Clinical Investigation of Leukocyte DNA Damage in COVID-19 Patients.

This prospective cross-sectional study aimed to evaluate leukocyte DNA damage in coronavirus disease (COVID-19) patients. In this study, 50 COVID-19-positive patients attending the Erzurum City Hospital Internal Medicine Outpatient Clinic and 42 control group patients were included. DNA damage was detected in living cells through leukocyte isolation in 50 COVID-19-positive patients using the comet assay method. DNA tail/head (olive) moments were evaluated and compared. White blood cells (WBC), red blood cells (RBC), hemoglobin (HGB), neutrophils (NEU), lymphocytes (LYM), eosinophils (EO), monocytes (MONO), basophils (BASO), platelets (PLT), and the neutrophil/lymphocyte ratio (NLR) were analyzed. The RBC, lymphocyte, eosinophil, and monocyte means were significantly higher in the control group (p < 0.05), whereas the HGB and neutrophile means were significantly higher in the study group (p < 0.05). There were significant negative correlations between COVID-19 and RBC (r = -0.863), LYM (r = -0.542), EO (r = -0.686), and MONO (r = -0.385). Meanwhile, there were significant positive correlations between COVID-19 and HGB (r = 0.863), NEU (r = 0.307), tail moment (r = 0.598), and olive moment (r = 0.582). Both the tail and olive moment mean differences were significantly higher in the study group, with higher ranges (p < 0.05). COVID-19 infection caused statistically significant increases in both the tail and olive damage percentage in patients, causing DNA damage. Lastly, the NLR rate was associated with the presence and progression of COVID-19.

Can we predict unresponsiveness to methotrexate in rheumatoid arthritis? A pharmacogenetic study.

OBJECTIVE: Methotrexate (MTX) is the anchor drug in the treatment of rheumatoid arthritis (RA) and the therapeutic response to MTX has been observed to vary widely among these patients. The aim of this study was to investigate ABCB1 gene (the multidrug resistant 1 gene; MDR1 gene) polymorphism in patients with RA and to evaluate the relation between MTX unresponsiveness and this polymorphism. METHODS: Forty-five patients with RA administered MTX were included in this pharmacogenetic cross-sectional study. The gender, age, body mass index (BMI), rheumatoid factor (RF) positivity, anti-cyclic citrullinated peptide (anti-CCP) positivity, doses of MTX and glucocorticoids were recorded. In addition, initial and third month disease activity (DAS28, Simplified and Clinical Disease Activity Index; SDAI and CDAI) scores were evaluated. We also examined frequencies of two single-nucleotide polymorphisms (SNPs), G2677T and C3435T, within the gene encoding ABCB1. RESULTS: 22 patient's responsive and 20 patients unresponsive to MTX were enrolled. Initial demographic and disease related factors were similar between patients responsive or nonresponsive to MTX. In the third month evaluation, disease activity scores were significantly higher in patients unresponsive to MTX (p < 0.05). In addition, almost all patients unresponsive to MTX (19 of the 20 patients) presented heterozygosity in C3435T (p < 0.000). CONCLUSION: We determined heterozygosity in C3435T SNP of ABCB1 gene (multidrug resistant 1 gene) in almost all patients with RA who were non-responders to MTX. This result may contribute to predict unresponsiveness to MTX in RA. Individualized treatment strategies based on the pharmacogenetic characteristics of MTX may lead to optimization of the treatment.

Cytokine, C-Reactive Protein, and Heat Shock Protein mRNA Expression Levels in Patients with Active Behçet's Uveitis.

BACKGROUND To investigate the gene expression levels of interleukin 10 (IL10), IL18, interferon gamma (IFNG), IFN-gamma receptor (IFNGR), C-reactive protein (CRP), and heat shock protein 70 (HSP70) in patients with active Behçet's uveitis. MATERIAL AND METHODS Forty patients with Behçet's disease diagnosed according to the International Study Group criteria and 30 healthy individuals were included in the study. IL10, IL18, IFNG, IFNGR, CRP, and HSP70 gene expression levels were compared. RESULTS Expression levels of IL18, IFNG, IFNGR, and CRP were significantly higher in patients with active Behçet's uveitis than in control subjects (P<0.01 for all), whereas no significant differences were found in IL10 and HSP70 gene expression levels (P>0.01 for both). CONCLUSIONS IL18, IFNG, IFNGR, and CRP gene expression is significantly increased in active Behçet's uveitis. There was no significant difference between active Behçet's uveitis patients and controls in terms of IL10 and HSP70 gene expression levels. We conclude that drugs prescribed to Behçet's patients with active uveitis downregulate gene expression.

Resveratrol treatment ameliorates hepatic damage via the TGF-ß/SMAD signaling pathway in a phenobarbital/CCl4-induced hepatic fibrosis model.

Objectives: Liver fibrosis is a wound healing response characterized by excessive accumulation of extracellular matrix proteins. This study aimed to investigate the effects of resveratrol treatment on the TGF-ß/SMAD signaling pathway and related biochemical parameters, apoptosis, and liver regeneration phenobarbital-CCl4 induced hepatic fibrosis rat model. Materials and Methods: This model was created through phenobarbital and CCl4 (0.2-0.35 ml/kg). Resveratrol (1 mg/kg/day) was administered to the fibrosis and control groups. Immunohistochemical staining was performed to evaluate αSMA, TGF-ß1, and PCNA in liver tissue. The TUNEL method and Masson's Trichome staining were used to determine apoptosis and collagen accumulation. AST, ALP, ALT, total protein, and total bilirubin levels were measured to determine biochemical status. SMAD2, SMAD3, SMAD4, and SMAD7 expression levels were measured to determine TGF-ß1 related hepatic fibrosis. Results: The SMAD2, SMAD3, and SMAD4 mRNA expression levels were increased and the SMAD7 mRNA expression level was decreased in the fibrosis control group. The SMAD7 mRNA expression level was higher in the phenobarbital-CCl4 induced resveratrol treated group. Increased biochemical parameters indicating hepatic damage, increased number of apoptotic cells, and collagen accumulation surrounding the central vein were observed in the fibrosis group compared with the other groups. It was concluded that administration of resveratrol ameliorates the adverse effects of hepatic fibrosis by regulating biochemical parameters, controlling TGF-ß1/SMAD signaling, enhancing tissue regeneration, and reducing apoptosis in liver cells. Conclusion: Resveratrol can be a beneficial option for the prevention of liver damage in a phenobarbital-CCl4 induced hepatic fibrosis.

Expression levels of IL-17/IL-23 cytokine-targeting microRNAs 20, 21, 26, 155, and Let-7 in patients with relapsing-remitting multiple sclerosis.

OBJECTIVE: Although multiple sclerosis (MS) is known to be an immune-mediated disease, very little is known about its etiopathogenesis. MicroRNAs (miRNAs) are small non-coding proteins involved in the regulation of gene expression. T-cell activation potential in neurodegenerative diseases has been a research topic of interest in recent years Cytokines play an important role in the course and pathogenesis of MS, The aim of the present study was to analyze expression levels of miR-20, miR-21, miR-26, miR-155, and Let-7, which target the cytokines interleukin IL-17 and IL-23, in order to evaluate the relationship between MS and miRNAs that modulate the expression of cytokines involved in the autoimmune pathway.MATERIALS and METHODS: The study included 20 relapsing-remitting multiple sclerosis (MS) patients who were at least 18 years of age and were undergoing outpatient immunomodulatory therapy and 20 healthy, unrelated individuals who had no systemic disease and were not taking any medication as a control group. Peripheral blood samples were collected from all participants into EDTA-containing tubes and plasma was isolated for cDNA synthesis. From these cDNA samples, miRNA expression levels were quantitatively analyzed via melting curve analysis using the miScript SYBR Green kit in a Rotor-Gene Q real-time PCR device. RESULTS: Comparison of miRNA expression levels in the peripheral blood samples and MS patients and healthy subjects revealed that the MS patients had significant upregulation of miR-20 and downregulation of miR-26 and miR-155 compared to the control group (p<0.005).CONCLUSION: Dysregulation of miRNA expression may play a role in the pathogenesis of MS.

ERCC2 Lys751Gln rs13181 and XRCC2 Arg188His rs3218536 Gene Polymorphisms Contribute to Subsceptibility of Colon, Gastric, HCC, Lung And Prostate Cancer.

PURPOSE: Cancer is the leading cause of death in economically developed countries and the second leading cause of death in developing countries. The relationship between genetic polymorphisms and cancer risk has been extensively researched. In the present study, we evaluated the association between polymorphisms in two DNA repair genes, ERCC2 Lys751Gln (rs13181) and XRCC2 Arg188His (rs3218536) and the risk of colorectal, stomach, HCC, prostate and lung cancer. METHODS: This study was planned by the Medical Biology Unit and Department of Internal Medicine, Pathology and Surgical Medicine Sciences of Ataturk University. A total of 40 colon cancer, 40 gastric cancer, 40 hepatocellular carcinoma (HCC), 40 prostate cancer, and 40 lung cancer patients and 40 healthy individuals over 18 years of age were enrolled in the study (Controls). All patients and healthy subjects underwent ERCC2 Lys751Gln rs13181 and XRCC2 Arg188His rs3218536 genotyping. After collection of 10 ml venous blood from the patients, DNA was isolated and single nucleotide polymorphism (SNP) analysis was performed using Roche 480 Real-Time PCR device. Results were analyzed using SPSS version 23.0 software. RESULTS: There were statistically significant differences in ERCC2 Lys751Gln rs13181 polymorphism variants GG colon and GT in the colon control and GG,TTprostate cancer groups when compared with the control group.. GG variant of XRCC2 Arg188 rs3218536 was higher in the gastric patient group. AG variant of XRCC2 Arg188 rs3218536 was higher in gastric control group Conclusion: The results of the present study demonstrate that ERC22 Lys751Gln polymorphisms may be associated with the development of colon and prostate cancers in the Turkish population. This was a small-scale study, and the results should be corroborated with further research including larger groups of patients with each cancer type and more healthy controls.

Association of MICA Alleles and Human Leukocyte Antigen B in Turkish Patients Diagnosed With Behçet's Disease.

OBJECTIVES: This study aims to investigate whether or not MHC class I polypeptide-related sequence A (MICA) polymorphisms are associated with the susceptibility to Behçet's disease (BD) in a Turkish population. PATIENTS AND METHODS: The study included 38 Turkish BD patients (20 males, 18 females; mean age 34±10.9 years) and 51 ethnically matched healthy controls (30 males, 21 females; mean age 36±12.8 years). MICA and human leukocyte antigen B (HLA-B) alleles were determined in all subjects by using the Luminex technology. LABType sequence-specific oligonucleotide MICA test (One Lambda) and sequence-specific oligonucleotide B locus tests (Gene-Probe) were used for the typing studies. RESULTS: A total of 16 MICA alleles were found in BD patients as well as in control subjects. The gene frequency of MICA*006 was significantly higher in the BD patients compared to controls (14.5% vs. 0.9%; odds ratio [OR]: 17.092 95% confidence interval [CI] [2.155~135.554]; p<0.05). When haplotypes were evaluated, an association was found between the haplotypes HLA-B*51-MICA*006 (11.8% and 0.9%; OR: 13.567 95% CI [1.679~109.577]; p<0.001) and HLA-B*51-MICA*009 (27.6% and 13.7%; OR: 2.4 95% CI [1.127~5.109]; p<0.05). Frequencies of HLA-B*49-MICA*004 (0% and 6.8%) and HLA-B*52- MICA*009 (0% and 10.7%) were significantly higher in controls compared to BD patients (p<0.05). CONCLUSION: Our study shows that the MICA*006 (MICA-A6) and the MICA*009 alleles are associated with BD susceptibility in HLA-B*51 positive Turkish population, particularly in HLA-B*51 patients with MICA*006, which might be considered as a diagnostic biomarker for BD in the future.