Relation of STAT3 rs1053005 Variation and miR-452-3p with Osteoarthritis Susceptibility and Severity and the Clinical Response to High-Molecular-Weight Hyaluronic Acid Injection in Osteoarthritis Patients

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

Apelin rs2235306 polymorphism is not related to metabolic syndrome in Egyptian women

Background: Apelin is an adipokine that was identified to play a role in the control of glucose homeostasis. Apelin rs2235306 gene polymorphism was linked to insulin resistance and poor glycemic control. Aim of the study: To assess the relation of apelin rs2235306 polymorphism with metabolic syndrome and its component traits in Egyptian women from Suez Canal area. Subjects and methods: The study included 100 metabolic syndrome patients and 100 healthy female subjects. The component traits of metabolic syndrome were determined and the genotypes of the polymorphisms were assessed using tetra amplification refractory mutation system polymerase chain reaction (T-ARMS-PCR) technique. Results: There was no significant difference in the allele frequencies between the metabolic syndrome and control groups (P = 0.841). There was also no association of the different genotypes of this polymorphism with any of the component traits of metabolic syndrome. Conclusion: Apelin rs2235306 polymorphism is not associated with the incidence of metabolic syndrome in the studied population

Relation of locus 1p13 rs646776 polymorphism with the risk of preeclampsia

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

Anti-Oxidant and Anti-Inflammatory Effects of Lipopolysaccharide from Rhodobacter sphaeroides against Ethanol-Induced Liver and Kidney Toxicity in Experimental Rats

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 &mu;g/kg) before ethanol. Ethanol significantly increased the expression of nuclear factor kappa B (NF-&kappa;B) and levels of malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-&alpha;) 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-&kappa;B and the levels of TNF-&alpha; 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

Antioxidant and Anti-Inflammatory Activity of Cynanchum acutum L. Isolated Flavonoids Using Experimentally Induced Type 2 Diabetes Mellitus: Biological and In Silico Investigation for NF-κB Pathway/miR-146a Expression Modulation

Cynanchum acutum L. is a climbing vine that belongs to the family Apocynaceae. Using different chromatographic techniques, seven compounds were isolated from the methanolic extract of the plant. The isolated compounds include six flavonoid compounds identified as rutin (1), quercetin-3-O-neohesperidoside (2), quercetin-3-O-β-galactoside (3), isoquercitrin (4), quercetin (5), and kaempferol 3-O-β-glucoside (6), in addition to a coumarin, scopoletin (7). The structures of the compounds were elucidated based on 1D NMR spectroscopy and high-resolution mass spectrometry (HR-MS), and by comparison with data reported in the literature. The first five compounds were selected for in vivo investigation of their anti-inflammatory and antioxidant properties in a rat model of type 2 diabetes. All tested compounds significantly reduced oxidative stress and increased erythrocyte lysate levels of antioxidant enzymes, along with the amelioration of the serum levels of inflammatory markers. Upregulation of miR-146a expression and downregulation of nuclear factor kappa B (NF-κB) expression were detected in the liver and adipose tissue of rats treated with the isolated flavonoids. Results from the biological investigation and those from the validated molecular modeling approach on two biological targets of the NF-κB pathway managed to highlight the superior anti-inflammatory activity of quercetin-3-O-galactoside (3) and quercetin (5), as compared to other bioactive metabolites

Pioglitazone Ameliorates Hippocampal Neurodegeneration, Disturbances in Glucose Metabolism and AKT/mTOR Signaling Pathways in Pentyelenetetrazole-Kindled Mice

Disturbance of glucose metabolism, nerve growth factor (NGF) and m-TOR signaling have been associated with the pathophysiology of epilepsy. Pioglitazone (PGZ) is an anti-diabetic drug that shows a protective effect in neurodegenerative diseases including epilepsy; however, its exact mechanism is not fully elucidated. The present study aimed to investigate the potential neuroprotective effect of PGZ in pentylenetetrazole (PTZ) kindled seizure in mice. Swiss male albino mice were randomly distributed into four groups, each having six mice. Group 1 was considered the control. Epilepsy was induced by PTZ (35 mg/kg i.p.) thrice a week for a total of 15 injections in all other groups. Group 2 was considered the untreated PTZ group while Group 3 and Group 4 were treated by PGZ prior to PTZ injection at two dose levels (5 and 10 mg/kg p.o., respectively). Seizure activity was evaluated after each PTZ injection according to the Fischer and Kittner scoring system. At the end of the experiment, animals were sacrificed under deep anesthesia and the hippocampus was isolated for analysis of glucose transporters by RT-PCR, nerve growth factor (NGF) by ELISA and mTOR by western blotting, in addition to histopathological investigation. The PTZ-treated group showed a significant rise in seizure score, NGF and m-TOR hyperactivation, along with histological abnormalities compared to the control group. Treatment with PGZ demonstrated a significant decrease in NGF, seizure score, m-TOR, GLUT-1 and GLUT-3 in comparison to the PTZ group. In addition, improvement of histological features was observed in both PGZ treated groups. These findings suggest that PGZ provides its neuroprotective effect through modulating m-TOR signaling, glucose metabolism and NGF levels

Plicosepalus acacia Extract and Its Major Constituents, Methyl Gallate and Quercetin, Potentiate Therapeutic Angiogenesis in Diabetic Hind Limb Ischemia: HPTLC Quantification and LC-MS/MS Metabolic Profiling

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

Metabolic Profiling, Chemical Composition, Antioxidant Capacity, and In Vivo Hepato- and Nephroprotective Effects of Sonchus cornutus in Mice Exposed to Cisplatin

Sonchus cornutus (Asteraceae) is a wild. edible plant that represents a plentiful source of polyphenolic compounds. For the first time, the metabolic analysis profiling demonstrated the presence of anthocyanidin glycosides, coumarins, flavonoids and their corresponding glycosides, and phenolic acids. The total phenolic compounds were determined to be 206.28 &plusmn; 14.64 mg gallic acid equivalent/gm, while flavonoids were determined to be 45.56 &plusmn; 1.78 mg quercetin equivalent/gm. The crude extract of S. cornutus exhibited a significant 1,1-diphenyl-2-picrylhydrazyl free radical scavenging effect with half-maximal inhibitory concentration (IC50) of 16.10 &plusmn; 2.14 &micro;g/mL compared to ascorbic acid as a standard (10.64 &plusmn; 0.82 &micro;g/mL). In vitro total antioxidant capacity and ferric reducing power capacity assays revealed a promising reducing potential of S. cornutus extract. Therefore, the possible protective effects of S. cornutus against hepatic and renal toxicity induced by cisplatin in experimental mice were investigated. S. cornutus significantly ameliorated the cisplatin-induced disturbances in liver and kidney functions and oxidative stress, decreased MDA, ROS, and NO levels, and restored CAT and SOD activities. Besides, it reversed cisplatin-driven upregulation in inflammatory markers, including iNOS, IL-6, and IL-1&beta; levels and NF-&kappa;B and TNF-&alpha; expression, and elevated anti-inflammatory IL-10 levels and Nrf2 expression. Additionally, the extract mitigated cisplatin alteration in apoptotic (Bax and caspase-3) and anti-apoptotic (Bcl-2) proteins. Interestingly, hepatic, and renal histopathology revealed the protective impacts of S. cornutus against cisplatin-induced pathological changes. Our findings guarantee a protective effect of S. cornutus against cisplatin-induced hepatic and renal damage via modulating oxidative stress, inflammation, and apoptotic pathways