Evaluation of miRNA-146a, miRNA-34a, and pro-inflammatory cytokines as a potential early indicators for type 1 diabetes mellitus.

Background: Type I diabetes mellitus (T1DM) is one of the most common chronic autoimmune diseases worldwide. miRNAs are a class of small non-coding RNA molecules that have been linked to immune system functions, ß-cell metabolism, proliferation, and death, all of which contribute to pathogenesis of TIDM. Dysregulated miRNAs have been identified in Egyptian TIDM patients. Aim: Several miRNAs were profiled in Egyptian TIDM patients to determine whether they can be used as molecular biomarkers for T1DM. The relationship between the investigated miRNAs and pro-inflammatory cytokines (TNF-α and IL-6) has also been evaluated in the development of TIDM, in addition to the creation of a proposed model for TIDM prediction. Patients & methods: Case-control study included 177 Egyptian patients with confirmed type I diabetes mellitus and 177 healthy individuals. MiRNA-34 and miRNA-146 were detected in serum samples using real-time PCR, whereas TNF-α and IL-6 levels were assessed using ELIZA. Results: Patients with TIDM showed a significant decrease in the expression of miRNA-146, with a cut-off value ≤ 3.3, 48 % specificity, and 92.1 % sensitivity, whereas miRNA-34 had the highest sensitivity (95.5 %) and specificity (97.2 %) for differentiating diabetic patients from controls. Furthermore, other diagnostic proinflammatory markers showed lower sensitivity and specificity. Conclusion: Serum levels of miRNA-34a, miRNA-146, IL-6, and TNF-α provide new insights into T1DM pathogenesis and could be used for screening and diagnosis purposes. They can be also a potential therapeutic target, as well as allowing for more strategies to improve T1DM disease outcomes.

Case-control study: Unveiling human polyomaviruses and papillomavirus in Egyptian colorectal cancer patients.

BACKGROUND: Colorectal cancer (CRC) is a cancer type that is thought to be influenced by human papillomaviruses (HPVs) and human polyomaviruses (HPyVs). In Egypt, CRC ranks as the 7th most common cancer, accounting for 3.47% of male cancers and 3% of female cancers. However, there is currently a lack of information regarding the presence of PyVs and HPVs co-infection specifically in CRC cases in Egypt. Therefore, the aim of this study was to investigate the occurrence of HPVs and HPyVs (JCPyV, BKPyV, and SV40) infections, as well as co-infections, among CRC patients in Egypt. Additionally, the study aimed to assess any potential association between these viral infections and tumor stages. METHODS: In the present study, we analyzed a total of 51 tissue samples obtained from Egyptian CRC patients, along with 19 polyps' samples. Our investigation focused on the detection and genotyping of HPyVs using Real-Time PCR. Additionally, we employed real-time PCR for the detection of HPVs, and for their genotyping, we utilized a combination of PCR amplification followed by sequencing. RESULTS: In our study, we found evidence of HPyVs infection in the CRC patients, specifically SV40 (25.5%) and BKPyV (19.6%). However, JCPyV was not detected in the samples that were examined. Additionally, we discovered that HPV was present in 43.1% of the CRC patients. When considering viral co-infections, 19.6% of the CRC samples showed coexistence of multiple viruses, while no co-infections were found in the polyps samples. Importantly, we observed a significant correlation between the presence of HPVs and advanced colorectal tumor grades B2 and D. CONCLUSION: Our findings provide valuable data for the detection of oncogenic viruses in colorectal cancer (CRC) and underscore the association of viral co-infections with advanced tumor stages. However, further research with larger cohorts is necessary to validate these findings and strengthen their significance in the field of CRC.

Molecular Epidemiology of Omicron CH.1.1 Lineage: Genomic and Phenotypic Data Perspective.

BACKGROUND: The Omicron variant (B.1.1.529 lineage) of SARS-CoV-2 represents a substantial global health challenge due to its high transmissibility and potential resistance to immunity from vaccines or previous infections. Among the rapidly evolving Omicron lineages, the BA.2.75 and the emerging CH.1.1 have garnered attention. While BA.2.75 is marked by mutations that may enhance immune evasion, CH.1.1 is distinguished by the S: L452R mutation, linked to increased pathogenicity and transmission. Initially identified in India by the end of 2021, these variants have exhibited global dissemination, signaling an urgent need to track and analyze their progression. METHODS: In this study, the genomic and geographical distribution data of CH.1.1 were collected from the Global Initiative on Sharing Avian Influenza Data (GISAID), PANGOLIN, CoV-Spectrum, and NextStrain databases. Due to the unavailability of epidemiological and genomic data of the CH.1.1 lineage, PubMed and ScienceDirect were used as sources of the phenotypic data of the lineage variations. Amino acid variations utilized in the data mining included S: R346T, S: K444T, S: L452R, and S: F486S. RESULTS: The current epidemiological data indicate that CH.1.1 is more likely to become one of the dominant spreading lineages in the United Kingdom, New Zealand, Australia, and the United States based on a 32% growth advantage, present CH.1.1 lineage cases number, and the amino acid variation's impact. CONCLUSION: A significant increase in the newly detected lineage CH.1.1 is highly anticipated. The rise in the detected sequences number from 13,231 on January 21, 2023, to 23,181 on February 6, 2023, supports the prediction and growth advantage of the lineage detected cases. Increases in viral transmissibility caused by higher affinity to ACE2 receptors and immune evasion are deduced from amino acid variations analyzed in the study.

Exploring the promising potential of noscapine for cancer and neurodegenerative disease therapy through inhibition of integrin-linked kinase-1.

Integrin-linked kinase (ILK), a ß1-integrin cytoplasmic domain interacting protein, supports multi-protein complex formation. ILK-1 is involved in neurodegenerative diseases by promoting neuro-inflammation. On the other hand, its overexpression induces epithelial-mesenchymal transition (EMT), which is a major hallmark of cancer and activates various factors associated with a tumorigenic phenotype. Thus, ILK-1 is considered as an attractive therapeutic target. We investigated the binding affinity and ILK-1 inhibitory potential of noscapine (NP) using spectroscopic and docking approaches followed by enzyme inhibition activity. A strong binding affinity of NP was measured for the ILK-1 with estimated Ksv (M-1) values of 1.9 × 105, 3.6 × 105, and 4.0 × 105 and ∆G0 values (kcal/mol) -6.19554, -7.8557 and -8.51976 at 298 K, 303 K, and 305 K, respectively. NP binds to ILK-1 with a docking score of -6.6 kcal/mol and forms strong interactions with active-site pocket residues (Lys220, Arg323, and Asp339). The binding constant for the interaction of NP to ILK-1 was 1.04 × 105 M-1, suggesting strong affinity and excellent ILK-1 inhibitory potential (IC50 of ∼5.23µM). Conformational dynamics of ILK-1 were also studied in the presence of NP. We propose that NP presumably inhibits ILK-1-mediated phosphorylation of various downstream signalling pathways that are involved in cancer cell survival and neuroinflammation.