RESUMO
Since the first receiver independent exchange format (RINEX) version was released in 1989, it has gone through several versions, making the existing software, such as TEQC, incompatible with certain later versions. This study proposes a new Python package named PyRINEX, which is developed to batch process the most generally used versions of RINEX files, namely 2.0 and 3.0. The proposed package can be used to manage and edit numerous RINEX files as well as perform a data quality check function. PyRINEX can be easily imported into any Python IDE similar to any other open-source Python package, it also makes secondary development easy for users.
RESUMO
Dasatinib treatment is approved as first-line therapy for chronic myeloid leukemia. However, pulmonary hypertension (PH) is a highly morbid and often fatal side-effect of dasatinib, characterized by progressive pulmonary vascular remodeling. Melatonin exerts strong antioxidant capacity against the progression of cardiovascular system diseases. The present work aimed to investigate the effect of melatonin on dasatinib-aggravated hypoxic PH and explore its possible mechanisms. Dasatinib-aggravated rat experimental model of hypoxic PH was established by utilizing dasatinib under hypoxia. The results indicated that melatonin could attenuate dasatinib-aggravated pulmonary pressure and vascular remodeling in rats under hypoxia. Additionally, melatonin attenuated the activity of XO, the content of MDA, the expression of NOX4, and elevated the activity of CAT, GPx, and SOD, the expression of SOD2, which were caused by dasatinib under hypoxia. In vitro, dasatinib led to decreased LDH activity and production of NO in human pulmonary microvascular endothelial cells (HPMECs), moreover increased generation of ROS, and expression of NOX4 both in HPMECs and primary rat pulmonary arterial smooth muscle cells (PASMCs) under hypoxia. Dasatinib up-regulated the expression of cleaved caspase-3 and the ratio of apoptotic cells in HPMECs, and also elevated the percentage of S phase and the expression of Cyclin D1 in primary PASMCs under hypoxia. Melatonin ameliorated dasatinib-aggravated oxidative damage and apoptosis in HPMECs, meanwhile reduced oxidative stress level, proliferation, and repressed the stability of HIF1-α protein in PASMCs under hypoxia. In conclusion, melatonin significantly attenuates dasatinib-aggravated hypoxic PH by inhibiting pulmonary vascular remodeling in rats. The possible mechanisms involved protecting endothelial cells and inhibiting abnormal proliferation of smooth muscle cells. Our findings may suggest that melatonin has potential clinical value as a therapeutic approach to alleviate dasatinib-aggravated hypoxic PH.
RESUMO
Hypoxia-induced oxidative stress and excessive proliferation of pulmonary artery smooth muscle cells (PASMCs) play important roles in the pathological process of hypoxic pulmonary hypertension (HPH). Grape seed procyanidin extract (GSPE) possesses antioxidant properties and has beneficial effects on the cardiovascular system. However, the effect of GSPE on HPH remains unclear. In this study, adult Sprague-Dawley rats were exposed to intermittent chronic hypoxia for 4 weeks to mimic a severe HPH condition. Hemodynamic and pulmonary pathomorphology data showed that chronic hypoxia significantly increased right ventricular systolic pressures (RVSP), weight of the right ventricle/left ventricle plus septum (RV/LV+S) ratio and median width of pulmonary arteries. GSPE attenuated the elevation of RVSP, RV/LV+S, and reduced the pulmonary vascular structure remodeling. GSPE also increased the levels of SOD and reduced the levels of MDA in hypoxia-induced HPH model. In addition, GSPE suppressed Nox4 mRNA levels, ROS production and PASMCs proliferation. Meanwhile, increased expression of phospho-STAT3, cyclin D1, cyclin D3 and Ki67 in PASMCs caused by hypoxia was down-regulated by GSPE. These results suggested that GSPE might potentially prevent HPH via antioxidant and antiproliferative mechanisms.