Vascular calcification is a prominent feature of many diseases, including atherosclerosis, and it has emerged as a powerful predictor of cardiovascular morbidity and mortality. A number of studies have examined the association between selenium and risk of cardiovascular diseases, but little is known about the role of selenium in vascular calcification. To determine the role of selenium in regulating vascular calcification, we assessed the effect of sodium selenite on oxidative-stress-enhanced vascular smooth muscle cell (VSMC) calcification and the underlying mechanism. Oxidative stress induced by xanthine/xanthine oxidase increased apoptosis, as determined by Hoechst 33342 staining and annexin V/propidium iodide staining, and it enhanced osteoblastic differentiation and calcification of VSMCs, on the basis of alkaline phosphatase activity, the expression of Runx2 and type I collagen, and calcium deposition. These effects of oxidative stress were significantly inhibited by selenite. The following processes may explain the inhibitory effects of selenite: (1) selenite significantly suppressed oxidative stress, as evidenced by the decrease of the oxidative status of the cell and lipid peroxidation levels, as well as by the increase of the total protein thiol content and the activity of the antioxidant selenoenzyme glutathione peroxidase; (2) selenite significantly attenuated oxidative-stress-induced activation of the phosphatidylinositol 3-kinase/AKT and extracellular-signal-regulated kinase signaling pathways, resulting in decreased osteoblastic differentiation of VSMCs; (3) selenite significantly inhibited oxidative-stress-activated endoplasmic reticulum stress, thereby leading to decreased apoptosis. Our results suggest a potential role of selenium in the prevention of vascular calcification, which may provide more mechanistic insights into the relationship between selenium and cardiovascular diseases.
Atherosclerosis and related cardiovascular diseases (CVD) represent one of the greatest threats to human health worldwide. The protection of vascular smooth muscle cells (VSMCs) from apoptosis in the plaque has become an important therapeutic target for atherosclerotic plaque stabilization. A significant association of selenoprotein S (SelS) gene polymorphism with atherosclerotic CVD has been reported in epidemiologic studies, but the underlying mechanism remains unknown. In this paper, SelS expression in the thoracic aorta and its role in the protection of VSMCs from apoptosis have been studied. Western blot analysis showed that SelS was highly expressed in rat thoracic aorta. SelS gene silence by small interference RNA (siRNA) rendered VSMCs more sensitive to hydrogen peroxide- or tunicamycin- induced injury and apoptosis, as determined by MTT assay, Hoechst staining, and annexin V/propidium iodide staining. SelS silence aggravated hydrogen peroxide-induced oxidative stress and phosphorylation of p38 MAPK and c-Jun N-terminal kinase (JNK) in VSMCs. Furthermore, SelS silence enhanced endoplasmic reticulum (ER) stress induced by hydrogen peroxide or tunicamycin, as showed by the increased protein levels of ER chaperone 78 kDa glucose-regulated protein (GRP78), ER stress transducer phosphorylated protein kinase RNA like ER kinase (PERK), and the proapoptotic transcription factor C/EBP homologous protein (CHOP). In conclusion, the present study suggested that SelS highly expressed in the blood vessel might protect VSMCs from apoptosis by inhibiting oxidative stress and ER stress. Our finding provided mechanistic insights for the potential preventive role of SelS in atherosclerotic CVD.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in thousands of deaths in the world. Information about prediction model of prognosis of SARS-CoV-2 infection is scarce. We used machine learning for processing laboratory findings of 110 patients with SARS-CoV-2 pneumonia (including 51 non-survivors and 59 discharged patients). The maximum relevance minimum redundancy (mRMR) algorithm and the least absolute shrinkage and selection operator logistic regression model were used for selection of laboratory features. Seven laboratory features selected in the model were: prothrombin activity, urea, white blood cell, interleukin-2 receptor, indirect bilirubin, myoglobin, and fibrinogen degradation products. The signature constructed using the seven features had 98% [93%, 100%] sensitivity and 91% [84%, 99%] specificity in predicting outcome of SARS-CoV-2 pneumonia. Thus it is feasible to establish an accurate prediction model of outcome of SARS-CoV-2 pneumonia based on laboratory findings.
Dear Editor,The diagnostic value of CT for SARS-CoV-2 infection has been widely reported [1,2]. However, performing CT is very difficult in critically ill patients in ICU, whereas mobile Xrays serve as an alternative. From Feb. 20 to Mar. 20, 542 mobile chest X-rays were performed in 229 COVID patients who were under assisted ventilation. Table 1 summarizes the main characteristics of the cohort.Among the 229, a significant underlying disease existed in 165 (72%): hypertension in 31%, chronic heart disease in 13%, chronic pulmonary disease in 12%, and malignancy in 11%. As of Mar. 30, 95 (41%) of 229 patients had died, and 134 (59%) survived. Among them, 58 were discharged and 76 still in hospital. Table 1 shows the number of X-rays performed per patient. There were 229 initial examination and 313 were follow-ups. The image quality was diagnostic for all these X-rays.Extensive pneumonia was seen on the initial X-rays in all patients. Other findings were pneumothorax (7%) and pleural effusion (23%). Subcutaneous emphysema, hiatal hernia, and intrapulmonary cavity were rare findings ( Table 1). All patients with pneumothorax died. Compared to previous X-rays, increase of pneumonia was seen in 119 (38%) of 313 followup X-rays, while no changes were seen in 57 (18%), and improvement in 137 (44%).Among non-survivors (n = 95), 61 patients did not have follow-up X-rays and died 1~4 days after the initial examination; 34 patients had 55 follow-up X-rays. Pneumonia progress was seen in 53 (96%) out of 55 follow-up X-rays when compared to previous radiograph (Fig. 1).Among survivors (n = 134), 111 patients had 258 followup X-rays. Pneumonia progress was seen in 66/258 radiographs (26%) of follow-up X-rays in 37 survivors; however, improvement was seen later.We found mobile X-rays provided adequate image quality for diagnosing pneumonia, at least in this population of severely ill patients. Although obviously less informative than CT, X-rays can nevertheless detect serious complications like pneumothorax or lung cavitation, and estimate the evolution of pneumonia. Therefore, it is a simple but reliable alternative in critically ill SARS-CoV-2 patients who could not undergo chest CT.
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