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      Characteristics of Tibetan pig lung tissue in response to a hypoxic environment on the Qinghai–Tibet Plateau

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          Abstract

          To adapt to the plateau environment, Tibetan pigs' lungs have developed a unique physiological mechanism during evolution. The vascular corrosion casting technique and scanning electron microscopy were used to understand arterial architecture. Blood physiological index and quantitative real-time PCR (qRT-PCR) were used for assessing whether the lung can regulate the body through anatomical, physiological and molecular mechanisms to adapt to hypoxic environments. Our study showed that the lungs of Tibetan pigs were heavier and wider and that the pulmonary arteries were thicker and branched and had a denser vascular network than those of Landrace pigs. The hemoglobin (HGB), mean corpuscular hemoglobin concentration (MCHC) values of high-altitude pigs were significantly higher than those of low-altitude pigs. The expression levels of HIF- 1 α , EPAS1, EPO and VEGF, but not those of eNOS and EGLN1, were significantly higher in the lungs of high-altitude pigs than in those from pigs at a lower altitude ( P < 0.05 ). These findings and a comprehensive analysis help elucidate the pulmonary mechanism of hypoxic adaptation in pigs.

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          Origin and differentiation of vascular smooth muscle cells

          Abstract Vascular smooth muscle cells (SMCs), a major structural component of the vessel wall, not only play a key role in maintaining vascular structure but also perform various functions. During embryogenesis, SMC recruitment from their progenitors is an important step in the formation of the embryonic vascular system. SMCs in the arterial wall are mostly quiescent but can display a contractile phenotype in adults. Under pathophysiological conditions, i.e. vascular remodelling after endothelial dysfunction or damage, contractile SMCs found in the media switch to a secretory type, which will facilitate their ability to migrate to the intima and proliferate to contribute to neointimal lesions. However, recent evidence suggests that the mobilization and recruitment of abundant stem/progenitor cells present in the vessel wall are largely responsible for SMC accumulation in the intima during vascular remodelling such as neointimal hyperplasia and arteriosclerosis. Therefore, understanding the regulatory mechanisms that control SMC differentiation from vascular progenitors is essential for exploring therapeutic targets for potential clinical applications. In this article, we review the origin and differentiation of SMCs from stem/progenitor cells during cardiovascular development and in the adult, highlighting the environmental cues and signalling pathways that control phenotypic modulation within the vasculature.
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            Endothelial Cells

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              Hypoxia-inducible factor-1 (HIF-1) inhibitors from the last decade (2007 to 2016): A "structure-activity relationship" perspective.

              Tumor hypoxia is a common feature in most solid tumors and is associated with overexpression of the hypoxia response pathway. Overexpression of the hypoxia-inducible factor (HIF-1) protein leads to angiogenesis, metastasis, apoptosis resistance, and many other pro-tumorigenic responses in cancer development. HIF-1 is a promising target in cancer drug development to increase the patient's response to chemotherapy and radiotherapy as well as the survival rate of cancer patients. Since up to 1% of genes are hypoxia-sensitive, a target-specific HIF-1 inhibitor may be a better clinical candidate in cancer drug discovery. Though no HIF-1 inhibitor is clinically available to date, a lot of effort has been applied during the last decade in search of potent HIF-1 inhibitors. In this review, we will summarize the structure-activity relationship of ten different chemotypes reported to be HIF-1 inhibitors in the last decade (2007-2016), their mechanisms of action for HIF-1 inhibition, progress in the way of target-specific inhibitors, and problems associated with current inhibitors. It is anticipated that the results of these research on the medicinal chemistry of HIF-1 inhibitors will provide decent information in the design and development of future inhibitors.
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                Author and article information

                Contributors
                Journal
                Arch Anim Breed
                Arch Tierz
                AAB
                Archives Animal Breeding
                Copernicus GmbH
                0003-9438
                2363-9822
                28 June 2021
                2021
                : 64
                : 1
                : 283-292
                Affiliations
                [1 ] College of Animal Science and Technology, Gansu Agricultural University, Lanzhou 730070, China
                [2 ] State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150069, China
                Author notes
                [*] Correspondence:Shengguo Zhao ( zhaosg@ 123456gsau.edu.cn )
                Article
                01021829
                10.5194/aab-64-283-2021
                8253108
                34235247
                5cbf6c3e-4409-4c95-a0a7-655b3a7b14ac
                Copyright: © 2021 Yanan Yang et al.

                This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this licence, visit https://creativecommons.org/licenses/by/4.0/

                History
                : 24 March 2021
                : 18 May 2021
                Categories
                Original Study

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