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We established a semi-high-throughput in vivo screening platform using hyperactive piggyBac (hyPB) transposons (designated as PB-miR) to identify microRNAs (miRs) that inhibit hepatocellular carcinoma (HCC) development in vivo, following miR overexpression in hepatocytes. PB-miRs encoding six different miRs from the miR-17-92 cluster and nine miRs from outside this cluster were transfected into mouse livers that were chemically induced to develop HCC. In this slow-onset HCC model, miR-20a significantly inhibited HCC. Next, we developed a more aggressive HCC model by overexpression of oncogenic Harvey rat sarcoma viral oncogene homolog (HRASG12V) and c-MYC oncogenes that accelerated HCC development after only 6 weeks. The tumor suppressor effect of miR-20a could be demonstrated even in this rapid-onset HRASG12V/c-MYC HCC model, consistent with significantly prolonged survival and decreased HCC tumor burden. Comprehensive RNA expression profiling of 95 selected genes typically associated with HCC development revealed differentially expressed genes and functional pathways that were associated with miR-20a-mediated HCC suppression. To our knowledge, this is the first study establishing a direct causal relationship between miR-20a overexpression and liver cancer inhibition in vivo. Moreover, these results demonstrate that hepatocyte-specific hyPB transposons are an efficient platform to screen and identify miRs that affect overall survival and HCC tumor regression. Induction of endogenous cardiomyocyte (CM) proliferation is one of the key strategies for heart regeneration. Increasing evidence points to the potential role of microRNAs (miRNAs) in the regulation of CM proliferation. Here, we used human embryonic stem cell (hESC)-derived CMs (hESC-CMs) as a tool to identify miRNAs that promote CM proliferation. We profiled miRNA expression at an early stage of CM differentiation and identified a list of highly expressed miRNAs. https://www.selleckchem.com/products/tertiapin-q.html Among these miRNAs, miR-25 was enriched in early-stage hESC-CMs, but its expression decreased over time. Overexpression of miR-25 promoted CM proliferation. RNA sequencing (RNA-seq) analysis revealed that genes related to cell-cycle signal were strongly influenced by miR-25 overexpression. We further showed that miR-25 promoted CM proliferation by targeting FBXW7. Finally, the function of miR-25 in the regulation of CM proliferation was demonstrated in zebrafish. Our study suggested that miR-25 is a promising molecule for heart regeneration. Acid Mine Drainage (AMD) has been a serious environmental issue that threats soil and aquatic ecosystems. In this study, an acid-tolerant sulfate reducing bacterium, strain S4 was isolated from the mud of an AMD storage pond in Vietnam via enrichment in anoxic mineral medium at pH5. Comparative analyses of sequences of the 16S rRNA gene and dsrB gene involving in sulfate reduction revealed that the isolate belonged to the genus Desulfovibrio, most closely related to Desulfovibrio oxamicus (with 99% homology in 16S rDNA sequence and 98% homology in dsrB gene sequence). DGGE analyses of dsrB genes showed that strain S4 represented one of the two most abundant groups developed in the enrichment culture. Notably, strain S4 was capable of reducing sulfate in low pH environments (from 2 and above), and resistance to extremely high concentration of heavy metals (Fe 3000 mg/l, Zn 100 mg/l, Cu 100 mg/l). In a batch incubation experiment in synthetic AMD with pH 3.5, strain S4 showed strong effects in facilitating growth of a neutrophilic, metal sensitive Desulfovibrio sp. strain SR4H which was not capable of growing alone in such environment. Thus, it is postulated that under extreme conditions such as AMD environment, acid- and metal-tolerant SRB like strain S4 would facilitate the growth of other widely distributed SRB by starting to reduce sulfate at low pH, thus increasing pH and lowering the metal concentration in the environment. Owing such unique physiological characteristics, strain S4 showed a great application potential for sustainable remediation of AMD.Abelmoschus manihot (Linn.) is a medicinal herbal plant that is commonly used to treat chronic kidney disease and hepatitis. However, its effect on cell proliferation has not been clearly revealed. In this report, we sought to determine the effect of the flower extract of Amelmoschus manihot (FA) on cell proliferation. Based on our findings, FA increased the proliferation of human diploid fibroblast (HDF) and HEK293 cells. Through cell cycle analysis, FA was found to increase the number of HDF cells in the S phase and G2/M phase. FA also increased the expression of cyclin D1 and enhanced the migration of HDF cells. By administering FA to HDF cells with ≥30 passages, a decrease in the number of senescence-associated β galactosidase-positive cells was observed, thereby indicating that FA can ameliorate cellular senescence. Collectively, our findings indicate that FA increases cyclin D1 expression and regulates cell proliferation.In the present study, an anaerobic microbial consortium for the degradation of hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) was selectively enriched with the co-addition of RDX and starch under nitrogen-deficient conditions. Microbial growth and anaerobic RDX biodegradation were effectively enhanced by the co-addition of RDX and starch, which resulted in increased RDX biotransformation to nitroso-derivatives at a greater specific degradation rate than those for previously reported anaerobic RDX-degrading bacteria (isolates). The accumulation of the most toxic RDX degradation intermediate (MNX [hexahydro-1-nitroso-3,5-dinitro-1,3,5-triazine]) was significantly reduced by starch addition, suggesting improved RDX detoxification by the co-addition of RDX and starch. The subsequent MiSeq sequencing that targeted the bacterial 16S rRNA gene revealed that the Sporolactobacillus, Clostridium, and Paenibacillus populations were involved in the enhanced anaerobic RDX degradation. These results suggest that these three bacterial populations are important for anaerobic RDX degradation and detoxification. The findings from this work imply that the Sporolactobacillus, Clostridium, and Paenibacillus dominant microbial consortium may be valuable for the development of bioremediation resource for RDX-contaminated environments.
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