Comparison of renal safety and bone mineral density of tenofovir and entecavir in patients with chronic hepatitis B: a systematic review and meta-analysis.

OBJECTIVES: Tenofovir disoproxil fumarate (TDF) and entecavir (ETV) are recommended as first-line treatments for chronic hepatitis B (CHB). However, the safety of these two drugs remains controversial. This study aimed to evaluate and compare renal function and bone mineral density in patients with CHB who took TDF or ETV. METHODS: The electronic databases of the Cochrane Library, PubMed, and Embase were searched. The keywords were: "CHB", "tenofovir", and "entecavir". Heterogeneity and subgroups were analyzed. RESULTS: A total of 16 studies met the inclusion criteria. There was no significant difference in serum creatinine levels between the TDF and the ETV group. There was a significant standardized mean difference (SMD) in the serum estimated glomerular filtration rate between months (12 months: SMD [95% confidence interval] = -0.07 [-0.12, -0.01]; 18-24 months: SMD [95% confidence interval] = -0.11 [-0.17, -0.05]), but no significant difference emerged in the long-term drug use for over 24 months. There was no significant difference in the incidence of osteopenia/osteoporosis (I2 = 41%, risk ratio [95% confidence interval] = 1.29 [0.93, 1.77], P-value = 0.13 >0.05). CONCLUSION: Compared with the ETV group, a greater reduction in estimated glomerular filtration rate and serum phosphorus levels was observed in the TDF group. There was no significant difference in the incidence of osteopenia/osteoporosis between the two groups.

IL-17A inhibits autophagic activity of HCC cells by inhibiting the degradation of Bcl2.

Hepatocellular carcinoma (HCC) is associated with poor prognosis due to many unknowns about its inflammatory microenvironment. As a pivotal proinflammatory cytokine, IL-17A exerts a protective effect on the survival and function of HCC cells. It is widely accepted that IL-17A plays an important role in regulating autophagy. Bcl2, a key molecule promoting the survival of HCC cells, also plays an indispensable role as an autophagy regulator. The aim of this study was to investigate the role of Bcl2 in IL-17A-regulated autophagy of HCC cells. The results showed that IL-17A not only inhibited autophagic activity, but also increased Bcl2 levels in HCC cells under starvation. Besides, IL-17A could prevent the dissociation of autophagy protein Beclin1 from Bcl2-Beclin1 complex upon starvation. Overexpression of Beclin1 rescued the autophagy deficiency of HCC cells in presence of IL-17A. Moreover, RNAi-induced Bcl2 silencing impaired the function of IL-17A in inhibiting the activation of autophagy, subsequently reducing the viability and migration of HCC cells, while the inhibition of Beclin1 by spautin-1 could reduce autophagic activity to a certain degree, thus restoring the viability and migration of HCC cells. In summary, it was suggested that the inhibition of Bcl2 degradation may be an important mechanism by which IL-17A inhibits autophagy response, subsequently maintaining the survival in HCC cells.

Columbamine suppresses hepatocellular carcinoma cells through down-regulation of PI3K/AKT, p38 and ERK1/2 MAPK signaling pathways.

Hepatocellular carcinoma (HCC) as primary liver cancer in adults is the most common cause led to internal cirrhosis responsible for patients' death, which resulted in nearly a million deaths worldwide on both males and females in the developing and developed countries. Unfortunately, up to date, there are no highly effective treatment of medicine on HCC as lack of comprehensive cellular and molecular mechanism. According to the sources of human ancient history of medicine, traditional medicine could provide unique treatment to discontinue the challenging HCC. In this study, we inspected the effect of Columbamine (Col; C20H21NO5), an alkaloid isolated from calumba, on HCC utilizing three HCC cell-lines i.e. SMMC7721, HepG2 and Hep3B. Our data collected from these cell-lines exhibit strong Col suppression on the cell growth accompanying the dosage-dependent suppression, and we further confirmed the suppression on the tumor-growth in animal model. Rational of the Col suppression presents cellular mechanism by limiting the proliferation and colony formation of the cells marked with decreased expression of PCNA. Meanwhile decreases of migration indicated with increasing expression of E-cadherin and decreasing expression of N-cadherin, and of invasion labelled with decreasing expressions of MMP2 and MMP9, are accompanying the Col suppression along with the Col promoted apoptosis of the tumor cells. This programmed cell death marketed with cleaved Caspase 3 plus PAPR proteins, up-regulation of BAD and down-regulation of BCL2 is linked the Col suppression to unique calcium-related pathways. Our results unveiled that the Columbamine suppression on HCC based on the traditional medicine are clearly associated with PI3K/AKT, p38 and ERK1/2 MAPKs signaling pathways and guide further research orientation for developing the Col medicine against hepatocellular carcinoma.