Anti-proliferative and anti-apoptotic potential effects of epigallocatechin-3-gallate and/or metformin on hepatocellular carcinoma cells: in vitro study.

The effects of epigallocatechin-3-gallate (EGCG) and metformin single treatment have been tested against hepatocellular carcinoma (HCC). This study aimed to assess the combination effects of EGCG and metformin on proliferation and apoptosis of HepG2cells and identified new potential molecular targets. The effect of EGCG and metformin against cell proliferation in HepG2 was determined using MTT assay. Reverse transcription polymerase chain reaction was applied to examine the gene expression of cyclin D1, lncRNA-AF085935, caspase-3, survivin and VEGF. The level of protein expression of glypican-3 was assessed by western blot. In HepG2 cells, EGCG and metformin combination treatment exhibited high significant effect against tumor proliferation. It significantly reduced cyclin D1, lncRNA-AF085935, glypican-3 and promoted apoptosis through increasing caspase3 and decreasing survivin compared to control cells. Moreover, EGCG and metformin treated cells showed decreased expression levels of VEGF. Our study provided new insights of the anticarcinogenic effects of EGCG and metformin on HCC through their effects on glypican-3 and lncRNA-AF085935.

Comparative study on effect of mesenchymal stem cells and endothelial progenitor cells on treatment of experimental CCL4-induced liver fibrosis.

BACKGROUND: We speculated impacts of BM-MSCs and UC-EPCs on reversal of hepatic injury induced by carbon tetrachloride (CCl4). Fifty adult rats were divided into five groups: control group, CCl4A group, CCl4B group, CCl4/BM-MSCs group and CCl4/UC-EPCs group. Blood samples were driven to measure concentration of albumin and ALT. Quantitative expression of HGF, TGF-ß, MMP-2, and VEGF were assessed by PCR. Histological and immunohistochemistry examination of the liver tissue were performed. RESULTS: There was elevating albumin (p < .05) and reducing ALT (p < .05) concentrations in groups treated with BM-MSCs and UC-EPCs compared to untreated CCL4A&B groups. UC-EPCs treated group have significantly higher MMP-2 and VEGF (p < .01) genes expression than BM-MSCs treated group. Furthermore, UC-EPCs were more valuable than BMMSCs in increasing gene expression of HGF (p < .05) and immunohistochemistry of α-SMA and Ki-67 (p < .01). BM-MSCs have significantly lower TGF-ß (p < .00) compared to UC-EPCs. CONCLUSION: This study highlighted on liver regeneration role of both UC-EPCs and BM-MSCs in liver fibrosis.

Frequency of Genotypes and Allelic Polymorphisms of Vitamin D Receptor in Egyptian Psoriatic Patients and Their Association With Disease Severity, Immune Modulation of IL-22 Levels and The Response to Topical Calcipotriol Treatment: A Case Control Study.

Objective: This study was performed to determine the genotype and allelic frequencies (polymorphisms) of the four genes of vitamin D receptor (VDR) among Egyptian psoriatic patients and healthy controls to explore their association with disease severity (PASI) score and immune modulation of IL-22 cytokine and to predict the response to topical calcipotriol treatment. Patients and Methods: The frequencies of the four VDR gene polymorphisms (FokI, ApaI, TaqI, and BsmI) in blood samples of 51 adult Egyptian patients with psoriasis vulgaris and 50 healthy controls were evaluated using restriction fragment length polymorphism (RFLP)-PCR. Serum levels of IL-22 were measured by ELISA. Results: The most frequent genotype (wild) in the studied patients was Apa1; AA (88.2%) followed by Fok1; FF (47.1%) and Taq1; TT (47%), while Bsm1; BB genotype was (27.7%). The most frequent allele polymorphisms either in one allele (Bb) or both alleles (bb) in psoriatic patients were 72.5%, followed by Ff, ff (52.9%) and Tt, tt (52.9%). The less frequent allelic polymorphism was Aa, aa (27.7%). Insignificant differences in the frequency of genotype (wild) and allelic polymorphisms were detected between patients and controls (P > 0.05). A significantly higher serum concentration of IL-22 (ng/mL) was detected in patients than controls (P = 0.001). Further, 66.6% of patients displayed a clinical response, while 33.4% were non-responders. A significantly higher expression of TaqI polymorphism was detected in (100%) of non-responders (P < 0.001), which was also correlated with disease severity (r = 0.515, P < 0.01). Conclusion: These results suggest that the VDR TaqI polymorphism is the only gene correlated to psoriasis susceptibility in the Egyptian population, and affects the response to topical calcipotriol treatment but does not affect IL-22 immune modulation.