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      Ganoderic acid A attenuates lipopolysaccharide-induced lung injury in mice

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          Abstract

          The present study aimed to investigate the protective effects of ganoderic acid A (GAA) on lipopolysaccharide (LPS)-induced acute lung injury. In mouse model of LPS-induced acute lung injury, we found that GAA led to significantly lower lung wet-to-dry weight ratio and lung myeloperoxidase activity, and attenuated pathological damages. In addition, GAA increased superoxide dismutase activity, but decreased malondialdehyde content and proinflammatory cytokines levels in the bronchoalveolar lavage fluid. Mechanistically, GAA reduced the activation of Rho/ROCK/NF-κB pathway to inhibit LPS-induced inflammation. In conclusion, our study suggests that GAA attenuates acute lung injury in mouse model via the inhibition of Rho/ROCK/NF-κB pathway.

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          Activation of RhoA/ROCK regulates NF-κB signaling pathway in experimental diabetic nephropathy.

          Both RhoA/ROCK and NF-κB signaling pathways play important roles in the pathogenesis of diabetic nephropathy (DN). However, it remains unknown whether and how RhoA/ROCK regulates NF-κB signaling in diabetic kidneys. In cultured glomerular mesangial cells (GMCs), the high glucose-activated NF-κB nuclear translocation and DNA binding activity were attenuated by ROCK inhibitor Y27632 or dominant-negative RhoA mutant, indicating that RhoA/ROCK signaling regulates high glucose-activated NF-κB pathway. Furthermore, NF-κB-regulated inflammatory factors ICAM-1 and TGF-β1 were markedly increased in high glucose-treated GMCs, leading to accumulation of fibronectin (FN), an important component of extracellular matrix (ECM), This effect was also effectively attenuated by Y27632 or dominant-negative RhoA mutant. In STZ-induced diabetic rats, treatment with ROCK inhibitor fasudil suppressed the RhoA/ROCK activation and NF-κB nuclear translocation, and significantly reduced the renal FN, ICAM-1 and TGF-β1 protein levels. Thus, the RhoA/ROCK pathway may regulate NF-κB to upregulate inflammatory genes and mediate the development of DN. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.
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            Antiinflammatory effect of Rho kinase blockade via inhibition of NF-kappaB activation in rheumatoid arthritis.

            There is increasing evidence that the RhoA signaling pathway may play a critical role in the inflammatory response. This study was undertaken to examine the effects of RhoA and its downstream effector Rho kinase (ROK) in synovial inflammation in rheumatoid arthritis (RA). RhoA activity was assessed by pull-down assay. Fasudil and Y27632, both specific inhibitors of ROK, were used to examine the role of ROK in inflammatory responses in vivo and in vitro. Nuclear translocation of NF-kappaB was measured by confocal fluorescence microscopy, and DNA binding activity was assessed with a sensitive multiwell colorimetric assay. Enzyme-linked immunosorbent assay was used to detect cytokine production. Increased activation of RhoA was found in inflamed synovial membrane cells isolated from patients with RA and from rats with collagen-induced arthritis (CIA). Intraperitoneal administration of fasudil in rats with CIA significantly reduced synovial inflammation and ROK activity. In vitro, treatment with fasudil or Y27632 decreased production of tumor necrosis factor alpha (TNFalpha), interleukin-1beta (IL-1beta), and IL-6 by synovial membrane cells, peripheral blood mononuclear cells, and fibroblast-like synoviocytes from patients with active RA. Inhibition of ROK by specific inhibitors or ROK small interfering RNA suppressed lipopolysaccharide- or TNFalpha-induced NF-kappaB nuclear translocation, DNA binding activity, luciferase reporter gene expression, and IkappaBalpha degradation. The results of this study provide new evidence that blockade of ROK inhibits activation of NF-kappaB and production of proinflammatory cytokines, suggesting a critical role of ROK in the synovial inflammation of RA. Specific inhibition of ROK may be a novel therapeutic approach in RA.
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              A double-blind placebo-controlled randomized study of Chinese herbal medicine as complementary therapy for reduction of chemotherapy-induced toxicity.

              Chinese herbal medicine (CHM) is a common complementary therapy used by patients with cancer for reduction of chemotherapy-induced toxic effects. This study applied the highest standard of clinical trial methodology to examine the role of CHM in reducing chemotherapy-induced toxicity, while maintaining a tailored approach to therapy. Patients with early-stage breast or colon cancer who required postoperative adjuvant chemotherapy were eligible for the study. Enrolled patients were randomly assigned to one of three Chinese herbalists who evaluated and prescribed a combination of single-item packaged herbal extract granules. Patients received either CHM or placebo packages with a corresponding serial number. The placebo package contained nontherapeutic herbs with an artificial smell and taste similar to a typical herbal tea. The primary end points were hematologic and non-hematologic toxicity according to the National Cancer Institute Common Toxicity Criteria Version 2. One hundred and twenty patients were accrued at the time of premature study termination. Patient characteristics of the two groups were similar. The incidence of grade 3/4 anemia, leukopenia, neutropenia, and thrombocytopenia for the CHM and placebo groups were 5.4%, 47.3%, 52.7%, and 1.8% and 1.8%, 32.2%, 44.7%, and 3.6%, respectively (P = 0.27, 0.37, 0.63, and 0.13, respectively). Incidence of grade 2 nausea was the only non-hematologic toxicity that was significantly reduced in the CHM group (14.6% versus 35.7%, P = 0.04). Traditional CHM does not reduce the hematologic toxicity associated with chemotherapy. CHM, however, does have a significant impact on control of nausea.
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                Author and article information

                Journal
                Biosci Rep
                Biosci. Rep
                ppbioscirep
                BSR
                Bioscience Reports
                Portland Press Ltd.
                0144-8463
                1573-4935
                09 May 2019
                31 May 2019
                24 May 2019
                : 39
                : 5
                : BSR20190301
                Affiliations
                [1 ]Department of Respiratory and Critical Care Medicine, the Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing 210002, China
                [2 ]Jiangsu Province Key Laboratory of Geriatrics, Department of Geriatric Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China
                [3 ]Department of Respiratory Medicine, Jinling Clinical Medical College of Nanjing Medical University, Nanjing 21002, China
                [4 ]Department of Comprehensive Internal Medicine, Chenzhou First People’s Hospital, Chenzhou 423000, China
                [5 ]Department of Immunology, Key Laboratory for Laboratory Medicine of Jiangsu Province, Jiangsu University Medical School, Zhenjiang 212013, China
                Author notes
                Correspondence: Xiuwei Zhang ( zhangxiuweiywy@ 123456126.com )
                [*]

                These authors contributed equally to this work.

                Author information
                http://orcid.org/0000-0002-4331-8583
                Article
                10.1042/BSR20190301
                6533208
                31072918
                928f49f0-dff6-460f-943b-c84ab4bbc9df
                © 2019 The Author(s).

                This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY).

                History
                : 04 February 2019
                : 18 April 2019
                : 06 May 2019
                Page count
                Pages: 7
                Categories
                Research Articles
                Research Article
                60
                49
                45

                Life sciences
                ganoderic acid a,lipopolysaccharide,lung injury,nuclear factor kappab,rho-associated protein kinases

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