Zinc finger 259 gene polymorphisms in Egyptian patients with metabolic syndrome and its association with dyslipidemia.

BACKGROUND: Zinc finger protein 1 (ZPR1), encoded by the ZNF259 gene, plays crucial roles in transcriptional regulation and cell cycle progression. Despite its known functions, its specific involvement in Metabolic Syndrome (MetS) remains debated. Genome-wide association studies have identified several genes, including ZNF259, implicated in lipid metabolism and associated with MetS. Single nucleotide polymorphisms (SNPs) in ZNF259 have been linked to altered lipid metabolism during the development of MetS. This study aims to investigate the association between MetS in Egyptian patients and three specific ZNF259 SNPs: rs964184, rs2075294, and rs2075290. The objective is to explore how these SNPs correlate with MetS development, other health outcomes, and their interaction with dyslipidemia biomarkers. METHODS: 200 Egyptian participants were enrolled, and divided into two groups: 100 patients diagnosed with dyslipidemia and 100 healthy controls. The study involved comprehensive assessments, including lipid profile analysis, anthropometric measurements, and genotyping of rs964184, rs2075290, and rs2075294 in the ZNF259 gene using Real-Time Polymerase Chain Reaction (PCR). RESULTS: The findings indicate that rs964184 SNP correlates significantly with elevated plasma triacylglycerol (TG) levels, while rs2075290 and rs2075294 are associated with higher total serum cholesterol (TC) and TG levels. Among these SNPs, rs2075294 showed the highest predictive value (area under the curve of 0.748), followed by rs2075290 (0.738), and rs964184 (0.583), suggesting rs2075294 as the most influential SNP in MetS prediction. CONCLUSION: This study underscores the predictive role of ZNF259 SNPs in MetS risk among Egyptians. Future research should further explore the implications of ZNF259 in MetS pathogenesis and its potential as a biomarker for personalized health interventions.

Epigenetic alterations in preeclampsia: a focus on microRNA149 and tetrahydrofolate reductase gene polymorphisms in Egyptian women.

BACKGROUND: Preeclampsia (PE) poses a substantial risk to prenatal and maternal health. Folic acid (FA) and methylenetetrahydrofolate reductase (MTHFR) play roles in DNA methylation and genomic integrity maintenance, with MTHFR polymorphisms potentially impacting PE occurrence. Human microRNA 149 (miR-149) remains underexplored in PE despite its involvement in folate metabolism. This study seeks to evaluate serum miR-149 levels with the MTHFR C677T polymorphism for diagnosing PE. METHODS: Seventy females aged 28-40 gestational weeks were divided into control and Preeclampsia groups. Serum miR-149 and MTHFR gene levels were evaluated using real-time PCR. RESULTS: Preeclamptic patients showed significantly lower serum miR-149 levels than healthy controls (P ≤ 0.01). PE cases showed a higher frequency of the TT genotype and T allele of the C677T polymorphism (OR = 0.181, 2.882, respectively), implicating them as genetic risk factors. The CT genotype also increased PE risk (OR = 0.26), while no significant difference was observed in the CC genotype. CONCLUSION: Merging miR-149 and MTHFR polymorphism assessment improves discrimination between healthy and PE groups, offering valuable insights into PE pathogenesis and potential diagnostic strategies.

Cross-Country Discrepancies in Monkeypox Vaccine Hesitancy Among Postgraduate and Undergraduate Medical Students.

BACKGROUND: Medical students hold significant importance, as they represent the future of healthcare provision. This study aimed to explore psychological antecedents towards the monkeypox (mpox) vaccines among postgraduate and undergraduate medical students across countries. METHODS: A cross-sectional survey was conducted among medical students aged 18 years old and above in 7 countries; Egypt, Romania, Malaysia, and Yemen, Iraq, India, and Nigeria. We used social media platforms between September 27 and November 4, 2022. An anonymous online survey using the 5C scale was conducted using snowball and convenience Sampling methods to assess the 5 psychological antecedents of vaccination (i.e., confidence, constraints, complacency, and calculation, as well as collective responsibility). RESULTS: A total of 2780 participants were recruited. Participants' median age was 22 years and 52.1% of them were males. The 5C psychological antecedents of vaccination were as follows: 55% were confident about vaccination, 10% were complacent, 12% experienced constraints, and 41% calculated the risk and benefit. Lastly, 32% were willing to be vaccinated for the prevention of infection transmission to others. The Country was a significant predictor of confidence, complacency, having constraints, and calculation domains (P < 0.001). Having any idea about the mpox vaccine was linked to 1.6 times higher odds of being more confident [OR = 1.58 (95% CI, 1.26-1.98), P < 0.001] Additionally, living in a rural area significantly increased complacency [OR = 1.42 (95% CI, 1.05-1.95), P = 0.024] as well as having anyone die from mpox [OR = 3.3 (95% CI, 1.64-6.68), P < 0.001]. Education level was associated with increased calculation [OR = 2.74 (95% CI, 1.62-4.64), P < 0.001]. Moreover, being single and having no chronic diseases significantly increased the calculation domain [OR = 1.40 (95% CI, 1.06-1.98), P = 0.02] and [OR = 1.54 (95% CI, 1.10-2.16), P = 0.012] respectively. Predictors of collective responsibility were age 31-45 years [OR = 2.89 (95% CI, 1.29-6.48), P = 0.01], being single [OR = 2.76 (95% CI, 1.94 -3.92), P < 0.001], being a graduate [OR = 1.59 (95% CI (1.32-1.92), P < 0.001], having no chronic disease [OR = 2.14 (95% CI, 1.56-2.93), P < 0.001], and not knowing anyone who died from mpox [OR = 2.54 (95% CI, 1.39-4.64), P < 0.001), as well as living in a middle-income country [OR = 0.623, (95% CI, 0.51-0.73), P < 0.001]. CONCLUSIONS: This study underscores the multifaceted nature of psychological antecedents of vaccination, emphasizing the impact of socio-demographic factors, geographic location, and awareness, as well as previous experiences on individual attitudes and collective responsibility towards vaccination.

Molecular functions of microRNAs in colorectal cancer: recent roles in proliferation, angiogenesis, apoptosis, and chemoresistance.

MiRNAs (microRNAs) constitute a group of diminutive molecules of non-coding RNA intricately involved in regulating gene expression. This regulation is primarily accomplished through the binding of miRNAs to complementary sequences situated in the 3'-UTR of the messenger RNA (mRNA) target; as a result, they are degraded or repressed. The multifaceted biogenesis of miRNAs is characterized by a meticulously orchestrated sequence of events encompassing transcription, processing, transportation, and decay. Colorectal cancer stands as a pervasive and formidable ailment, afflicting millions across the globe. Colorectal cancer is not well diagnosed early, and metastasis rates are high, which results in low survival rates in advanced stages. The genesis and progression of colorectal cancer are subject to the influence of genetic and epigenetic factors, among which miRNAs play a pivotal role. When it comes to colorectal cancer, miRNAs have a dual character, depending on the genes they target, functioning as either tumor suppressors or oncogenes and the prevailing cellular milieu. Their impact extends to modulating critical facets of colorectal cancer pathogenesis, including proliferation, angiogenesis, apoptosis, chemoresistance, and radiotherapy response. The discernible potential of miRNAs which are used as biomarkers to diagnose colorectal cancer, prognosis, and treatment response has come to the forefront. Notably, miRNAs are easily found and detected readily in a variety of biological fluids, including saliva, blood, urine, and feces. This prominence is attributed to the inherent advantages of miRNAs over conventional biomarkers, including heightened stability, specificity, sensitivity, and accessibility. Various investigations have pinpointed miRNA signatures or panels capable of differentiating colorectal cancer patients from their healthy counterparts, predicting colorectal cancer stage and survival, and monitoring colorectal cancer recurrence and therapy response. Although there has been research on miRNAs in various diseases, there has been less research on miRNAs in cancer. Moreover, updated results of preclinical and clinical studies on miRNA biomarkers and drugs are required. Nevertheless, the integration of miRNAs as biomarkers for colorectal cancer is not devoid of challenges and limitations. These encompass the heterogeneity prevalent among colorectal cancer subtypes and stages, the variability in miRNA expression across different tissues and individuals, the absence of standardized methodologies for miRNA detection and quantification, and the imperative for validation through extensive clinical trials. Consequently, further research is imperative to conclusively establish the clinical utility and reliability of miRNAs as colorectal cancer biomarkers. MiR-21 demonstrates carcinogenic characteristics by targeting several tumor suppressor genes, which encourages cell division, invasion, and metastasis. On the other hand, by controlling the Wnt/ß-catenin pathway, the tumor suppressor miRNA miR-34a prevents CRC cell proliferation, migration, and invasion. Furthermore, in colorectal cancer, the miR-200 family increases chemotherapy sensitivity while suppressing epithelial-mesenchymal transition (EMT). As an oncogene, the miR-17-92 cluster targets elements of the TGF-ß signaling pathway to encourage the growth of CRC cells. Finally, miR-143/145, which is downregulated in CRC, influences apoptosis and the progression of the cell cycle. These miRNAs affect pathways like Wnt, TGF-ß, PI3K-AKT, MAPK, and EMT, making them potential clinical biomarkers and therapeutic targets. This review summarizes recent research related to miRNAs, their role in tumor progression and metastasis, and their potential as biomarkers and therapeutic targets in colorectal cancer. In addition, we combined miRNAs' roles in tumorigenesis and development with the therapy of CRC patients, leading to novel perspectives on colorectal cancer diagnosis and treatment.

A promising RNA nanotechnology in clinical therapeutics: a future perspective narrative review.

Nanotechnology is the use of materials that have unique nanoscale properties. In recent years, nanotechnologies have shown promising results for human health, especially in cancer treatment. The self-assembly characteristic of RNA is a powerful bottom-up approach to the design and creation of nanostructures through interdisciplinary biological, chemical and physical techniques. The use of RNA nanotechnology in therapeutics is about to be realized. This review discusses different kinds of nano-based drug delivery systems and their characteristic features.

A branch of nanotechnology called RNA nanotechnology involves designing, studying, and utilizing synthetic structures based on RNA. This review discusses different kinds of nano-based drug delivery systems and their characteristic features. It aims to provide an overview of nanoparticles as a delivery system for gene therapy to treat diseases such as cancer. In order to enhance nanoparticle efficacy, these systems should be designed with this in mind in order to develop and test delivery systems rationally and scientifically.

Study the association of microRNA polymorphisms (miR-146a, miR-4513) with the risk of coronary heart diseases in Egyptian population.

Coronary heart disease (CHD) is the most prevalent cause of cardiovascular mortality in the world. It is well established that microRNAs (miRNAs) and their variants have an essential role in regulating the development of cardiovascular physiology, thus impacting the pathophysiology of heart diseases. This study was designed to determine the possible association of miRNA polymorphisms (miRNA-146a rs2910164C/G and miR-4513 rs2168518G/A) with susceptibility to CHD in Egyptian patients and their correlation with different biochemical parameters. The study comprised 300 participants, including 200 unrelated patients with CHD and 100 healthy controls. Anthropometric and blood biochemical parameters were measured as well genetic analysis for rs2910164C/G and rs2168518G/A polymorphisms were performed for all subjects using TaqMan real-time PCR assay. Our results revealed that the biomedical parameters have a significant correlation between CHD patients and healthy controls with a p < 0.05. Analyses of genotype distribution for (rs2910164 and rs2168518) revealed a significant association with CHD [odd ratio = 4.54, confidence interval (CI 95%) = (2.41-8.53)] and [odd ratio = 0.88, (CI 95%) = (0.83-0.92)], respectively. Furthermore, a statistically significant difference was detected between lipid profile levels and both rs2910164 and rs2168518 polymorphisms. The present study's findings indicated that the selected polymorphisms, miR-146a rs2910164 and miR-4513 rs2168518 could represent a useful biomarker for susceptibility to CHD in the Egyptian population. These genetic characteristics and personal habits and environmental factors may contribute to the development of CHD.

SUMO pathway, blood coagulation and oxidative stress in SARS-CoV-2 infection.

Severe Acute Respiratory Syndrome Corona Virus 2 (SARS CoV-2) is currently an international pandemic causing coronavirus disease 19 (COVID-19). Viral entry requires ACE2 and transmembrane protease serine 2 (TMPRSS2) for membrane fusion or through endosomal pathway. This Study aims to assess transcriptomic changes and differentially expressed genes (DFGs) in COVID-19. METHODS: Transcriptomic data of the publicly available dataset (GSE147507) was quantile normalized and analysed for DFGs, network analysis and pathway analysis. RESULTS: DFG sets showed that 8 genes (SAE1, AEBP2, ATP1A1, DKK3, MAFF, NUDC, TRAP1, and VAV1) were significantly dysregulated in all studied groups. Functional analysis revealed that negative regulation of glucocorticoid biosynthesis, protein SUMOylation (SAE1), blood coagulation (VAV1) and cellular response to stress were affected by SARS CoV-2 infection. Cell line transduction with ACE2 vector didn't show significant changes in the dysregulated pathways. Also, no significant change was observed in expression levels of ACE2 or TMPRSS2 in response to SARS CoV-2 infection. Further analysis showed dysregulation of several genes in the SUMOylation pathway and blood coagulation process in human and cell lines transcriptome. Also, several Cathepsins proteases were significantly dysregulated in case of SARS CoV-2 infection. Genes related to cellular response to stress such as TRAP-1 and NOX were dysregulated in cases of SARS CoV-2 infection. CONCLUSION: Dysregulation in genes of protein SUMOylation, blood coagulation and response to oxidative stress pathways in SARS CoV-2 infection could be critical for disease progression. Drugs acting on SUMO pathway, VAV1, NOX genes could be studied for potential benefit to COVID-19 patients.

MMP-2 and MMP-9 as prognostic markers for the early detection of urinary bladder cancer.

The present study assessed protein and gene expression levels of tissue inhibitor of metalloproteinase-2 (TIMP-2), matrix metalloproteinase-2 (MMP-2), and MMP-9 in urine and blood samples of 50 patients with bladder carcinoma. The expression of TIMP-2, MMP-2, and MMP-9 levels with tumor stage and grade was also assessed. Results showed that the expression levels of MMP-2 and MMP-9 in both blood and urine were significantly elevated in group 1 when compared with groups 2 and 3 healthy subjects. The discriminatory ability in the diagnosis of bladder carcinoma of MMP-2 and MMP-9 expression was confirmed by receiver operating characteristic curve analysis that revealed a sensitivity and specificity of 100%. MMP-2 and MMP-9 levels were not correlated with grade or stage of the tumor. With respect to TIMP-2 blood and urine levels, results showed a significant decrease in gene expression levels in bladder carcinoma group, whereas, TIMP-2 protein showed a significant increase in bladder carcinoma.