e., GLUT4 and AKT2) expression displayed marked downregulation in diabetic samples. CRISPR/Cas9 successfully knocked out LncRNA-RP11-773H22.4, as evidenced by the reversal of the gene expression of the identified network at RNA and protein levels to the normal expression pattern after gene editing. Conclusions: The present study provides the significance of this ceRNA based network and its related target genes panel both in the pathogenesis of insulin resistance and as a therapeutic target for gene editing in T2DM.

Background: Colorectal dysplasia represents an early stage of colorectal carcinogenesis and is closely associated with chronic inflammation and altered microRNA (miRNA) expression. Probiotic strains such as Weizmannia coagulans (formerly Bacillus coagulans) and Saccharomyces boulardii possess anti-inflammatory properties and may influence host miRNA expression, suggesting their potential as prophylactic agents against inflammation-associated colorectal dysplasia. Methods: Mice received prophylactic oral administration of Weizmannia coagulans or Saccharomyces boulardii beginning one week before azoxymethane/dextran sulfate sodium (AOM/DSS) induction and continuing throughout the experimental period. Histopathological examination, TNF-α immunohistochemistry, serum pro-inflammatory cytokine measurements, and miRNA expression profiling using reverse transcription quantitative polymerase chain reaction (RT-qPCR) were performed to evaluate the prophylactic effects of both probiotic strains. Results: Prophylactic administration of both probiotic strains significantly attenuated early dysplastic alterations and inflammatory cell infiltration compared with the AOM/DSS group ( p < 0.05). These histopathological improvements were accompanied by significantly lower serum levels of the pro-inflammatory cytokines IL-6 and IL-1β, together with reduced TNF-α immunoreactivity ( p < 0.05). In addition, probiotic pretreatment attenuated the altered miRNA expression profile induced by AOM/DSS. Compared with the model group, expression of miR-122-5p, miR-29b-5p, and miR-15b-5p was significantly reduced, whereas miR-98-5p, miR-202-5p, miR-21-5p, and let-7i-5p showed increased expression and were associated with miRNA expression patterns that more closely resembled those of the control group ( p < 0.01). Conclusion: Prophylactic administration of Weizmannia coagulans and Saccharomyces boulardii reduced inflammation-associated early dysplastic changes while preserving normal miRNA expression patterns in an AOM/DSS-induced murine model. These findings support the potential of probiotic prophylaxis as an early preventive strategy against colorectal dysplasia and provide a foundation for future studies investigating its clinical applicability.

Background: Lupus nephritis (LN) represents a major complication in systemic lupus erythematosus (SLE). The objective of this study was to evaluate the TRIM8 gene and its associated non-coding RNAs ( lnc-SSBP2-1:1 and hsa-miR-126-5p ) as potential non-invasive biomarkers for LN activity. Methods: Bioinformatics analyses were initially employed to identify candidate mRNA and associated non-coding RNAs (ncRNAs) implicated in LN. Expression profiles of TRIM8lnc-SSBP2-1:1 and hsa-miR-126-5p were validated in blood samples from 40 active LN, 30 inactive LN patients, and 20 healthy individuals via real-time PCR. Results: TRIM8 mRNA and lnc-SSBP2-1:1 lncRNA levels were notably upregulated in active LN ( p < 0.001), while hsa-miR-126-5p was reduced ( p < 0.001). SLEDAI-2K scores correlated positively with TRIM8 mRNA and lnc-SSBP2-1:1 , and negatively with hsa-miR-126-5p . Conclusions: This study highlights TRIM8 -associated ncRNA regulatory network as promising biomarkers in LN activωity, with potential clinical impact. Graphical