Intrahepatic expression of HBcAg and delta antigen in anti-HBe positive HBsAg carriers with acute exacerbation or chronic active liver disease

Intrahepatic expression of HBcAg and hepatitis delta antigen (HDAg) was studied in 43 patients with acute exacerbation AE and 37 with chronic active liver disease CALD, in order to evaluate the role of hepatitis B virus (HBV) replication and hepatitis delta virus (HDV) superinfection in development of AE or CALD in anti-HBe positive HBsAg carriers in Taiwan, and the results were compared with 37 patients with only minor hepatitic activity. Only 8.1% of patients with minor hepatitic activity were HBcAg positive, and none were HDAg positive. In contrast, 41.8% and 32.6% of patients with AE were positive for HBcAg and HDAg, respectively, and the other 25.6% were negative for both. The clinical features of AE showed no difference in relation to HBcAg and HDAg activity in the liver except that patients without HBcAg and HDAg were predominantly older adults. These patients might be supposed to have non-A, non-B hepatitis (NANB) virus superinfection, as many reports have shown a predominance of older patients in acute NANB hepatitis. Of the patients with CALD, 40.5% were HBcAg positive, 27.0% were HDAg positive, and 32.5% were positive for neither. Histological features of CALD were identified in 83.3% and 100% of patients with HBcAg and HDAg activity, respectively, but only in 26.1% of those without HBcAg and HDAg. The etiology of CALD in the latter group remains unclear. Furthermore, some of the anti-delta seropositive patients with AE or CALD expressed HBcAg rather than HDAg in the liver.(ABSTRACT TRUNCATED AT 250 WORDS)     

Diallyl trisulfide inhibits cell migration and invasion of human melanoma a375 cells via inhibiting integrin/facal adhesion kinase pathway

Melanoma is the leading cause of death from skin disease due to its propensity for metastasis. Studies have shown that integrin‐mediated focal adhesion kinase (FAK) signal pathway is implicated in cell proliferation, survival and metastasis of tumor cells. Our previous results indicated that diallyl trisulfide (DATS) provided its antimelanoma activity via inducing cell cycle arrest and apoptosis. The aim of this study was to explore DATS mediated antimetastatic effect and the corresponding mechanism in human melanoma A375 cells. We found that DATS exhibited an inhibitory effect on the abilities of migration and invasion in A375 cells under noncytotoxic concentrations analyzed by wound healing assays and Matrigel invasion chamber system. DATS attenuated invasion of A375 cells with characteristic of decreased activities and protein expressions of matrix metalloproteinase‐2 (MMP‐2) and MMP‐9. Moreover, DATS exerted an inhibitory effect on cell adhesion of A375 cells, which is in correlation with the change in integrin signaling pathway. Results of Western blotting showed that DATS decreased the levels of several integrin subunits, including α4, α5, αv, β1, β3 and β4. Subsequently, DATS induced a strong decrease in total FAK, phosphorylated FAK Tyr‐397,‐576, ?577, and disorganized F‐actin stress fibers, resulting in a nonmigratory phenotype. These results suggest that the antimetastatic potential of DATS for human melanoma cells might be due to the disruption of integrin/FAK signaling pathway.     

Genistein inhibits rat aortic smooth muscle cell proliferation through the induction of p27kip1

Diet is one of the most important factors that influence the risks for cardiovascular diseases. Genistein, an isoflavone found in soy, may benefit the cardiovascular system. Here, we investigated the effect of genistein on platelet-derived growth factor (PDGF)-BB-induced proliferation of primary cultured rat aortic smooth muscle cells (RASMCs). Genistein significantly inhibited 25 ng/ml PDGF-BB-induced RASMC proliferation and [3H]-thymidine incorporation into DNA at 10, 20, and 40 microM. In accordance with these findings, genistein blocked the PDGF-BB-inducible progression through G0/G1 to S phase of the cell cycle in synchronized cells. Western blot analysis showed that genistein not only inhibited phosphorylation of retinoblastoma protein (pRb) and expression of cyclin E, cyclin-dependent kinase (CDK) 2, and proliferating cell nuclear antigen (PCNA) protein, but also inhibited downregulation of cyclin-dependent kinase inhibitor (CKI) p27kip1. However, genistein did not affect p21cip1, CDK4, and cyclin D1 expression or early signal transduction through PDGF beta-receptor, extracellular signal-regulated kinases 1/2 (ERK1/2), Akt, and phospholipase C (PLC) gamma1 phosphorylation. These results suggest that genistein inhibits PDGF-BB-induced RASMC proliferation via G0/G1 arrest in association with induction of p27kip1, which may contribute to the beneficial effects of genistein on the cardiovascular system.     

YSK2821, a newly synthesized indoledione derivative, inhibits cell proliferation and cell cycle progression via the cell cycle-related proteins by regulating phosphatidylinositol-3 kinase cascade in vascular smooth muscle cells

Indoledione derivatives have pronounced biological effects, i.e., cytotoxic activities against cancer cell lines and antifungal and antibacterial activities. The present study was designed to investigate the effects of YSK2821, a newly synthesized indoledione derivative, on platelet-derived growth factor (PDGF-BB)-induced vascular smooth muscle cell (VSMC) proliferation, as well as the molecular mechanisms of the anti-proliferative effects of YSK2821 in VSMCs. We found that YSK2821 caused the accumulation of cells in the G1 phase of the cell cycle and inhibited [3H]-thymidine incorporation. We demonstrated that YSK2821 remarkably decreased Akt kinase phosphorylation as the mechanism by which YSK2821 suppressed cell signal transduction events in VSMC proliferation. Furthermore, in terms of the effects of YSK2821 on cell cycle-related proteins, YSK2821 enhanced the expression of the cyclin-dependent protein kinase (CDK) inhibitor p27 and down-regulated CDK2 and cyclin E expression, but did not affect CDK4 and cyclin D1 expression. YSK2821 also inhibited the phosphorylation of Rb, a key regulator in the cell cycle. These results indicate that YSK2821, a newly synthesized indoledione derivative, may inhibit VSMC proliferation via a phosphatidylinositol (PI)-3 kinase-dependent pathway, and thus shed light on a novel role for YSK2821 as a potential preventive regulator of cardiovascular disease.