Acute Effects of Microcystins on the Transcription of 14 Glutathione S-Transferase Isoforms in Wistar Rat

ABSTRACT: The glutathione S-transferases (GST) play important roles in the detoxification of microcystins (MCs). For better understanding of the responses of GST isforms to MCs exposure, informations about the effects of MCs on GSTs are necessary. In this experiment, we cloned the full length cDNA of 14 GST isoforms (GST alpha, kappa, mu, omega, pi, theta, zeta, and microsomal GST) from Wistar rat. The mRNA abundance of each rat GST isoform in the liver, kidney, and testis was analyzed by real time quantitative PCR. Multiple GST isoforms were constitutively expressed in all examined organs, but some isoforms were expressed at higher level in one organ than in others. The relative changes of the mRNA abundance in the liver, kidney, and testis of Wiatar rat i.v. injected with crude MCs extract at dose of 1LD 50 were also analyzed. Generally, the expression of most GSTs in the liver and testis was suppressed while that in kidney was induced after being injected with MCs. It is suggested that the transcription of GST isoforms varied in different ways within an organ and between organs of Wistar rat exposed to MCs. # 2009 Wiley Periodicals, Inc. Environ Toxicol 26: 187-194, 2011

Effect of Aerobic Exercise on Inflammatory Markers in Healthy Middle-Aged and Older Adults: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background: Chronic inflammation plays a significant role in accelerating the aging process and is closely associated with the initiation and progression of a broad range of age-related diseases. Physical exercise is considered beneficial in alleviating these conditions, but the effects of aerobic exercise on inflammatory markers in a healthy population should be furtherly clarified.Objective: The purpose of this systematic review and meta-analysis was to evaluate the effect of aerobic exercise on inflammatory markers in middle-aged and older adults.Methods: The literature search was conducted utilizing PubMed, Web of Science, Embase, and the Cochrane Library from their inception through April 2018, and the reference lists were screened to identify appropriate studies. Only randomized controlled trials that investigated the effect of aerobic exercise on inflammatory markers in middle-aged and older adults were eligible for this review.Results: Eleven studies involving 1,250 participants were retrieved from the databases for analysis. The pooled results showed that aerobic exercise significantly reduced inflammatory markers (C-reactive protein (CRP): SMD = 0.53, 95% CI 0.26–0.11, p = 0.0002; tumor necrosis factor-alpha (TNF-α): SMD = 0.75, 95% CI 0.31–1.19, p = 0.0007; interleukin 6 (IL-6): SMD = 0.75, 95% CI 0.31–1.19, p = 0.0007). No significant improvement was found in relation to interleukin 4 (IL-4).Conclusions: Aerobic exercise may have a positive effect on reduction of CRP, TNF-α, and IL-6 in middle-aged and older adults. Further randomized controlled trials (RCTs) need to be conducted to determine the effect of aerobic exercise on additional inflammatory markers in the population of middle-aged and older adults

Identification of a venetoclax-resistance prognostic signature base on 6-senescence genes and its clinical significance for acute myeloid leukemia

BackgroundSatisfactory responses can be obtained for acute myeloid leukemia (AML) treated by Venetoclax (VEN)-based therapy. However, there are still quite a few AML patients (AMLs) resistant to VEN, and it is critical to understand whether VEN-resistance is regulated by senescence.MethodsHere, we established and validated a signature for predicting AML prognosis based on VEN resistance-related senescence genes (VRSGs). In this study, 51 senescence genes were identified with VEN-resistance in AML. Using LASSO algorithms and multiple AML cohorts, a VEN-resistance senescence prognostic model (VRSP-M) was developed and validated based on 6-senescence genes.ResultsAccording to the median score of the signature, AMLs were classified into two subtypes. A worse prognosis and more adverse features occurred in the high-risk subtype, including older patients, non-de novo AML, poor cytogenetics, adverse risk of European LeukemiaNet (ELN) 2017 recommendation, and TP53 mutation. Patients in the high-risk subtype were mainly involved in monocyte differentiation, senescence, NADPH oxidases, and PD1 signaling pathway. The model’s risk score was significantly associated with VEN-resistance, immune features, and immunotherapy response in AML. In vitro, the IC50 values of ABT-199 (VEN) rose progressively with increasing expression of G6PD and BAG3 in AML cell lines.ConclusionsThe 6-senescence genes prognostic model has significant meaning for the prediction of VEN-resistance, guiding personalized molecularly targeted therapies, and improving AML prognosis

Transcriptional alteration of cytoskeletal genes induced by microcystins in three organs of rats

This study explored the mechanisms of toxicity of microcystins by measuring the transcription levels of nine cytoskeletal genes (actin, tubulin, vimentin, ezrin, radixin, moesin, MAP1b, tau, stathmin) in the liver, kidney and spleen of male Wistar rats treated with microcystins at a dose of 80 mu g MC-LReq kg(-1) bw. Microcystins disrupted the transcriptional homeostasis of cytoskeletal genes in these organs. Changes in the transcription of four genes (beta-actin, ezrin, radixin and tau) in liver, one gene (stathmin) in kidney, and one gene (radixin) in spleen were significantly correlated with the tissue concentration of microcystins. However, the influences on the transcription of most genes we studied were greater in the liver than in the kidney or spleen. The effects of microcystins on the transcription of cytoskeletal genes may explain some of the morphological and pathological changes observed in these organs and provide new information on the hepatotoxicity of these compounds. Additionally, transcriptional changes in tumor-associated cytoskeletal genes (ezrin, moesin and stathmin) that were observed in the present study provide a possible clue to the tumor-promoting potential of microcystins and their influences on the transcription of MAP1b and tau imply possible neurological toxicity of microcystins in vertebrates. (C) 2010 Published by Elsevier Ltd

Cell Membrane Is Impaired, Accompanied by Enhanced Type III Secretion System Expression in Yersinia pestis Deficient in RovA Regulator

BACKGROUND: In the enteropathogenic Yersinia species, RovA regulates the expression of invasin, which is important for enteropathogenic pathogenesis but is inactivated in Yersinia pestis. Investigation of the RovA regulon in Y. pestis at 26 °C has revealed that RovA is a global regulator that contributes to virulence in part by the direct regulation of psaEFABC. However, the regulatory roles of RovA in Y. pestis at 37 °C, which allows most virulence factors in mammalian hosts to be expressed, are still poorly understood. METHODOLOGY/PRINCIPAL FINDINGS: The transcriptional profile of an in-frame rovA mutant of Y. pestis biovar Microtus strain 201 was analyzed under type III secretion system (T3SS) induction conditions using microarray techniques, and it was revealed that many cell-envelope and transport/binding proteins were differentially expressed in the ΔrovA mutant. Most noticeably, many of the T3SS genes, including operons encoding the translocon, needle and Yop (Yersinia outer protein) effectors, were significantly up-regulated. Analysis of Yop proteins confirmed that YopE and YopJ were also expressed in greater amounts in the mutant. However, electrophoresis mobility shift assay results demonstrated that the His-RovA protein could not bind to the promoter sequences of the T3SS genes, suggesting that an indirect regulatory mechanism is involved. Transmission electron microscopy analysis indicated that there are small loose electron dense particle-like structures that surround the outer membrane of the mutant cells. The bacterial membrane permeability to CFSE (carboxyfluorescein diacetate succinimidyl ester) was significantly decreased in the ΔrovA mutant compared to the wild-type strain. Taken together, these results revealed the improper construction and dysfunction of the membrane in the ΔrovA mutant. CONCLUSIONS/SIGNIFICANCE: We demonstrated that the RovA regulator plays critical roles in the construction and functioning of the bacterial membrane, which sheds considerable light on the regulatory functions of RovA in antibiotic resistance and environmental adaptation. The expression of T3SS was upregulated in the ΔrovA mutant through an indirect regulatory mechanism, which is possibly related to the altered membrane construction in the mutant

Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome : Insights from the LUNG SAFE study

Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). Conclusions: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073publishersversionPeer reviewe

Recent progress in graphene-based optical modulators on silicon photonics platform

Graphene is a 2D material which has attracted tremendous interest from academia and industry, due to its attractive electrical and optical properties. By integrating graphene onto silicon photonics platform, various high-performance electro-optic and thermo-optic modulators have been demonstrated. In this paper, such graphene-based optical modulators are reviewed. The concept and principle of optical modulations are firstly analyzed and then an overview of the developing trends of optical modulators is presented. Meanwhile, the performances of graphene-based optical modulators, including power consumptions and speeds of electro-optic modulators as well as tuning efficiencies of thermo-optic modulators, are then evaluated and discussed in detail. All these optical modulators would play important roles in a wide range of applications including telecom, interconnects, computing, quantum information processing, and beam steering

Effect of Baduanjin exercise on cerebral blood flow and cognitive frailty in the community older adults with cognitive frailty: A randomized controlled trial

Objectives: Regular Baduanjin exercise training has been shown to be beneficial to the physical and cognitive health of older adults, but the underlying mechanisms remain to be investigated. This study examined the influence of Baduanjin on cerebral hemodynamics in community-dwelling older adults with cognitive frailty. Design: Randomized controlled trial. Methods: A total of 102 eligible participants were randomly allocated into the Baduanjin exercise intervention group (BEG) or usual physical activity control group (CG) for 24 weeks. Cerebral hemodynamic parameters of bilateral middle/anterior cerebral artery and basilar artery, cognitive ability and physical frailty were assessed using Transcranial Doppler (TCD), Montreal Cognitive Assessment (MoCA) and Edmonton Frailty Scale (EFS) at baseline and 24 weeks post-intervention. Results: After 24 weeks intervention, the changes in peak systolic velocity (PSV), mean blood flow velocity (MBFV), and end diastolic velocity (EDV) in the right middle cerebral artery and basilar artery were better in the BEG than in the CG; the increase in MoCA scores and the decrease in EFS scores were significantly higher in the BEG than in the CG. Moreover, the interaction of exercise and time on those variables showed obvious significance. Conclusions: The 24 weeks Baduanjin exercise training had a positive beneficial effect on cerebral blood flow in community-dwelling older adults with cognitive frailty. This may be a potential mechanism by which Baduanjin exercise improves the cognitive frailty in older adults. Trial registration: Chinese Clinical Trial Registry, ChiCTR1800020341. Date of registration: December 25, 2018, http://www.chictr.org.cn/showproj.aspx?proj=29846