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Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by the involvement of multiple organs and dysregulation of the immune system. Zinc finger (ZNF) proteins act as DNA-binding transcription factors, thereby regulating gene expression. Polymorphisms, specifically single-nucleotide polymorphisms (SNPs), within ZNF-coding genes, have been implicated in susceptibility to autoimmune diseases, including the ZNF-76 gene in SLE. This investigation aimed to elucidate the association between ZNF-76 gene expression, protein levels, and rs10947540 SNP in a cohort of Egyptian SLE patients. One hundred healthy controls and one hundred SLE patients were recruited. Quantitative real-time PCR was employed to identify ZNF-76 (C/T) rs10947540 genotypes and quantify serum ZNF-76 mRNA expression. Additionally, serum ZNF-76 protein levels were measured using ELISA. Our results revealed downregulation of ZNF-76 mRNA expression in approximately 75% of SLE patients, with a significant decrease (0.23-fold) in median expression compared to controls. Furthermore, SLE patients exhibited a higher prevalence of high-risk TT genotype and demonstrably lower serum ZNF-76 protein levels. In conclusion, this study suggests a strong association between decreased serum ZNF-76 mRNA expression and increased susceptibility to SLE in the studied Egyptian population. Specific SNP in the ZNF-76 gene may be potential markers for inherited predisposition to SLE in this population., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier B.V. All rights reserved.)

Aims: Sigma-1 receptor (S1R) activation was recently identified as a promising target for preventing diabetic nephropathy (DN) by mitigating hypoxia, oxidative stress, and inflammation. This study aimed to investigate the potential reno-protective effect of the S1R agonist afobazole against streptozotocin (STZ)-induced DN in rats compared to metformin., Materials and Methods: Rats were split into six groups: the normal control group; the diabetic control group received STZ (55 mg/kg i.p.); the other four groups received STZ and were treated with different doses of either afobazole (10, 15, and 20 mg/kg) or metformin (200 mg/kg). Metabolic parameters and renal function were assessed. Expression levels of oxidative stress markers and inflammatory cytokines were measured using ELISA, apoptosis-related proteins were evaluated using immunohistochemistry, and gene expression of S1R, Nrf2, NF-κB, and TLR-4 was determined. Histopathological analysis was performed on kidney tissues., Key Findings: Both afobazole and metformin exerted hypoglycemic effects, alleviating renal injury, reducing blood urea nitrogen (BUN) and serum creatinine, and restoring oxidant/antioxidant balance in diabetic rats. Both treatments boosted renal S1R and Nrf2 levels, suppressed inflammatory proteins and cytokines, and reduced apoptotic features., Significance: The study revealed that afobazole provided nephroprotection in STZ-induced DN through a hypoglycemic, antioxidant, anti-inflammatory, and anti-apoptotic potential mediated by activating the S1R/Nrf2 antioxidant axis. The 15 mg/kg dose elicited the most pronounced nephroprotective effects, outperforming other treatment groups., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier Inc. All rights reserved.)

Background: Coronary artery spasm is among the etiology of myocardial infarction. Oxidative stress is involved in the pathogenesis of coronary artery spasm (CAS). Paraoxonase-1 (PON1) is an HDL-bound antioxidant enzyme that protects LDL from oxidative modification. Oxidative-stress-related genetic factors and certain polymorphisms in the paraoxonase 1 gene might influence the pathogenesis of CAS. We aimed to investigate the association between PON1 gene polymorphism and its enzymatic activity and coronary artery spasm during cardiac catheterization., Methods and Results: The study population was 150 patients who underwent elective coronary angiography. Subjects were genotyped to the Q192R polymorphism (rs662) on the PON1 gene by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), and PON1 activity was quantitatively analyzed by enzyme linked immunosorbent assay. Results showed that the subjects carrying the RR genotype and R allele were significantly more likely to develop coronary artery spasm (OR=4.2, 2.03, P < 0.006, P ˂0.02, respectively). Moreover, serum PON1 levels were significantly decreased ( P ˂0.001) in the CAS group. RR genotype of PON1 Q192R polymorphism, Tc, LDLc, TG, catheter size, and paroxonase-1 serum level are independent predictors of coronary spasm., Conclusion: We conclude that the PON1 (rs662) gene polymorphism is associated with CAS during cardiac catheterization in Egyptians. The PON1-192R allele and lower serum enzyme concentration may play an important role in coronary spasm.

Objective: This study aims to determine the prevalence of Occult Hepatitis B and C Infections among Egyptian injection drug users (IDUs) and identify key risk factors contributing to their occurrence within this high-risk group., Methods: In this cross-sectional study, 200 Egyptian IDUs were assessed. Participants were negative for Hepatitis B surface antigen and hepatitis C virus (HCV) RNA, with anti-HCV positive patients who achieved sustained virologic response after treatment included. Quantitative polymerase chain reaction (PCR) was used to detect HCV RNA in plasma and peripheral blood mononuclear cells, while HBV DNA was identified via nested PCR. Comparisons were made between Occult Hepatitis B infection (OBI) positive and OBI negative subgroups, as well as between other comprehensive income (OCI) positive and OCI negative subgroups. A significance level of 0.05 was set, with P-values below this indicating statistical significance. Statistical comparisons between OBI and OCI-positive and negative groups were performed using the Mann-Whitney U test and Chi-square test., Results: OBI was found in 32% of IDUs, while OCI was detected in 42% of IDUs, and was present in 53.6% of seropositive individuals. All OBI patients showed a significant increase in all liver function tests, while OCI patients had significant elevations in alanine transaminase and aspartate transaminase values. HIV coinfection was identified in 39.1% and 26.1% of OBI and OCI cases respectively. OBI and OCI coinfection were detected in 31 patients., Conclusion: Hidden infections such as OBI and OCI remain an overlooked public health issue in Egypt's IDU population. These findings highlight the need for targeted strategies to address these reservoirs of infection and could inform similar approaches in countries with comparable HBV/HCV epidemiology., Competing Interests: The authors declare that they have no competing interests., (Copyright: © International Journal of Health Sciences.)

Background: Leptin (LEP) is an anti-obesity hormone that regulates food intake, energy expenditure, and glucose metabolism. The genetic variants in LEP and the LEP receptor (LEPR) gene may play an important role in the pathogenesis of type 2 diabetes mellitus (T2DM) and obesity. The current study aimed to investigate the association of serum LEP levels, and LEP polymorphisms in LEP (rs7799039, 2548 G/A) with T2DM in Egyptian patients., Methods: A total of 205 subjects were included in the present case-control study, consisting of 100 T2DM patients and 105 healthy controls. The anthropometric, psychometric, and biochemical measurements were taken from all the subjects. The genotyping of LEP gene variants was carried out by polymerase chain reaction TaqMan technology. Serum LEP levels were measured by the ELISA technique., Results: T2DM patients had significantly elevated levels of glycated haemoglobin (HbA1c), fasting blood sugar (FBS), postprandial blood sugar (PPBS), international normalisation ratio (INR), creatinine, urea, cholesterol, triglyceride (TG), and low-density lipoproteins (LDL) and significantly decreased high-density lipoprotein (HDL) compared to healthy subjects. serum LEP levels were significantly decreased p (<0.001) as compared to the control group. LEP gene SNP rs7799039 was associated with an increased diabetic risk with A allele being more frequent in T2DM patients than control subjects. The distribution of the AA genotype and GA genotype of LEP SNP rs7799039 was higher in the diabetic group than control one. In addition, AA + GA genotype carriers had significantly elevated HbA1c, FBS, PPBS, TG, and LDL levels and on the contrary, decreased serum LEP levels compared to GG homozygotes., Conclusion: The genetic polymorphism rs7799039 showed a highly significant correlation with blood LEP. The co-dominant and dominant models of the LEP genetic polymorphism (rs7799039, 2548 G/A) were shown to have a significant correlation with complicated and uncomplicated diabetes individuals, but we have found that serum LEP levels were inversely related with control and diabetes patients. A positive significant association was found between LEP genetic polymorphism (rs7799039, 2548 G/A) and serum LEP in patients and controls. LEP levels and its rs7799039 genetic variant may play a vital role in increasing T2DM susceptibility.

Breast cancer is the most prevalent type of cancer among women worldwide. Non-coding RNAs play a fundamental role in regulating the expression of different genes. MicroRNAs (miRNAs) are known to bind to mRNA and either induce its degradation or repress its translation. Also, miRNA can modulate the expression of long non-coding RNAs (lncRNA) through different mechanisms. This study aims to determine the role of miRNA-205-5p in breast cancer cell lines. miR-205-5p was bioinformatically predicted to interact with LRP6 mRNA and lncRNAs MALAT1, NEAT1, SNHG5, and SNHG16. Then, the levels of miR-205-5p and its target genes and lncRNAs in breast cancer cell lines MCF-7 and MDA-MB-231 were determined. In addition, MCF-7 and MDA-MB-231 breast cancer cells were transfected with miR-205-5p mimic or miRNA mimic negative control using lipofectamine 3000, and the effect of miR-205-5p overexpression on cellular proliferation and migration was assessed. Moreover, we probed the impact of miR-205-5p overexpression on the expression levels of LRP6, Wnt/β-catenin pathway genes, lncRNAs, and apoptotic markers. miR-205-5p upregulation resulted in decreasing the growth and migration and induced apoptosis markers in the two tested breast cancer subtypes. Additionally, miR-205-5p overexpression resulted in decreasing the expression of LRP6 in MCF-7 and MDA-MB-231 cells leading to downregulation of Wnt/β-catenin target genes, c-Myc, cyclin D1, and PPARδ and had various regulatory effects on the expression of lncRNAs MALAT1, NEAT1, SNHG5, and SNHG16. miR-205-5p inhibits the proliferation and migration of breast cancer through diverse mechanisms including targeting LRP6, Wnt/β-catenin pathway, and its regulatory effects on lncRNAs., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Type I diabetes mellitus (T1DM) is a significant health challenge, especially for children, owing to its chronic autoimmune nature. Although the exact etiology of T1DM remains elusive, the interplay of genetic predisposition, immune responses, and environmental factors are postulated. Genetic factors control immune reactivity against β-cells. Given the pivotal roles of CIITA and CLEC2D genes in modulating a variety of immune pathologies, we hypothesized that genetic variations in CIITA and CLEC2D genes may impact T1DM disease predisposition. This study was designed to explore the association between gene polymorphisms in CIITA (rs8048002) and CLEC2D (rs2114870) and type 1 diabetes (T1DM), with a focus on analyzing the functional consequence of those gene variants., Methods: The study enlisted 178 healthy controls and 148 individuals with type 1 diabetes (T1DM) from Suez Canal University Hospital. Genotyping for CIITA and CLEC2D was done using allelic-discrimination polymerase chain reaction (PCR). Levels of glycated hemoglobin (HbA1c) and lipid profiles were determined through automated analyzer, while fasting blood glucose and insulin serum levels were measured using the enzyme-linked immunosorbent assay (ELISA) technique. RegulomeDB was used to examine the regulatory functions of CIITA (rs8048002) and CLEC2D (rs2114870) gene variants., Results: Analysis of the genotype distribution of the CIITA rs8048002 polymorphism revealed a significantly higher prevalence of the rare C allele in T1DM patients compared to the control group (OR = 1.77; P  = 0.001). Both the CIITA rs8048002 heterozygote TC genotype (OR = 1.93; P  = 0.005) and the rare homozygote CC genotype (OR = 3.62; P  = 0.006) were significantly more frequent in children with T1DM when compared to the control group. Conversely, the rare A allele of CLEC2D rs2114870 was found to be significantly less frequent in T1DM children relative to the control group (OR = 0.58; P  = 0.002). The heterozygote GA genotype (OR = 0.61; P  = 0.033) and the rare homozygote AA genotype (OR = 0.25; P  = 0.004) were also significantly less frequent in T1DM patients compared to the control group. Both CIITA (rs8048002) and CLEC2D (rs2114870) gene variants were predicted to have regulatory functions, indicated by a RegulomeDB score of (1f) for each., Conclusion: The rare C allele of CIITA rs8048002 genetic variant was associated with an increased risk of developing T1DM, while the less common A allele of CLEC2D rs2114870 was associated with a reduced risk of T1DM., Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-024-01402-w., Competing Interests: conflicts of interestThe authors declare no conflicts of interest., (© The Author(s), under exclusive licence to Tehran University of Medical Sciences 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Breast cancer is the most common type of cancer in Egyptian females. Polymorphisms in the angiogenesis pathway have been implicated previously in cancer risk and prognosis. The aim of the current study was to determine whether certain polymorphisms in the genes of vascular endothelial growth factor A (VEGFA), vascular endothelial growth factor receptor 2 (VEGFR2), vascular endothelial growth inhibitor (VEGI), and hypoxia-inducible factor-1α (HIF1A) associated with breast cancer development. The study included 154 breast cancer patients and 132 apparently healthy age-matched females as a control group. VEGFA rs25648 genotyping was performed using (ARMS) PCR technique; while VEGFR2 rs2071559, VEGI rs6478106, and HIF-1α rs11549465 were genotyped by the PCR-RFLP method. Serum levels of VEGF, VEGFR2, VEGI, and HIF1A proteins in breast cancer patients and controls were measured by ELISA. There was a significant association between the VEGFA rs25648 C allele and breast cancer risk (OR 2.5, 95% CI 1.7-3.6, p < 0.001). VEGFA rs25648 C/C genotype was statistically significantly higher in breast cancer patients vs. control (p < 0.001). Participants with the T/T and T/C VEGFR2 rs2071559 genotypes had 5.46 and 5 higher odds, respectively, of having breast cancer than those with the C/C genotype. For the VEGI rs6478106 polymorphism, there was a higher proportion of C allele in breast cancer patients vs. control (p = 0.003). Moreover, the C/C genotype of VEGI rs6478106 was statistically significantly higher in breast cancer patients vs. control (p = 0.001). There was no significant difference in genotypes and allele frequencies of HIF1A rs11549465 polymorphism between breast cancer cases and control individuals (p > 0.05). Serum levels of VEGFA, VEGI, and HIF1A were considerably greater in women with breast cancer than in the control (p < 0.001). In conclusion, the genetic variants VEGFA rs25648, VEGFR2 rs2071559, and VEGI rs6478106 revealed a significant association with increased breast cancer risk in Egyptian patients., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Lung cancer is the most common type of cancer, causing worldwide mortality. Therefore, this study is necessary for continuing research into new effective and safe treatments. Recently, herbal medicines have been used for the treatment of various diseases such as cancer. This study aimed to investigate the potential anti-proliferative activity and investigate the mechanisms of hesperidin extract on the non-small lung cancer cells A549 and H460 vs. cisplatin via targeting the miR 34a/PD-L1/NF- κ B signalling pathway., Material and Methods: To determine the cytotoxic effects of the hesperidin extract on non-small lung cancer cells, sulphorhdamine B assay was performed. To show the inhibition of migration by hesperidin extract, wound healing assay was conducted. A quantitative polymerase chain reaction test was used to quantify the expressions of miR-34a , programmed cell death ligand-1 ( PDL-1 ), epidermal growth factor receptor ( EGFR ), and P53 genes, which are involved in apoptosis pathway. Also, cell cycle assay was performed by using a flow cytometer., Results: The hesperidin extract could significantly inhibit proliferation of non-small lung cancer cells A549 and H460. Western blot assay demonstrated that hesperidin induced suppression of nuclear factor κB signalling pathway. The messenger RNA expression levels of MiR-34a and P53 were up-regulated significantly by hesperidin treatment, while the EGFR and P53 genes were down-regulated. The flow cytometer confirmed that cell cycle arrest occurred at the sub-G1 and G2 phases in A549 and H460, respectively., Conclusions: Our study demonstrated that hesperidin extract could significantly inhibit non-small lung cancer cell growth by induction of the apoptosis signalling pathway. Therefore, hesperidin might open novel strategies for effective and safe cancer treatment and reduce the adverse side effects of several chemotherapeutic treatments such as cisplatin., Competing Interests: None., (Copyright © 2024 Termedia.)

Background: Type 2 diabetes mellitus (T2DM) is a chronic progressive disease due to insulin resistance. Oxidative stress complicates the etiology of T2DM. Saxagliptin is a selective dipeptidyl peptidase-4 (DPP-4) inhibitor, while Pioglitazone is a thiazolidinedione insulin sensitizer. This study aimed to assess the effect of Saxagliptin and Pioglitazone monotherapy and combination therapy on the biochemical and biological parameters in streptozotocin (STZ)-induced diabetic rats., Methods: The study included thirty-five male albino rats. Diabetes mellitus was induced by intraperitoneal STZ injection (35 mg/kg). For a 1-month duration, rats were divided into five groups. Glucose homeostasis traits, lipid profiles, kidney functions, liver enzymes, and oxidative stress markers were measured. Gene expression of miRNA-29a, phosphoenolpyruvate carboxykinase (PEPCK), phosphoinositide-3-kinase (PI3K), and interleukin 1 beta (IL-1β) was assessed using qRT-PCR., Results: At a 1-month treatment duration, combination therapy improves oxidative stress markers more than either drug alone. The combination therapy had significantly higher levels of SOD, catalase, and GSH and lower levels of MDA compared to the monotherapy. Additionally, the diabetic group showed a significant increase in the expression levels of miRNA-29a, PEPCK, and IL-1β and a significant decrease in PI3K compared to the normal control group. However, combination therapy of Saxagliptin and Pioglitazone was more effective than either Saxagliptin or Pioglitazone alone in reversing these results, especially for PEPCK and IL-1β., Conclusions: Our findings revealed that combining Saxagliptin and Pioglitazone improves glycemic control and genetic and epigenetic expression profiles, which play an essential regulatory role in normal metabolism.

Polymorphisms in the 3' untranslated region of STAT3 mRNA can derange STAT3 gene expression via modifying the microRNA-binding site. This study aimed to examine the impact of STAT3 rs1053005 variation and miR-452-3p expression on osteoarthritis (OA) susceptibility and severity and the efficacy of intra-articular high-molecular-weight hyaluronic acid (HMW-HA) injection as a therapy option for knee OA. Two hundred and fifty-eight OA patients and 200 healthy controls were enrolled in the study. STAT3 genotyping and STAT3 and miR-452-3p expression were carried out using allelic-discrimination PCR and quantitative real-time PCR. Functional assessment and pain evaluation were performed for all patients. Eighty-three patients received HMW-HA injections, and multiple follow-up visits were performed. STAT3 mRNA was upregulated, and expression was positively associated with plasmin, TNF-α, MMP-3, and STAT3 serum levels, whereas miR-452-3p was downregulated and negatively associated with the previously mentioned parameters in OA patients. Osteoarthritis patients had a lower prevalence of the minor allele of the rs1053005 variant ( p < 0.001). Plasmin, TNF, MMP-3, and STAT3 mRNA and protein levels were significantly decreased, and miR-452-3p expression was significantly increased in the GG genotype compared to AG and AA genotypes. HMW-HA injection improved OA patients' clinical scores with concomitant decreased STAT3 levels and enhanced expression of miR-452-3p. More efficient improvement was observed in rs1053005 AG + GG genotype carriers vs. AA genotype carriers. The G allele of STAT3 rs1053005 (A/G) polymorphism was associated with decreased OA susceptibility and severity and enhanced clinical response to HMW-HA injection, possibly via enhancing miR-452-3p binding and a subsequent decrease in STAT3 expression.

Worldwide mortality from hepatic fibrosis remains high, due to hepatocellular carcinoma and end stage liver failure. The progressive nature of hepatic fibrosis from inflammation to cicatrized tissues warrants subtle intervention with pharmacological agents that hold potential. Empagliflozin (Empa), a novel hypoglycemic drug with antioxidant and anti-inflammatory properties, has lately been proposed to have additional antifibrotic activities. In the current study, we examined the antifibrotic effect of the Empa through modulating the activity of hepatic stellate cells by hedgehog (Hh) pathway. We also assessed the markers of inflammatory response and endoplasmic reticulum (ER) stress. Male Albino rats were treated with either CCl 4 (0.4 mg/kg twice/week) and/or Empa (10 mg/kg/day) for eight weeks. In this study, CCl 4 rats had active Hh signaling as indicated by overexpression of Patched 1, Smoothened and Glioblastoma-2. CCl 4 induced ER stress as CHOP expression was upregulated and ERAD was downregulated. CCl 4 -induced inflammatory response was demonstrated through increased levels of TNF-α, IL-6 and mRNA levels of IL-17 while undetectable expression of IL-10. Conversely, Empa elicited immunosuppression, suppressed the expression of Hh markers, and reversed markers of ER stress. In conclusion, Empa suppressed CCl 4 -induced Hh signaling and proinflammatory response, meanwhile embraced ER stress in the hepatic tissues, altogether provided hepatoprotection., (© 2023. The Author(s).)

Introduction: Chronic inflammation causes articular bone and cartilage degeneration in people with rheumatoid arthritis (RA). Despite recent advancements in the management of RA, adverse side effects and ineffective treatments remain a problem. Effective treatment is usually hampered by financial issues. As a result, less expensive medications that reduce both inflammation and bone resorption are required. Mesenchymal stem cells (MSCs) have recently been identified as a potential therapy for RA., Aim of the Study: This study aimed to examine the anti-arthritic effect of rat bone marrow-derived mesenchymal stem cells (rBM-MSCs), oligosaccharides (Os), and human placental extract (HPE), individually and combined, on an RA model, using Complete Freund's adjuvant (CFA)-induced arthritis in rats., Materials and Methods: In female rats, RA was induced by injecting CFA in the paw of the hind limb. Rat bone marrow-MSCs, oligosaccharides, and human placental extract (HPE) were given individually and in combination via the intraperitoneal route. A complete blood count (CBC), erythrocyte sedimentation rate (ESR), serum cortisol, urea, uric acid, and other biochemical parameters were measured to determine the safety and efficacy of the different treatments. Histopathological analysis of bone sections was carried out., Results: Combining oligosaccharides and HPE therapy with the infusion of rat-bone marrow MSCs had beneficial antiarthritic and anti-inflammatory effects in CFA-induced arthritis in rats: overall such triple therapy significantly reduced serum levels of IL-6, IL-10, and TNF-alpha in comparison with all other combinations (all P > 0.05). Meanwhile, the triple therapy did not have negative effects on levels of CBC, serum cortisol, ESR, and liver enzymes (all NS) as well as on renal functions (NS). Also, the histopathological analysis showed significant improvements in the healing and remodelling of osteoporotic lesions in arthritic rats. As shown by counting apoptotic cells as a histopathological substitute for measuring apoptotic or regeneration markers, the lowest count was found in the group treated with a triple therapy of rat bone marrow-derived mesenchymal stem cells (rBM-MSCs), oligosaccharides, and HPE., Conclusion: The combination of rat MSCs, oligosaccharides, and HPE has the potential to be an effective treatment for rheumatoid arthritis., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Colorectal cancer (CRC) is a common tumor worldwide. CRC is influenced by several types of miRNAs and long non-coding RNAs. This study aims to evaluate the correlation of lncRNA ZFAS1/ miR200b/ ZEB1 protein with presence of CRC., Methods: Quantitative real-time polymerase chain reaction was used to measure serum expression of lncRNA ZFAS1 and microRNA-200b in 60 CRC patients and 28 control subjects. ZEB1 protein in serum was measured by ELISA., Results: Lnc ZFAS1 and ZEB1 were up-regulated in CRC patients in compare to control subjects while miR-200b was down-regulated. There was a linear correlation between ZAFS1 expression and miR-200b and ZEB1 in CRC., Conclusion: ZFAS1 is a key player of CRC progression and could be a potential therapeutic target by sponging miR-200b. In-addition the association between ZFAS1, miR-200b and ZEB1 highlights their potential value as a novel diagnostic biomarker in human CRC., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

Carpal tunnel syndrome (CTS) is a common entrapment neuropathy in which one of the body's peripheral nerves becomes pinched or crushed. Transforming growth factor beta 1 (TGF-β1) plays an important role in the pathogenesis of CTS. An association between TGF-β1 polymorphisms and the susceptibility or progression of a number of diseases has been reported. In this study, three TGF-β1 single nucleotide polymorphisms (SNPs), serum TGF-β1, and macrophage inflammatory protein 1 beta (MIP-1β) were investigated as potential diagnostic markers for the progression of CTS in Egyptian patients. One hundred CTS patients and 100 healthy controls were recruited for the study. TGF-β1 SNPs +915G/C, -509C/T and -800G/A were determined by TaqMan genotyping assay. Serum TGF-β1 and MIP-1β levels were measured by ELISA. Serum TGF-β1 and MIP-1β levels increased significantly and were strongly correlated with the occurrence of CTS. The C allele of +915G/C, the T allele of -509C/T, and the G allele of -800G/A occurred more frequently in patients from CTS than in controls. The serum levels of TGF-β1 and MIP-1β in the group of carriers of the genotypes +915G/C GC and CC, the genotype -509C/T TT and the genotype -800G/A GA and AA were significantly higher in CTS patients. TGF-β1 and its +915G/C, -509C/T, and -800G/A SNPs and MIP-1β could be useful prognostic markers for the occurrence of CTS.

The established correlation between obesity and cognitive impairment portrays pharmacological products aimed at both disorders as an important therapeutic advance. Modulation of dysregulated adipokines and neurotransmitters is hence a critical aspect of the assessment of in-use drugs. At the cellular level, repairments in brain barrier integrity and cognitive flexibility are the main checkpoints. The aim of this study was to investigate whether melatonin and histidine, alone or in combination, could produce weight loss, meanwhile improve the cognitive processes. In this study, obese rat model was established by feeding high fat diet (HFD) composed of 25% fats (soybean oil) for 8 weeks, accompanied by melatonin (10 mg/kg), histidine (780 mg/kg), and combination of both in conventional form and nanoform. At the end of the study, adiposity hormones, neuronal monoamines and amino acids, brain derived neurotrophic factor (BDNF) and zonula occluden-1 (ZO-1) were assessed. HFD feeding resulted in significant weight gain and poor performance on cognitive test. Coadministration of histidine in the nanoform increased the level of ZO-1; an indicator of improving the brain barrier integrity, along with adjusting the adipokines and neurotransmitters levels, which had a positive impact on learning tasks. Cotreatment with melatonin resulted in an increase in the level of BDNF, marking ameliorated synaptic anomalies and learning disabilities, while reducing weight gain. On the other hand, the combination of melatonin and histidine reinstated the synaptic plasticity as well as brain barrier junctions, as demonstrated by increased levels of BDNF and ZO-1, positively affecting weight loss and the intellectual function., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interests., (Copyright © 2022 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.)

The 14-3-3 Eta (14-3-3 η) biomarker platform is a relatively recent discovery with the potential to significantly address the diagnosis and prognosis of rheumatoid arthritis (RA) disease. Hypoxia-inducible factor (HIF)-1α and vascular endothelial growth factor (VEGF) have been implicated in inflammatory mechanisms in RA. We hypothesized a molecular association of the coding YWHAH gene and its expressed protein 14-3-3 η with hypoxia and angiogenesis in RA. One hundred healthy subjects and 100 RA patients were enrolled in the study. YWHAH gene expression was determined using quantitative PCR, and its gene polymorphism rs2858750 was assessed by Taqman genotyping assay. Serum levels of 14-3-3 η, HIF-1α, and VEGF were measured using the ELISA technique, and clinical parameters were routinely examined. In RA patients, significant positive correlations were found between 14-3-3 η, HIF-1α (r = 0.84), and VEGF (r = 0.85). YWHAH gene expression was upregulated 10.8 fold (CI 95% 10.1-11.5) in RA patients and significantly correlated with all disease activity parameters, ACPA, and levels of 14-3-3 η, HIF-1α, and VEGF. RA patients showed a higher frequency of YWHAH rs2858750 A allele than healthy subjects (p = 0.02). The risk A allele carriers showed higher disease activity parameters, ACPA, YWHAH gene expression, and increased serum levels of 14-3-3 η (p < 0.001), HIF-1α (p = 0.002), and VEGF (p = 0.001) than the G allele. Serum 14-3-3 η and its rs2858750 genetic variant are associated with increased hypoxia and angiogenesis in RA and activity, and severity of the disease., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Rheumatoid arthritis (RA) is a joint destructive disorder. This study aimed to assess lncRNA MEG3 expression and its variant rs941576 in Egyptian patients with RA., Subjects and Methods: 100 RA patients and 100 healthy individuals were enrolled in the study. Quantitative PCR was used for expression analysis and allelic discrimination technology for genotyping., Results: LncRNA MEG3 was down-regulated in RA patients and negatively associated with RA clinical features and HIF-1α and VEGF serum levels. On the contrary, it was positively associated with BAX serum levels in RA patients. The major A allele of rs941576 variant was associated with RA patients ( p  = .0003). AA genotype showed a significant decrease in lncRNA MEG3 expression and BAX and increase in HIF-1α and VEGF., Conclusions: Serum lncRNA MEG3 expression showed negative association with increased susceptibility to RA. MEG3 gene rs941576 (A/G) polymorphism was associated with increased severity of RA in the current population.

Type 2 diabetes mellitus (T2DM) is a heterogeneous disease with numerous abnormal targets and pathways involved in insulin resistance, low-grade inflammation, oxidative stress, beta cell dysfunction, and epigenetic factors. Botanical drugs provide a large chemical space that can modify various targets simultaneously. Matricaria aurea (MA, golden chamomile) is a widely used herb in Middle Eastern communities for many ailments, including diabetes mellitus, without any scientific basis to support this tradition. For the first time, this study aimed to investigate the possible antidiabetic activity of MA in a type 2 diabetic rat model, identify chemical constituents by LC-MS/MS, and then elucidate the molecular mechanism(s) using enzyme activity assays, q-RTPCR gene expression analysis, network pharmacology analysis, and molecular docking simulation. Our results demonstrated that only the polar hydroethanolic extract of MA had remarkable antidiabetic activity. Furthermore, it improved dyslipidemia, insulin resistance status, ALT, and AST levels. LC-MS/MS analysis of MA hydroethanolic extract identified 62 compounds, including the popular chamomile flavonoids apigenin and luteolin, other flavonoids and their glycosides, coumarin derivatives, and phenolic acids. Based on pharmacokinetic screening and literature, 46 compounds were chosen for subsequent network analysis, which linked to 364 candidate T2DM targets from various databases and literature. The network analysis identified 123 hub proteins, including insulin signaling and metabolic proteins: IRS1, IRS2, PIK3R1, AKT1, AKT2, MAPK1, MAPK3, and PCK1, inflammatory proteins: TNF and IL1B, antioxidant enzymes: CAT and SOD, and others. Subsequent filtering identified 40 crucial core targets (major hubs) of MA in T2DM treatment. Functional enrichment analyses of the candidate targets revealed that MA targets were mainly involved in the inflammatory module, energy-sensing/endocrine/metabolic module, and oxidative stress module. q-RTPCR gene expression analysis showed that MA hydroethanolic extract was able to significantly upregulate PIK3R1 and downregulate IL1B, PCK1, and MIR29A. Moreover, the activity of the antioxidant hub enzymes was substantially increased. Molecular docking scores were also consistent with the networks' predictions. Based on experimental and computational analysis, this study revealed for the first time that MA exerted antidiabetic action via simultaneous modulation of multiple targets and pathways, including inflammatory pathways, energy-sensing/endocrine/metabolic pathways, and oxidative stress pathways., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ismail, Fahmy, Ghattas, Ahmed, Zehry, Saleh and Abo-elmatty.)

Aims: The first-line treatment for advanced hepatocellular carcinoma (HCC) is the multikinase inhibitor sorafenib (SOR). Sofafenib resistance is linked to protein kinase B/ mammalian target of rapamycin (AKT/mTOR) and nuclear factor kappa B (NF-κB) activation, apoptosis inhibition and oxidative stress. This study investigated selenium nanoparticles (SeNps) to overcome SOR resistance in thioacetamide (TAA) induced HCC in rats., Materials and Methods: TAA (200 mg/kg/twice weekly, i.p.) was administered for 16 weeks to induce HCC.s. Rats were treated with oral SOR (10 mg/Kg daily), selenium, and SeNps (5 mg/kg three times/week) alone or in combination, for two weeks. Apoptosis, proliferation, angiogenesis, metastasis and drug resistance were assessed. Cleaved caspase 3 (C. CASP3), mTOR, and NF-κB were determined by western blotting. Expression of p53 gene and long-noncoding RNA-AF085935 was determined by qRT-PCR. Expression of B- Cell Leukemia/Lymphoma 2 (Bcl2), Bcl associated X protein (Bax)and glypican 3 (GPC3) was determined by enzyme-linked immunosorbent assay. Liver functions, antioxidant capacity, histopathology and CD34 immunohistochemistry were performed., Key Findings: SOR/SeNps reversed TAA-induced HCC in rats, through reduction of oxidative stress, activation of p53, Bax and CASP3, and inhibition of Bcl2. SOR/SeNps ameliorated the HCC-induced effect on cell proliferation and drug resistance by targeting mTOR and NF-κB pathways. SOR/SeNps decreased CD34 immunostaining indicating a decrease in angiogenesis and metastasis. SOR/SeNps regulated HCC epigenetically through the lncRNA-AF085935/GPC3 axis., Significance: SOR/SeNps are a promising combination for tumor suppression and overcoming sorafenib resistance in HCC by modulating apoptosis, AKT/mTOR and NF-κB pathways, as well as CD34 and lncRNA-AF085935/GPC3 axis., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Aims: The current study aimed to elucidate the neurotoxic potential of DOX to induce AD-like pathology paying attention to the role of wingless-integrated/β-catenin (Wnt/β-catenin) signaling pathway. A major aim was to evaluate the efficacy of infliximab (IFX) either individually or in combination with 2-mercaptoethane sulfonate sodium (MESNA) on the DOX-induced neurotoxicity in rats., Methodology: AD-like pathology was induced in adult male Wistar rats by intraperitoneal (i.p.) administration of DOX at a dose of 3.5 mg/kg twice a week for 3 weeks. DOX-injected rats were then treated with either INF at a single dose of 5 mg/kg i.p. (IFX group), MESNA at a dose of 160 mg/kg/day i.p. for 4 weeks (MESNA group) or their combination at the same specified doses (INF + MESNA group). At the end of the study period, behavioral assessment was performed and the brain tissue samples were harvested at sacrifice., Key Findings: DOX-treated rats significantly exhibited AD-like brain injury, increased amyloid burden, enhanced neuroinflammation and apoptosis, and multifocal histological injury in the cerebral cortex with widespread vacuolations. IFX and MESNA significantly reversed all the aforementioned detrimental effects in the DOX-treated rats., Significance: The study has provided sufficient evidence of the potential of IFX and/or MESNA to ameliorate the DOX-induced neurotoxicity, with the best improvement observed with their combined administration. A new insight has been introduced into the critical role of Wnt/β-catenin activation., (Copyright © 2022. Published by Elsevier Inc.)

Background and Aims: Currently, liver biopsy is the gold standard method for diagnosis of non-alcoholic fatty liver severity. It is critical to develop non-invasive diagnostic method to diagnose nonalcoholic fatty liver rather than invasive techniques. Our case-control study was to address the value of circulating miRNA-122 and serum pro-neurotensin as a potential non-invasive biomarker for the diagnosis of non-alcoholic fatty acid diseases., Methods: Clinical assessment, laboratory investigations, and anthropometric measurements were reported for 157 patients with proven NAFLD. Apparently, healthy participants (n=100) were enrolled as a control group. Serum samples were tested for micro-RNAs-122 and pro-neurotensin., Results: Compared with the control subjects, both mi-RNA-122 and serum proneurotensin levels were increased in NAFLD (p<0.001) and at a cut-off ≥6.83, mi-RNA-122 had 51.0% sensitivity, 70.0% specificity to differentiate NAFLD from healthy controls, while serum proneurotensin had 80.0% sensitivity and 80.0% specificity at a cutoff ≥108., Conclusion: The circulating pro-neurotensin might be used as a novel biomarker for diagnosis of patients with NAFLD, wherefore the integration of a circulating mi-RNA-122 and serum pro-neurotensin could be beneficial to diagnose NAFLD cases. Large-scale studies are needed to investigate the possible role of mi-RNA-122 and pro-neurotensin in the development, progression, and prognosis of NAFLD and NASH., Competing Interests: The authors declare no conflict of interest, financial or otherwise., (© 2022 Mohamed et al.)

Context: ZNF804a and CDK1 genes code for proteins involved in inflammatory pathways., Objective: This study aimed to investigate the correlation of ZNF804a and CDK1 expression profiles in RA with the activity and the severity of the disease and to assess their association with inflammatory reactions in the Egyptian RA patients., Methods: ZNF804a and CDK1 expression profiles were assessed using quantitative PCR (qRT-PCR). Clinical and laboratory parameters were evaluated., Results: ZNF804a expression was down-regulated by 0.177-fold while CDK1 expression was up-regulated to 3.29-fold in RA patients compared with healthy controls ( p  < .001). ZNF804a down-regulation was negatively correlated with CRP, RF, disease activity score of 28 joints (DAS) using CRP (DAS-CRP) and TNF-α. CDK1 overexpression was correlated with IFN-1 and ACPA in RA patients., Conclusion: ZNF804a and CDK1 genes are implicated in RA pathogenesis due to their influences on TNF-α and IFN-1 which contribute to inflammation in RA patients.

Some studies suggest that thyroid hormones and disorders can influence breast (BC) and ovarian (OC) cancers risks. However, studies regarding their effect on these tumors progression are limited. Thyroid-stimulating hormone (TSH), T4, free T4 (FT4), T3, and free T3 (FT3) were detected in patients with BC, OC, benign breast and ovary diseases, and healthy controls using highly sensitive chemiluminescence assay. In contrast to OC, hypothyroidism prevalence was associated with BC late stage (11/24 vs . 2/46), high grade (11/23 vs . 4/47), lymph node invasion (11/42 vs . 0/28), positive distant metastasis (11/25 vs . 1/45), and large tumor size (14/25 vs . 1/45) compared to tumor early stages, low grades, negative lymph node, and distant metastasis and small size, respectively. Patients with late stage, high grade, large tumor size, positive lymph nodes, or positive distant metastasis were significantly ( P < 0.05) associated with elevated levels of TSH and decreased levels of T4, FT4, T3, and FT3. There were both significant positive correlation of serum TSH and significant inverse correlation of T4, FT4, T3, and FT3 with these tumor worse outcomes. In conclusion, our results identify hypothyroidism as potentially important prognostic factor in BC not in OC that is associated with poor outcomes of BC patients.

Objectives: Although there are numerous drugs available for the treatment of gastric ulcers (GU), these drugs are not always effective. Antidepressant medications have been used for a variety of non-psychiatric indications, including antiulcer activity in various ulcer models. The purpose of this study was to compare the antiulcer effects of fluvoxamine and mirtazapine in two rat GU experimental models and to determine their relationship to antioxidant and antisecretory mechanisms., Materials and Methods: The antiulcer activities of various doses of fluvoxamine and mirtazapine on water immersion restraint stress (WIRS) and pyloric ligation-induced GU in rats have been studied against the positive control antiulcer drug famotidine. Various oxidative stress markers were evaluated., Results: Fluvoxamine and mirtazapine significantly protected against WIRS and pyloric ligation-induced gastric lesions, as evidenced by a dose-dependent decrease in ulcer index, myeloperoxidase (MPO) activity, lipid peroxidation, and an increase in prostaglandin E2, nitric oxide (NO), and reduced glutathione levels, as well as increased antioxidant enzyme activity. In the pyloric ligation model, fluvoxamine and mirtazapine improved GU more than famotidine. Furthermore, a 30 mg/kg dose of mirtazapine significantly improves both NO levels and MPO activity compared to famotidine., Conclusions: The results highlighted the relationship in correlating the antiulcer effect of drugs from different antidepressant classes across two animal GU models, implying that antidepressants that affected both norepinephrine and serotonin levels (mirtazapine) had a more potent antiulcer effect in WIRS-induced gastric model than drugs that only affected serotonin levels (fluvoxamine)., (Copyright: © International Journal of Health Sciences.)

Occult hepatitis C virus infection (OCI) is the absence of HCV RNA in serum and the presence of actively replicating HCV RNA in hepatocytes and peripheral blood mononuclear cells (PBMCs), as evidenced by the presence of antigenomic negative sense single-stranded RNA. This study aimed to determine the prevalence of OCI in Egyptian lymphoma patients and assess changes in biochemical parameters in patients with confirmed OCI. The current study was conducted on 100 apparently healthy subjects as control group and 100 patients with lymphoma as a case group. HCV RNA was extracted and detected in both plasma and PBMCs using qRT-PCR. Total protein, albumin, ALT, AST, and total and direct bilirubin were measured in serum. OCI was detected in 6% of the patient group. OCI patients had lower levels of total protein and serum albumin and higher ALT and AST compared with lymphoma patients without OCI. Our study revealed that six out of 100 patients with lymphoma disorders had occult HCV infection (6%). Therefore, the possibility of this infection should be considered in patients with lymphoma.

Hepatocellular carcinoma (HCC) is the most common form of malignancy in the liver. Autophagy was found to have a significant effect in controlling HCC. Anthocyanins, which are naturally occurring pigments in a variety of fruits and vegetables, have been thoroughly documented to be involved in a variety of bioactive activities and are widely employed for their antioxidant capabilities. Cyanidin-3-glucoside (C3G) extracted from Morus alba L. has promising antioxidant and anti-tumour activities. The current study aims to examine the protective action of C3G against hepatocellular carcinoma through the investigation of the autophagy protein ATG16L1 expression along with its related RNA molecules (hsa&#95;circ&#95;0001345 and miRNA106b) in Wistar rats. In vivo precancerous lesions (PCL) were induced using diethylnitrosamine (DEN) and acetamidofluorene (2-AAF). Rats were treated with C3G (10, 15, and 20 mg/kg; 4 times weekly) for 112 days (16 weeks). Liver function tests, alfa fetoprotein, ATG16L1 expression, hsa&#95;circ&#95;0001345, and miRNA106b differential expression were examined. Liver sections were examined by histological and immunohistochemical approaches. The current study's findings indicated that C3G administration protects against the negative effects of DEN-2-AAF on liver functions and liver histopathological sections, which nominated C3G as a potential prophylactic agent against HCC.

Purpose: Diabetic peripheral neuropathy can injure the hand median nerve and cause extensive nerve damage. PKC and ALR are associated with progression of diabetic complications. We hypothesized a genetic association between the ALR polymorphisms (-106C → T/-12C → G) and elevated serum PKC-δ levels in diabetic neuropathy and its adverse effects on handwriting in Egyptian population., Methods: One hundred DPN were compared with 100 DP and 100 healthy volunteers. ALR -106C → T/-12C → G variants were studied using the PCR-RFLP method. A routine set of standard laboratory markers was determined. Serum PKC-δ concentration was determined by ELISA. Logistic regression analysis and areas under the receiver characteristic curves (AUCs) were evaluated to investigate the predictors of diabetic neuropathy. Arabic handwriting was analyzed based on the recognition of functional features, word shape, and ascending/descending parts of letters., Results: Individuals carrying ALR-106C → C and -12G → G had a significantly higher risk of developing diabetic neuropathy than individuals with -106C → T and -12C → G genotypes ( P  = 0.01, P  = 0.02). Carriers of the (-106C → T) CC and (-12C → G) GG genotypes had significantly increased serum levels of PKC-δ, FBG, TC, and LDL-c. PKC- δ serum levels were significantly correlated with glycemic and lipid indicators ( P  < 0.001). PKC-δ is a significant predictor of diabetes with or without neuropathy at a cutoff value of 16.6, sensitivity was 89%, and specificity 100%. All DPN showed complete deterioration of handwriting after the onset of diabetic neuropathy., Conclusion: The genetic variants ALR-106C → C / -12G → G and PKC-δ in serum may help in the detection and treatment of diabetic neuropathy in Egyptian population before writing performance is affected., Competing Interests: Disclosure of interestThe authors have no relevant financial or non-financial interests to disclose. On behalf of all authors, the corresponding author states that there is no conflict of interest., (© Springer Nature Switzerland AG 2022.)

Background and Aim: Gold nanorods (AuNRs) have gained much attention recent years due to their promising optical and chemical properties and are hence used in applied research and industrial nanotechnology. This study was designed to investigate the effect of gold nanoparticle shape (Gold nanorods vs. gold nanosphere) on immune response in rabbit., Materials and Methods: Thirty New Zealand white rabbits were divided into six groups (n=5 rabbits). The first group is the control negative received an intravenous (IV) injection of normal saline 0.9%; the second group (vaccinated) is the control positive, and the other four groups were vaccinated and received a single-dose or repeated five consecutive IV doses of 300 mg/kg body weight 50 nm AuNRs or 50 nm gold nanosphere (50 nm AuNSs) dissolved in ultrapure water. Blood and serum were collected for the hematological and biochemical analysis., Results: White blood cells (WBCs) count, lymphocytes, monocytes, eosinophils, and basophils showed significantly (p<0.05) higher values with the repeated-dose AuNRs. g-globulin levels showed a significant difference after 15 days in the single-dose AuNSs. Single-dose AuNSs significantly (p<0.05) increased the immunoglobulin G (IgG) and significantly (p<0.05) decreased the tumor necrosis factor-alpha. In addition, it elicited a significant (p<0.05) decrease in the malondialdehyde levels and a significant (p<0.05) increase of the superoxide dismutase, glutathione peroxidase, and catalase levels. Moreover, evoked red blood cells count, mean corpuscular volume, and mean corpuscular hemoglobin were significantly (p<0.05) lower than the control group. The platelet count, lysozymes, and nitric oxide were significantly (p<0.05) higher in repeated-dose AuNRs., Conclusion: The effect of AuNPs is shape and dose-dependent. The repeated 5 days IV 50 nm AuNRs doses over 15 days showed a significant antioxidant effect, with no considerable toxicity or vascular reactions., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Mehanna, et al.)

Aim: Nephrotoxicity is the major limiting factor for the clinical use of vancomycin (VCM) for treatment against multi-resistant Gram-positive bacteria. The present research aimed to investigate the ability of selenium nanoparticles (SeNPs) to protect against VCM-induced nephrotoxicity in rats., Main Methods: Experimental rats were divided into five groups; the first was the normal control, the second was treated with VCM (200 mg/kg twice/day, i.p.) for 7 days. The third, fourth, and fifth groups were treated orally with SeNPs (0.5, 1, and 2 mg/kg/day); respectively. SeNPs were administered for 12 days before VCM, 1 week simultaneously with VCM, and for another 1 week after its administration., Key Findings: Levels of malondialdehyde (MDA), inducible nitric oxide synthase (iNOS), nitric oxide (NO), tumor necrosis factor-alpha (TNF-α), and kidney injury molecule-1 (KIM-1) were significantly increased in kidney tissue after VCM administration. Expression of adenosine 5'-monophosphate-activated protein kinase (AMPK), Bcl-2 associated X protein (Bax), caspase 3 and caspase 9 in kidney tissue was significantly increased, while the antioxidant enzymes, mitochondrial complexes, the ATP levels and B-cell lymphoma protein 2 (Bcl-2) were decreased in kidney in the VCM-treated rats compared to the normal control group. Treatment with SeNPs significantly decreased levels of MDA, iNOS, NO, TNF-α, and KIM-1 in the kidney tissue. Administration of SeNPs also downregulated the expression of the proapoptotic agents and enhanced the activities of the antioxidant enzymes and the mitochondrial enzyme complexes in the kidney., Significance: SeNPs alleviated VCM-induced nephrotoxicity through their anti-oxidant, anti-inflammatory, anti-apoptotic and mitochondrial protective effects., (Copyright © 2021 Elsevier Inc. All rights reserved.)

This study aimed to investigate the protective effects of lipopolysaccharide from Rhodobacter sphaeroides (LPS-RS) against ethanol-induced hepatotoxicity and nephrotoxicity in experimental rats. The study involved an intact control group, LPS-RS group, two groups were given ethanol (3 and 5 g/kg/day) for 28 days, and two other groups (LPS-RS + 3 g/kg ethanol) and (LPS-RS + 5 g/kg ethanol) received a daily dose of LPS-RS (800 μg/kg) before ethanol. Ethanol significantly increased the expression of nuclear factor kappa B (NF-κB) and levels of malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) in the liver tissue and decreased anti-oxidant enzymes. Hepcidin expression was downregulated in the liver, with increased serum levels of ferritin and iron. Prior-administration of LPS-RS alleviated the increase in oxidative stress and inflammatory markers, and preserved iron homeostasis markers. In the kidney, administration of ethanol caused significant increase in the expression of NF-κB and the levels of TNF-α and kidney injury markers; whereas LPS-RS + ethanol groups had significantly lower levels of those parameters. In conclusion; this study reports anti-oxidant, anti-inflammatory and iron homeostasis regulatory effects of the toll-like receptor 4 (TLR4) antagonist LPS-RS against ethanol induced toxicity in both the liver and the kidney of experimental rats.

Plicosepalus acacia (Fam. Loranthaceae) has been reported to possess hypoglycemic, antioxidant, antimicrobial, and anti-inflammatory effects. Liquid chromatography combined with tandem mass spectrometry (LC-MS/MS) analysis revealed the presence of a high content of polyphenolic compounds that are attributed to the therapeutic effects of the crude extract. In addition, methyl gallate and quercetin were detected as major phytomedicinal agents at concentrations of 1.7% and 0.062 g%, respectively, using high-performance thin layer chromatography (HPTLC). The present study investigated the effect of the P. acacia extract and its isolated compounds, methyl gallate and quercetin, on hind limb ischemia induced in type 1 diabetic rats. Histopathological examination revealed that treatment with P. acacia extract, methyl gallate, and quercetin decreased degenerative changes and inflammation in the ischemic muscle. Further biochemical assessment of the hind limb tissue showed decreased oxidative stress, increased levels of nitric oxide and endothelial nitric oxide synthase (eNOS), and enhancement of the levels of heme oxygenase-1 (HO-1) and vascular endothelial growth factor (VEGF) in the groups treated with methyl gallate and quercetin. Expression levels of hypoxia inducible factor-1 alpha (HIF-1α), VEGF, fibroblast growth factor-2 (FGF-2), and miR-146a were upregulated in the muscle tissue of methyl gallate- and quercetin-treated groups along with downregulation of nuclear factor kappa B (NF-κB). In conclusion, P. acacia extract and its isolated compounds, methyl gallate and quercetin, mediated therapeutic angiogenesis in diabetic hind limb ischemia.

Background: Liver fibrosis is a major medical problem with high mortality and morbidity rates where the formation of regenerative nodules and cirrhosis leads to loss of liver function and may result in the development of hepatocellular carcinoma. bone marrow mesenchymal stem cells (BM-MSCs) have drawn attention as a novel approach for treatment of liver fibrosis. This study aimed to evaluate the therapeutic effect of BM-MSCs on the liver structure in carbon tetrachloride (CCl 4 ) induced liver fibrosis in male rats relative to resveratrol and Silybum marianum as standard drugs derived from herbal plants., Methods: Fifty adult male albino rats (Sprague Dawley strain; 180-220 g mean body weight) were purchased from the Laboratory Animal Unit in the Nile Center of Experimental Research, Mansoura, Egypt. Liver function were determined, isolation and preparation of BM- MSCs and detection of cell-surface markers by flow cytometry., Results: Animals exposed to CCl 4 developed liver injury characterized by significant increase of liver enzymes, malondialdehyde (MDA), tumor necrosis factor alpha (TNFα), and CYP450, inhibition of antioxidant enzymes, and decreased albumin. Treatment with stem cells enhanced liver state more effectively than resveratrol and S. marianum. It significantly decreased AST, ALT, ALP, MDA, TNF-α, and CYP450 and increased albumin, SOD, GSH, GST, and CAT. Histopathological study and atomic force microscope results confirmed the therapeutic effects of MSCs., Conclusions: BM-MSCs could restore liver structure and function in CCL 4 induced liver fibrosis rat model, ameliorating the toxicity of CCl 4 and improving liver function tests., Competing Interests: Conflicts of Interest The authors declare no conflicts of interests., (Copyright © 2020 Chang Gung University. Published by Elsevier B.V. All rights reserved.)

Adipokines were shown to exert crucial roles in rheumatic diseases. This study aimed to assess the role of chemerin, apelin, vaspin, and omentin adipokines and their genetic variants rs17173608, rs2235306, rs2236242, and rs2274907, respectively, in rheumatoid arthritis (RA) pathogenesis in Egyptian patients. A total of 150 RA patients and 150 healthy individuals were recruited. Blood samples were collected and used for genotyping. Serum was separated and used for expression analysis by quantitative PCR, and various biochemical markers determination by ELISA. Serum protein levels of chemerin and vaspin, as well as their gene expression levels were higher, while those of apelin and omentin were lower in RA patients and were associated with most of RA clinical and laboratory characteristics. G allele of chemerin rs17173608, T allele of vaspin rs2236242, and T allele of omentin rs2274907 were more frequent in RA patients. Serum levels and gene expression levels of chemerin in GG genotype carriers and vaspin in TT genotype group were significantly higher, while those of omentin in TT genotype carriers were significantly lower than RA patients with other genotypes. There was no association between apelin rs2235306 and RA. Chemerin rs17173608, vaspin rs2236242, and omentin rs2274907 polymorphisms were associated with increased susceptibility to RA.

Cisplatin is a powerful anti-neoplastic drug that displays multi-organ toxicity, especially to the liver and kidneys. Consumption of phytomedicines is a promising strategy to overcome the side effects of chemotherapy. Carrichtera annua extract proved to possess potent antioxidant activity. Its protective potential against cisplatin-induced hepato-nephrotoxicity was scrutinized. Moreover, a phytochemical study was conducted on C. annua ethyl acetate fraction which led to the isolation of five known phenolic compounds. Structure determination was achieved utilizing 1 H- and 13 C-NMR spectral analyses. The isolated phytochemicals were trans -ferulic acid ( 1 ), kaempferol ( 2 ), p -coumaric acid ( 3 ), luteolin ( 4 ) and quercetin ( 5 ). Regarding our biological study, C. annua has improved liver and kidney deteriorated functions caused by cisplatin administration and attenuated the histopathological injury in their tissues. Serum levels of ALT, AST, blood urea nitrogen and creatinine were significantly decreased. C. annua has modulated the oxidative stress mediated by cisplatin as it lowered MDA levels while enhanced reduced-GSH concentrations. More importantly, the plant has alleviated cisplatin triggered inflammation, apoptosis via reduction of INFγ, IL-1β and caspase-3 production. Moreover, mitochondrial injury has been ameliorated as remarkable increase of mtDNA was noted. Furthermore, the MTT assay proved the combination of cisplatin- C. annua extract led to growth inhibition of MCF-7 cells in a notable additive way. Additionally, we have investigated the binding affinity of C. annua constituents with caspase-3 and IFN-γ proteins using molecular simulation. All the isolated compounds exhibited good binding affinities toward the target proteins where quercetin possessed the most auspicious caspase-3 and IFN-γ inhibition activities. Our results put forward that C. annua is a promising candidate to counteract chemotherapy side effects and the observed activity could be attributed to the synergism between its phytochemicals.

In recent times, the counterfeiting of pharmaceuticals has been considered a serious trouble especially in developing countries that acquire poor inspection programs. Sildenafil, vardenafil and tadalafil (phosphodiesterase type 5 inhibitors) products have gained wide popularity in treating sexual disorders, for which they are subjected to counterfeiting. For this purpose, a simple, rapid, and novel HPLC method with ultraviolet detection has been simply developed for the simultaneous determination of vardenafil, sildenafil, and tadalafil, and their counterfeits (dapoxetine, paroxetine, citalopram, tramadol and yohimbine) in pharmaceutical dosage forms and counterfeit products such as instant coffee and honey. The separation was carried out on a C 18 column, with acetonitrile and an aqueous 0.05% formic acid solution as the mobile phase with a gradient program and at a flow rate of 1 mL min -1 . UV detection was accurately set at 230 nm. The total run time was 11 min for elution of these eight drugs. A UPLC-MS/MS method was also developed, by which compounds were separated in only 6 min, and it was used as a confirmatory tool for studied compounds by identification of their mass spectra. Proposed methods were validated by following ICH guidelines. Both methods were found to be linear, specific, precise and accurate, and they were efficiently applied to analyze 50 commercial products including honey sachets, instant coffee and pharmaceutical products marketed as aphrodisiacs and suspected to contain PDE5-inhibitors., Competing Interests: The authors have declared no conflict of interest., (This journal is © The Royal Society of Chemistry.)

Metastasis in breast cancer is a leading cause of mortality among women in many countries. This study investigated the anti-cancer role of benzoimidazoquinazoline and benzimidazotriazin; two novel compounds that were designed, synthesized, structurally elucidated, and biologically evaluated as potent anti-angiogenic agents that act through inhibition of vascular endothelial growth factor receptor-2 (VEGFR2). Breast cancer was induced by inoculation of Ehrlich Ascites Carcinoma (EAC) cells. Seventy swiss albino mice were randomly divided into 7 groups, 10 animals each: (1) normal, (2) control EAC group, (3) cisplatin treated group, (4&5) benzoimidazoquinazoline treated (5 mg/kg and 10 mg/kg), (6&7) benzimidazotriazin treated (5 mg/kg and 10 mg/kg). The expression of miR-122 was assessed in the tumor tissue by quantitative PCR, and the VEGF level was determined in serum by ELISA. VEGFR2 and cluster of differentiation (CD)34 were assessed by immunohistochemistry. Serum ALT, AST, creatinine, and urea were measured. Treatment with benzoimidazoquinazoline and benzimidazotriazin decreased tumor weight and serum levels of VEGF, and down-regulated expression of VEGFR2 and CD34 in the tumor tissue. miR-122 was upregulated, particularly in the benzimidazotriazin (10 mg/kg) group. Relative to cisplatin, the novel compounds were less toxic to kidneys. Benzoimidazoquinazoline and benzimidazotriazin are promising anti-cancer agents that act through inhibition of angiogenesis and thus provide a new strategy for advancement of chemotherapy., (Copyright © 2020 Elsevier B.V. All rights reserved.)

This study aimed to investigate the impact of ginger extract (GE) loaded into chitosan nanoparticles (CNPs) in enhancing cytotoxicity and reducing cardiotoxicity of doxorubicin (DXN) in hepatocellular carcinoma (HCC) induced mice. DXN and GE were loaded into CNPs and cytotoxicity of loaded and unloaded drugs against HepG2 cells was evaluated. HCC was induced in male albino mice by injection of diethylnitrosamine (DINA). Mice were divided into eight groups ( n  = 15): (1) normal control, (2) DINA, (3) CNPs, (4) free DXN, (5) CNPs DXN, (6) free GE, (7) CNPs GE, and (8) CNPs DXN + CNPs GE. Both GE and DXN loaded into CNPs showed a greater decline in cell viability of HepG2 cells than the unloaded forms. GE CNPs displayed pronounced anticancer activity In Vivo through apoptosis, greater down-regulation of multidrug resistance 1, enhancement of anti-oxidant activity and depletion of vascular endothelial growth factor content in liver tissues. GE CNPs in combination with DXN CNPs showed nearly normal hepatic lobule architecture and the greatest increase in apoptotic cell count. Co-treatment group had decreased cardiac malondialdehyde, tumor necrosis factor-α and serum activity of creatine kinase and lactate dehydrogenase. Combination of GE CNPs and DXN CNPs might be a potentially effective therapeutic approach for HCC.

Objectives: Among tropical diseases, schistosomiasis caused by Schistosoma mansoni is the second major cause of morbidity and mortality worldwide. Inflammation was considered as an adverse event that contributes to the pathology associated with schistosomiasis. Heme oxygenase-1 (HO-1) and vascular endothelial growth factor (VEGF) have been implicated in the process of angiogenesis. The current study aimed to evaluate the effect of S. mansoni infection on HO-1 gene expression, IL-4, IL-12, and VEGF to address the role of these factors in the pathogenesis of schistosomiasis., Methods: Thirty mice divided equally into three groups comprised a non-infected control group and two S. mansoni -infected groups. Infected animals were studied at 8 and 12 weeks post-infection. Serum IL-4, IL-12, and VEGF were measured. HO-1 mRNA was detected by RT-PCR of liver homogenates and HO activity was assessed as percentage of carboxy hemoglobin., Results: S. mansoni -infected mice showed a progressive increase in serum IL-4 and VEGF and decrease in IL-12 levels. In addition, HO-1 expression and activity were increased in infected mice compared to control group with the maximum increase at egg deposition stage., Conclusion: Our results suggested that the body response to acute stage of S. mansoni infection by elevating the expression of the stress gene HO-1 and that VEGF may serve as a new indicator of progression of S . mansoni associated angiogenesis which regulates granuloma and/or fibrosis development in the liver of infected mice. Understanding the role of HO-1 and VEGF in pathogenesis of S. mansoni may provide a new pharmacological target., (Copyright: © International Journal of Health Sciences.)

Aims: Notch signaling is highly implicated in several cancers and chemoresistance. Therefore, Notch-targeted therapies might be beneficial in enhancing chemotherapeutic effect and cancer regression. This study aimed to investigate implication of Notch in development and progression of solid Ehrlich carcinoma (SEC) and enhancement of anticancer effect of cisplatin (CIS) by addition of thymoquinone (TQ) and pentoxifylline (PTX) through modulation of Notch., Main Methods: SEC was induced in mice as model for mammary carcinoma by s.c. injection of 1 × 10 6 Ehrlich cells into back of the mice. On 12 th day, solid tumor was developed and mice were divided into seven groups; tumor control, early CIS (ECIS), ECIS + ETQ, ECIS + ETQ + EPTX, late CIS (LCIS), LCIS + LTQ, and LCIS + LTQ + LPTX. Early treatment was started on 12 th day, whereas late treatment was begun on 19 th day from tumor inoculation. At the endpoint, samples were collected for detection of Notch1, Hes1, Jagged1, β-catenin, TNF-α, IL-6, IFN-γ, IL-2, VEGF, apoptosis, CD4, and CD8., Key Findings: Adding PTX and TQ to CIS significantly reduced Notch1, Hes1, Jagged1, β-catenin, TNF-α, IL-6, IFN-γ, and VEGF with increment in IL-2, CD4, CD8, and apoptotic cells. Moreover, early treated groups showed remarkable attenuation in tumor growth and the relevant parameters compared to their counterpart later groups., Significance: Addition of PTX with TQ to CIS showed a synergistic chemotherapeutic action and induced better oncostatic effect mainly through Notch suppression. Consequently, shutting Notch could be of great interest in promoting chemosensetivity and cancer control., Competing Interests: Declaration of competing interest The authors have no conflicts of interests related to this study., (Copyright © 2020 Elsevier Inc. All rights reserved.)

There is increasing evidence of a link between type 2 diabetes mellitus (T2DM) and cognitive decline. T2DM has been recognized as a risk factor for Alzheimer's disease (AD). The aim of this research was to investigate the biochemical and physiological effects of vildagliptin treatment alone, and in combination with memantine, in a rat model of combined T2DM and AD. The experimental study was carried out on 75 male Wistar rats weighing 180-200 g. The rats were divided into five groups (n = 15): normal group, Alzheimer diabetic control, treated with vildagliptin (10 mg/kg/day), treated with memantine (30 mg/kg/day), and treated with combination of drugs. Serum glucose, lipid profile, acetylcholinesterase (AChE), homocysteine (Hcy), and amyloid beta peptide (Aβ) were determined. Lipid peroxidation was measured in brain tissue. Expression of amyloid precursor protein (APP) in the brain was assessed by q-PCR, and expression of total and phosphorylated tau was determined by Western Blotting. Vildagliptin alone and in combination with memantine caused a decrease in blood glucose, HOMA-IR, lipid profile, Hcy, malanodialdhyde, and acetylcholinesterase, and an increase in apolipoprotein E. Expression of APP and phosphorylated tau protein was decreased with combined vildagliptin and memantine treatment. In conclusion, vildagliptin treatment, either alone or in combination with memantine, modulates AD-associated biochemical changes and downregulates amyloid precursor protein and phosphorylated tau expression in diabetic rats.

Preeclampsia and gestational diabetes are common pregnancy disorders that may be interrelated. MIR146A rs2910164 (G/C) is a functional polymorphism that was associated with several diseases. This study aimed to investigate the frequency of rs2910164 polymorphism and its possible correlation with the incidence of preeclampsia in gestational diabetes patients. The study involved 250 pregnant women divided into 80 healthy control subjects, 85 gestational diabetes patients only, and 85 patients of gestational diabetes combined with preeclampsia. Systolic and diastolic blood pressures, urinary proteins, kidney and liver functions, glucose homeostasis parameters, and lipid profile were determined. Genotyping of the polymorphism was conducted by PCR-RFLP. The frequency of the minor C allele of rs2910164 polymorphism was significantly higher among patients of gestational diabetes combined with preeclampsia compared to the control group (p = 0.012) and the gestational diabetes group (p = 0.014). Patients of gestational diabetes and preeclampsia carrying CC genotype showed higher systolic and diastolic blood pressure, and increased urea, creatinine, urine protein, and dyslipidemia compared to the carriers of GG and GC genotypes. In conclusion, the results of the current study suggest that the rare CC genotype of MIR146A rs2910164 (G/C) polymorphism may be related to increased incidence of preeclampsia in gestational diabetes patients.

Background: Cuscuta pedicellata and some of its isolated compounds were suggested previously to have an anti-obesity effect in rats. This study aimed to investigate the effect of ten isolated compounds from C. pedicellata on insulin resistance, some oxidative stress markers and expression of the mitochondrial uncoupling protein-1 (UCP-1) and Carnitine palmitoyltransferase-I (CPT-1) genes in brown adipose tissue of high fat diet (HFD) rats., Methods: One hundred and four male albino rats were divided into 13 groups. Group (1) was considered as normal untreated rats. Obesity was induced in all other groups by HFD. Group (2) served as obese control group and groups (3-11) were treated for four weeks with C. pedicellata extract or one of its isolated compounds (naringenin, kaempferol, aromadenderin, quercetin, 3,5,7,30,50-pentahydroxy flavanone, naringenin-7-O-b-d-glucoside, aromadenderin-7-O-b-d-glucoside, taxifolin 7-O-b-d-glucoside, kaempferol-3-O-b-d-glucoside [astragalin], and quercitin-3-O-b-d-glucoside [isoquercitrin]). At the end of the experiment, rats were then sacrificed under anesthesia and their brown adipose tissues were dissected out for determination of UCP-1 and CPT-1 genes using quantitative PCR. Blood samples were collected for determination of blood glucose, insulin, thiobarbituric acid reactive substances (TBARS), superoxide dismutase (SOD) and catalase., Results: A significant reduction in homeostasis model assessment-insulin resistance (HOMA-IR) and TBARS levels was observed in rats treated with C. pedicellata crude extract and some of its isolated compounds, with a significant increase in SOD and catalase levels and upregulation of UCP-1 and CPT-1 genes expression compared to the obese control group., Conclusions: This study suggests a beneficiary role of C. pedicellata in reducing insulin resistance, oxidative stress and enhancing energy expenditure., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Essential hypertension is a chronic medical condition affecting thousands of people worldwide. Hypertension results from interplay of genetic and environmental factors. MicroRNAs regulate gene expression and can be biomarkers for disease. MicroRNA let-7e and microRNA 296-5p have been linked to different cardiovascular diseases. This study aimed to determine association of serum miRNA let-7e and miRNA 296-5p with essential hypertension in Egyptian patients. MicroRNA let-7e and miRNA-296-5p expression was determined in sera of 25 hypertensive patients and 25 normotensive controls by quantitative real-time polymerase chain reaction. Hypertensive patients showed significantly higher expression of miRNA let-7e (3.23-fold increase, p = 0.036) in comparison with normotensive controls. In hypertensive patients, miRNA let-7e expression was positively correlated with increased systolic and diastolic blood pressure. Furthermore, miRNA 296-5p expression was negatively correlated with serum total cholesterol and low-density lipoprotein. Results from this study indicate that miRNA let-7e can potentially be a biomarker for essential hypertension.

Obesity is a proven risk factor for neurodegenerative disease like Alzheimer's disease (AD). Accumulating evidences suggested that nutritional interventions provide potential for prevention and treatment of AD. The present study aimed to investigate the effect of dietary treatment of obese rats with natural Raspberry ketone (RK) and their relationship with neurodegeneration. Obesity was first induced in 40 male Wistar rats (140-160 g) by feeding high fat diet (HFD) for 16 weeks. Obese rats were then assigned into 4 groups (n = 10 each). (O-AD) is obese induced AD group maintained on HFD for another 6 weeks. OCR is obese group received calorie restricted diet for 6 weeks. OCRRK is obese group received calorie restricted diet and RK (44 mg/kg body weight, daily, orally) for 6 weeks and OCRD is obese group received calorie restricted diet and orlistate (10 mg/kg body weight, daily orally) for 6 weeks. Another 10 normal rats received normal diet were used as normal control group (NC). Body weight, visceral white adipose tissue weight (WAT), lipid profile, oxidative stress markers, adiponectin, cholinergic activity and amyloid extracellular plaques were examined. In addition to histological changes in brain tissues were evaluated.Raspberry ketone (RK) via its antioxidant properties attenuated oxidative damage and dyslipidemia in O-AD group. It inhibited acetylcholinesterase enzyme (AchE) and hence increased acetylcholine level (Ach) in brain tissues of O-AD rats. It is also impeded the upregulation of beta-secretase-1 (BACE-1) and the accumulation of amyloid beta (Aβ) plaques which crucially involved in AD. The combination of CR diet with RK was more effective than CR diet with orlistate (antiobese drug) in abrogating the neurodegenerative changes induced by obesity. Results from this study suggested that concomitant supplementation of RK with calorie restricted regimen effectively modulate the neurodegenerative changes induced by obesity and delay the progression of AD., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

The human pathogen Staphylococcus aureus encodes the ESAT6-like Secretion System (ESS). The ESS pathway secretes pathogenic substrates such as EsxA, EsxB, EsxC, EsxD and EssD that mediate staphylococcal establishment in persistent abscess lesions. The biochemical behavior of these substrates is not fully understood. EsxC is species-specific lysine-rich homodimer that lacks recognizable topogenic sequence. Studies have shown that EsxC is required for the secretion of other substrates, thereby revealing its biomedical importance. Here, EsxC self-association was investigated in the presence of several metal ion chelators. Results show that EsxC homodimerization is abolished in the presence of EDTA and EGTA, suggesting a role for calcium in mediating EsxC self-association. Complementation experiments confirm that EsxC homodimerization is calcium-dependent. N- and C-terminal truncations of EsxC were constructed, followed by bacterial two-hybrid screening. Results show that EsxC self-association is mediated by its C-terminal domain. Affinity purification of recombinant EsxC to apparent homogeneity, followed by chemical crosslinking and SDS-PAGE led to the detection of the monomeric and dimeric forms of the protein. In contrast and when a purified EsxC variant lacking the C-terminus was subjected to similar conditions, only the monomeric form was observed. These in vivo and in vitro data highlight the contribution of the C-terminus of the virulence factor EsxC to self-association, and document a previously unreported role for calcium in mediating protein-protein interactions in this pathogenic secretion system., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Objective: This study aimed to assess the relation of locus 1p13 rs646776 (T/C) polymorphism with preeclampsia in Egyptian women., Methods: The study included 100 healthy pregnant female subjects and 100 preeclampsia patients. The genotypes of the polymorphisms were assessed. Endothelin-1 level was determined in plasma., Results: The major T allele of the 1p13.3 genomic region rs646776 polymorphism had a higher frequency in preeclampsia patients. Carriers of C allele had significantly lower endothelin-1 levels, lower systolic and diastolic blood pressure, decreased proteinuria, and increased HDL-C in the patients., Conclusion: The rare C allele of rs646776 polymorphism in chromosomal locus 1p13.3 is associated with decreased risk of preeclampsia.

Pre-miRNA-499 gene is associated with autoimmune disease. Mir-449 rs3746444 polymorphism is inconsistent for rheumatoid arthritis (RA). This study aimed to investigate association of mir-499 rs3746444 polymorphism with RA activity and severity in Egyptian population. The study population was conducted as case control study in 100 RA patients diagnosed according to the American College of Rheumatology classification criteria for RA, and the control group included 100 healthy subjects who were age-and sex-matched to the RA group. Different genotypes were assessed using polymerase chain reaction-restriction fragment length polymorphism. 95% Confidence interval and odds ratio were defined to assess the strength of association. Regarding patients, thirty-three patients carried TT genotype, fifty-three patients carried TC genotype and fourteen patients carried CC genotype. So the frequency of the minor C allele in RA patients was significantly higher than the control subjects ( P  = 0.037). TC, CC genotypes and C allele frequencies were significantly associated with disease severity as they had high rheumatoid factor (55.78 µIU/ml) and anti-cyclic citrullinated peptide (Anti-CCP) antibody (297.32 µIU/ml). Moreover, the heterozygote TC had more severe and more active form of the disease compared with homozygote CC or TT as they had high Anti-CCP antibody, and disease activity score 28 (score 5). Our work suggests that C allele of Pre-miRNA rs3746444 polymorphism contributes to heritability of susceptibility to RA compared to T allele. This polymorphism was associated with the activity and severity of the disease., Competing Interests: Compliance with Ethical StandardsNone of the authors have any conflicts of interest.

Context: Interleukin-1A (IL-1A) is a cytokine involved in inflammatory process. IL-1A (rs3783553) gene polymorphism is comprised in the regulation of IL-1A expression., Objective: This study aims to evaluate association of IL-1A (I/D) gene polymorphism with NAFLD and its component traits among Egyptian populations., Methods: The study included 75 healthy subjects and 75 patients with NAFLD. Different genotypes of IL-1A (I/D) gene polymorphism were determined by PCR-PAGE technique, serum IL-1A level and other biochemical parameters were measured., Results: The major D allele was significantly associated with NAFLD patients (p = .002). DD genotype showed a significant increase in BMI and decrease in HDL-C. Also serum IL-1A was significantly correlated with the DD genotype. Serum IL-1A showed a significant positive correlation with BMI, triglycerides, total cholesterol, LDL-C, VLDL-C and FBG, and a significant negative correlation with HDL-C., Conclusions: Major D allele of IL-1A (I/D) gene polymorphism is associated with NAFLD in the Egyptian population.