• Hyldgaard Bonner posted an update 6 months, 4 weeks ago

    Scope The development of novel compounds that trigger non-apoptotic cell death may represent alternative therapeutic strategies for esophageal squamous cell carcinoma (ESCC) treatment. Cellular senescence suppresses tumorigenesis by halting the proliferation of tumor cells, implying the induction of senescence as a promising anticancer strategy, especially when combined with senolytic agents that specially kill senescent cells. This study is designed to screen novel anti-ESCC compounds from a natural product resource and identify its mechanism-of-action. Methods and results Identified are the significant anti-cancer effect and underlying mechanism of SFN, an isothiocyanate derived from cruciferous vegetables, through RNA sequencing, western blot, and immunofluorescent assays. It is found that SFN inhibits proliferation of ESCC cells through inducing senescence. Mechanistically, SFN induces reactive oxygen species (ROS) via disrupting the balance between glutathione and oxidized glutathione, leading to DNA damage. In addition, ROS deregulates autophagy and promotes lysosome abnormal biogenesis through regulating mTOR/TFE3 axis. Finally, the inhibited autophagic flux facilitates exosome production, resulting in exosome-mediated paracrine senescence. Conclusions This study suggests the important roles of autophagy and exosome-mediated paracrine senescence in cancer therapy and highlights SFN as a potent anti-ESCC drug candidate.We have read with great interest the article published by Ramadan et al(1). This manuscript assembled an interdisciplinary team with the expertise to examine the primary areas of clinical management for kidney transplantation in transgender and non-binary (TGNB) people, which was exemplified by a small case series at their institution. We commend the authors for discussing several key points relevant to this scenario. However, we would like to highlight a key collaborator and value that the authors omitted from their review – the clinical laboratory and eGFR measurements.Background Butyrate has shown anti-inflammatory and regenerative properties, providing symptomatic relief when orally supplemented in patients suffering from various colonic diseases. We investigated the effect of a colonic-delivery formulation of butyrate on the fecal microbiota of patients with inflammatory bowel diseases (IBDs). Methods In this double-blind, placebo-controlled, pilot study, 49 IBD patients (n = 19 Crohn’s disease, CD and n = 30 ulcerative colitis, UC) were randomized to oral administration of microencapsulated-sodium-butyrate (BLM) or placebo for 2 months, in addition to conventional therapy. Eighteen healthy volunteers (HVs) were recruited to provide a healthy microbiota model of the local people. Fecal microbiota from stool samples was assessed by 16S sequencing. Clinical disease activity and quality of life (QoL) were evaluated before and after treatment. Key results At baseline, HVs showed a different microbiota composition compared with IBD patients. Sodium-butyrate altered the gut microbiota of IBD patients by increasing bacteria able to produce SCFA in UC patients (Lachnospiraceae spp.) and the butyrogenic colonic bacteria in CD patients (Butyricicoccus). see more In UC patients, QoL was positively affected by treatment. Conclusions and inferences Sodium-butyrate supplementation increases the growth of bacteria able to produce SCFA with potentially anti-inflammatory action. The clinical impact of this finding requires further investigation.Recently proposed rulemaking from CMS would change how organ procurement organizations (OPO’s) are evaluated. The proposals include using national inpatient death data to define a standardized denominator to calculate comparable donation rates among OPO’s. Based on these objective metrics, OPO’s not performing at a pre-specified threshold will be required to rapidly improve performance to avoid decertification. We sought to determine whether rapid OPO improvement was possible based on objective donation metrics, and whether leadership change was associated with rapid improvement. We evaluated UNOS and CDC data from 2011-2018, and measured donation rates using CDC data on inpatient deaths from causes consistent with donation, based on the location of deaths. During the two four-year cycles, we found that an OPO’s ranking relative to other OPO’s were fairly static, with more than 90% of the OPO’s at risk of flagging at the end of each four-year cycle (2014, 2018) being in the bottom 75% of OPO’s in the preceding three years. Leadership changes were only associated with an improvement in OPO rankings during the 2011-2014 cycle. These data demonstrate that rapid improvements in OPO performance are uncommon, and while leadership changes increase the odds of rapid improvement, they do not guarantee improvement.Background Raoiella indica Hirst (Acari Tenuipalpidae) is the most critical coconut and banana pest recently introduced in Brazil. Once mite pests are introduced, it is essential to understand their dynamics in important crops under open-field climatic conditions to implement strategies for their management and determine the periods when species populations may increase in the field. Modelling tools have been used to determine the potential distribution of species and implications for the management of invasive species. Thus, our aim in this study was to determine the seasonal variation in R. indica and the influence of the monthly climate using CLIMEX modelling. We adjusted the CLIMEX model for R. indica based on distribution data, additional biological characteristics, and fluctuations in the R. indica population in a commercial coconut plantation. Results The model for the current climate shows a good match between the ecoclimatic index and the global distribution of R. indica. The model results demonstrate that most states of Brazil and several regions worldwide include areas with highly suitable climatic conditions for R. indica. We observed variations in the density of R. indica in commercial coconut crops, with the highest incidence occurring during the first months of the year. Conclusion Our results showed different alterations in seasonal suitability for R. indica that may provide information for the implementation of methods for time management, such as strategies for sampling and control during periods with a high degree of suitability for R. indica. This article is protected by copyright. All rights reserved.

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