Arginine methylation-dependent cGAS stability promotes non-small cell lung cancer cell proliferation.

Cyclic GMP-AMP synthase (cGAS), promotes non-small cell lung cancer (NSCLC) cell proliferation. However, the specific mechanisms of cGAS-mediated NSCLC cell proliferation are largely unknown. In this study, we found asymmetric dimethylation by protein arginine methyltransferase 1 (PRMT1) at R127 of cGAS. This facilitated the binding of deubiquitinase USP7 and contributed to deubiquitination and stabilization of cGAS. PRMT1-and USP7-dependent cGAS stability, which also played a pivotal role in accelerating NSCLC cell proliferation through activating AKT pathway. We validated that the expression of cGAS and PRMT1 were positive correlated in human non-small cell lung cancer samples. Our study demonstrates a unique mechanism for managing cGAS stability by arginine methylation and indicates that PRMT1-cGAS-USP7 axis is a potential therapeutic target for NSCLC.

A potential correlation between adipokines, skeletal muscle function and bone mineral density in middle-aged and elderly individuals.

BACKGROUND: Evidence exists of a strong association between inflammation and a decrease in skeletal muscle function and bone mineral density (BMD); however, the specific mechanisms of these associations remain unclear. Adipokines, as key regulators of the inflammatory response, may be implicated in these processes. The objective of this study was to explore the potential correlation between adipokines, skeletal muscle function and BMD in middle-aged and elderly individuals. METHODS: A comparative cross-sectional study was carried out at the Huadong Hospital Affiliated with Fudan University (Shanghai, China). A total of 460 middle-aged and elderly individuals were recruited, and 125 were enrolled in the analysis. Their biochemical indices, body composition, skeletal muscle function and BMD were measured. Bioinformatic analysis was also employed to identify potential adipokine targets linked to skeletal muscle function and BMD. To validate these targets, plasma and peripheral blood mononuclear cells (PBMCs) were harvested from these individuals and subjected to western blotting (WB) and enzyme-linked immunosorbent assay (ELISA). RESULTS: Individuals in this cross-sectional study were categorized into 2 groups according to their median skeletal muscle mass (SMM) (28.8 kg for males and 20.6 kg for females). Individuals with lower SMM exhibited poorer grip strength (P = 0.017), longer 5-Times-Sit-to-Stand Test (FTSST) duration (P = 0.029), lower total hip BMD (P = 0.043), lower femoral neck BMD (P = 0.011) and higher levels of inflammatory markers in comparison with individuals with higher SMM. Bioinformatics analysis identified LEP, ADIPOQ, RBP4, and DPP4 as potential adipokine targets associated with skeletal muscle function and BMD. In vitro experiments demonstrated that individuals with decreased skeletal muscle function and BMD expressed higher levels of these adipokines. CONCLUSIONS: Skeletal muscle function is positively correlated with BMD and negatively correlated with levels of inflammatory markers among middle-aged and elderly individuals. Those with lower skeletal muscle function and BMD tend to have a higher expression of LEP, ADIPOQ, RBP4 and DPP4.

Prediction of overall survival after radical gastrectomy using nomograms created by tumor markers.

Prediction of prognosis after radical resection of gastric cancer has not been well established. Therefore, we aimed to establish a prognostic model based on a new score system of patients with gastric cancer. A total of 1235 patients who underwent curative gastrectomy at our hospital from October 2015 to April 2017 were included in this study. Univariate and multivariate analyses were used to screen for prognostic risk factors. Construction of the nomogram was based on Cox proportional hazard regression models. The construction of the new score models was analyzed by the receiver operating characteristic curve (ROC curve), calibration curve, and decision curve. Multivariate analysis showed that tumor size, T, N, carcinoembryonic antigen, CA125, and CA19-9 were independent prognostic factors. The new score model had a greater AUC (The area under the ROC curve) than other systems, and the C-index of the nomogram was highly reliable for evaluating the survival of patients with gastric cancer. Based on the tumor markers and other clinical indicators, we developed a precise model to predict the prognosis of patients with gastric cancer after radical surgery. This score system can be helpful to both surgeons and patients.

High Expression of Heterogeneous Nuclear Ribonucleoprotein A1 Facilitates Hepatocellular Carcinoma Growth.

Purpose: Hepatocellular carcinoma (HCC) represents one of the most common tumors in the world. Our study aims to explore new markers and therapeutic targets for HCC. Heterogeneous Nuclear ribonucleoprotein A1 (hnRNPA1) has recently been found to be involved in the progression of several types of cancer, but its role in HCC remains uncovered. Methods: We performed bioinformatic analysis to preliminarily show the relationship between hnRNPA1 and liver cancer. Then the correlation of the hnRNPA1 gene expression with clinicopathological characteristics of HCC patients was verified by human liver cancer tissue microarrays. The functional role of this gene was evaluated by in vivo and vitro experiments. Results: Results showed that the expression of hnRNPA1 was upregulated in HCC tissues and was associated with pathological stage of HCC patients. Knockdown of hnRNPA1 gene markedly inhibited tumor growth in vivo, and reversed the effects on proliferation, migration and invasion and promoted apoptosis in vitro. Furthermore, down-regulation of hnRNPA1 gene expression can inhibit the activity of the MEK/ERK pathway. Conclusion: In our work, we combined bioinformatic analysis with in vivo and in vitro experiments to initially elucidate the function of hnRNPA1 in liver cancer, which may help to explore biomarkers and therapeutic targets for HCC patients.

Impact of Aluminum Oxide Nanocoating on Drug Release from Amorphous Solid Dispersion Particles.

Atomic layer coating (ALC) is emerging as a particle engineering strategy to inhibit surface crystallization of amorphous solid dispersions (ASDs). In this study, we turn our attention to evaluating drug release behavior from ALC-coated ASDs, and begin to develop a mechanistic framework. Posaconazole/hydroxypropyl methylcellulose acetate succinate was used as a model system at both 25% and 50% drug loadings. ALC-coatings of aluminum oxide up to 40 nm were evaluated for water sorption kinetics and dissolution performance under a range of pH conditions. Scanning electron microscopy with energy dispersive X-ray analysis was used to investigate the microstructure of partially released ASD particles. Coating thickness and defect density (inferred from deposition rates) were found to impact water sorption kinetics. Despite reduced water sorption kinetics, the presence of a coating was not found to impact dissolution rates under conditions where rapid drug release was observed. Under slower releasing conditions, underlying matrix crystallization was reduced by the coating, enabling greater levels of drug release. These results demonstrate that water was able to penetrate through the ALC coating, hydrating the amorphous solid, which can initiate dissolution of drug and/or polymer (depending on pH conditions). Swelling of the ASD substrate subsequently occurs, disrupting and cracking the coating, which serves to facilitate rapid drug release. Water sorption kinetics are highlighted as a potential predictive tool to investigate the coating quality and its potential impact on dissolution performance. This study has implications for formulation design and evaluation of ALC-coated ASD particles.

Metagenomics analysis revealed the coupling of lignin degradation with humus formation mediated via shell powder during composting.

This study was the first to explore the effect of shell powder (SP) on lignin degradation and humus (HS) formation during composting. The results showed that the treatment group (T) with SP consumed more polyphenols, reducing sugar and amino acids than the control group (CK), especially the rate of reducing sugar consumption in T (50.61 %) was significantly higher than CK (28.40 %). SP greatly enhanced the efficiency of lignin degradation (T:45.47 %; CK:24.63 %) and HS formation (T:34.93 %; CK:20.16 %). The content of HA in T was 12.94 mg/g while CK was 12.06 mg/g. SP maintained a continuous increase in the relative abundance of AA1, AA3 after cooling phase. Meanwhile, T (48.98 %) significantly increased the abundance of Actinobacteria compared with CK (37.19 %). Actinobacteria, AA1 and AA3 were identified as the main factors promoting lignin degradation and HS formation by correlation analysis. Therefore, adding SP could be a novel strategy to improve compost quality.

Current research development of single cell genome in urological tumor.

The technique of whole genome amplification is advancing rapidly and generating attention on detecting genomic lesions in individual cancer cells. Also, single-cell genome could label the uniqueness of each cell, its individual mutations and structural variations especially in cancer studies. In this Review, we provide the insight into the current state of single-cell genome in urological tumor mainly including kidney cancer, bladder cancer and prostate cancer. We put more forward on the new progress of the technique used by single-cell genomes and different results of the genes transform on random tumor tissue from single cell isolated on account of tumor heterogeneity. With the advent of more complete and accurate genome information, single-cell sequencing will become a standard tool in early diagnosis and targeted therapy and prognosis judgement.

New Progress of Epigenetic Biomarkers in Urological Cancer.

Urological cancers consist of bladder, kidney, prostate, and testis cancers and they are generally silenced at their early stage, which leads to the loss of the best opportunity for early diagnosis and treatment. Desired biomarkers are scarce for urological cancers and current biomarkers are lack of specificity and sensitivity. Epigenetic alterations are characteristic of nearly all kinds of human malignances including DNA methylation, histone modification, and miRNA regulation. Besides, the detection of these epigenetic conditions is easily accessible especially for urine, best target for monitoring the diseases of urinary system. Here, we summarize some new progress about epigenetic biomarkers in urological cancers, hoping to provide new thoughts for the diagnosis, treatment, and prognosis of urological cancers.

Temporal evolution in caveolin 1 methylation levels during human esophageal carcinogenesis.

BACKGROUND: Esophageal cancer ranks eighth among frequent cancers worldwide. Our aim was to investigate whether and at which neoplastic stage promoter hypermethylation of CAV1 is involved in human esophageal carcinogenesis. METHODS: Using real-time quantitative methylation-specific PCR (qMSP), we examined CAV1 promoter hypermethylation in 260 human esophageal tissue specimens. Real-time RT-PCR and qMSP were also performed on OE33 esophageal cancer cells before and after treatment with the demethylating agent, 5-aza-2'-deoxycytidine (5-Aza-dC). RESULTS: CAV1 hypermethylation showed highly discriminative ROC curve profiles, clearly distinguishing esophageal adenocarcinomas (EAC) and esophageal squamous cell carcinomas (ESCC) from normal esophagus (NE) (EAC vs. NE, AUROC = 0.839 and p < 0.0001; ESCC vs. NE, AUROC = 0.920 and p < 0.0001). Both CAV1 methylation frequency and normalized methylation value (NMV) were significantly higher in Barrett's metaplasia (BE), low-grade and high-grade dysplasia occurring in BE (D), EAC, and ESCC than in NE (all p < 0.01, respectively). Meanwhile, among 41 cases with matched NE and EAC or ESCC, CAV1 NMVs in EAC and ESCC (mean = 0.273) were significantly higher than in corresponding NE (mean = 0.146; p < 0.01, Student's paired t-test). Treatment of OE33 EAC cells with 5-Aza-dC reduced CAV1 methylation and increased CAV1 mRNA expression. CONCLUSIONS: CAV1 promoter hypermethylation is a frequent event in human esophageal carcinomas and is associated with early neoplastic progression in Barrett's esophagus.

MAL hypermethylation is a tissue-specific event that correlates with MAL mRNA expression in esophageal carcinoma.

MAL promoter hypermethylation was examined in 260 human esophageal specimens using real-time quantitative methylation-specific PCR (qMSP). MAL hypermethylation showed highly discriminative ROC curve profiles which clearly distinguished esophageal adenocarcinomas (EAC) from both esophageal squamous cell carcinomas (ESCC) and normal esophagus (NE). Both MAL methylation frequency and normalized methylation value (NMV) were significantly higher in Barrett's esophagus (BE), dysplastic BE, and EAC than in ESCC or in NE. Among matched NE and EAC samples, MAL NMVs in EAC were significantly higher than in corresponding NE. There was a significant correlation between MAL hypermethylation and BE segment length. Treatment with 5-aza-2'-deoxycytidine reversed MAL methylation and reactivated MAL mRNA expression in OE33 EAC cells. MAL mRNA levels in EACs with unmethylated MAL were significantly higher than in EACs with methylated MAL. MAL hypermethylation is a common, tissue-specific event in human EAC and correlates with clinical neoplastic progression risk factors.