Ginseng total saponin improves red blood cell oxidative stress injury by regulating tyrosine phosphorylation and glycolysis in red blood cells.

BACKGROUND: Oxidative stress is the main cause of many diseases, but because of its complex pathogenic factors, there is no clear method for treating it. Ginseng total saponin (GTS) an important active ingredients in Panax ginseng C.A. Mey (PG) and has potential therapeutic ability for oxidative stress due to various causes. However, the molecular mechanism of GTS in the treating oxidative stress damage in red blood cells (RBCs) is still unclear. PURPOSE: This study aimed to examine the protective effect of GTS on RBCs under oxidative stress damage and to determine its potential mechanism. METHODS: The oxidative stress models of rat RBCs induced by hydrogen peroxide (H2O2) and exhaustive swimming in vivo and in vitro was used. We determined the cell morphology, oxygen carrying capacity, apoptosis, antioxidant capacity, and energy metabolism of RBCs. The effect of tyrosine phosphorylation (pTyr) of Band 3 protein on RBCs glycolysis was also examined. RESULTS: GTS reduced the hemolysis of RBCs induced by H2O2 at the lowest concentration. Moreover, GTS effectively improved the morphology, enhanced the oxygen carrying capacity, and increased antioxidant enzyme activity, adenosine triphosphate (ATP) levels, and adenosine triphosphatase (ATPase) activity in RBCs. GTS also promoted the expression of membrane proteins in RBCs, inhibited pTyr of Band 3 protein, and further improved glycolysis, restoring the morphological structure and physiological function of RBCs. CONCLUSIONS: This study shows, that GTS can protect RBCs from oxidative stress damage by improving RBCs morphology and physiological function. Changes in pTyr expression and its related pTyr regulatory enzymes before and after GTS treatment suggest that Band 3 protein is the main target of GTS in the treating endogenous and exogenous oxidative stress. Moreover, GTS can enhance the glycolytic ability of RBCs by inhibiting pTyr of Band 3 protein, thereby restoring the function of RBCs.

Chest lesion CT radiological features and quantitative analysis in RT-PCR turned negative and clinical symptoms resolved COVID-19 patients.

BACKGROUND: Many studies have described lung lesion computed tomography (CT) features of coronavirus disease 2019 (COVID-19) patients at the early and progressive stages. In this study, we aim to evaluate lung lesion CT radiological features along with quantitative analysis for the COVID-19 patients ready for discharge. METHODS: From February 10 to March 10, 2020, 125 COVID-19 patients (age: 16-67 years, 63 males) ready for discharge, with two consecutive negative reverse transcription-polymerase chain reaction (RT-PCR) and no clinical symptoms for more than 3 days, were included. The pre-discharge CT was performed on all patients 1-3 days after the second negative RT-PCR test, and the follow-up CTs were performed on 44 patients 2-13 days later. The imaging features and quantitative analysis were evaluated on both the pre-discharge and the follow-up CTs, by both radiologists and an artificial intelligence (AI) software. RESULTS: On the pre-discharge CT, the most common CT findings included ground-glass opacity (GGO) (99/125, 79.2%) with bilateral mixed distribution, and fibrosis (56/125, 44.8%) with bilateral subpleural distribution. Enlarged mediastinal lymph nodes were also commonly observed (45/125, 36.0%). AI enabled quantitative analysis showed the right lower lobe was mostly involved, and lesions most commonly had CT value of -570 to -470 HU consistent with GGO. Follow-up CT showed GGO decrease in size and density (40/40, 100%) and fibrosis reduction (17/26, 65.4%). Compared with the pre-discharge CT results, quantitative analysis shows the lung lesion volume regressed significantly at follow-up. CONCLUSIONS: For COVID-19 patients ready for discharge, GGO and fibrosis are the main CT features and they further regress at follow-up.

Aldehyde dehydrogenase 2 protects against oxidative stress associated with pulmonary arterial hypertension.

The cardioprotective benefits of aldehyde dehydrogenase 2 (ALDH2) are well established, although the regulatory role of ALDH2 in vascular remodeling in pulmonary arterial hypertension (PAH) is largely unknown. ALDH2 potently regulates the metabolism of aldehydes such as 4-hydroxynonenal (4-HNE), the endogenous product of lipid peroxidation. Thus, we hypothesized that ALDH2 ameliorates the proliferation and migration of human pulmonary artery smooth muscle cells (HPASMCs) by inhibiting 4-HNE accumulation and regulating downstream signaling pathways, thereby ameliorating pulmonary vascular remodeling. We found that low concentrations of 4-HNE (0.1 and 1µM) stimulated cell proliferation by enhancing cyclin D1 and c-Myc expression in primary HPASMCs. Low 4-HNE concentrations also enhanced cell migration by activating the nuclear factor kappa B (NF-κB) signaling pathway, thereby regulating matrix metalloprotein (MMP)-9 and MMP2 expression in vitro. In vivo, Alda-1, an ALDH2 agonist, significantly stimulated ALDH2 activity, reducing elevated 4-HNE and malondialdehyde levels and right ventricular systolic pressure in a monocrotaline-induced PAH animal model to the level of control animals. Our findings indicate that 4-HNE plays an important role in the abnormal proliferation and migration of HPASMCs, and that ALDH2 activation can attenuate 4-HNE-induced PASMC proliferation and migration, possibly by regulating NF-κB activation, in turn ameliorating vascular remodeling in PAH. This mechanism might reflect a new molecular target for treating PAH.