A novel marker based on necroptosis-related long non-coding RNA for forecasting prognostic in patients with clear cell renal cell carcinoma.

Background: The incidence of clear cell renal cell carcinoma (ccRCC) is high and has increased gradually in recent years. At present, due to the lack of effective prognostic indicators, the prognosis of ccRCC patients is greatly affected.Necroptosis is a type of cell death, and along with cell necrosis is considered a new cancer treatment strategy. The aim of this study was to construct a new marker for predicting the prognosis of ccRCC patients based on long non-coding RNA (nrlncRNAs) associated with necroptosis. Methods: RNA sequence data and clinical information of ccRCC patients from the Cancer Genome Atlas database (TCGA) were downloaded. NrlncRNA was identified by Pearson correlation study. The differentially expressed nrlncRNA and nrlncRNA pairs were identified by univariate Cox regression and Lasso-Cox regression. Finally, a Kaplan-Meier survival study, Cox regression, clinicopathological features correlation study, and receiver operating characteristic (ROC) spectrum were used to evaluate the prediction ability of 25-nrlncrnas for markers. In addition, correlations between the risk values and sensitivity to tumor-infiltrating immune cells, immune checkpoint inhibitors, and targeted drugs were also investigated. Results: In the current research, a novel marker of 25-nrlncRNAs pairs was developed to improve prognostic prediction in patients with ccRCC. Compared with clinicopathological features, nrlncRNAs had a higher diagnostic validity for markers, with the 1-year, 3-years, and 5-years operating characteristic regions being 0.902, 0.835, and 0.856, respectively, and compared with the stage of 0.868, an increase of 0.034. Cox regression and stratified survival studies showed that this marker could be an independent predictor of ccRCC patients. In addition, patients with different risk scores had significant differences in tumor-infiltrating immune cells, immune checkpoint, and semi-inhibitory concentration of targeted drugs. The feature could be used to evaluate the clinical efficacy of immunotherapy and targeted drug therapy. Conclusion: 25-nrlncRNAs pair markers may help to evaluate the prognosis and molecular characteristics of ccRCC patients, which improve treatment methods and can be more used in clinical practice.

Synthesis and biological evaluation of scutellarein derivatives as neuroprotective agents via activating Nrf2/HO-1 pathway.

Oxidative stress has been considered as the main factor of neurodegenerative diseases. Activation of the Nrf2/HO-1 pathway, as one of the most crucial endogenous protection systems, was regarded as an effective strategy to against oxidative injury. Here, a series of phosphate esters or phosphonates of scutellarein derivatives were designed, synthesized and evaluated on SH-SY5Y cell lines to examine neuroprotective effects against H2O2 induced damage. Among them, compound 16d exhibited more potent cytoprotective effect than the lead compound scutellarin. Preliminary mechanism studies showed that compound 16d could prevent H2O2 induced neuronal apoptosis, significantly decrease ROS generation, elevate SOD and reduce MDA levels in a dose-dependent manner in SH-SY5Y cell lines. Furthermore, western blot assay disclosed that compound 16d could activate Nrf2, and increase the expression of its downstream genes HO-1 in a concentration-dependent manner, thus displaying potent neuroprotective activity. Overall, these findings demonstrated that compound 16d, as a promising neuroprotective agent, deserved further development.

COP21 Roadmap: Do innovation, financial development, and transportation infrastructure matter for environmental sustainability in China?

The purpose of the present study is to explain the long-run and causal effects of innovation, financial development, and transportation infrastructure on CO2 emissions using the combined cointegration and wavelet coherence approaches over the period from 1971 to 2018, while using economic growth as a control variable in the model. The outcomes of the Bayer-Hanck cointegration test show that there is an important cointegration equation among CO2 emissions, innovation, financial development, transportation infrastructure, and real GDP. Moreover, the findings from a wavelet power spectrum reveal that there is a significant vulnerability in innovation, financial development, transportation infrastructure, and CO2 emissions at different time frames and frequencies. Furthermore, the outcomes of wavelet coherence approach reveal that (i) Innovation is observed as a significant predictor of CO2 emissions over the period from 2007 to 2013; (ii) In the long run, there are negative correlations between CO2 emissions and financial development; (iii) Over the periods from 2000 to 2015, and from 1985 to 1989, transportation significantly causes CO2 emissions. Our findings have substantial policy implications that suggest there is a need to strengthen innovation and transportation infrastructure to achieve environmental sustainability targets.

MicroRNA31-NDRG3 regulation axes are essential for hepatocellular carcinoma survival and drug resistance.

BACKGROUNDS: Hepatocellular carcinoma (HCC) is an epithelial cancer that originates from hepatocytes and it is the most common primary malignant tumor of the liver. Till now the prognosis of HCC patients is generally poor. The molecular mechanism giving rise to HCC development and recurrence is still largely unknown. MicroRNA-31 (miR-31) is among the most commonly altered microRNAs in human cancers, and alternations of miR-31 expression were reported to play pivotal roles in tumorigenesis and tumor progression. METHODS: In this work, the primary biological function of miR-31 in HCC tumorigenesis was investigated. RESULTS: Our data showed that overexpression of miR-31 induced markedly inhibition of HCC cell proliferation, migration in vitro and inhibited xenograft tumor growth in vivo. One target gene of miR-31, NDRG3, was also demonstrated indispensable for HCC cell survival. Furthermore, miR-31 and NDRG3 were both essential for HCC cell drug resistance in adriamycin. CONCLUSIONS: We conclude that miR-31 is a crucial regulator in hepatocellular carcinoma, miR-31 and its target gene NDRG3 may be potential therapeutic targets for HCC treatment in the future.

Detecting protein carbonylation in adipose tissue and in cultured adipocytes.

Reactive oxygen species-mediated attack of the acyl chains of polyunsaturated fatty acids and triglycerides leads to the formation of lipid hydroperoxides. Lipid hydroperoxides are subject to nonenzymatic Fenton chemistry producing a variety of reactive aldehydes that covalently modify proteins in a reaction referred to as protein carbonylation. Given the significant content of triglycerides in fat tissue, adipose proteins are among the most heavily carbonylated. The laboratory has utilized two methodologies for the detection of protein carbonylation in tissue- and cell-based samples. The first utilizes biotin coupled to a hydrazide moiety and takes advantage of the numerous biotin detection systems. The second method utilizes an anti 4-hydroxy-trans-2,3-nonenal (4-HNE)-directed antibody that can detect both 4-HNE and the corresponding 4-oxo derivative when the samples are reduced. Using such methods, we have evaluated the profile of carbonylated proteins in epididymal white adipose tissue and 3T3-L1 adipocytes using both methods. In addition, we have investigated the effects of two antidiabetic drugs, pioglitazone and metformin, on protein carbonylation in 3T3-L1 adipocytes. Overall, the biotin hydrazide method is rapid, inexpensive, and easy to use, but its usefulness is limited because it detects a wide variety of carbonylated derivatives, which makes assignments of individual proteins difficult. Compared to the biotin hydrazide method, the anti-HNE antibody method detects specific proteins more readily but identifies only a subset of carbonylated proteins. As such, the combination of both methods allows for a comprehensive evaluation of protein carbonylation plus provides a means towards identification of specific carbonylation targets.