A pan-cancer analysis of RNASEH1, a potential regulator of the tumor microenvironment.

BACKGROUND: RNASEH1 (Ribonuclease H1) encodes an endonuclease that specifically degrades the RNA of RNA-DNA hybrids and acts in DNA replication and repair. Although there are many studies on RNASEH1, the research of RNASEH1 in cancers is still insufficient. Therefore, in order to clarify the physiological mechanism of RNASEH1 in tumor cells, we evaluated the role of RNASEH1 by combining The Cancer Genome Atlas (TCGA) pan-cancer data and Genotype-Tissue Expression (GTEx) normal tissue data. METHODS: RNASEH1 expression was analyzed by using RNAseq data from TCGA and the GTEx database. The Human Protein Atlas (HPA), GeneCards and STRING database were used to explore the protein information of RNASEH1. The prognostic value of RNASEH1 was analyzed by using the clinical survival data from TCGA. Differential analysis of RNASEH1 in different cancers was performed by using R package "DESeq2", and enrichment analysis of RNASEH1 was conducted by using R package "clusterProfiler". We downloaded the immune cell infiltration score of TCGA samples from published articles and online databases, and the correlation analysis between immune cell infiltration levels and RNASEH1 expression was performed. Not only that, we further evaluated the association of RNASEH1 with immune activating genes, immunosuppressive genes, chemokines and chemokine receptors. At the end of the article, the differential expression of RNASEH1 in pan-cancer was validated by using GSE54129, GSE40595, GSE90627, GSE106937, GSE145976 and GSE18672, and qRT-PCR was also performed for verification. FINDINGS: RNASEH1 was significantly overexpressed in 19 cancers and the overexpression was closely correlated with poor prognosis. Moreover, the expression of RNASEH1 was significantly correlated with the regulation of the tumor microenvironment. In addition, RNASEH1 expression was closely associated with immune cell infiltration, immune checkpoints, immune activators, immunosuppressive factors, chemokines and chemokine receptors. Finally, RNASEH1 also was closely associated with DNA-related physiological activities and mitochondrial-related physiological activities. INTERPRETATION: Our studying suggests that RNASEH1 is a potential cancer biomarker. And RNASEH1 may be able to regulate the tumor microenvironment by regulating the relevant physiological activities of mitochondrial and thereby regulating the occurrence and development of tumors. Thus, it could be used to develop new-targeted drugs of tumor therapy.

Graptopetalum paraguayense Inhibits Liver Fibrosis by Blocking TGF-ß Signaling In Vivo and In Vitro.

BACKGROUND AND AIMS: Liver fibrosis is the excessive accumulation of extracellular matrix proteins, including collagen, which occurs in most types of chronic liver diseases. Advanced liver fibrosis results in cirrhosis, liver failure, and portal hypertension. Activated hepatic perivascular stellate cells, portal fibroblasts, and myofibroblasts of bone marrow origin have been identified as major collagen-producing cells in the injured liver. These cells are activated by fibrogenic cytokines, such as TGF-ß1. The inhibition of TGF-ß1 function or synthesis is a major target for the development of antifibrotic therapies. Our previous study showed that the water and ethanol extracts of Graptopetalum paraguayense (GP), a Chinese herbal medicine, can prevent dimethylnitrosamine (DMN)-induced hepatic inflammation and fibrosis in rats. METHODS: We used rat hepatic stellate HSC-T6 cells and a diethylnitrosamine (DEN)-induced rat liver injury model to test the potential mechanism of GP extracts and its fraction, HH-F3. RESULTS: We demonstrated that GP extracts and HH-F3 downregulated the expression levels of extracellular matrix (ECM) proteins and inhibited the proliferation and migration via suppression of the TGF-ß1 pathway in rat hepatic stellate HSC-T6 cells. Moreover, the HH-F3 fraction decreased hepatic collagen content and reduced plasma AST, ALT, and γ-GT activities in a DEN-induced rat liver injury model, suggesting that GP/HH-F3 has hepatoprotective effects against DEN-induced liver fibrosis. CONCLUSION: These findings indicate that GP/HH-F3 may be a potential therapeutic agent for the treatment of liver fibrosis. The inhibition of TGF-ß-mediated fibrogenesis may be a central mechanism by which GP/HH-F3 protects the liver from injury.

Effects of melanocortin 1 receptor (MC1R) gene polymorphisms on plumage color in mule ducks

The objective of the present study was to investigate the effect of single nucleotide polymorphism (SNP) of the melanocortin 1 receptor (MC1R) gene on plumage coloration in mule ducks. PCR-high-resolution melting analysis (PCR-HRM) and DNA sequencing were used to identify the SNP variability of the MC1R gene in white common ducks. Three non-synonymous SNP (MC1R gene exon 1, c.52G>A, c.376G>A, and c.409G>A) were identified in white Tsaiya ducks. Mating test (white Tsaiya ducks × white Muscovy drakes) in combination with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was performed to investigate the effect of non-synonymous SNP of different maternal lines on plumage coloration in mule ducks. Genotyping results from 58 white Tsaiya ducks revealed the significant associations between genetic variations (c.52G>A, c.376A>G, and c.409G>A) and plumage color in two maternal populations. After genotyping of 266 mule ducks, these three non-synonymous SNP identified in white Tsaiya ducks were significantly associated with plumage color of mule ducks. Therefore, the polymorphisms of MC1R gene at c.52G>A, c.376A>G, and c.409G>A in white Tsaiya duck could be used in marker-assisted selection to improve the plumage color of mule ducks.(AU)

Changes in antimicrobial susceptibility of commonly clinically significant isolates before and after the interventions on surgical prophylactic antibiotics (SPAs) in Shanghai

Surveillances and interventions on antibiotics use have been suggested to improve serious drug-resistance worldwide. Since 2007, our hospital have proposed many measures for regulating surgical prophylactic antibiotics (carbapenems, third gen. cephalosporins, vancomycin, etc.) prescribing practices, like formulary restriction or replacement for surgical prophylactic antibiotics and timely feedback. To assess the impacts on drug-resistance after interventions, we enrolled infected patients in 2006 (pre-intervention period) and 2014 (post-intervention period) in a tertiary hospital in Shanghai. Proportions of targeted pathogens were analyzed: methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus spp. (VRE), imipenem-resistant Escherichia coli (IREC), imipenem-resistant Klebsiella pneumoniae (IRKP), imipenem-resistant Acinetobacter baumannii (IRAB) and imipenem-resistant Pseudomonas aeruginosa (IRPA) isolates. Rates of them were estimated and compared between Surgical Department, ICU and Internal Department during two periods. The total proportions of targeted isolates in Surgical Department (62.44%, 2006; 64.09%, 2014) were more than those in ICU (46.13%, 2006; 50.99%, 2014) and in Internal Department (44.54%, 2006; 51.20%, 2014). Only MRSA has decreased significantly (80.48%, 2006; 55.97%, 2014) (p < 0.0001). The percentages of VRE and IREC in 3 departments were all <15%, and the slightest change were also both observed in Surgical Department (VRE: 0.76%, 2006; 2.03%, 2014) (IREC: 2.69%, 2006; 2.63%, 2014). The interventions on surgical prophylactic antibiotics can be effective for improving resistance; antimicrobial stewardship must be combined with infection control practices.(AU)

Changes in antimicrobial susceptibility of commonly clinically significant isolates before and after the interventions on surgical prophylactic antibiotics (SPAs) in Shanghai

Abstract Surveillances and interventions on antibiotics use have been suggested to improve serious drug-resistance worldwide. Since 2007, our hospital have proposed many measures for regulating surgical prophylactic antibiotics (carbapenems, third gen. cephalosporins, vancomycin, etc.) prescribing practices, like formulary restriction or replacement for surgical prophylactic antibiotics and timely feedback. To assess the impacts on drug-resistance after interventions, we enrolled infected patients in 2006 (pre-intervention period) and 2014 (post-intervention period) in a tertiary hospital in Shanghai. Proportions of targeted pathogens were analyzed: methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus spp. (VRE), imipenem-resistant Escherichia coli (IREC), imipenem-resistant Klebsiella pneumoniae (IRKP), imipenem-resistant Acinetobacter baumannii (IRAB) and imipenem-resistant Pseudomonas aeruginosa (IRPA) isolates. Rates of them were estimated and compared between Surgical Department, ICU and Internal Department during two periods. The total proportions of targeted isolates in Surgical Department (62.44%, 2006; 64.09%, 2014) were more than those in ICU (46.13%, 2006; 50.99%, 2014) and in Internal Department (44.54%, 2006; 51.20%, 2014). Only MRSA has decreased significantly (80.48%, 2006; 55.97%, 2014) (p < 0.0001). The percentages of VRE and IREC in 3 departments were all <15%, and the slightest change were also both observed in Surgical Department (VRE: 0.76%, 2006; 2.03%, 2014) (IREC: 2.69%, 2006; 2.63%, 2014). The interventions on surgical prophylactic antibiotics can be effective for improving resistance; antimicrobial stewardship must be combined with infection control practices.

Changes in antimicrobial susceptibility of commonly clinically significant isolates before and after the interventions on surgical prophylactic antibiotics (SPAs) in Shanghai.

Surveillances and interventions on antibiotics use have been suggested to improve serious drug-resistance worldwide. Since 2007, our hospital have proposed many measures for regulating surgical prophylactic antibiotics (carbapenems, third gen. cephalosporins, vancomycin, etc.) prescribing practices, like formulary restriction or replacement for surgical prophylactic antibiotics and timely feedback. To assess the impacts on drug-resistance after interventions, we enrolled infected patients in 2006 (pre-intervention period) and 2014 (post-intervention period) in a tertiary hospital in Shanghai. Proportions of targeted pathogens were analyzed: methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus spp. (VRE), imipenem-resistant Escherichia coli (IREC), imipenem-resistant Klebsiella pneumoniae (IRKP), imipenem-resistant Acinetobacter baumannii (IRAB) and imipenem-resistant Pseudomonas aeruginosa (IRPA) isolates. Rates of them were estimated and compared between Surgical Department, ICU and Internal Department during two periods. The total proportions of targeted isolates in Surgical Department (62.44%, 2006; 64.09%, 2014) were more than those in ICU (46.13%, 2006; 50.99%, 2014) and in Internal Department (44.54%, 2006; 51.20%, 2014). Only MRSA has decreased significantly (80.48%, 2006; 55.97%, 2014) (p<0.0001). The percentages of VRE and IREC in 3 departments were all <15%, and the slightest change were also both observed in Surgical Department (VRE: 0.76%, 2006; 2.03%, 2014) (IREC: 2.69%, 2006; 2.63%, 2014). The interventions on surgical prophylactic antibiotics can be effective for improving resistance; antimicrobial stewardship must be combined with infection control practices.

Evaluation of the medicinal herb Graptopetalum paraguayense as a treatment for liver cancer.

BACKGROUND: Hepatocellular carcinoma (HCC) is the fifth most common malignancy and the third most common cause of cancer-related death worldwide. Sorafenib is the only drug for patients with advanced-stage hepatocellular carcinoma (HCC) that has been shown to confer a survival benefit to patients with HCC; however, it has many side effects. Thus, alternate therapeutic strategies with improved safety and therapeutic efficacy for the management of HCC should be developed. METHODS AND FINDINGS: We demonstrate that an extract of Graptopetalum paraguayense (GP) down-regulated the expression levels of several onco-proteins, including AURKA, AURKB, and FLJ10540, in HCC cells. To isolate the active components in the GP extracts, we prepared extracts fractions and assessed their effects on the expression of onco-proteins in HCC cells. The fraction designated HH-F3 was enriched in active ingredients, exhibited cytotoxic effects, and suppressed the expression of the onco-proteins in HCC cells. The structure of the main active compound in HH-F3 was found to be similar to that of the proanthocyanidin compounds derived from Rhodiola rosea. In addition, a distinct new compound rich in 3, 4, 5-trihydroxy benzylic moieties was identified in the HH-F3 preparations. Mechanistic studies indicated that HH-F3 induced apoptosis in HCC cells by promoting the loss of mitochondrial membrane potential and the production of reactive oxygen species. HH-F3 also enhanced PTEN expression and decreased AKT phosphorylation at Ser473 in a concentration-dependent manner in HCC cells. Moreover combination of GP or HH-F3 and sorafenib synergistically inhibits the proliferation of Huh7 cells. The treatment of a rat model with diethylnitrosamine (DEN)-induced liver cancer with extracts of GP and HH-F3 decreased hepatic collagen contents and inhibited tumor growth. CONCLUSIONS: These results indicate that GP extracts and HH-F3 can protect the liver by suppressing tumor growth; consequently, these compounds could be considered for the treatment of HCC.

Urokinase gene 3'-UTR T/C polymorphism is not associated with bladder cancer

Urokinase degrades basement proteins and is hypothesized to play a role in cancer progression. We investigated the hypothesis of C/T polymorphism in the 3'-untranslated region (3'-UTR) of the urokinase gene being associated with the development of bladder cancer. Such an association seems unlikely, since the genotype distributions in 114 bladder cancer patients did not differ from those of 105 controls.