ABSTRACT
RIPK1 is a global cellular sensor that can determine the survival of cells. Generally, RIPK1 can induce cell apoptosis and necroptosis through TNF, Fas and lipopolysaccharide stimulation, while its scaffold function can sense the fluctuation of cellular energy and promote cell survival. Sepsis is a nonspecific disease that seriously threatens human health. There is some dispute in the literature about the role of RIPK1 in sepsis. In this review, the authors attempt to comprehensively discuss the differential results for RIPK1 in sepsis by summarizing the underlying molecular mechanism and putting forward a tentative idea as to whether RIPK1 can serve as a biomarker for the monitoring of treatment and progression in sepsis.
Sepsis is a syndrome that poses a serious threat to human life and health and is classified as a medical emergency by the WHO. RIPK1 can regulate the onset of apoptosis and necrosis in several ways and is known as a sensor of cell survival status. A series of clinical trials of RIPK1 drugs has been conducted this year and have demonstrated promising efficacy in inflammatory diseases, in particular. In this paper, the authors summarize recent studies on the function and mechanism of RIPK1 in sepsis and combine them with the progress in RIPK1 drug development to provide information for the study of RIPK1 in sepsis.
Subject(s)
Apoptosis , Sepsis , Humans , Sepsis/therapy , Tumor Necrosis Factor-alpha/metabolism , Receptor-Interacting Protein Serine-Threonine KinasesABSTRACT
The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has stimulated the search for effective drugs for its prevention and treatment. Natural products are an important source for new drug discovery. Here, we report that, NK007(S,R), a tylophorine malate, displays high antiviral activity against SARS-CoV-2 with an EC50 0.03 µM in vitro, which is substantially lower than that of remdesivir (EC50: 0.8 µM in vitro), the only authorized drug to date. The histopathological research revealed that NK007(S,R) (5 mg/kg/dose) displayed a protection effect in lung injury induced by SARS-CoV-2, which is better than remdesivir (25 mg/kg/dose). We also prepared two nanosized preparations of NK007(S,R), which also showed good efficacy (EC50: NP-NK007, 0.007 µM in vitro; LP-NK007, 0.014 µM in vitro). Our findings suggest that tylophora alkaloids, isolated from the traditional Chinese medicine Cynanchum komarovii AL, offer a new skeleton for the development of anticoronavirus drug candidate.
ABSTRACT
BACKGROUND: Among discharged COVID-19 patients, the health-related quality of life is poor, and patients suffer from significant physical and psychological impairment. This study was designed to investigate the effects of Liuzijue exercise on the rehabilitation of COVID-19 patients. METHODS: Thirty three eligible patients with COVID-19 were enrolled in the study after discharge. All the participants practiced Liuzijue exercise once per day for 20 minutes over 4âweeks. Data were collected at baseline and the end of the intervention. Primary outcomes involved functional capacity and secondary outcomes involved quality of life. RESULTS: The maximal inspiratory pressure (MIP), peak inspiratory flow (PIF), and diaphragm movement in deep breathing (DM-DB) of patients increased significantly after 4âweeks of intervention. The dyspnea was also alleviated and exercise capacity was significantly improved. In terms of quality of life, physical functioning and role-physical scores were significantly increased. Moreover, Liuzijue could significantly alleviate the depression and anxiety status of the patients. CONCLUSION: Liuzijue exercise is a viable alternative home exercise program that produced better functional capacity and quality of life in discharged patients with COVID-19. These findings also showed the necessity of rehabilitation intervention for cured COVID-19 patients.