Crosstalk between miR-146a and pro-inflammatory cytokines in patients with systemic lupus erythematosus.

microRNA-146a (miR-146a) plays an essential role in immune anomalies and organ injury of systemic lupus erythematosus (SLE) by regulating the disease's inflammation and complications. Here, we analyzed the expression of miR-146a in SLE and a panel of pro-inflammatory cytokines (IL-1, IL-6, IL-8, IL-17, and TNF-α). Association between all measured parameters and the disease's clinical manifestation and response to treatment was monitored. Our study populations were 113 SLE patients and 104 healthy volunteers. miR-146a expression in peripheral blood mononuclear cells (PBMCs) was measured by quantitative real-time PCR (RT-qPCR). The content of the plasma cytokines (IL-1ß, IL-6, IL-8, IL-17, and TNF-α) was detected by enzyme-linked immunosorbent assay (ELISA). Compared with healthy controls, miR-146a expression was significantly increased (p < 0.05) in lupus patients. The analysis of the receiver operator characteristic curve (ROC) of miR-146a showed 91% sensitivity and 70% specificity. IL-1ß, IL-6, and IL-17 cytokines were significantly increased (p < 0.001), while IL-8 and TNF-α were significantly decreased (p < 0.001) in SLE patients against controls. The expression of miR-146a and TNF-α was upregulated considerably in SLE patients with severe disease activity. miR-146a expression was positively correlated with IL-6. Our results pointed to the elevation of miR-146a as a trade marker of SLE patients. Reduction of IL-8 and TNF-α in combination with an elevation of IL-1ß, IL-6, and IL-17 might refer to miR-146a's dual effect in controlling inflammation in lupus. Although we shed some light on the role of miR-146a in SLE, further study is recommended to improve our results.

mir-146a genetic polymorphisms in systemic lupus erythematosus patients: Correlation with disease manifestations.

This study aimed to investigate the genetic polymorphisms of miR-146a SNPs (rs2910164, rs57095329, and rs2431697) in systemic lupus erythematosus (SLE) patients and their association with clinical manifestations. The implication of SNPs on miR-146a expression level was also evaluated. SLE patients (113) and healthy controls (104) were registered in this study. The miR-146a SNPs were genotyped by polymerase chain reaction/restriction fragment length polymorphism (PCR-RFLP). Quantitative real-time PCR was used to measure the miR-146a expression in peripheral blood mononuclear cells (PBMCs). Our results showed that the genotype frequency of miR-146a SNPs didn't deviate significantly from the Hardy-Weinberg equilibrium (HWE). The AG genotype and G allele of miR-146a (rs57095329 A/G) might be considered a risk factor for the disease (OR = 2.27; CI: 0.78-6.57 and OR: 2.35; CI: 0.79-6.92 for AG genotype and G allele, respectively). Although, no statistical significance in the distribution of miR-146a SNPs (rs2910164, rs57095329, and rs2431697) was found, indicating the lack of association between the three SNPs and SLE susceptibility. Significantly, the higher frequency of the AA genotype of miR-146a (rs57095329) was associated with pancytopenia (P < 0.05), while the CT genotype of miR-146a (rs2431697) was associated (P < 0.05) with the antiphospholipid syndrome (APS). SLE patients had significantly higher levels of miR-146a compared to controls (P < 0.05). Elevation of miR-146a was independent of any SNP genotypes. In conclusion, this pilot study shows no association between miR-146a SNPs in our population group and susceptibility to lupus. Studies concerning other miRNAs in larger sample sizes are essential for a better understanding of their role in susceptibility to SLE disease.

The Mechanical Autophagy as a Part of Cellular Immunity; Facts and Features in Treating the Medical Disorders.

Autophagy is a cellular housekeeping process that incorporates lysosomal-degradation to maintain cell survival and energy sources. In recent decades, the role of autophagy has implicated in the initiation and development of many diseases that affect humanity. Among these diseases are autoimmune diseases and neurodegenerative diseases, which connected with the lacking autophagy. Other diseases are connected with the increasing levels of autophagy such as cancers and infectious diseases. Therefore, controlling autophagy with sufficient regulators could represent an effective strategy to overcome such diseases. Interestingly, targeting autophagy can also provide a sufficient method to combat the current epidemic caused by the ongoing coronavirus. In this review, we aim to highlight the physiological function of the autophagic process to understand the circumstances surrounding its role in the cellular immunity associated with the development of human diseases.

Schiff base 4-ethyl-1-(pyridin-2-yl) thiosemicarbazide up-regulates the antioxidant status and inhibits the progression of Ehrlich solid tumor in mice.

Cisplatin is an approved cancer therapeutic drug used to treat many solid tumors but its accumulation in the kidney, which causes nephrotoxicity, limits its clinical use. Therefore, investigators seek new alternatives to cisplatin that may be more effective and/or safer. Thiosemicarbazides are of great significance due to their expected biological activity including anticancer activities. The aim of this work is the study of the antitumor effect of Schiff base 4-ethyl-1-(pyridin-2-yl) thiosemicarbazide (HEPTS) on Ehrlich solid tumor-bearing mice in comparison to cancer therapeutic drug cisplatin. The experiment was run using sixty adult female Swiss albino mice. Mice were allocated into six groups (n = 10 mice). Healthy control, EAC control (untreated tumor), EAC + cisplatin, EAC + HEPTS, Healthy + HEPTS, and Healthy + solvent. After scarification, blood samples, liver organs, and solid tumors were collected. Tumor weights and volumes were registered. The concentrations of malondialdehyde (MDA), reduced glutathione (GSH), SOD, catalase (CAT), total antioxidant capacity (TAC), nitric oxide (NO), uric acid, creatinine, and urea were assessed. Median survival time (MST) and the percentage increase in lifespan (%ILS) were also calculated. Treatment of tumorized mice with HEPTS significantly reduced both tumor volume and weight while it significantly increased the MST, antioxidant marks and prolonged the %ILS. It also, significantly reduced MAD, creatinine, urea, uric acid, and NO levels. Compared to cisplatin, HEPTS effects were better. Our results recommend HEPTS as one of the probable cisplatin-alternatives for tumor treatment after more validation.

Association between interleukin-6 gene polymorphism and iron regulation in hemodialysis patients infected with HCV / Associação entre polimorfismo do gene da interleucina-6 e regulação do ferro em pacientes em hemodiálise infectados pelo HCV

ABSTRACT Backgrounds: Hepcidin is related to the pathogenesis of chronic renal failure anemia, which is considered a chronic inflammatory state as well as HCV infection. IL-6 stimulates the release of hepcidin from the liver, suppresses intestinal iron uptake, and releases iron from internal stores. Method: To detect the association between IL-6 gene polymorphism and anemia markers, 80 hemodialysis (HD) patients [40 negative HCV HD patients and 40 positive HCV HD patients] were studied by routine chemistry and complete blood count, in addition to the assessment of serum hepcidin, iron parameters [serum iron and serum ferritin], and hepatitis C markers. IL-6 polymorphism -174G/C was determined by MS-PCR, while IL-6 polymorphisms -597G/A and -572 G/C were detected by PCR-SSP. Results: Hepcidin was non-significantly elevated in HCV-positive compared with HCV-negative hemodialysis patients. A statistically significant difference was detected between the negative and positive HCV HD patients in frequencies of IL-6 -174 G/C and -597 G/A (P≤ 0.01 and P≤ 0.001, respectively). On the other hand, a non-significant difference was reported between negative and positive HCV HD patients in the frequencies of IL-6 -572 G/C. Conclusions: Our study indicated that IL-6 -174 G/C and -597 G/A polymorphisms may play a role in HCV susceptibility in HD patients. Additional prospective studies on a larger population are needed to confirm our findings.

RESUMO Introdução: A hepcidina está associada à patogênese da anemia por insuficiência renal crônica, considerada um estado inflamatório crônico e também infecção por HCV. A IL-6 estimula a liberação de hepcidina a partir do fígado, suprime a captação intestinal de ferro e libera ferro das reservas internas. Método: Para detectar a associação entre o polimorfismo do gene IL-6 e os marcadores de anemia, 80 pacientes em hemodiálise (HD) [40 pacientes em HD, negativos para HCV; e 40 em HD, positivos para HCV] foram avaliados por exames químicos de rotina e hemograma completo, além da avaliação da hepcidina sérica, parâmetros do ferro [ferro sérico e ferritina sérica] e marcadores de hepatite C. O polimorfismo da IL-6 -174G/C foi determinado por MS-PCR, enquanto os polimorfismos de IL-6 -597G/A e -572 G/C foram detectados por PCR-SSP. Resultados: A hepcidina não esteve significativamente elevada em pacientes com HCV em comparação com pacientes em hemodiálise negativos para HCV. Uma diferença estatisticamente significativa foi detectada entre os pacientes em HD HCV negativos comparados aos positivos nas frequências de IL-6 -174 G/C e -597 G/A (P≤ 0,01 e P≤ 0,001, respectivamente). Por outro lado, foi relatada uma diferença não significativa entre pacientes em HD HCV negativos e positivos nas frequências de IL-6 -572 G/C. Conclusões: Nosso estudo indicou que os polimorfismos de IL-6 -174 G/C e -597 G/A podem desempenhar um papel na suscetibilidade ao HCV em pacientes em HD. Ainda necessitamos de estudos prospectivos adicionais em uma população maior para confirmar nossos achados.

EGYVIR: An immunomodulatory herbal extract with potent antiviral activity against SARS-CoV-2.

Due to the challenges for developing vaccines in devastating pandemic situations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), developing and screening of novel antiviral agents are peremptorily demanded. Herein, we developed EGYVIR as a potent immunomodulatory herbal extract with promising antiviral activity against SARS-CoV-2. It constitutes of a combination of black pepper extract with curcumin extract. The antiviral effect of EGYVIR extract is attributed to the two key phases of the disease in severe cases. First, the inhibition of the nuclear translocation of NF-kß p50, attenuating the SARS-CoV-2 infection-associated cytokine storm. Additionally, the EGYVIR extract has an in vitro virucidal effect for SARS-CoV-2. The in vitro study of EGYVIR extract against SARS-CoV-2 on Huh-7 cell lines, revealed the potential role of NF-kß/TNFα/IL-6 during the infection process. EGYVIR antagonizes the NF-kß pathway in-silico and in-vitro studies. Consequently, it has the potential to hinder the release of IL-6 and TNFα, decreasing the production of essential cytokines storm elements.

Association between interleukin-6 gene polymorphism and iron regulation in hemodialysis patients infected with HCV.

BACKGROUNDS: Hepcidin is related to the pathogenesis of chronic renal failure anemia, which is considered a chronic inflammatory state as well as HCV infection. IL-6 stimulates the release of hepcidin from the liver, suppresses intestinal iron uptake, and releases iron from internal stores. METHOD: To detect the association between IL-6 gene polymorphism and anemia markers, 80 hemodialysis (HD) patients [40 negative HCV HD patients and 40 positive HCV HD patients] were studied by routine chemistry and complete blood count, in addition to the assessment of serum hepcidin, iron parameters [serum iron and serum ferritin], and hepatitis C markers. IL-6 polymorphism -174G/C was determined by MS-PCR, while IL-6 polymorphisms -597G/A and -572 G/C were detected by PCR-SSP. RESULTS: Hepcidin was non-significantly elevated in HCV-positive compared with HCV-negative hemodialysis patients. A statistically significant difference was detected between the negative and positive HCV HD patients in frequencies of IL-6 -174 G/C and -597 G/A (P≤ 0.01 and P≤ 0.001, respectively). On the other hand, a non-significant difference was reported between negative and positive HCV HD patients in the frequencies of IL-6 -572 G/C. CONCLUSIONS: Our study indicated that IL-6 -174 G/C and -597 G/A polymorphisms may play a role in HCV susceptibility in HD patients. Additional prospective studies on a larger population are needed to confirm our findings.

Lack of Any Relationship Between Circulating Autoantibodies and Interleukin­6 Levels in Egyptian Patients Infected with the Hepatitis C Virus

Introduction: Elevated serum interleukin (IL) 6 has been reported in patients infected with the hepatitis C virus (HCV), but it remains debatable whether this influences the production of autoantibodies and the biochemical profile of HCV disease. Therefore, this current study was conducted to evaluate the relationship between IL-6 and circulating autoantibody levels in HCV positive patients. Methods: Levels of IL-6 in serum samples from 102 patients with HCV and 103 normal controls were determined by enzyme linked immunosorbent assay (ELISA). Autoantibodies were detected by immunofluorescence. Results: Levels of IL-6 were significantly higher (p=0.028) in patients infected with (HCV) compared with normal group. Autoantibodies were noted in in 43.1% of the patients; of these, 23.5% featured anti-nuclear antibodies (ANA+), 16.7% anti-smooth muscle antibodies (ASMA+), 7.8% anti-mitochondrial antibodies (AMA+), 17.6% anti-parietal cell antibodies (APCA+), 7.8% anti canalicular antibodies, and 2.9% anti reticulin antibodies (ARA+). No patients were found to be positive for anti-brush border antibodies (ABBA) or anti-ribosomal antibodies. (ARiA). No links with IL-6 levels were apparent. Conclusions: IL-6 levels are increased in patients infected with HCV disease and could influence the production of autoantibodies. However, this study did not provide evidence of a specific relationship between IL6 and circulating autoantibodies in such cases.

Adipocytokines in Patients with Chronic Kidney Disease Stage 5.

BACKGROUND: Chronic kidney disease (CKD) leading to kidney failure and end stage renal disease (ESRD) is a common health problem associated with wasting syndrome characterized by inadequate nutrient intake and decrease tissue anabolism and/or catabolism. In CKD adipokines, especially leptin and adiponectin (ADPN), accumulate in serum due to reduced renal clearance. Although, rapidly growing, knowledge of adipocytokines is limited and much is still unknown of the altered adipocytokine pattern in patients with impaired renal function. The aim of this study is to assess the adipocytokines, leptin, and adiponectin in relation to weight loss in pediatric patients with CKD stage-5 treated conservatively (CT) or undergoing maintenance hemodialysis (MHD). METHODS: 41 CKD stage-5 patients and 20 healthy controls were included in this study. Serum levels of leptin and adiponectin were determined by ELISA. Leptin gene expression was analyzed using quantitative real time-polymerase chain reactions (QPCR). RESULTS: Patients had significantly elevated ADPN levels and non significantly elevated serum leptin levels as compared to controls (p < 0.001, p = 0.354, respectively). Leptin gene expression and body mass index (BMI) were highly significantly reduced in CKD stage-5 compared to controls (p < 0.001 for each). There were no significant differences between patients treated conservatively and those undergoing MHD with respect to all studied parameters. Finally, univariate logistic regression analysis revealed no association between leptin, ADPN, and weight loss in CKD stage-5 patients. CONCLUSIONS: The present study showed non significantly elevated or even normalized serum leptin levels, elevated serum adiponectin level and reduced leptin gene expression in CKD stage-5 patients as compared to healthy controls. Patients had significantly lower weight than healthy controls but there was no association between leptin, adiponectin, and weight loss in CKD stage-5 studied patients so, further studies are needed to clarify the role of the two adipokines in body weight loss in those patients.

Amelioration of adriamycin-induced cardiotoxicity by Salsola kali aqueous extract is mediated by lowering oxidative stress.

OBJECTIVES: To assess the cardioprotective effect of the Salsola kali aqueous extract against adriamycin (ADR)-induced cardiotoxicity in male Swiss albino mice. METHODS: The aqueous extract of S. kali was phytochemically screened by traditional methods for different classes and further evaluated for antioxidant activity in vitro. In vivo, cardioprotective evaluation of the extract was designed to have four groups of mice: (1) control group (distilled water, orally; normal saline, intraperitoneally (i.p.)); (2) ADR group (15 mg/kg, i.p.); (3) aqueous S. kali extract (200 mg/kg, orally); and (4) ADR + S. kali group. ADR (5 mg/kg) was injected three times over 2 weeks while S. kali was orally administered daily for 3 weeks (1 week before and 2 weeks during ADR treatment). Cardioprotective properties were assessed using biochemical and histopathological approaches. RESULTS: ADR caused a significant increase in serum enzymes (lactate dehydrogenase, creatine phosphokinase, aspartate aminotransferase, and alanine aminotransferase). Myocardial levels of malondialdehyde, nitric oxide, and reduced glutathione, as well as the activities of superoxide dismutase and catalase increased while the activities of glutathione peroxidase and glutathione S-transferase declined. Histopathological examination of heart sections revealed that ADR caused myofibrils loss, necrosis and cytoplasmic vacuolization. DISCUSSION: Pretreatment with S. kali aqueous extract normalized serum and antioxidant enzymes minimized lipid peroxidation and cardiac damage. These results have suggested that the extract has antioxidant activity, indicating that the mechanism of cardioprotection during ADR treatment is mediated by lowering oxidative stress.