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.

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.

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.

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.

The Preventive and Therapeutic Effects of Ajwa Date Fruit Extract Against Acute Diclofenac Toxicity-Induced Colopathy: An Experimental Study.

Background: Studies regarding treatment of acute toxicity with diclofenac (ATD) are quite few. Diclofenac is commonly prescribed in neurology, psychiatry, and general medicine practice. This study investigated possible colon-protective effects exerted by Ajwa date fruit extract (ADFE), a prophetic medicine remedy native to Al-Madinah, Saudi Arabia against ATD. Phytochemicals in ADFE as gallic acid and quercetin have reported protective effects against ATD. Methods: Total phenols and flavonoids in ADFE were estimated as equivalents to gallic acid and quercetin. Four experimental groups were allocated each of six rats: control group, ATD group received a single dose of 150 mg diclofenac intraperitoneally, toxicity prevention group received a single dose of ADFE orally followed 4 hours later by diclofenac injection, and toxicity treatment group received a similar diclofenac dose followed 4 hours later by a single dose of ADFE. Four days later, animals were sacrificed. Histological and biochemical examinations were done. Results: ADFE has a total phenolic content of 331.7 gallic acid equivalent/gram extract and a total flavonoid content of 70.23 quercetin equivalent/gram. ATD significantly increased oxidative stress markers as serum malondialdehyde (MDA) and hydrogen peroxide (H2O2). Serum MDA and H2O2 were significantly scavenged by ADFE. ATD significantly (p<0.001) decreased antioxidant power as serum total antioxidant capacity and catalase activity. That was reversed by ADFE in both prevention and treatment groups. Histologically, ATD caused complete destruction of colonic crypts architecture, patchy loss of the crypts, loss of the surface epithelium, absent goblet cells and submucosal exudate, heavy infiltration of the lamina propria and submucosa with inflammatory cells, mainly lymphocytes and eosinophils. There were mucosal haemorrhages and submucosal dilated congested blood vessels. All that was prevented and treated using ADFE. Conclusion: ADFE is rich in quercetin and gallic acid equivalents that exert potent antitoxic effects. ADFE is strongly recommended for preventive and therapeutic colon effects against ATD.

Evaluation of performance of hearing aid users using Acoustic Change Complex (ACC) and behavioral measures.

OBJECTIVE: To validate the clinical use of Acoustic Change Complex (ACC) as an objective tool in children who use hearing Aids and explore how far ACC response parameters could be correlated to behavioral tests. METHOD: Sixty Arabic speaking children, using binaural Hearing Aids (H.As), participated in the present study. Their age ranged from 6 to 12 years. Evaluation of Hearing aid device performance was performed through questionnaire, speech in noise tests and aided/unaided ACC recordings. Two stimuli '' vowel/o/with SNR (0 &+8) ''were developed and standardized to elicit ACC response. The replicated ACC waveforms were collected and analyzed and the aided ACC responses were compared with unaided ACC and correlated to behavioral tests. RESULTS: The ACC percent identification in children using H.As using vowel/o/with SNR (+8 & 0) stimuli was 75% and 45% respectively in aided condition, the percent decreased to 40% and 15% in unaided condition. Speech in noise stimuli showed significant difference of ACC-N1 latency between the aided and unaided groups being longer in the unaided condition. The correlations between behavioral tests and ACC response (latency and amplitude) were irrelevant. CONCLUSIONS: Hearing-impaired subjects can process speech stimulus at the level of the auditory cortex, and in a more effective manner when they used their H.As. ACC can be used as an objective measure for selective auditory attention ability using vowel-in-noise. However, it couldn't replace Behavioral measures.

The evolving role of long noncoding RNA HIF1A-AS2 in diabetic retinopathy: a cross-link axis between hypoxia, oxidative stress and angiogenesis via MAPK/VEGF-dependent pathway.

BACKGROUND: Diabetic retinopathy (DR) signifies a frequent serious diabetic complication influencing retinal structure and function. Dysregulation of lncRNAs drives a wide array of human diseases especially diabetes; thus, we aimed to study lncRNA HIF1A-AS2 role and its interplay with hypoxia, oxidative stress (OS), and angiogenesis in DR. MATERIALS AND METHODS: 60 DM patients in addition to 15 healthy subjects. were enrolled. LncRNA HIF1A-AS2 mRNA relative gene expression was assessed. Hypoxia inducible factor 1-alpha (HIF-1α), vascular endothelial growth factor (VEGF), mitogen activated protein kinase (MAPK), and endoglin levels were assessed. Detection of DNA damage using comet assay, and Redox status parameters were also detected. RESULTS: LncRNA HIF1A-AS2 expression was significantly increased in diabetic patients with the highest levels in proliferative DR patients. Moreover, HIFα, VEGF, MAPK, and Endogolin levels were significantly higher in the diabetic patients compared to control group with the highest levels in in proliferative DR patients. Significant DNA damage in comet assay was observed to be the highest in this group. CONCLUSION: We observed for the first time the imminent role of long noncoding RNA HIF1A-AS2 in DR throughout its stages and its interplay with hypoxia, OS, and angiogenesis via MAPK/VEGF-dependent pathway.

The emerging role of irisin in experimentally induced arthritis: a recent update involving HMGB1/MCP1/Chitotriosidase I-mediated necroptosis.

OBJECTIVES: Necroptosis is a tightly adjusted inflammatory necrotizing cell death signaling pathway that participates in pathogenesis of discrete diseases as rheumatoid arthritis (RA). Irisin is a myokine with immuno-modulatory effect. Evaluation of irisin efficiency as a novel therapeutic agent in experimentally induced RA via modulating immuno-inflammatory, necroptotic molecular and biochemical signaling pathways. METHODS: RA was induced in 30 female Wister albino rats by a single subcutaneous injection of collagen-II with incomplete Freund's adjuvant (CII-IFA) followed by booster immunization dose 10 days later. After 14 days of the injection, arthritis chronic phase was precipitated. 15 rats were treated by S.C irisin injection daily for 4 weeks. Joint tissue homogenate RIPK-3, MLKL, HMGB1, MCP1, IL-6, CHIT1, MDA, and PN levels were assessed calorimetrically. However, TNF-α mRNA expression level was evaluated by the qrt-PCR technique. RESULTS: The results showed that irisin significantly decreases the level of all assessed biochemical parameters, except MDA, which was significantly increased in comparison with the correspondent values in the arthritic group with no treatment (ttt). CONCLUSIONS: Irisin exhibits therapeutic anti-inflammatory and antioxidant effects via modulating immuno-inflammatory, necroptotic molecular, and biochemical signaling pathways in experimentally induced RA in rats. ABBREVIATIONS: RA: rheumatoid arthritis; RIPK3: receptor-interacting protein kinase 1; MLKL: mixed lineage kinase domain-like protein; HMGB1: High-mobility group protein box 1; MCP1: Monocyte chemoattractant protein 1; IL-6: Interleukin 6; CHIT1: Chitotriosidase; MDA: Malondialdehyde; PN: Peroxynitrite; TNF-α: Tumor Necrosis Factor; qrt-PCR: quantitative real-time reverse transcription PCR; CII-IFA: collagen-II with incomplete Freund's adjuvant; ttt: treatmentNote: TNF-α gene (NCBI GenBank Nucleotide accession # NM_012675.3); The housekeeping gene GAPDH (NCBI GenBank Nucleotide accession # NM_017008.4).

Liver function test abnormalities in COVID-19 patients and factors affecting them - a retrospective study.

AIM OF THE STUDY: We aimed to study liver function test abnormalities in our COVID-19 patients and factors affecting them and to evaluate whether liver function test abnormalities are related to the severity of COVID-19. MATERIAL AND METHODS: Our retrospective study included 118 patients who were SARS-CoV-2 positive. Their median age was 40 years. Fifty percent were male. Clinical and biochemical data were collected from patient records during the period from the start of June 2020 to the end of July 2020. Liver function test abnormalities included: alanine aminotransferase (ALT) > 40 U/l, aspartate aminotransferase (AST) > 40 U/l, serum albumin < 3.5 mg/dl, total bilirubin > 1.2 mg/dl, and international normalized ratio (INR) > 1.2. RESULTS: Forty-four percent of COVID-19 patients had liver function test (LFT) abnormalities. In patients with severe SARS-CoV-2, AST, total bilirubin and INR levels were significantly higher than in patients with the non-severe disease. Levels of hemoglobin, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), serum ferritin, D-dimer, and serum glucose were significantly higher in SARS-CoV-2 patients with LFT abnormalities than those with normal liver function. CONCLUSIONS: LFT abnormalities are very common in SARS-CoV2 positive patients, especially those with the severe form. Levels of ESR, CRP, serum ferritin, and D-dimer were higher in COVID-19 patients with LFT abnormalities than those with normal LFT. High serum ferritin levels might be potential risk factors for LFT abnormalities.

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.

Zamzam water is pathogen-free, uricosuric, hypolipidemic and exerts tissue-protective effects: relieving BBC concerns.

Zamzam water is the most frequently used drinking water by millions of people in Saudi Arabia. It is carried all the time by millions of pilgrims to their home countries as gifts to close and near relatives and friends. Safety of constituents of Zamzam water is a vital health topic. British Broadcasting Corporation (BBC) raised many health concerns regarding the high serum arsenic and nitrate contents in Zamzam water that may cause cancer. It is role of scientific research to present scientific facts to relieve such concerns. Arsenic is a carcinogen while nitrate causes methemogloinemia that affect oxygen carriage by haemoglobin. An ethical committee approval was obtained. Eighteen white albino mice (40-45 g) were used in this study. Three experimental groups were allocated (six mice per group): tap water group, distilled water group and Zamzam water group. Our data revealed that Zamzam water exerts tissue-protective effects that contradict malignancy. Our data proved that Zamzam water is pathogen-free causing no bacterial growth on CLED agar colonies. Zamzam water consumption for three consecutive months in mice was quite safe for the general health and significantly decreased serum uric acid (p < 0.05) (possibly due to Zamzam-induced urine alkalinisation facilitating uric acid excretion). Regular Zamzam water consumption significantly decreased serum cholesterol (p < 0.05) and serum triglycerides (p < 0.05). Hypolipidemic effects of Zamzam water may be due to its high mineral content facilitating increased lipids metabolism. Our data confirmed safety of prolonged use of Zamzam water comparable to other drinking water types regarding the metabolic and synthetic functions of the liver. Nitrates in Zamzam water are thought to be an original constituent that may be useful (exerting vasodilation, antithrombotic, and immunoregulatory effects) and not harmless. This may occur due to high Zamzam content of calcium, magnesium and selenium. Histologically, our data confirmed that Zamzam water was quite safe to renal parenchyma and comparable to other types of drinking water. In conclusion, health concerns raised by BBC regarding Zamzam water safety were a good chance for fruitful scientific research investigations that confirmed safety and beneficial effects of Zamzam water for human health.

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.

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.

Melatonin maximizes the therapeutic potential of non-preconditioned MSCs in a DEN-induced rat model of HCC.

Pretreatment of mesenchymal stem cells (MSCs) with melatonin (Mel) improves their potential therapeutic effect on chronic diseases and cancers. However, this preconditioning strategy may direct the effect of Mel toward MSCs alone and deprive cancer cells of the oncostatic effect of Mel. Herein, we hypothesized that Mel given before transplantation of non-preconditioned MSCs may maximize the therapeutic outcome via the oncostatic effect of Mel by preparing a suitable tumor microenvironment for MSCs. Female rats (n = 60) were equally divided into 6 groups; normal control, diethylnitrosamine (DEN), DEN + Mel, DEN + MSCs, DEN + MSCs preconditioned with Mel, and DEN + MSCs + Mel. The obtained data revealed that administration of Mel before MSCs treatment without preconditioning yielded a better ameliorative effect against DEN-induced hepatocellular carcinoma (HCC) as evidenced by: 1) reduced serum levels of alpha fetoprotein and gamma-glutamyl transferase; 2) decreased number and area of glutathione S-transferase placental positive foci; 3) induced apoptosis (as indicated by increased cleaved caspase-3 activity, upregulated expression of proapoptotic genes Bax and caspase 3 and downregulated expression of anti-apoptotic genes Bcl2, survivin); 4) decreased malondialdehyde level and increased activities of superoxide dismutase, catalase, and glutathione peroxidase enzymes; and 5) reduced inflammation, angiogenesis and metastasis as indicated by downregulated expression of interleukin 1 beta, nuclear factor kappa B, vascular endothelial growth factor, and matrix metallopeptidase 9 genes and upregulated expression of metalloproteinase inhibitor 1 gene. Thus, administration of Mel before MSCs (without preconditioning) fostered the survival and therapeutic potential of MSCs in HCC, possibly through induction of apoptosis and inhibition of inflammation and oxidative stress. This new strategy showed better therapeutic outcomes and may improve MSC-based therapies for HCC.

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.

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.

Synergistic Cardioprotective Effects of Combined Chromium Picolinate and Atorvastatin Treatment in Triton X-100-Induced Hyperlipidemia in Rats: Impact on Some Biochemical Markers.

Hyperlipidemia is one of the major risk factors for atherosclerosis and ischemic heart disease. Chromium (Cr) mineral is playing a crucial role in glucose and lipid homeostasis. The aim of this study was to evaluate the protective effects of combined chromium picolinate (CrPic) and atorvastatin treatment against hyperlipidemia-induced cardiac injury. Seventy-five male albino rats were divided into five groups (15 rats each). Hyperlipidemia was induced by intraperitoneal injection of a single dose of Triton X-100 (300 mg/kg body weight (b.w) (group ІІ). Treatment of hyperlipidemic rats was induced by daily administration of CrPic at a dose of 200 µg/kg b.w/day (group ІІІ), atorvastatin at a dose of 10 mg/kg/day (group IV), and combined treatment with both (group V) by gavage for 7 days. At the end of experiment, serum and heart tissues were obtained. Hyperlipidemia was confirmed by histopathology of heart tissues, marked serum dyslipidemia, increased atherogenic indices, and values of ischemia-modified albumin. In addition to increased values of proprotein convertase subtilisin/kexin type 9, activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase enzyme and high relative expression levels of pentraxin-3 were observed. However, paraoxonase-1 activity was markedly decreased in the hyperlipidemic group. Significant improvement in all assessed parameters was observed in the rat group treated with both CrPic and atorvastatin. It can be concluded that combined CrPic and atorvastatin treatments had synergistic cardioprotective effects against hyperlipidemia which may be through modulating atherosclerosis as well as cardiac and aortic damage and/or activation of anti-inflammatory and anti-oxidant pathways, thus reversing endothelial dysfunction.

Alternative Chk1-independent S/M checkpoint in somatic cells that prevents premature mitotic entry.

Genomic instability is the hallmark of cancer. Checkpoint kinase-1 (Chk1) is required for cell cycle delay after DNA damage or blocked DNA replication. Chk1-depleted tumor cells undergo premature mitosis and apoptosis. Here we analyzed the depletion of Chk1 in normal somatic cells in the absence of DNA damage in order to investigate alternative cell cycle checkpoint mechanism(s). By means of adenoviruses, flow cytometry, immunofluorescence and Western blotting, Chk1-depleted mouse embryonic fibroblasts (MEFs) were investigated. Chk1-/- MEFs arrested at the S/G2 boundary of the cell cycle with decreased protein levels of many cell cycle key players. Cyclin B1 was predominantly cytoplasmic. Interestingly, overexpression of nuclear dominant Cyclin B1 leads to nuclear translocation and premature mitosis. Chk1-/- MEFs exhibited the absence of double-strand breaks, yet cells showed delayed DNA damage recovery with pan-nuclear immunostaining pattern of Histone H2AX. Activation of this checkpoint would elicit a senescent-like phenotype. Taken together, our elaborated data revealed the existence of an additional S/M checkpoint functioning via γH2AX signaling and cytoplasmic retention of Cyclin B1 in somatic cells.

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.

Protective Effects of Combined Selenium and Punica granatum Treatment on Some Inflammatory and Oxidative Stress Markers in Arsenic-Induced Hepatotoxicity in Rats.

Oxidative stress is one of the major mechanisms implicated in inorganic arsenic poisoning. Punica granatum is known by its free radical scavenging properties. The aim of this study was to evaluate the protective role of combined selenium and P. granatum against arsenic-induced liver injury. Seventy-five female albino rats were divided into five groups (of 15 rats each). Toxicity was induced by oral sodium arsenite (5.5 mg/kg body weight (bw) daily) (group ІІ). Treatment of arsenic-intoxicated rats was induced by daily oral administration of sodium selenite (3 mg/kg bw) (group ІІІ), 100 mg of P. granatum ethanol extract per kilogram body weight dissolved in 300 mL distilled water in three divided doses (100 mL of this suspension every 8 h) (group IV), and combined daily oral treatment with both selenite and P. granatum ethanol extract (group V). After 3 weeks, serum and liver tissues were obtained from the decapitated rats for different estimations. Hepatotoxicity was demonstrated by significant elevation in liver weights and activities of liver enzymes, alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and decrease in serum total proteins and albumin (p < 0.05) which were confirmed by histopathological examination. Additionally, arsenic hepatotoxicity led to an increased values of malondialdehyde, advanced oxidation protein products, nitric oxide, and interleukin-6 (IL-6) (p < 0.05) and decreased activity of thioredoxin reductase, values of total anti-oxidant capacity, and nuclear factor erythroid 2-related factor 2 (Nrf2) gene expression. Significant improvement in all assessed parameters was observed in rat group treated with both P. granatum and selenium. It was concluded that combined P. granatum and selenium treatment had a synergistic hepatoprotective effect against arsenic toxicity through activation of Nrf2 anti-oxidant pathway.