• Butcher Balle posted an update 6 months ago

    MicroRNAs are frequently clustered in the genome and polycistronically transcribed, regulating targeted genes in diverse signaling pathways. The miR-17-92 cluster is a typical miRNA cluster, playing crucial roles in the organogenesis and homeostasis of physiological processes in vertebrates. Here, we identified three miRNAs (csa-miR-92a, csa-miR-92b, and csa-miR-92c) that belonged to the miR-92 family and formed a miRNA cluster in the genome of a urochordate marine ascidian Ciona savignyi. Except for miR-92a and miR-92b, other homologs of the vertebrate miR-17-92 cluster members could not be identified in the Ciona genome. We further found that the mature sequences of urochordate miR-92 family members were highly conserved compared with the vertebrate species. The expression pattern revealed that three miR-92 family members had consistent expression levels in adult tissues and were predominantly expressed in heart and muscle tissue. We further showed that, at the embryonic and larval stages, csa-miR-92c was expressed in the notochord of embryos during 18-31 h post fertilization (hpf) by in situ hybridization. Knockout of csa-miR-92c resulted in the disorganization of notochord cells and the block of lumen coalescence in the notochord. Fibroblast growth factor (FGF), mitogen-activated protein kinase (MAPK), and wingless/integrated (Wnt)/planar cell polarity (PCP) signaling pathways might be involved in the regulatory processes, since a large number of core genes of these pathways were the predicted target genes of the miR-92 family. Taken together, we identified a miR-92 cluster in urochordate Ciona and revealed the expression patterns and the regulatory roles of its members in organogenesis. Our results provide expression and phylogenetic data on the understanding of the miR-92 miRNA cluster’s function during evolution.B cell activation is an early event in the development of systemic sclerosis (SSc). The classical activation of B cells downstream of the B-cell receptor (BCR) involves the phosphatidylinositol-3 kinase (PI3K) pathway that integrates the effects of multiple co-stimulatory receptors. Our analysis of PI3K pathway associated molecules in peripheral blood B cells of early diffuse cutaneous SSc (dcSSc) patients showed altered mRNA expression of Toll-like receptor (TLR) homolog CD180, TLR4, complement component 3, IL-4 receptor and secreted phosphoprotein 1 (SPP1). Parallel to this, we found elevated basal SPP1 secretion in dcSSc B cells, but, with BCR + IL-4 receptor co-stimulation, we could not induce further secretion. CD180 stimulation alone resulted in NF-κB activation in more B cells than CD180 + BCR co-stimulation both in dcSSc and healthy control (HC), but the co-engagement increased the phosphorylation of NF-κB only in dcSSc B cells. Additionally, in contrast with HC B cells, the lower basal production of IL-10 by dcSSc B cells could not be elevated with CD180 stimulation. Furthermore, activation via CD180 increased the percentage of CD86+ switched memory (CD27+IgD-) B cells in dcSSc compared to HC. Our results suggest that alternative B cell activation and CD180 dysfunction cause imbalance of regulatory mechanisms in dcSSc B cells.Few studies have simultaneously considered the effects of significant others and medical professionals’ advice to quit smoking on smoking cessation intention. The present study involved 3841 current adult Korean smokers, divided into four groups with an intention to quit within 1 month, within 6 months, someday, and without intention to quit. Multinomial multiple logistic regression analysis was conducted according to smoking cessation intention level, adjusted for potential confounders, including past smoking cessation attempts. Smokers who had been advised to quit smoking by both significant others and medical professionals, significant others only, and medical professionals only were 2.63 (95% confidence interval (CI) 1.62-4.29), 1.84 (95% CI 1.17-2.89), and 1.44 (95% CI 0.70-2.94) times more likely to intend to quit within 1 month, respectively, than those who were not advised to quit. The odds ratios of an intention to quit within 6 months were 2.91 (95% CI 1.87-4.54), 2.49 (95% CI 1.69-3.68), and 0.94 (95% CI 0.44-2.05), respectively. To promote smokers’ intention to quit, the role of significant others should be considered. Medical professionals’ advice to quit smoking remains important, increasing the effects of significant others’ advice.The transferrin receptor 1 (TFR-1) has been found overexpressed in a broad range of solid tumors in humans and is, therefore, attracting great interest in clinical oncology for innovative targeted therapies, including nanomedicine. LB-100 supplier TFR-1 is recognized by H-Ferritin (HFn) and has been exploited to allow selective binding and drug internalization, applying an HFn nanocage loaded with doxorubicin (HFn(DOX)). In veterinary medicine, the role of TFR-1 in animal cancers remains poorly explored, and no attempts to use TFR-1 as a target for drug delivery have been conducted so far. In this study, we determined the TFR-1 expression both in feline mammary carcinomas during tumor progression, as compared to healthy tissue, and, in vitro, in a feline metastatic mammary cancer cell line. The efficacy of HFn(DOX) was compared to treatment with conventional doxorubicin in feline mammary cancer cells. Our results highlighted an increased TFR-1 expression associated with tumor metastatic progression, indicating a more aggressive behavior. Furthermore, it was demonstrated that the use of HFn(DOX) resulted in less proliferation of cells and increased apoptosis when compared to the drug alone. The results of this preliminary study suggest that the use of engineered bionanocages also offers unprecedented opportunities for selective targeted chemotherapy of solid tumors in veterinary medicine.Personalized medicine (PM) approaches have revolutionized healthcare delivery by offering new insights that enable healthcare providers to select the optimal treatment approach for their patients. However, despite the consensus that these approaches have significant value, implementation across the US is highly variable. In order to address barriers to widespread PM adoption, a comprehensive and methodical approach to assessing the current level of PM integration within a given organization and the broader healthcare system is needed. A quantitative framework encompassing a multifactorial approach to assessing PM adoption has been developed and used to generate a rating of PM integration in 153 organizations across the US. The results suggest significant heterogeneity in adoption levels but also some consistent themes in what defines a high-performing organization, including the sophistication of data collected, data sharing practices, and the level of internal funding committed to supporting PM initiatives. A longitudinal approach to data collection will be valuable to track continued progress and adapt to new challenges and barriers to PM adoption as they arise.

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