Altered microRNA expression profile with miR-146a upregulation in CD4+ T cells from patients with rheumatoid arthritis

Introduction: Increasing evidence indicates that microRNAs (miRNAs) play a critical role in the pathogenesis of inflammatory diseases. The aim of the study was to investigate the expression pattern and function of miRNAs in CD4 + T cells from patients with rheumatoid arthritis (RA).Methods: The expression profile of miRNAs in CD4 + T cells from synovial fluid (SF) and peripheral blood of 33 RA patients was determined by microarray assay and validated by qRT-PCR analysis. The correlation between altered expression of miRNAs and cytokine levels was determined by linear regression analysis. The role of miR-146a overexpression in regulating T cell apoptosis was evaluated by flow cytometry. A genome-wide gene expression analysis was further performed to identify miR-146a-regulated genes in T cells.Results: miRNA expression profile analysis revealed that miR-146a expression was significantly upregulated while miR-363 and miR-498 were downregulated in CD4 + T cells of RA patients. The level of miR-146a expression was positively correlated with levels of tumor necrosis factor-alpha (TNF-α), and in vitro studies showed TNF-α upregulated miR-146a expression in T cells. Moreover, miR-146a overexpression was found to suppress Jurkat T cell apoptosis. Finally, transcriptome analysis of miR-146a overexpression in T cells identified Fas associated factor 1 (FAF1) as a miR-146a-regulated gene, which was critically involved in modulating T cell apoptosis.Conclusions: We have detected increased miR-146a in CD4 + T cells of RA patients and its close correlation with TNF-α levels. Our findings that miR-146a overexpression suppresses T cell apoptosis indicate a role of miR-146a in RA pathogenesis and provide potential novel therapeutic targets. © 2010 Li et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.published_or_final_versio

Synthesis and biological activities of novel danshensu amide derivatives as anti-myocardial ischemia agents

A series of novel danshensu amide derivatives were synthesized, and the protective effects of all the compounds on rat myocardial cell lines H9C2 by hypoxia were investigated. The results showed that all the seven compounds could significantly increased cell viability compared with hypoxia group. Among these compounds, 3-(3,4-dimethoxyphenyl)-2-hydroxy-N-propylpropanamide (6) exhibited good activities, with cell viability reached 94.2 % compared to the normal. The novel danshensu amide derivatives, possessing an additional lipophilic alkyl chain showed a good lipophilicity.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Advancing stem cell technologies for conservation of wildlife biodiversity.

Wildlife biodiversity is essential for healthy, resilient and sustainable ecosystems. For biologists, this diversity also represents a treasure trove of genetic, molecular and developmental mechanisms that deepen our understanding of the origins and rules of life. However, the rapid decline in biodiversity reported recently foreshadows a potentially catastrophic collapse of many important ecosystems and the associated irreversible loss of many forms of life on our planet. Immediate action by conservationists of all stripes is required to avert this disaster. In this Spotlight, we draw together insights and proposals discussed at a recent workshop hosted by Revive & Restore, which gathered experts to discuss how stem cell technologies can support traditional conservation techniques and help protect animal biodiversity. We discuss reprogramming, in vitro gametogenesis, disease modelling and embryo modelling, and we highlight the prospects for leveraging stem cell technologies beyond mammalian species

Actively implementing an evidence-based feeding guideline for critically ill patients (NEED): a multicenter, cluster-randomized, controlled trial

Background: Previous cluster-randomized controlled trials evaluating the impact of implementing evidence-based guidelines for nutrition therapy in critical illness do not consistently demonstrate patient benefits. A large-scale, sufficiently powered study is therefore warranted to ascertain the effects of guideline implementation on patient-centered outcomes. Methods: We conducted a multicenter, cluster-randomized, parallel-controlled trial in intensive care units (ICUs) across China. We developed an evidence-based feeding guideline. ICUs randomly allocated to the guideline group formed a local "intervention team", which actively implemented the guideline using standardized educational materials, a graphical feeding protocol, and live online education outreach meetings conducted by members of the study management committee. ICUs assigned to the control group remained unaware of the guideline content. All ICUs enrolled patients who were expected to stay in the ICU longer than seven days. The primary outcome was all-cause mortality within 28 days of enrollment. Results: Forty-eight ICUs were randomized to the guideline group and 49 to the control group. From March 2018 to July 2019, the guideline ICUs enrolled 1399 patients, and the control ICUs enrolled 1373 patients. Implementation of the guideline resulted in significantly earlier EN initiation (1.20 vs. 1.55 mean days to initiation of EN; difference − 0.40 [95% CI − 0.71 to − 0.09]; P = 0.01) and delayed PN initiation (1.29 vs. 0.80 mean days to start of PN; difference 1.06 [95% CI 0.44 to 1.67]; P = 0.001). There was no significant difference in 28-day mortality (14.2% vs. 15.2%; difference − 1.6% [95% CI − 4.3% to 1.2%]; P = 0.42) between groups. Conclusions: In this large-scale, multicenter trial, active implementation of an evidence-based feeding guideline reduced the time to commencement of EN and overall PN use but did not translate to a reduction in mortality from critical illness. Trial registration: ISRCTN, ISRCTN12233792. Registered November 20th, 2017

Actively implementing an evidence-based feeding guideline for critically ill patients (NEED): a multicenter, cluster-randomized, controlled trial.

BackgroundPrevious cluster-randomized controlled trials evaluating the impact of implementing evidence-based guidelines for nutrition therapy in critical illness do not consistently demonstrate patient benefits. A large-scale, sufficiently powered study is therefore warranted to ascertain the effects of guideline implementation on patient-centered outcomes.MethodsWe conducted a multicenter, cluster-randomized, parallel-controlled trial in intensive care units (ICUs) across China. We developed an evidence-based feeding guideline. ICUs randomly allocated to the guideline group formed a local "intervention team", which actively implemented the guideline using standardized educational materials, a graphical feeding protocol, and live online education outreach meetings conducted by members of the study management committee. ICUs assigned to the control group remained unaware of the guideline content. All ICUs enrolled patients who were expected to stay in the ICU longer than seven days. The primary outcome was all-cause mortality within 28 days of enrollment.ResultsForty-eight ICUs were randomized to the guideline group and 49 to the control group. From March 2018 to July 2019, the guideline ICUs enrolled 1399 patients, and the control ICUs enrolled 1373 patients. Implementation of the guideline resulted in significantly earlier EN initiation (1.20 vs. 1.55 mean days to initiation of EN; difference - 0.40 [95% CI - 0.71 to - 0.09]; P = 0.01) and delayed PN initiation (1.29 vs. 0.80 mean days to start of PN; difference 1.06 [95% CI 0.44 to 1.67]; P = 0.001). There was no significant difference in 28-day mortality (14.2% vs. 15.2%; difference - 1.6% [95% CI - 4.3% to 1.2%]; P = 0.42) between groups.ConclusionsIn this large-scale, multicenter trial, active implementation of an evidence-based feeding guideline reduced the time to commencement of EN and overall PN use but did not translate to a reduction in mortality from critical illness.Trial registrationISRCTN, ISRCTN12233792 . Registered November 20th, 2017

Actively implementing an evidence-based feeding guideline for critically ill patients (NEED): a multicenter, cluster-randomized, controlled trial (vol 26, 46, 2022)

BackgroundPrevious cluster-randomized controlled trials evaluating the impact of implementing evidence-based guidelines for nutrition therapy in critical illness do not consistently demonstrate patient benefits. A large-scale, sufficiently powered study is therefore warranted to ascertain the effects of guideline implementation on patient-centered outcomes.MethodsWe conducted a multicenter, cluster-randomized, parallel-controlled trial in intensive care units (ICUs) across China. We developed an evidence-based feeding guideline. ICUs randomly allocated to the guideline group formed a local "intervention team", which actively implemented the guideline using standardized educational materials, a graphical feeding protocol, and live online education outreach meetings conducted by members of the study management committee. ICUs assigned to the control group remained unaware of the guideline content. All ICUs enrolled patients who were expected to stay in the ICU longer than seven days. The primary outcome was all-cause mortality within 28 days of enrollment.ResultsForty-eight ICUs were randomized to the guideline group and 49 to the control group. From March 2018 to July 2019, the guideline ICUs enrolled 1399 patients, and the control ICUs enrolled 1373 patients. Implementation of the guideline resulted in significantly earlier EN initiation (1.20 vs. 1.55 mean days to initiation of EN; difference - 0.40 [95% CI - 0.71 to - 0.09]; P = 0.01) and delayed PN initiation (1.29 vs. 0.80 mean days to start of PN; difference 1.06 [95% CI 0.44 to 1.67]; P = 0.001). There was no significant difference in 28-day mortality (14.2% vs. 15.2%; difference - 1.6% [95% CI - 4.3% to 1.2%]; P = 0.42) between groups.ConclusionsIn this large-scale, multicenter trial, active implementation of an evidence-based feeding guideline reduced the time to commencement of EN and overall PN use but did not translate to a reduction in mortality from critical illness.Trial registrationISRCTN, ISRCTN12233792 . Registered November 20th, 2017

Integral Reinforcement-Learning-Based Optimal Containment Control for Partially Unknown Nonlinear Multiagent Systems

This paper focuses on the optimal containment control problem for the nonlinear multiagent systems with partially unknown dynamics via an integral reinforcement learning algorithm. By employing integral reinforcement learning, the requirement of the drift dynamics is relaxed. The integral reinforcement learning method is proved to be equivalent to the model-based policy iteration, which guarantees the convergence of the proposed control algorithm. For each follower, the Hamilton–Jacobi–Bellman equation is solved by a single critic neural network with a modified updating law which guarantees the weight error dynamic to be asymptotically stable. Through using input–output data, the approximate optimal containment control protocol of each follower is obtained by applying the critic neural network. The closed-loop containment error system is guaranteed to be stable under the proposed optimal containment control scheme. Simulation results demonstrate the effectiveness of the presented control scheme

Integral Reinforcement-Learning-Based Optimal Containment Control for Partially Unknown Nonlinear Multiagent Systems

This paper focuses on the optimal containment control problem for the nonlinear multiagent systems with partially unknown dynamics via an integral reinforcement learning algorithm. By employing integral reinforcement learning, the requirement of the drift dynamics is relaxed. The integral reinforcement learning method is proved to be equivalent to the model-based policy iteration, which guarantees the convergence of the proposed control algorithm. For each follower, the Hamilton–Jacobi–Bellman equation is solved by a single critic neural network with a modified updating law which guarantees the weight error dynamic to be asymptotically stable. Through using input–output data, the approximate optimal containment control protocol of each follower is obtained by applying the critic neural network. The closed-loop containment error system is guaranteed to be stable under the proposed optimal containment control scheme. Simulation results demonstrate the effectiveness of the presented control scheme

Green and Effective Removal of Aqueous Graphene Oxide under UV-Light Irradiation

The potential extensive application of graphene oxide (GO) in various fields results in the possibility of its release into the natural environment with negative impacts on humans and the ecosystem. The UV-induced removal behavior of aqueous GO was evaluated in this study, and the effect of various parameters (including initial GO concentration, initial solution pH and co-existing ions) on removal rate of GO were investigated in detail. The results showed that UV-light induced a maximum removal rate of GO of 99.1% after 32 h irradiation without any additives, and that the photo-induced removal process in all cases fitted well with pseudo-first-order kinetics. Under optimal conditions, GO was completely removed, with initial GO concentrations of 10 mg/L while adjusting solution pH to 3 or adding Ca2+-containing salt. The GO and photoreduced graphene oxide (prGO) were characterized using High-resolution Transmission Microscopy (HRTEM), X-ray Photoelectron Spectroscopy (XPS), and Fourier-transform Infrared Spectroscopy (FT-IR). The radical species trapping experiments and Electron Spin Resonance (ESR) tests indicated that self-reduction of GO upon UV-light exposure could be achieved via photogenerated electrons from a GO semiconductor. Further mechanism study showed that the high efficiency of UV-induced GO removal came from UV-induced photoreduction, and pH-induced or cation-induced coagulation. This study provided a green and effective method to remove GO from aqueous solutions

Synthesis and Antifungal Activity of Novel Triazole Compounds Containing Piperazine Moiety

Design and synthesis of triazole library antifungal agents having piperazine side chains, analogues to fluconazole were documented. The synthesis highlighted utilization of the click chemistry on the basis of the active site of the cytochrome P450 14α-demethylase (CYP51). Their structures were characterized by 1H-NMR, 13C-NMR, MS and IR. The influences of piperazine moiety on in vitro antifungal activities of all the target compounds were evaluated against eight human pathogenic fungi