Salvianolic acid B regulates collagen synthesis: Indirect influence on human dermal fibroblasts through the microvascular endothelial cell pathway.

BACKGROUND: Salvianolic acid B (SAB) is one of the main active ingredients of Salvia Miltiorrhiza. It has significant skin anti-aging, whitening, and sun protection properties. AIMS: The study aimed at studying the mechanism underlying the effect of salvianolic acid Bon collagen synthesis, which has good anti-aging efficacy and modulates microcirculation. METHODS: This study employed available public databases, bioinformatics methodologies, and the inverse docking approach to explore the effectiveness of SAB in the regulating collagen synthesis, and then used an human dermal fibroblast (HDF)- Human dermal microvascular endothelial cell (HDMEC) in vitro model to validate the predicted mechanism of SAB in influencing collagen synthesis. RESULTS: The results showed that NO production in SAB-treated HDMEC-conditioned medium was increased compared to that in control media, and the same tendency was also observed for growth factor production. SAB also upregulated HDMEC cellular eNOS and VEGF. When SAB-treated HDMEC conditioned medium was transferred to HDFs, the expression of collagen I, collagen III, and elastin in HDFs was upregulated and MMP-1 was downregulated. CONCLUSIONS: The results show that SAB regulates collagen through the HDMEC-HDF pathway. Furthermore, the mechanisms might be closely related to the microcirculation factors NO and VEGF.

A Novel Ferroptosis-Related 4-Gene Prognostic Signature for Cholangiocarcinoma and Photodynamic Therapy.

Cholangiocarcinoma is the second most common malignant tumor in the hepatobiliary system. Compared with data on hepatocellular carcinoma, fewer public data and prognostic-related studies on cholangiocarcinoma are available, and effective prognostic prediction methods for cholangiocarcinoma are lacking. In recent years, ferroptosis has become an important subject of tumor research. Some studies have indicated that ferroptosis plays an important role in hepatobiliary cancers. However, the prediction of the prognostic effect of ferroptosis in patients with cholangiocarcinoma has not been reported. In addition, many reports have described the ability of photodynamic therapy (PDT), a potential therapy for cholangiocarcinoma, to regulate ferroptosis by generating reactive oxygen species (ROS). By constructing ferroptosis scores, the prognoses of patients with cholangiocarcinoma can be effectively predicted, and potential gene targets can be discovered to further enhance the efficacy of PDT. In this study, gene expression profiles and clinical information (TCGA, E-MTAB-6389, and GSE107943) of patients with cholangiocarcinoma were collected and divided into training sets and validation sets. Then, a model of the ferroptosis gene signature was constructed using least absolute shrinkage and selection operator (LASSO)-penalized Cox regression analysis. Furthermore, through the analysis of RNA-seq data after PDT treatment of cholangiocarcinoma, PDT-sensitive genes were obtained and verified by immunohistochemistry staining and Western blot. The results of this study provide new insight for predicting the prognosis of cholangiocarcinoma and screening target genes that enhance the efficacy of PDT.

Prognostic significance of programmed cell death ligand 1 expression in patients with ovarian carcinoma: A systematic review and meta-analysis.

BACKGROUND: Programmed cell death ligand 1 (PD-L1) overexpression has been reported to be associated with poor prognosis in several human cancers. However, studies on the prognostic value of PD-L1 expression in ovarian carcinoma (OC) remain controversial. This meta-analysis aimed to evaluate comprehensively the prognostic value of PD-L1 in OC. METHODS: Electronic databases, including PubMed, EMBASE, and the Cochrane Library, were searched up until March 28, 2018. Hazard ratio (HR), along with 95% confidence interval (CI), was used to analyze the included outcomes. RESULTS: A total of 10 studies with 1179 OC patients were included in this meta-analysis. There was no significant correlation between PD-L1 expression and overall survival (OS) (HR 1.23, 95% CI 0.85-1.79) and progression-free survival (PFS) (HR 0.88, 95% CI 0.52-1.47) of OC patients. However, the subgroup analysis suggested that positive PD-L1 expression was significantly associated with poor OS (HR 1.66, 95% CI 1.08-2.55) and PFS (HR 2.17, 95% CI 1.31-3.61) among OC patients from Asian countries. Increased PD-L1 expression was also a favorable factor for OS (HR 0.73, 95% CI 0.53-0.99) and PFS (HR 0.58, 95% CI 0.45-0.75) in OC patients from non-Asian regions. No evidence of publication bias was detected by the Egger linear regression test and Begg funnel plot. Sensitivity analyses suggested that the results of this meta-analysis were robust. CONCLUSIONS: The results indicated that PD-L1 expression may be a negative predictor for prognosis of OC patients from Asian countries, and a good predictor for favorable prognosis of OC patients from non-Asian countries. PD-L1 expression has potential to be a prognostic biomarker to guide clinicians for the selection of individuals who may get clinical benefit from anti-PD-1/PD-L1 immunotherapy. Prospective clinical studies are needed to support these findings.

Photodynamic therapy for high-grade dysplasia of bile duct via a choledochoscope.

When a distal common bile duct neoplasm is at the stage of carcinoma in situ or high-grade dysplasia, it is difficult for the surgeon to decide whether to perform pancreaticoduodenectomy. Here we describe a patient with a progressive dysplastic lesion in the common bile duct, which developed from moderate-high to high-grade dysplasia in approximately 2 mo. The patient refused major surgery. Therefore, endoscopic-assisted photodynamic therapy was performed. The result at follow-up using a trans-T-tube choledochoscope showed that the lesion was completely necrotic. This report is the first to describe the successful treatment of high-grade dysplasia of the distal bile duct using photodynamic therapy via a choledochoscope.