Effects of mesenchymal stem cells versus curcumin on sonic hedgehog signaling in experimental model of Hepatocellular Carcinoma.

BACKGROUND: Sonic Hedgehog (SHH) is a fundamental signaling pathway that controls tissue reconstruction, stem cell biology, and differentiation and has a role in gut tissue homeostasis and development. Dysregulation of SHH leads to the development of HCC. METHODS, AND RESULTS: The present study was conducted to compare the effects of mesenchymal stem cells (MSCs) and curcumin on SHH molecular targets in an experimental model of HCC in rats. One hundred rats were divided equally into the following groups: control group, HCC group, HCC group received MSCs, HCC group received curcumin, and HCC group received MSCs and curcumin. Histopathological examinations were performed, and gene expression of SHH signaling target genes (SHH, PTCH1, SMOH, and GLI1) was assessed by real-time PCR in rat liver tissue. Results showed that SHH target genes were significantly upregulated in HCC-untreated rat groups and in MSC-treated groups, with no significant difference between them. Administration of curcumin with or without combined administration of MSCs led to a significant down-regulation of SHH target genes, with no significant differences between both groups. As regards the histopathological examination of liver tissues, both curcumin and MSCs, either through separate use or their combined use, led to a significant restoration of normal liver pathology. CONCLUSIONS: In conclusion, SHH signaling is upregulated in the HCC experimental model. MSCs do not inhibit the upregulated SHH target genes in HCC. Curcumin use with or without MSCs administration led to a significant down-regulation of SHH signaling in HCC and a significant restoration of normal liver pathology.

Circulating hsa-miR-221 as a possible diagnostic and prognostic biomarker of diabetic nephropathy.

BACKGROUND: Diabetic nephropathy (DN), which is a chronic outcome of diabetes mellitus (DM), usually progresses to end-stage renal disease (ESRD). The DN pathophysiology, nevertheless, is not well-defined. Several miRNAs were reported to be either risk or protective factors in DN. METHODS, AND RESULTS: The present study sought to inspect the potential diagnostic and prognostic value of hsa-miR-221 in DN. The study included 200 participants divided into four groups: Group 1 (50 patients with DN), Group 2 (50 diabetic patients without nephropathy), Group 3 (50 nondiabetic patients with CKD), and Group 4 (50 healthy subjects as a control group). Patients in groups 1 and 3 were further classified based on the presence of macroalbuminuria and microalbuminuria. Hsa-miR-221 expression was measured by RT- qRT-PCR. DN patients had significantly elevated serum hsa-miR-221 levels than the other groups, while diabetic patients without nephropathy exhibited elevated levels compared to both nondiabetic patients with CKD, and the control group. The DN patients with macroalbuminuria revealed significantly higher mean values of hsa-miR-221 relative to the patients with microalbuminuria. Significant positive associations were observed in the DN group between serum hsa-miR-221 and fasting insulin, fasting glucose, HOMA IR, ACR, and BMI. The ROC curve analysis of serum hsa-miR-221 in the initial diagnosis of DN in DM revealed high specificity and sensitivity. CONCLUSIONS: It is concluded that hsa-miR-221 has the potential to be a useful biomarker for prognostic and diagnostic purposes in DN.

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.