Macrophages are important mediators of inflammatory cardiovascular diseases, and various macrophage phenotypes exert opposite effects during inflammation. In our previous study, we proved that suppressed androgen receptor (AR) alleviated inflammation during experimental autoimmune myocarditis (EAM). As anti-inflammatory cells, whether M2 macrophages are involved in this process remains unclear. Here, we showed that anti-inflammatory cytokines and M2 macrophages were elevated when AR was suppressed during EAM. In IL-4 stimulation-induced M2 macrophages, impaired AR with ASC-J9 increased the expression of M2 macrophage-related factors. Moreover, suppressed AR expression resulted in macrophage M2 polarization by reducing SOCS3 production and enhancing STAT3 activation. Taken together, our data suggest that AR plays a critical role in macrophage polarization and suppressed redundant AR expression promotes anti-inflammatory M2 macrophages reprogramming. This study suggests a potential therapeutic agent for inflammatory cardiomyopathy through the use of ASC-J9.
MicroRNA-21 (miR-21) is an oncomir overexpressed in most human tumors in that it promotes malignant growth and progression by acting on multiple targets. Here, we broaden the impact of miR-21 in cancer by showing that it regulates the formation of reactive oxygen species (ROS) that promote tumorigenesis. Key targets of miR-21 in mediating this function were SOD3 and TNFα. We found that miR-21 inhibited the metabolism of superoxide to hydrogen peroxide, produced either by endogenous basal activities or exposure to ionizing radiation (IR), by directing attenuating SOD3 or by an indirect mechanism that limited TNFa production, thereby reducing SOD2 levels. Importantly, both effects contributed to an elevation of IR-induced cell transformation. Our findings, therefore, establish that miR-21 promotes tumorigenesis to a large extent through its regulation of cellular ROS levels.
Based on a field survey of typical hospitals in Zhejiang, this paper drew a conclusion on three models of the mixed-ownership hospitals development in Zhejiang.It summed up the experiences learnt in the practice about how to maintain the public welfare of the public hospitals, how to ensure the essential health services supply as well as the incentive mechanism for social capital.Suggestions were proposed to develop the mixed-ownership hospitals based on the analysis.
Key words:
Zhejiang province; Mixed-ownership; Public welfare; Social capital
As the most widely consumed beverage in the world, tea has various nutritional, economic, and global cultural values. With the development of the third-generation sequencing technology, several genome sequences of tea plants have been published. These genomic data have pivotal information that is of benefit to tea plant breeders and biologists in advancing tea plant improvement and the final quality of tea products. We hereby present the integrative online database, Tea Plant Genome Database (TeaPGDB; http://eplant.njau.edu.cn/tea), which incorporates the published genome sequences of tea plants. The current release of TeaPGDB hosts published tea plant genome data with various online tools, including JBrowse, gene search, SSR search, BLAST. TeaPGDB also contains a download server, which provides access for the download of genome-related data and rich annotation files. TeaPGDB is committed to collecting, integrating, and annotating published tea plant genome data, providing data support for research on tea plant heredity, evolution, breeding for resistance, plant improvement, and facilitating the characterization of important traits or flavor related genes in the community. Compared with other tea plant databases, this database not only contains more complete genome data and gene annotation information, but also has a user-friendly interface for researchers in the field.
Abstract Background Excessive iron accumulation and lipid peroxidation are primary characteristics of ferroptosis in hepatocellular carcinoma (HCC). Ferroptosis inducer combined with immunotherapy has become a new hope for HCC patients. Therefore, the construction and validation of subtype‐specific sensitivity to ferroptosis inducer will be helpful for hierarchical management and precise individual therapy. Methods RNA‐seq transcriptome and clinical data of HCC patients were extracted from International Cancer Genome Consortium (ICGC) dataset and The Cancer Genome Atlas (TCGA) dataset. Consistency matrix and data clustering of the both cohorts were constructed by ‘ConsensusClusterPlus’ package. Single‐sample gene set enrichment analysis (ssGSEA) analysis was performed to evaluate immune infiltration. Cox analysis was utilized to construct a ferroptosis phenotype‐related prognostic model (FRPM) in HCC. The predictive efficiency of the constructed FRPM was evaluated through Kaplan Meier (K‐M) survival analyses and Receiver Operating Characteristic (ROC) curves. The expression levels of candidate genes were detected and validated by Real‐Time PCR between liver cancer tissues and adjacent non‐tumor liver tissues. Results 45 differentially expressed ferroptosis‐related genes (FRGs) were identified between HCC tissues and non‐tumor liver tissues. Furthermore, four ferroptosis‐associated clusters (FACs) of HCC were established via consensus clustering. Subsequently, we established a FRPM, consisting of four prognostic genes ( SLC7A11 , SLC1A5 , GCLM and SAT1 ), to evaluate the survival of HCC patients, based on which, patients were divided into high‐risk group and low‐risk group. The high‐risk group exhibited worse survival compared to low‐risk group ( p < 0.0001 both in TCGA and ICGC cohorts). Patients belong to different FACs or different risk scores showed distinct clinical characteristics. Moreover, in the validation experiment, the transcriptional expression levels of the four prognostic genes were consistent with the results drew from datasets. Conclusion We revealed a novel FRGs signature, which may provide the molecular characteristic data for effectively prognostic evaluation and potential personalized therapy for HCC patients.
Raised the differential method of resolving rational function into fractions, and formulas were suggested of the coefficients which correspond to liner factor and quadratic prime factor.
Adrenocortical carcinoma (ACC) is a rare malignant neoplasm that is prone to local invasion and metastasis. Meanwhile, overexpressed endothelial cell-specific molecule 1 (ESM1) is closely related to tumorigenesis of multitudinous tumors. However, the prognosis value and biological function of ESM1 in ACC remains undefined. In the current essay, the assessment in human ACC samples and multiple public cancer databases suggested that ESM1 was significantly overexpressed in ACC patients. The abnormal expression of ESM1 was evidently correlated with dismal overall survival (OS) in ACC patients. Then, the gene-set enrichment analysis (GSEA) was applied to unravel that ESM1 was mostly involved in cell cycle and Notch4 signaling pathway. Furthermore, in vitro experiment, RNA interference of ESM1 was carried out to state that ESM1 augments CDK1 and p21-mediated G2/M-phase transition of mitosis, cell proliferation via DLL4-Notch signaling pathway in human ACC cell line, SW13 cells. Additionally, two possible or available therapeutic strategies, including immunotherapy and chemotherapy, have been further explored. Immune infiltration analysis highlighted that no significant difference was found in ACC patients between EMS1high and EMS1low group for immune checkpoint-related genes. In addition, the overexpression of ESM1 might trigger the accumulation of tumor mutation burden (TMB) during the cell cycle of DNA replication in ACC. The gene-drug interaction network then indicated that ESM1 inhibitors, such as cisplatin, might serve as potential drugs for the therapy of ACC. Collectively, the results asserted that ESM1 and related regulators might act as underlying prognostic biomarkers or novel therapeutic targets for ACC.
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