Evaluation of gene expression of PLEKHS1, AADAC, and CDKN3 as novel genomic markers in gastric carcinoma.

Gastric cancer (GC) is considered lethal aggressive cancer. In Egypt, GC has a low incidence but unfortunately, it is mostly diagnosed at an advanced stage with a poor prognosis. Assessment of novel markers that can be used in the early detection of GC is an urgent need. The present study was performed to assess the association of the Pleckstrin homology domain-containing S1 (PLEKHS1)، arylacetamide deacetylase (AADAC, and Cyclin-dependent kinase inhibitor 3 (CDKN3) genes with GC and to correlate their gene expression levels with tumor stage, grade, and other clinicopathological features. The current work was performed on forty gastric tissue samples; twenty in Group 1 with GC tissues at different stages, and grades and twenty in Group 2 (control group) with non-tumorous tissue. PLEKHS1, AADAC, and CDKN3 gene expression were assessed by RT-qPCR. AADAC, CDKN3 genes were significantly (p<0.001) upregulated, while PLEKHS1 gene was significantly (p<0.001) downregulated in the GC group than the control group. AADAC gene expression exhibited a high significant (p<0.001) positive correlation with the tumor grades and the tumor stages. A high significant negative correlation between AADAC, and CDKN3 gene expression (r = -.760, p<0.001) was found. The three studied parameters showed high significant sensitivity and specificity in the prediction of the presence of GC. PLEKHS1, AADAC, and CDKN3 gene expressions were suggested to be used as diagnostic and predictive biomarkers of GC, additionally, AADAC may be used as a prognostic marker in these patients for further future confirming studies.

Antioxidant and anti-inflammatory properties of alpha-lipoic acid protect against valproic acid-induced liver injury.

Valproic acid (VPA) is one of the most used antiepileptic drugs despite of its many adverse effects such as anemia, leucopenia, thrombocytopenia, and liver toxicity. The hepatoprotective effect of alpha-lipoic acid (ALA) was confirmed. The aim of this study was to detect the protective effect of ALA against the adverse effects of VPA. To study this, 30 white albino Wistar male rats were divided into four groups. Group I was the control group; Group II included rats that received ALA (100 mg·kg-1·day-1) orally for 14 days; Group III and Group IV included rats that received VPA (500 mg·kg-1·day-1) for 15 days intraperitoneally, but Group IV rats received ALA (100 mg·kg-1·day-1) orally for 14 days prior to VPA. Blood samples were collected and livers were excised from rats for colorimetric analysis and quantitative real-time PCR. The rats that received VPA showed leucopenia, thrombocytopenia, a significant decrease of superoxide dismutase, glutathione, nuclear factor erythroid 2-related factor 2, and sirtuin 1, besides a significant increase of malondialdehyde and tumor necrosis factor α. Prior treatment with ALA prevented all these results; ALA protected against VPA-induced liver damage and hematological disturbance via antioxidant and anti-inflammatory properties.

Thymoquinone alleviates mitochondrial viability and apoptosis in diclofenac-induced acute kidney injury (AKI) via regulating Mfn2 and miR-34a mRNA expressions.

The current study was prepared to assess the underlying mechanism of diclofenac (Diclo)-stimulated renal oxidative damage (50 mg/kg/day for two consecutive days I.P) and antioxidative, and antiapoptotic effects of Thymoquinone (20 mg/kg/day for 21 days P.O). Exposure of rats to Diclo significantly increased serum urea and creatinine, decreased GSH, catalase, and total antioxidant capacity with a concomitant increase of lipid peroxidation. Diclo significantly decreased renal mitochondrial viability %, increased DNA fragmentation %, caspase 3 activity, and cytochrome C (Cyt C) concentration. Molecular investigations revealed that Diclo administration caused a significant reduction of mitofusin-2 (Mfn2) and increase of microRNA-34a (miR-34a) mRNA expressions with a concomitant decrease of Nrf2 and HO-1 mRNA expressions/protein levels and increase of NF-κB mRNA expressions. Thymoquinone restored renal oxidative/antioxidant redox. Thymoquinone significantly increased the renal mitochondrial viability % and reduced renal DNA fragmentation %, caspase 3 activity, and Cyt C. Moreover, thymoquinone modulated renal Mfn2 and miR-34a as compared to Diclo group. Our findings were confirmed by immunohistochemical assays for detecting the iNOS and NOX4 in renal tissue as well as histopathological investigations. Obtained results demonstrated that thymoquinone possess a potential antioxidant, antiapoptotic defense and exhibited a strong nephroprotective activity against Diclo-induced toxicity.

Alpha lipoic acid protects against dexamethasone-induced metabolic abnormalities via APPL1 and PGC-1 α up regulation.

BACKGROUND: Glucocorticoids (GCs) have various uses in the medicine in different specialties. However, GCs administration is usually accompanying with multiple side effects such as hyperglycemia and hyperlipidemia. Alpha lipoic acid (ALA) has been documented to posse anti-diabetic properties. AIM OF THE STUDY: this study highlights the role of ALA in avoiding dexamethasone induced metabolic disturbance. MATERIALS & METHODS: 30 rats were randomly divided into 5 groups: Group (1): Control group; Groups 3, 4, and 5: rats received dexamethasone 1 mg/kg/day for 10 days; Groups 2, 4, and 5: Rats received ALA 100 mg/kg/day all the duration of the study, 2 weeks before dexamethasone, or concomitant with dexamethasone respectively. For each rat, we collected blood samples for measurement of glucose, lipid profiles, adiponectin, irisin, and Phosphoinositide 3-kinase (PI3K). We also isolated gastrocnemius muscles for measurement of insulin receptor substrate-1(IRS-1), peroxisome proliferator-activated receptor γ coactivator 1 α(PGC1-α), and adaptor protein, phosphotyrosine interacting with PH domain and leucine zipper 1(APPL) gene expression. RESULTS: Dexamethasone administration caused hyperglycemia, hyperlipemia, decrease the level of adiponectin, irisin, and PI3K besides decreasing the gene expression of IRS-1, PGC-1 α, and APPL1. ALA administration pre or concomitant to dexamethasone avoided these results. CONCLUSION: ALA can prevent metabolic abnormalities induced by dexamethasone via PGC1α and APPL1 upregulation.