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n of breast cancer cells via the FTO/miR-181b-3p/ARL5B signaling pathway.Graft-versus-host disease (GVHD), a common complication after peripheral blood stem cell or bone marrow transplantation, rarely occurs in kidney and pancreas transplant recipients. The true incidence may be confounded by the rarity of the disorder, with a resultant lack of appreciation of the diagnosis as a potential cause of common clinical manifestations such as cytopenias and immune dysfunction. Reports of GVHD in kidney and pancreas transplant recipients almost uniformly describe patients in the early posttransplant period (days to months) with the typical manifestations of acute GVHD involving the skin, liver, and intestines. In contrast, reports of solid organ transplant recipients with clinical features more consistent with chronic GVHD (cGVHD) are lacking, raising concern of underrecognition of this severe complication. Occurrence later after transplant may be even more likely to result in lack of recognition. We report 2 cases of possible cGVHD occurring in recipients of pancreas after kidney transplantation, which were diagnosed at 5.5 and 42 months after pancreas transplant. Both patients presented with severe pancytopenia, multiple opportunistic infections, and features suggestive of cGVHD. Transplant professionals should be aware of the possibility of acute and cGVHD in pancreas after kidney transplant recipients and be able to recognize the clinical manifestations.Post-translational modifications (PTMs) within the first 17 amino acids (Nt17) of exon 1 of the Huntingtin protein (Httex1) play important roles in modulating its cellular properties and functions in health and disease. In particular, phosphorylation of threonine and serine residues (T3, S13, and/or S16) has been shown to inhibit Htt aggregation in vitro and inclusion formation in cellular and animal models of Huntington's disease (HD). In this paper, we describe a new and simple methodology for producing milligram quantities of highly pure wild-type or mutant Httex1 proteins that are site-specifically phosphorylated at T3 or at both S13 and S16. This advance was enabled by 1) the discovery and validation of novel kinases that efficiently phosphorylate Httex1 at S13 and S16 (TBK1), at T3 (GCK) or T3 and S13 (TNIK and HGK), and 2) the development of an efficient methodology for producing recombinant native Httex1 proteins by using a SUMO-fusion expression and purification strategy.[26] As a proof of concept, we demonstrate how this method can be applied to produce Httex1 proteins that are both site-specifically phosphorylated and fluorescently or isotopically labeled. Together, these advances should increase access to these valuable tools and expand the range of methods and experimental approaches that can be used to elucidate the mechanisms by which phosphorylation influences Httex1 or HTT structure, aggregation, interactome, and function(s) in health and disease.Photoluminescent (PL) carbon quantum dots (CQDs) were prepared successfully using a facile and green procedure. They exhibited striking blue fluorescence and excellent optical properties, with a quantum yield as high as 61.44%. Due to the fluorescence quenching effect and the stronger complexing ability of the phosphoric acid group of 1-hydroxyethane-1,1-diphosphonic acid (HEDP) to Fe3+ , CQDs doped with Fe3+ were adequately constructed as an efficient and sensitive fluorescent probe for HEDP-specific sensing. The proposed fluorescent probe had a sensitive and rapid response in the range 5-70 μM. 10-Deacetylbaccatin-III purchase Furthermore, quantitative molecular surface (QMS) analysis based on the Multiwfn program was applied to explore the complexation mode of HEDP and metal ions. The distribution of electrostatic potential (ESP), average local ionization energy (ALIE), the minimum value points and the position of the lone pair electrons on the surface of molecular van der Waals were further determined. More strikingly, this experiment achieved the quantitative detection of water-soluble phosphonate-HEDP, for the first time using fluorescence spectrometry. It has been proved to be an effective and intuitive sensing method for the detection of HEDP in real samples.Long noncoding RNAs (LncRNAs) have emerged as important players in cancer biology. Increasing evidence suggests that LncRNAs are frequently dysregulated in cancer and may function as oncogenes or tumor suppressors. Urothelial carcinoma associated 1 (UCA1), a LncRNA, firstly identified in bladder transitional cell carcinoma, seems to act as an oncogene in many different types of human cancers by promoting cell proliferation and migration. In this study, we revealed a novel biological function of UCA1, which was different from that reported by previous studies, was responsible for maintaining the low-tumorigenic, nonmetastatic phenotypes in primary prostate epithelial cells. UCA1 could stabilize E-cadherin protein by preventing the interaction between E-cadherin and its E3 ligase MDM2, which suppressed MDM2-mediated ubiquitination and degradation of E-cadherin. In addition, we also found that UCA1 acted as a sponge of miR-296-3p, which targeted E-cadherin gene CDH1 messenger RNA at the posttranscription level. Taken together, these findings demonstrated that UCA1 had a new important role in effectively keeping E-cadherin at a high level through a dual mechanism, which maintained primary prostate cancer cells at the low-tumorigenic and nonmetastatic status.
Despite substantial evidence of the efficacy of naltrexone in treating alcohol use disorder (AUD), naltrexone is used infrequently and often for short durations. Understanding factors related to the initiation and continued use of naltrexone could identify targets for improving its use in clinical practice.
We used the Fiscal year 2012 national data from the Veterans Health Administration to identify the proportion of veterans diagnosed with AUD who initiated and then continued to receive naltrexone for AUD over a 6-month period (N = 67,788). We further examined correlates of any use and continued use, and patterns of use in inpatient and outpatient mental health services and psychotropic prescription fills. Comparisons were made using bivariate analyses and multinomial logistic regression.
Among the veterans diagnosed with AUD, 2.02% initiated treatment with naltrexone. Naltrexone initiation was associated with recent homelessness, concurrent psychiatric disorders, receipt of psychiatric outpatient services, psychotropic prescription fills, residential treatment, and psychiatric and medical-surgical hospitalization.