G protein-coupled estrogen receptor (GPER) selective agonist G1 attenuates the neurobehavioral, molecular and biochemical alterations induced in a valproic acid rat model of autism.

Aims: Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder with a rising prevalence in boys rather than girls. G protein-coupled estrogen receptor (GPER) activation by its agonist G1 showed a neuroprotective effect, similar to estradiol. The present study aimed to examine the potential of the selective GPER agonist G1 therapy on the behavioral, histopathological, biochemical, and molecular alterations induced in a valproic acid (VPA)-rat model of autism.

Probiotic-prebiotic-synbiotic modulation of (YAP1, LATS1 and NF2 mRNAs/miR-1205/lncRNA SRD5A3-AS1) panel in NASH animal model.

Aim: To investigate the prophylactic efficacy of gut microbiota-based treatments on nonalcoholic steatohepatitis (NASH) management via modulation of Hippo signaling pathway-related genes (YAP1, LATS1 and NF2), and their epigenetic regulators (miR-1205 and lncRNA SRD5A3-AS1) retrieved from in-silico data analysis.

Materials & Methods: Histopathological, biochemical, molecular and immunohistochemistry analyses were used to assess the effects of multistrain probiotic mixture and prebiotic inulin fiber on high sucrose high fat (HSHF) diet-induced NASH in rats. These treatments were administered orally either alone or in combination, along with HSHF diet.

Chemopreventive Potential of Myrtenal against Nitrosamine-Initiated, Radiation-Promoted Rat Bladder Carcinogenesis.

The present study was undertaken to evaluate the chemopreventive activity of myrtenal, a natural monoterpene, against bladder carcinoma in rats induced with N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN) and promoted with γ-ionizing radiation (γ-IRR) as well as to assess the involvement of inflammation, apoptosis and oxidative damage in tumor development. Histopathological examination of rat bladder revealed the presence of noninvasive papillary transitional cell carcinoma (Grade 2) in sections from BBN group indicating the credibility of the applied carcinogenesis model. Myrtenal treatment caused improvement in urinary bladder mucosa with cells more likely in Grade 1.

Proteome Oxidative Modifications and Impairment of Specific Metabolic Pathways During Cellular Senescence and Aging.

Accumulation of oxidatively modified proteins is a hallmark of organismal aging in vivo and of cellular replicative senescence in vitro. Failure of protein maintenance is a major contributor to the age-associated accumulation of damaged proteins that is believed to participate to the age-related decline in cellular function. In this context, quantitative proteomics approaches, including 2-D gel electrophoresis (2-DE)-based methods, represent powerful tools for monitoring the extent of protein oxidative modifications at the proteome level and for identifying the targeted proteins, also referred as to the "oxi-proteome.

4-Phenylbutyric acid and rapamycin improved diabetic status in high fat diet/streptozotocin-induced type 2 diabetes through activation of autophagy.

An accumulating body of evidence supports the role of autophagy in the pathophysiology of T2DM. Also, abnormal endoplasmic reticulum (ER) stress response that has been implicated as a cause of insulin resistance (IR) could also be affected by the autophagic status in β-cells. The present study was designed to investigate whether autophagy is regulated in T2DM as well as to investigate the modulatory effect of the ER stress inhibitor 4-phenylbutyric acid (4-PBA) and the autophagy inducer rapamycin (Rapa) on the autophagic and diabetic status using type 2 diabetic animal model with IR.

Circulating MiR-210 and MiR-1246 as Potential Biomarkers for Differentiating Hepatocellular Carcinoma from Metastatic Tumors in the Liver.

Background: To date few reports have pointed out the role of circulating miRNAs in discriminating metastatic liver tumors from primary hepatocellular (HCC) tumors. Such discrimination will have significant therapeutic and prognostic implications. The purpose of this study was to evaluate the potential value of a panel of HCC-related circulating miRNAs (miR-142, miR-182, miR-200a, mir-210, miR-211, miR-302b, miR-324, miR-338, miR-340 and miR-1246) as noninvasive biomarkers for discriminating primary HCC from metastatic tumors in the liver.

Ursodeoxycholic acid suppresses the formation of fructose/streptozotocin-induced diabetic cataract in rats.

The main objective of this study was to investigate the potential protective effect of ursodeoxycholic acid (UDCA) on fructose/streptozotocin-induced diabetic cataract in rats. The diabetic model (DM) was induced through the administration of 10% fructose in drinking water for 2 weeks followed by streptozotocin injection (intraperitoneal). One week later, hyperglycemia was assisted and diabetic animals were treated with UDCA either as local eye drops (0.

The Synonymous Isocitrate Dehydrogenase 1 315C>T SNP Confers an Adverse Prognosis in Egyptian Adult Patients with NPM1-/CEBPA-Negative Acute Myeloid Leukemia.

Although the clinical features of isocitrate dehydrogenase () genetic aberrations have been well-characterized in acute myeloid leukemia (AML), definitive information on their prognostic significance is lacking. We aimed to explore the prognostic significance of gene alterations in an Egyptian cohort of adult patients with AML. Diagnostic peripheral blood samples from 51 AML patients were analyzed for the presence of mutations/SNPs in exon 4 of and genes using polymerase chain reaction amplification followed by direct sequencing.

Phenolic constituents of Pulicaria undulata (L.) C.A. Mey. sub sp. undulata (Asteraceae): Antioxidant protective effects and chemosystematic significances.

One new naturally isoflavone compound, 5,7,2',3',4' penta hydroxyl isoflavone-4'-O-β-glucopyranoside (1) was isolated from the aqueous methanol extract (AME) of Pulicaria undulata subsp. undulata, together with seven known compounds: kaempferol (2), kaempferol 3-O-β-glucoside (3), quercetin (4), quercetin 3-O-β-glucoside (5), quercetin 3-O-β-galactoside (6), quercetin 3,7-di OCH (7), and caffeic acid (8). Their structures were established through chemical (acid hydrolysis) and spectral analysis (UV, NMR, and ESIM).

Proteome oxidative carbonylation during oxidative stress-induced premature senescence of WI-38 human fibroblasts.

Accumulation of oxidatively damaged proteins is a hallmark of cellular and organismal ageing, and is also a phenotypic feature shared by both replicative senescence and stress-induced premature senescence of human fibroblasts. Moreover, proteins that are building up as oxidized (i.e.

Circulating microRNAs panel as a diagnostic tool for discrimination of HCV-associated hepatocellular carcinoma.

Early diagnosis of hepatocellular carcinoma (HCC) can significantly improve the overall survival of HCC patients. However, current diagnostic markers are compromised and limited by their low sensitivity and specificity. In this work, circulating microRNAs (miRs) were utilized as a diagnostic tool to test their efficiency to segregate HCC and hepatitis C virus (HCV)-infected patients from healthy subjects.

Neuroprotective and Therapeutic Effect of Caffeine on the Rat Model of Parkinson's Disease Induced by Rotenone.

The present study aimed to investigate the protective and therapeutic effects of caffeine on rotenone-induced rat model of Parkinson's disease (PD). Rats were divided into control, PD model induced by rotenone (1.5 mg/kg intraperitoneally (i.

Protein oxidative damage at the crossroads of cellular senescence, aging, and age-related diseases.

Protein damage mediated by oxidation, protein adducts formation with advanced glycated end products and with products of lipid peroxidation, has been implicated during aging and age-related diseases, such as neurodegenerative diseases. Increased protein modification has also been described upon replicative senescence of human fibroblasts, a valid model for studying aging in vitro. However, the mechanisms by which these modified proteins could impact on the development of the senescent phenotype and the pathogenesis of age-related diseases remain elusive.

Protein modification and replicative senescence of WI-38 human embryonic fibroblasts.

Oxidized proteins as well as proteins modified by the lipid peroxidation product 4-hydroxy-2-nonenal (HNE) and by glycation (AGE) have been shown to accumulate with aging in vivo and during replicative senescence in vitro. To better understand the mechanisms by which these damaged proteins build up and potentially affect cellular function during replicative senescence of WI-38 fibroblasts, proteins targeted by these modifications have been identified using a bidimensional gel electrophoresis-based proteomic approach coupled with immunodetection of HNE-, AGE-modified and carbonylated proteins. Thirty-seven proteins targeted for either one of these modifications were identified by mass spectrometry and are involved in different cellular functions such as protein quality control, energy metabolism and cytoskeleton.

Protein oxidative modifications and replicative senescence of WI-38 human embryonic fibroblasts.

The age-related accumulation of oxidized proteins is dependent on the balance between the generation of oxidatively modified proteins and their elimination by protein degradation and repair systems. Previous studies have demonstrated that replicative senescence represents a valid model of in vitro aging and that senescent cells do accumulate oxidized proteins while both proteasome, which is the major intracellular proteolytic system implicated in the removal of abnormal and oxidized proteins, and the oxidized protein-repair enzymes, methionine sulfoxide reductases, are being impaired. Declining proteasome activity with age has been attributed to decreased proteasome subunits expression and/or inactivation upon alteration of proteasome subunits, as well as accumulation of endogeneous inhibitors, such as highly oxidized and cross-linked proteins.