Biochemical study of ZNF76 rs10947540 and SCUBE3 rs1888822 single nucleotide polymorphisms in the Egyptian patients with systemic lupus Erythematosus.

Systemic lupus erythematosus (SLE) is a common autoimmune disease marked by the formation of apoptotic debris and the presence of autoantibodies that target nuclear components. At this moment, the actual cause of SLE is uncertain. Genetic variables have been well proven to have a significant role in the propensity of SLE. This study aimed to investigate the effect of (ZNF76) rs (10947540) and (SCUBE) rs (1888822) gene polymorphism in patients with systemic lupus erythematosus. A case control study has been carried out at Medical Biochemistry & Molecular biology and Rheumatology unit of Internal Medicine Departments, Faculty of Medicine, Menoufia University, Egypt, for 1-year duration between 1 June 2022 and 1 June 2023. Sixty patients were females (75%) and twenty patients were males (25%). Their ages ranged from 19 to 53 years. Their disease durations ranged from 7 months to 20 years. The findings indicated that the TC genotype of the ZNF76 rs10947540 gene increases the risk of SLE by 2.274-fold, while the dominant TC + CC increases the risk by 2.472-fold, and the C allele increases the risk by 2.115-fold. Additionally, the results showed that the TT genotype of the SCUBE3 rs1888822 gene increases the risk of SLE by 3.702-fold, the dominant GT + TT increases the risk by 2.304-fold, and the T allele increases the risk by 2.089-fold, while the GT genotype increases the risk by 1.918-fold. The study revealed significant associations between the genotypes of these polymorphisms and certain clinical parameters in SLE patients. These findings highlight the potential genetic contributions to SLE susceptibility and its clinical manifestations, providing valuable insights for future research and potential personalized approaches to the management of this complex autoimmune disease.

Study of serum level of kisspeptin and interferon-beta in genital wart patients.

Background: Researchers are interested in genital wart (GW) studies due to their increased incidence. In a single experimental research, virally infected mouse models showed elevated kisspeptin levels and low interferon levels. Objective: The objective of the study was to evaluate the serum levels of kisspeptin and interferon (INF)-beta in GW patients. Patients and Methods: Forty patients with GWs and forty healthy participants of comparable age and sex as a control group were included in this case-control study. Serum levels of kisspeptin and IFN-beta were measured using ELISA during the period from December 2021 to April 2022. Results: Kisspeptin was significantly higher among cases than controls, whereas IFN-beta level was lower among cases than controls (P < 0.001). There were no significant relations between kisspeptin and IFN-beta levels and the clinical data for the studied participants, and there was no significant correlation between both (P > 0.05). Conclusion: The reported increased kisspeptin level which was associated with decreased interferon-beta level in patients with GWs might indicate a new insight into viral infection pathogenesis. Further research including all steps in kisspeptin/G protein-coupled receptor 54 pathway is required. Targeted therapy for this pathway may be of value for those patients.

Study the relationship between long non-coding RNA (CCAT1) expression and CDK4 expression levels in Egyptian patients with preeclampsia.

Background: Maternal and perinatal mortality is caused by a variety of factors, including preeclampsia. PE's onset and progression may be influenced by lncRNAs. The effect of long non-coding RNA (lncRNA) Colon cancer-associated transcription factor 1 (CCAT1) expression in the placenta of preeclampsia patients on preeclampsia progression was the focus of this investigation. Objectives: The aim of the current study is to check if the levels of expression of Colon cancer-associated transcription factor 1 (CCAT1) and Cyclin-dependent protein kinase 4 (CDK4) are associated with preeclampsia vulnerability and biogenesis. Subjects: and methods: This work included the participation of 160 people. Eighty of the patients had preeclampsia. The control group included 80 normal pregnant women. The two groups were almost of the same age. A thorough clinical examination was performed in all groups (including taking a detailed history, concentrating on parity, age and previous background of diabetes or hypertension). The expression levels of CCAT1 and CDK4 in placental tissue were determined using a real-time q PCR technique. Results: Expression levels of CCAT1 and CDK4 differed significantly between the study groups. preeclamptic patients having the highest level of CCAT1in comparison with control group, However, preeclamptic patients having lower level of CDK4 than controls. There was a strong negative association between CDK4 expression level and DBP, SBP, creatinine, urea and CCAT1 level of expression in the preeclamptic group, whereas there was a positive correlation between CCAT1 level of expression and DBP, SBP, urea and creatinine in patients group. Conclusion: Based on the findings of this study, it is possible that CCAT1 and CDK4 expression levels could be used to aid in the diagnosis and biogenesis of preeclampsia.

Mir-142-5p as an indicator of autoimmune processes in childhood idiopathic nephrotic syndrome and as a part of MicroRNAs expression panels for its diagnosis and prediction of response to steroid treatment.

BACKGROUND: Nephrotic syndrome (NS) is the most frequent glomerular disease among children. Renal biopsy is the most precise procedure for diagnosing and following childhood NS; however, it is an invasive procedure with potential complications. As a result, early non-invasive diagnostic and prognostic indicators and new treatment targets are urgently needed for this disease. PURPOSE: To assess the miR-142-5p expression in peripheral blood as an indicator of the autoimmune processes in children with NS and the role of differential microRNAs (miR) expression and expression panels in diagnosing and predicting the response to steroid treatment in children with NS. METHODS: Eighty (80) children with NS and 100 subjects matched for age and gender used as controls constitute the study sample in this case-control study. MiR-142-5p, miR-191, miR-181-5p, miR-30a-5p and miR-50a-5p expression are measured in all enrolled children by real-time PCR. We assessed the sensitivity and accuracy of different MicroRNAs panels. RESULTS: miR-142-5p, miR-191, miR-181-5p, miR-30a-5p and miR-150a-5p expressions were significantly increased in the children with NS than controls. There was a significant difference in the five mRNAs differential expressions between steroid-resistant and steroid-sensitive children with NS. Of the selected five microRNAs, miR-142a-5p was the best to allow very good discrimination of the children with NS and predict steroid resistance (AUC = 0.965 and 1.00, respectively), suggesting the possible autoimmunity processes' role in the pathogenesis of NS and the resistance to steroids. The (miR-142a-5p with miR-181a-5p and miR-30a-5p) was the best expression panel to diagnose new NS cases and predict steroid resistance. CONCLUSIONS: microRNAs expressions, either differential or as a panel, are important for early diagnosing childhood NS and may provide a non-invasive clue for the response to steroid treatment in these patients. The (miR-142a-5p, miR-181-5p, and miR-30a-5p) panel was the best one to cover both the diagnosis of the new cases and prediction of response to steroid treatment. Autoimmunity has an important role in NS pathogenesis and resistance to steroid treatment.

mRNA Expression of the CUB and Sushi Multiple Domains 1 (CSMD1) and Its Serum Protein Level as Predictors for Psychosis in the Familial High-Risk Children and Young Adults.

Background: Schizophrenia (SCZ) is still a challenging, refractory, and severe disorder. It is not a fully understood disease with genetic and epigenetic susceptibility and about 80% substantial heritability. The CUB and Sushi multiple domains 1 (CSMD1) gene is implicated in neurogenesis, memory, immunity, neuropsychology, and monoamine metabolism. Thus, it is one of the powerful genes involved in the pathogenesis of SCZ. Purpose: To evaluate the possible role of the CSMD1 gene's mRNA expression and its serum protein as markers for the early diagnosis of the first-episode SCZ in familial high-risk (FHR) Egyptian children and young adults. Subjects and methods: This case-control study included 80 first-episode drug-naïve SCZ patients from FHR Egyptian children and young adults and 80 healthy participants, as controls, from the FHR-susceptible children and young adults but did not develop SCZ. In this study, the CSMD1 gene's mRNA expression and CSMD1 serum levels were measured in the peripheral blood, and these levels were correlated with the lipid profile of the study populations. Results: The CSMD1 gene's mRNA expression and its' protein levels were significantly decreased in the SCZ patients compared to controls. The receiver operating characteristic (ROC) curve analysis succeeded in distinguishing SCZ patients from those not having SCZ using cutoff points of ≤0.711 and ≤4.83 ng/mL for the CSMD1 gene's mRNA expression and serum protein level, respectively. At these levels, the diagnostic sensitivities were 93.75 and 91.25%; specificity was 92.5%; positive predictive value (PPV) were 92.6 and 92.4%; and negative predictive values (NPVs) were 93.7 and 91.4%, respectively. Also, the ROC curve analysis succeeded in discriminating those with suicidal tendencies. Conclusion: CSMD1 gene's mRNA expression might be a reliable and early diagnostic predictor of first-episode SCZ in the FHR Egyptian children and young adults.

Expression of toll-like receptor 4 and its connection with type 2 diabetes mellitus.

Toll-like receptor 4 (TLR4) plays an important role in modulating innate immunity. Type 2 diabetes mellitus (T2DM) is a chronic disease that is characterized by impaired insulin resistance and abnormal immune response. Genetic background and consequently genetic factors might have a key role in both onset and progression of T2DM-related complications.  The aim of this work was to study the role of toll-like receptor 4 (TLR4) in the development of type 2 diabetes mellitus (T2DM). This study was carried out on 90 subjects, 30 type 2 diabetic patients, 30 patients with impaired glucose tolerance and 30 age and gender matched healthy controls. mRNA expression of (TLR4) was assessed by reverse transcriptase PCR (RT-PCR) using real time PCR.. Results showed significant statistical difference between the three studied groups  regarding BMI, serum FBG, HDL, TGs, TC, LDL, HOMA -IR and mRNA expression of TLR4 with highest level of TLR4 mRNA expression in T2DM patients. From this study, it might be concluded that high expression of (TLR4) is associated with T2DM.

Obesity and its Association with Irisin Level Among Individuals with FNDC5/Irisin Gene Variants RS16835198 and RS726344.

BACKGROUND: Irisin; a novel myokine/adipokine; encoded by FNDC5 gene have been suggested to play an important role in energy metabolism and obesity. However, the genetic variations at this locus and their effects on different metabolic parameters is still poorly understood. AIM: This study aimed to investigate the role of FNDC5/irisin gene polymorphisms (RS16835198 and RS726344) in obese individuals and their genotype phenotype correlation with circulating serum irisin level and other biochemical parameters like glucose, lipid metabolism and liver enzymes. METHODS: The study included 200 subjects divided into two groups: obese group (110 subject) and control non obese group (90 subject). All selected individuals were subjected to a comprehensive questionnaire, clinical assessment and laboratory investigations including fasting blood glucose (FBS), serum insulin, lipid profile (Total Cholesterol (TC), Triglycerides (TG), Low Density Lipoprotein (LDLc), High Density Lipoprotein (HDLc), liver enzymes (ALT, AST, GGT), Serum irisin level and HOMA-IR was calculated. DNA extraction and FNDC5 allelic discrimination analysis for FNDC5 SNPs, rs16835198and rs726344 using the TaqMan SNP genotyping assays by Real time PCR. RESULTS: In obese group; serum irisin was significantly lower (0.55 ± 0.2) than control group (1.7 ± 0.3) P value < 0.001. Regarding genotype and allele frequency, T allele of rs16835198 polymorphism is associated with high BMI, high total cholesterol, TG and LDL-C, low level of serum HDL-C, high FBS, low serum insulin, low HOMA-IR and low serum level of irisin. While G allele of rs726344 is significantly associated with high BMI, FBS, low serum insulin and HOMA-IR, High total cholesterol, TG, LDL-C, low level of HDL-C and low serum irisin. CONCLUSION: Our data suggest that FNDC5 SNPs, rs16835198and rs726344 are associated with obesity in Egyptian population. GG genotype and G allele of rs726344 variant and TT genotype and T allele of rs16835198 variant may increase the susceptibility to obesity and there were a genotype phenotype correlation with circulating serum irisin and several metabolic parameters.