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Melatonin reduces oxidative stress and improves vascular function in pulmonary hypertensive newborn sheep
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![点击此处可从《Journal of pineal research》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Flavio Torres Alejandro González‐Candia Camilo Montt Germán Ebensperger Magdalena Chubretovic María Serón‐Ferré Roberto V. Reyes Aníbal J. Llanos Emilio A. Herrera 《Journal of pineal research》2015,58(3):362-373
Pulmonary hypertension of the newborn (PHN) constitutes a critical condition with severe cardiovascular and neurological consequences. One of its main causes is hypoxia during gestation, and thus, it is a public health concern in populations living above 2500 m. Although some mechanisms are recognized, the pathophysiological facts that lead to PHN are not fully understood, which explains the lack of an effective treatment. Oxidative stress is one of the proposed mechanisms inducing pulmonary vascular dysfunction and PHN. Therefore, we assessed whether melatonin, a potent antioxidant, improves pulmonary vascular function. Twelve newborn sheep were gestated, born, and raised at 3600 meters. At 3 days old, lambs were catheterized and daily cardiovascular measurements were recorded. Lambs were divided into two groups, one received daily vehicle as control and another received daily melatonin (1 mg/kg/d), for 8 days. At 11 days old, lung tissue and small pulmonary arteries (SPA) were collected. Melatonin decreased pulmonary pressure and resistance for the first 3 days of treatment. Further, melatonin significantly improved the vasodilator function of SPA, enhancing the endothelial‐ and muscular‐dependent pathways. This was associated with an enhanced nitric oxide‐dependent and nitric oxide independent vasodilator components and with increased nitric oxide bioavailability in lung tissue. Further, melatonin reduced the pulmonary oxidative stress markers and increased enzymatic and nonenzymatic antioxidant capacity. Finally, these effects were associated with an increase of lumen diameter and a mild decrease in the wall of the pulmonary arteries. These outcomes support the use of melatonin as an adjuvant in the treatment for PHN. 相似文献
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Maria Gonzalez-Cao Cristina Carrera Juan Francisco Rodriguez Moreno Pedro Rodríguez-Jiménez Mónica Antoñanzas Basa Rosa Feltes Ochoa Teresa Puertolas Eva Muñoz-Couselo José Luis Manzano Ivan Marquez-Rodas Juan Martín-Liberal Ainara Soria Pilar Lopez Criado Almudena Garcia-Castaño Aram Boada Pablo Ayala de Miguel Susana Puig Guillermo Crespo Alfonso Berrocal 《Journal of the American Academy of Dermatology》2021,84(5):1412-1415
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目的 收集藿香正气汤的主要活性成分,通过分子对接及网络药理学探讨其防控新型冠状病毒肺炎(COVID-19)的有效成分及治疗机制。方法 通过基于配体-蛋白质相互作用的计算方法,以瑞德西韦为对照,探索藿香正气汤潜在治疗COVID-19的成分,并选出对接较好成分进行药理学机制预测,初探其药理学机制。结果 本研究筛选出5种与新冠病毒3CLpro结合能力强于瑞德西韦的小分子成分。网络药理学初步预测抗病毒途径可能是通过PI3K-Akt 信号通路影响病毒复制。结论 成分C1-C5与3CLpro结合良好,推测其可能是潜在的3CLpro的抑制剂,为抗病毒天然药物的开发提供了理论依据。 相似文献
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David M. Presby Michael C. Rudolph Vanessa D. Sherk Matthew R. Jackman Rebecca M. Foright Kenneth L. Jones Julie A. Houck Ginger C. Johnson Janine A. Higgins P. Darrell Neufer Robert H. Eckel Paul S. MacLean 《Diabetes》2021,70(4):867
Moderate weight loss improves numerous risk factors for cardiometabolic disease; however, long-term weight loss maintenance (WLM) is often thwarted by metabolic adaptations that suppress energy expenditure and facilitate weight regain. Skeletal muscle has a prominent role in energy homeostasis; therefore, we investigated the effect of WLM and weight regain on skeletal muscle in rodents. In skeletal muscle of obesity-prone rats, WLM reduced fat oxidative capacity and downregulated genes involved in fat metabolism. Interestingly, even after weight was regained, genes involved in fat metabolism were also reduced. We then subjected mice with skeletal muscle lipoprotein lipase overexpression (mCK-hLPL), which augments fat metabolism, to WLM and weight regain and found that mCK-hLPL attenuates weight regain by potentiating energy expenditure. Irrespective of genotype, weight regain suppressed dietary fat oxidation and downregulated genes involved in fat metabolism in skeletal muscle. However, mCK-hLPL mice oxidized more fat throughout weight regain and had greater expression of genes involved in fat metabolism and lower expression of genes involved in carbohydrate metabolism during WLM and regain. In summary, these results suggest that skeletal muscle fat oxidation is reduced during WLM and regain, and therapies that improve skeletal muscle fat metabolism may attenuate rapid weight regain. 相似文献
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PNPLA3 gene polymorphism and response to lifestyle modification in patients with nonalcoholic fatty liver disease
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Iria Montero Prez Laura Rodríguez‐Pazos Adriana lvarez‐Prez MªMercedes Pereiro Ferreirs Carlos Aliste Jose Manuel Suarez‐Pearanda Jaime Toribio 《Journal of cutaneous pathology》2015,42(11):889-893
Classical Kaposi sarcoma (KS) usually appears on lower extremities accompanied or preceded by local lymphedema. However, the development in areas of chronic lymphedema of the arms following mastectomy, mimicking a Stewart–Treves syndrome, has rarely been described. We report an 81‐year‐old woman who developed multiple, erythematous to purple tumors, located on areas of post mastectomy lymphedema. Histopathological examination evidenced several dermal nodules formed by spindle‐shaped cells that delimitated slit‐like vascular spaces with some red cell extravasation. Immunohistochemically, the human herpesvirus type 8 (HHV‐8) latent nuclear antigen‐1 was detected in the nuclei of most tumoral cells confirming the diagnosis of KS. Lymphedema could promote the development of certain tumors by altering immunocompetence. Although angiosarcoma (AS) is the most frequent neoplasia arising in the setting of chronic lymphedema, other tumors such as benign lymphangiomatous papules (BLAP) or KS can also develop in lymphedematous limbs. It is important to establish the difference between AS and KS because their prognosis and treatment are very different. Identification by immunohistochemistry of HHV‐8 is useful for the distinction between KS and AS or BLAP. 相似文献