Drug-induced liver injury (DILI) is an important clinical problem, which has received more attention in recent decades. It can be induced by small chemical molecules, biological agents, traditional Chinese medicines (TCM), natural medicines (NM), health products (HP), and dietary supplements (DS). Idiosyncratic DILI is far more common than intrinsic DILI clinically and can be classified into hepatocellular injury, cholestatic injury, hepatocellular-cholestatic mixed injury, and vascular injury based on the types of injured target cells. The CSH guidelines summarized the epidemiology, pathogenesis, pathology, and clinical manifestation and gives 16 evidence-based recommendations on diagnosis, differential diagnosis, treatment, and prevention of DILI.

Ovarian cancer is an aggressive gynecological malignancy with high metastatic potential. Recently, the CXC receptor (CXCR7) has been identified as a new receptor for stromal-derived factor-1 (SDF-1), and exerts important roles in cancer development. However, its effect on ovarian cancer and the underlying mechanism remain unknown. In this study, we detected abundant CXCR7 expression in ovarian cancer tissues and cells. Moreover, SDF-1 induced dramatically upregulation of CXCR7 mRNA and protein levels, indicating that the SDF-1/CXCR7 axis existed in ovarian cancer. Further analysis confirmed that SDF-1 enhanced cell adhesion and subsequent invasion, which were significantly attenuated when pretreated with CXCR7 small interference RNA (siRNA), indicating the critical function of SDF-1/CXCR7 in cell invasion. Further mechanistic analysis indicated that SDF-1/CXCR7 enhanced cell invasion by matrix metalloproteinase (MMP)-9, as pretreatment with MMP-9 siRNA significantly abrogated a number of invading cells. Additionally, SDF-1/CXCR7 induced phosphorylation of the p38 MAPK pathway, which was accounted for MMP-9 expression as preconditioning with the p38 MAPK inhibitor SB203580 obviously decreased MMP-9 expression. Together, our data implied that SDF-1/CXCR7 enhanced ovarian cancer cell invasion by MMP-9 expression through the p38 MAPK pathway. Thus, these findings confirmed the critical role of SDF-1/CXCR7 during the pathological processes of ovarian cancer and supported its potential targets for further development of antiovarian cancer therapy.

E-cadherin plays an important role in maintaining tissue architecture. Loss of E-cadherin expression has often been associated with cancer metastasis. This study assessed the immuno-expression of E-cadherin and methylation of CDH1 and correlated them with clinical features in primary epithelial ovarian cancer. Moreover, epithelial ovarian cancer cell SKOV3 was used to explore the mechanism how the demethylating agent 5-Aza inhibited cancer metastasis. Of 80 patients with primary ovarian cancer, we found that decreased immunoexpression pattern of E-cadherin was associated with clinical stage, lymph node metastasis, and degree of differentiation. Methylation of CDH1 detected by MSP occurred frequently and was correlated with reduced expression of E-cadherin protein. 5-Aza treatment could lead to re-expression of functional E-cadherin, followed by decreased MMP-2 and MMP-9 activity and inhibition of cell invasion in SKOV3 cells. Therefore, we conclude that assessment of E-cadherin immunoreactivity or methylation of CDH1 may be a useful prognostic indicator in ovarian cancer, complementary to established prognostic factors. The mechanism underlying 5-Aza's anti-metastasis activity is associated with restored functional expression of E-cadherin and decreased MMPs activity. Correction of aberrant DNA methylation by 5-Aza may provide a new strategy for ovarian cancer prevention and therapy.