Micro RNA 146a gene variant / TNF-α / IL-6 / IL-1 ß; A cross-link axis inbetween oxidative stress, endothelial dysfunction and neuro-inflammation in acute ischemic stroke and chronic schizophrenic patients.

This work was purposed to speculate the possible association of rs2910164hsa-miR-146a C>G gene single nucleotide polymorphism in the pathogenesis of schizophrenia and subsequently their relevance to neuro-inflammatory, vascular and oxidative stress pathways as acute ischemic stroke (AIS) risk factors in chronic schizophrenic patients. 450 subjects, 150 healthy controls (group I), 150 chronic schizophrenic patients without any evidences of stroke (group II) and 150 chronic schizophrenic patients with AIS (group III) were included. Genotypes (CC, CG&GG) for hsa-mir-146a gene polymorphism were identified using polymerase chain reaction-restriction fragment length polymorphism PCR-RFLP technique. Tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), interleukin 1ß (IL-1 ß), plasminogen activator-inhibitor 1 (PAI-1), thrombomodulin (TM) and 8-Hydroxy-2-deoxyguanosine (8-OHdG) serum levels were immunoassayed. Complete lipid profile was estimated. The CG and GG hsa-miR-146a genotypes were associated with increased risk of both schizophrenia and AIS in schizophrenic patients with thrombomodulin levels decrement in group II& III. On the other side, the risk genotypes were associated significantly with positive and negative syndrome scale PANSS scores, TNF-α, IL-6, IL-1 ß, PAI-1, and 8-OHdG increment levels in both groups II & III. By contrast, the CG and GG hsa-miR-146a genotypes did not affect the neuro-inflammatory and oxidative stress markers in healthy controls. These findings illustrate a new mechanism strengthening the occurrence of oxidative stress and DNA damage as a result of the neuro-inflammatory and endothelial dysfunction status originated from the hsa-miR-146a C>G gene single nucleotide polymorphism, thus, confirming their role in the pathogenesis of schizophrenia and its AIS risk.

Regenerative effects of glycyrrhizin and/or platelet rich plasma on type-II collagen induced arthritis: Targeting autophay machinery markers, inflammation and oxidative stress.

Rheumatoid arthritis (RA) is a systemic chronic autoimmune disease manifested by joint destruction and deformity, hence decreasing patient's life quality. The aim of the present work is to explore the mechanistic effects of glycyrrhizin (GL)and/or platelet rich plasma (PRP) treatment on collagen induced arthritis. 75 female Wistar rats were allocated into five equal groups. Group I: control group. Group II: arthritis group (A group); arthritis was induced by type-II collagen Group III: Glycyrrhizin treated group(A + GL group), Group IV: platelet rich plasma treated group(A + PRP group)and Group V: combined treatment group(A + GL + PRP group). Hind paw joint tissue levels of high-mobility group box 1 protein (HMGB-1), beclin-1 and nuclear factor (erythroid-2)-related factor 2 (Nrf2) DNA binding activity were detected by ELISA. Activities of myeloperoxidase (MPO) and catalase enzymes were determined spectrophotometrically. mRNA expression levels of microtubule associated protein light chain 3 (LC3) was detected by quantitative real time PCR. After 8 weeks treatment, there was improvement of inflammation and autophagy biomarkers by the significant reduction of HMGB-1 and beclin-1 levels, down regulation ofLC3mRNA expression. On the other hand, we monitored restoration of the anti-oxidant status through the inhibited MPO activity besides induction of both catalase and Nrf2-DNA binding activities. It could be concluded that, the mutual use of both PRP and GL had a greater effect than each alone against arthritis which is considered a novel finding that can highlight the regenerative and ameliorative effects of this combined treatmentthus launching promising avenues for RA treatment.

Hesperidin modulates dextran sulfate sodium-induced ulcerative colitis in rats: Targeting sphingosine kinase-1- sphingosine 1 phosphate signaling pathway, mitochondrial biogenesis, inflammation, and apoptosis.

Ulcerative colitis (UC) is a chronic gastrointestinal disorder interfering with life quality. A total of 60 male Wistar rats were divided into four equal groups: Control (group I), hesperidin only (group II), UC untreated (group III), and UC treated with hesperidin (group IV). Hesperidin had modulatory effects on UC pathogenesis, which might be through alleviating colonic sphingosine phosphate phosphatase 2 messenger RNA expression and sphingosine kinase-1 levels, thus suppressing the subsequent downstream inflammatory and apoptotic cascades represented by decreased macrophage inflammatory protein-1α and enhancement of B-cell lymphoma 2 immunohistochemistry expression. Also, it improved mitochondrial biogenesis by increasing the peroxisome proliferator-activated receptor-gamma-coactivator 1-α level. It successfully restored redox potential as evidenced by marked alleviations of the nitric oxide and peroxynitrite levels, increasing total antioxidant capacity, and activating the superoxide dismutase enzyme. Also, hesperidin alleviated the UC disease activity index and improved the histopathological picture. These findings may offer a new therapeutic strategy for UC treatment.

Soya bean rich diet is associated with adult male rat aggressive behavior: relation to RF amide-related peptide 3-aromatase-neuroestrogen pathway in the brain.

Relation between soya bean (SB) consumption and aggressive behavior has not been elucidated yet. Thus, this study was conducted to investigate the effect of large amount of SB consumption on adult male rats' aggressive behavior through investigating changes in the expression of gonadotropin-inhibitory hormone/ RF amide-related peptide 3 (GnIH/RFRP3), neuropeptide FF receptor, cytochrome P450, family 19, subfamily A, polypeptide 1 (Cyp19A1), estrogen receptors α and ß and the levels of neuroestrogen, dopamine, glutamate and testosterone as well as aromatase activity in the brain. Adult male rats were divided into three equal groups: group I, control group, received standard diet; group II and group III received 25% and 50% SB of their standard diet contents, respectively, for 12 weeks. The obtained results showed that feeding male rats with large amount of SB could induce aggressive behavior in a dose dependant manner possibly through inhibition of brain GnIH/RFRP-aromatase-neuroestrogen pathway. These effects may be through decreasing aromatase activity, neuroestrogen concentration, Cyp19A1 and ER ß mRNA levels and increasing ER α mRNA levels and immunostaining as well as testosterone, dopamine and glutamate levels in the brain. These findings also provide further support for the inhibitory role of RFRP3 on aggressive behavior of male rats. These data may open new avenues for the potential harmful effects of consumption large amounts of SB rich food on humans.

Role of Interleukin 37 as a Novel Proangiogenic Factor in Juvenile Idiopathic Arthritis.

OBJECTIVE: The aim of this study was to investigate interleukin 37 (IL-37) levels in the serum and synovial fluid of patients with juvenile idiopathic arthritis (JIA), its expression in peripheral blood mononuclear cells, and correlation with disease activity and angiogenesis. METHODS: Seventy JIA patients and 50 control subjects were examined. The Juvenile Arthritis Disease Activity Score in 27 joints (JADAS-27) was calculated. Immunoassays were used to measure the serum and synovial fluid levels of IL-37, vascular endothelial growth factor (VEGF), soluble VEGF receptor 1 (sVEGF-R1), and sVEGF-R2. Relative expression of IL-37 mRNA in peripheral blood mononuclear cells and the power Doppler ultrasound score of the affected joint were measured. RESULTS: Patients with JIA were subdivided as 20 systemic-onset, 20 polyarticular, and 30 oligoarticular (10 persistent, 20 extended) cases. Serum levels of IL-37, VEGF, VEGF-R1, and VEGF-R2 and relative IL-37 mRNA expression were significantly higher in JIA patients when compared with the control subjects (p < 0.001). These concentrations were significantly higher in systemic-onset JIA compared with those in polyarticular and oligoarticular JIA, and in polyarticular JIA when compared with oligoarticular JIA (p < 0.001). Serum, synovial, and mRNA expression levels of IL-37 were positively correlated with C-reactive protein, erythrocyte sedimentation rate, Juvenile Arthritis Disease Activity Score in 27 joints, power Doppler ultrasound score (p < 0.001), and the serum and synovial VEGF and VEGF-RI and -R2 levels (p < 0.05). CONCLUSIONS: Our results demonstrate that IL-37 levels and mRNA expression were significantly increased in JIA patients, and their levels were positively correlated with disease activity and markers of angiogenesis (VEGF and VEGF receptors), suggesting that IL-37 may be correlated with angiogenesis.

Ameliorative Effects of Curcumin on Fibrinogen-Like Protein-2 Gene Expression, Some Oxido-Inflammatory and Apoptotic Markers in a Rat Model of l-Arginine-Induced Acute Pancreatitis.

The aim of the study was to investigate the ameliorative effects of curcumin on fibrinogen like protein-2 (fgl-2), some oxido-inflammatory and apoptotic markers in rat-induced acute pancreatitis (AP). Seventy-five albino rats were divided into control group, l-arginine (l-Arg)-induced AP group, curcumin pre-treated group before AP induction, curcumin post-treated group after AP induction, and curcumin injected group only. AP group showed severe necrotizing pancreatitis confirmed by histopathological changes and elevations in serum amylase and lipase activities, levels of epithelial neutrophil-activating peptide 78, tissue content of protein carbonyls, levels of tumor necrosis factor α, and caspase-3 as well as myeloperoxidase activity. Significant elevation in pancreatic fgl-2 mRNA expression was detected in AP group. Improvement of all parameters was detected with increase of caspase-3 in both curcumin-treated groups that confirmed curcumin ameliorative effects against AP through induction of apoptosis and inhibition of micro-thrombosis, inflammation, and oxidative stress.

Plain set and stirred yogurt with different additives: implementation of food safety system as quality checkpoints.

Hazard Analysis Critical Control Point (HACCP) is a risk management protocol developed to ensure food safety through a precautionary approach that is believed to offer assurances in producing safe food for customers. Yogurt is made in a number of phases, commencing with the collection of raw milk and ending with consumer consumption. While this is happening, major economic and health issues might arise from exposing the manufacturing line to biological, chemical, and/or physical contaminations. As a result, the decision tree approach was used to determine the CCPs during the production of yogurt. Additionally, biological dangers are incorporated as a by-product of the system's implementation performance. In particular, the plain set and nut puree-honey-fortified stirred yogurt manufacturing techniques are highlighted for the first time in this study. The potential manufacturing risks are described for the first time, together with information on how HACCP plans may guard against major risks that could result in the production of yogurt that is not in compliance with established standards.

Type VI secretion system (T6SS) in Klebsiella pneumoniae, relation to antibiotic resistance and biofilm formation.

Background and Objectives: The type VI secretion system (T6SS) was identified as a novel virulence factor in many Gram-negative bacteria. This study aimed to investigate the frequency of the T6SS genes in Klebsiella pneumoniae-causing different nosocomial infections, and to study the association between T6SS, antibiotic resistance, and biofilm formation in the isolated bacteria. Materials and Methods: A total of fifty-six non-repetitive K. pneumoniae isolates were collected from different inpatients admitted at Sohag University Hospital from September 2022 to March 2023. Samples were cultured, colonies were identified, and antimicrobial sensitivity was done by VITEK® 2 Compact. Biofilm formation was checked using Congo red agar method. T6SS genes, and capsular serotypes were detected by PCR. Results: Fifty-six K. pneumoniae isolates were obtained in culture. 38 isolates (67.86%) produced biofilm and 44 (78.57%) were positive for T6SS in PCR. There was a significant association between the presence of T6SS and resistance to the following antibiotics: meropenem, ciprofloxacin, and levofloxacin. All biofilm-forming bacteria had T6SS, with significant differences towards T6SS -positive bacteria. There was no significant association between T6SS, and the presence of certain capsular types. Conclusion: The T6SS-positive K. pneumoniae has greater antibiotic resistance, and biofilm-forming ability which is considered a potential pathogenicity of this emerging gene cluster.

Estimation of immune response (IgG) to SARS-COV2 (COVID-19) after the third COVID-19 wave in Egypt, A cross-sectional Study.

Since the start of the pandemic, the number of cases has been increased rapidly. Due to asymptomatic and mild cases and restricted testing in many geographic locations, the overall number of actual COVID-19 cases is likely significantly higher than the number of verified cases. Several COVID-19-related comorbid diseases impair immune system function, which has an impact on COVID-19 responsiveness. So, we evaluated the immune response to SARS-CoV-2 after the third wave of COVID-19 and assessed the effect of comorbid diseases on this immune response. The current cross-sectional study was conducted in August 2021 after the third wave of COVID-19. The study included 287 participants. All participants were asked about their epidemiological data, comorbid diseases, data suggesting COVID-19 infection, and precautions measures to minimize the exposure to the disease. Of the 278 participants, 50% had a positive IgG response to COVID-19. Regarding comorbid diseases, the IgG antibody titer was significantly lower in patients with chronic kidney diseases (CKD) on dialysis, ischemic heart disease, and chronic obstructive lung diseases than other participants (p= 0.01, p= 0.02, p= 0.005, respectively). Neither precaution measures nor comorbid diseases had a role in risk factors of COVID-19 infections in our participants. In conclusion, high seroprevalence (50%) of SARS-CoV-2 IgG antibody after the third wave of COVID-19 was observed in the current study. Comorbid conditions as hypertension, chronic cardiac diseases, chronic chest problems, and CKD on dialysis could decrease the immune response against COVID-19 infection.

Associations between IL-17A G/A-rs2275913 and IL 23R A/G-rs11209026 gene polymorphisms and severe coronavirus disease 2019 (COVID-19).

Severe COVID-19 disease was linked to a severe proinflammatory response and cytokine storm interleukin 17 (IL-17) is one of these cytokines, was associated with severe acute lung injury and multiorgan dysfunction. Single nucleotide polymorphisms (SNPs) in genes coding IL-17 can affect level of IL-17 hence its role in diseases. Also, SNPs in IL-23 R which control IL-23 is the main activator of IL-17 production. This study aimed to determine whether the IL-17A (G/A-rs2275913), IL-23R (A/G rs11209026) SNPs and serum levels of IL-17 were related to the risk of severe COVID-19. This case-control study included 120 confirmed COVID-19 patients, divided into two categories according to the severity of the disease and 74 normal subjects as controls. COVID-19 patients were SARS-CoV-2 positive by a reverse transcription-polymerase chain reaction and subjected to full clinical examinations, routine laboratory tests, and radiographic evaluations. The IL-17 levels were assessed using ELISA method, and genotyping of IL-17A (197 A/G; rs2275913) and IL-23R rs11209026 (A/G) was performed by the TaqMan Genotyping Assay. There were no differences in the distribution of IL-17A or IL-23R genotypes between COVID-19 groups and the control group (p=0.93 and p=0.84, respectively). Severe COVID-19 patients had significantly higher IL-17 serum levels than non-severe COVID-19 (p=0.0001). The GG genotypes of IL-17A were significantly higher in severe COVID-19 patients (p=0.004). Multivariate logistic regression analysis revealed that AG, GG genotypes of IL-17 and IL-17A were independent predictors of COVID-19 disease severity (p < 0.0001, p=0.06 and p=0.04, respectively). ROC curve analysis for IL-17, as predictor of severe COVID-19 disease revealed a sensitivity of 87.9% and specificity of 66.1% at a cutoff point of 114 pg/ml with AUC = 0.799. In conclusion, these findings indicated that IL-17 may be considered a marker of severe COVID-19. IL-17A SNPs may have a role in COVID-19 severity. IL-23R SNPs had no role in COVID-19.