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      Progress in the mechanism and targeted drug therapy for COPD

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          Abstract

          Chronic obstructive pulmonary disease (COPD) is emphysema and/or chronic bronchitis characterised by long-term breathing problems and poor airflow. The prevalence of COPD has increased over the last decade and the drugs most commonly used to treat it, such as glucocorticoids and bronchodilators, have significant therapeutic effects; however, they also cause side effects, including infection and immunosuppression. Here we reviewed the pathogenesis and progression of COPD and elaborated on the effects and mechanisms of newly developed molecular targeted COPD therapeutic drugs. Among these new drugs, we focussed on thioredoxin (Trx). Trx effectively prevents the progression of COPD by regulating redox status and protease/anti-protease balance, blocking the NF-κB and MAPK signalling pathways, suppressing the activation and migration of inflammatory cells and the production of cytokines, inhibiting the synthesis and the activation of adhesion factors and growth factors, and controlling the cAMP-PKA and PI3K/Akt signalling pathways. The mechanism by which Trx affects COPD is different from glucocorticoid-based mechanisms which regulate the inflammatory reaction in association with suppressing immune responses. In addition, Trx also improves the insensitivity of COPD to steroids by inhibiting the production and internalisation of macrophage migration inhibitory factor (MIF). Taken together, these findings suggest that Trx may be the ideal drug for treating COPD.

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          AKT/PKB Signaling: Navigating the Network

          The Ser/Thr kinase AKT, also known as protein kinase B (PKB), was discovered 25 years ago and has been the focus of tens of thousands of studies in diverse fields of biology and medicine. There have been many advances in our knowledge of the upstream regulatory inputs into AKT, key multifunctional downstream signaling nodes (GSK3, FoxO, mTORC1), which greatly expand the functional repertoire of Akt, and the complex circuitry of this dynamically branching and looping signaling network that is ubiquitous to nearly every cell in our body. Mouse and human genetic studies have also revealed physiological roles for the AKT network in nearly every organ system. Our comprehension of AKT regulation and functions is particularly important given the consequences of AKT dysfunction in diverse pathological settings, including developmental and overgrowth syndromes, cancer, cardiovascular disease, insulin resistance and type-2 diabetes, inflammatory and autoimmune disorders, and neurological disorders. There has also been much progress in developing AKT-selective small molecule inhibitors. Improved understanding of the molecular wiring of the AKT signaling network continues to make an impact that cuts across most disciplines of the biomedical sciences.
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            Interpretative strategies for lung function tests.

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              AKT/PKB signaling: navigating downstream.

              The serine/threonine kinase Akt, also known as protein kinase B (PKB), is a central node in cell signaling downstream of growth factors, cytokines, and other cellular stimuli. Aberrant loss or gain of Akt activation underlies the pathophysiological properties of a variety of complex diseases, including type-2 diabetes and cancer. Here, we review the molecular properties of Akt and the approaches used to characterize its true cellular targets. In addition, we discuss those Akt substrates that are most likely to contribute to the diverse cellular roles of Akt, which include cell survival, growth, proliferation, angiogenesis, metabolism, and migration.
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                Author and article information

                Contributors
                tianhai2820044@yahoo.co.jp
                Journal
                Signal Transduct Target Ther
                Signal Transduct Target Ther
                Signal Transduction and Targeted Therapy
                Nature Publishing Group UK (London )
                2095-9907
                2059-3635
                27 October 2020
                27 October 2020
                2020
                : 5
                : 248
                Affiliations
                [1 ]GRID grid.412551.6, ISNI 0000 0000 9055 7865, Department of Basic Medicine, , Medical College, Shaoxing University, ; Shaoxing, 312000 China
                [2 ]GRID grid.31432.37, ISNI 0000 0001 1092 3077, Division of Dermatology, Department of Internal Related, , Kobe University Graduate School of Medicine, ; Kobe, 650-0017 Japan
                [3 ]GRID grid.258799.8, ISNI 0000 0004 0372 2033, Laboratory of Infection and Prevention, Department of Biological Response, Institute for Virus Research, , Kyoto University, ; Kyoto, 606-8501 Japan
                [4 ]Jiaozhimei Biotechnology (Shaoxing) Co, Ltd, Shaoxing, 312000 China
                Author information
                http://orcid.org/0000-0003-2026-8154
                Article
                345
                10.1038/s41392-020-00345-x
                7588592
                33110061
                603a02ec-eac4-48f0-babe-3e0f8df7e9cf
                © The Author(s) 2020

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 18 April 2020
                : 15 September 2020
                : 21 September 2020
                Categories
                Review Article
                Custom metadata
                © The Author(s) 2020

                drug screening,drug safety,molecular medicine
                drug screening, drug safety, molecular medicine

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