Innate immune sensing of self-derived double-stranded RNA by RIG-I-MAVS-TNF-α regulates the survival and senescence fate of SARS-2-S syncytia

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains an important health threat. Syncytial formation by infected cells mediated by the SARS-CoV-2 spike protein (SARS-2-S) is a hallmark of COVID-19-associated pathology. Although SARS-CoV-2 infection evokes cellular senescence, as in other viruses, the direct link between SARS-2-S-induced syncytia with senescence in the absence of viral infection and their senescence fate determinants remain unknown. Here, we show that syncytia formed by cells expressing exogenously delivered SARS-2-S exhibited a senescence-like phenotype in vitro and that SARS-2-S mRNA induced senescence phenotype in vivo. Extracellular vesicles (EVs) containing SARS-2-S also induced senescent syncytium formation independent of the de novo synthesis of SARS-2-S. Mechanistically, we show that the accumulation of endogenous dsRNA, partially that whose formation is induced by activation of the unfolded protein response (UPR), in SARS-2-S syncytia triggers RIG-I-MAVS signalling to drive the TNF--dependent survival and senescence fate of SARS-2-S syncytia. Our findings suggest that the fusogenic ability of SARS-2-S might contribute to the side effects of particular COVID-19 vaccines or perhaps long COVID-19 syndrome and provide insight into how these effects can be prevented.

SARS-CoV-2 manipulates the SR-B1-mediated HDL uptake pathway for its entry

The recently emerged pathogenic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread rapidly, leading to a global COVID-19 pandemic. Binding of the viral spike protein (SARS-2-S) to cell surface receptor angiotensin-converting enzyme 2 (ACE2) mediates host cell infection. In the present study, we demonstrate that in addition to ACE2, the S1 subunit of SARS-2-S binds to HDL and that SARS-CoV-2 hijacks the SR-B1-mediated HDL uptake pathway to facilitate its entry. SR-B1 facilitates SARS-CoV-2 entry into permissive cells by augmenting virus attachment. MAb (monoclonal antibody)-mediated blocking of SARS-2-S-HDL binding and SR-B1 antagonists strongly inhibit HDL-enhanced SARS-CoV-2 infection. Notably, SR-B1 is co-expressed with ACE2 in human pulmonary and extrapulmonary tissues. These findings revealed a novel mechanism for SARS-CoV-2 entry and could provide a new target to treat SARS-CoV-2 infection.

Cholesterol Metabolism--Impact for SARS-CoV-2 Infection Prognosis, Entry, and Antiviral Therapies

In this study, we specifically addressed the connection between the SARS-CoV-2 virus with host cholesterol metabolism. Plasma lipid profile was measured in 861 COVID-19 patients classified as mild (n=215), moderate (n=364), severe (n=217) or critical (n=65) and 1108 age- and sex-matched healthy individuals. We showed that the levels of both TG and HDL-C were significantly lower in patients with severe disease than in patients with moderate or mild disease. After successful treatment, cholesterol metabolism was reestablished in patients with SARS-CoV-2 infection. The serum concentrations of TC and HDL-C can be used as indicators of disease severity and prognosis in COVID-19 patients.

General and Specific Genetic Polymorphism of Cytokines-Related Gene in AITD.

Autoimmune thyroid disease (AITD) shows the highest incidence among organ-specific autoimmune diseases and is the most common thyroid disease in humans, including Graves' disease (GD) and Hashimoto's thyroiditis (HT). The susceptibility to autoimmune diseases is affected by increased autoantibody levels, susceptibility gene polymorphisms, environmental factors, and psychological factors, but the pathogenesis remains unclear. Various cytokines and related genes encoding them play important roles in the development and progression of AITD. CD152, an expression product of the CTLA-4 gene, downregulates T cell activation. The A/A genotype polymorphism in the CT60 locus may reduce the production of thyroid autoantibodies. The C1858T polymorphism of the PTNP22 gene reduces the expression of its encoded LYP, which increases the risk of GD and HT. GD is an organ-specific autoimmune disease involving increased secretion of thyroid hormone, whereas HT may be associated with the destruction of thyroid gland tissue and hypothyroidism. These two diseases exhibit similar pathogenesis but opposite trends in the clinical manifestations. In this review, we focus on the structure and function of these cytokines and related genes in AITD, as well as the association of polymorphisms with susceptibility to GD and HT, and attempt to describe their differences in pathogenesis and clinical manifestations.

Effect of Shenqi Fuzheng injection combined with IFN-α on the expression of STAT1 gene in hepatocellular carcinoma cells / 中国现代普通外科进展

Objective:To study the effect of Shenqi Fuzheng injection combined with interferon-α (IFN-α) on the expression of STAT1 gene in hepatocellular carcinoma cells,and to elucidate its mechanism of IFN-α synergistic effect.Methords:The effect of IFN-α injection alone or combined with Shenqi Fuzheng injection on the proliferation of MHCC97-L cells was detected by MTT assay.IFN-α was detected by Real-time PCR and Western-blot respectively.The expression of STAT1 mRNA and protein in the experimental group,the negative control group (NaCl) and the blank control group were determined,and the effect of Shenqi Fuzheng injection on the transcription and expression of STAT1 was determined.The expression of STAT1 in lentiviral vector MTT assay was used to detect the effect of IFN-α alone or in combination with Shenqi Fuzheng injection on the STAT1 gene silencing cells.The expression of STAT1 was detected by RT-PCR and Western-Blot in MHCC97L cells.Strain,on cell proliferation.Results:Compared with IFN-α alone,Shenqi Fuzheng injection combined with IFN-α enhanced the inhibitory effect of IFN-α on MHCC97-L (P＜0.01) and up-regulated the expression of STAT1mRNA and protein (P＜0.05).Successfully constructed the STAT1 gene silent in the MHCC97-L cell line.There was no significant difference in the inhibition rate of MHCC97-L between Shenqi Fuzheng injection and IFN-α (P＞0.05).Conclusion Shenqi Fuzheng Injection can up-regulate the expression of STAT1 in human hepatocellular carcinoma cell line MHCC97-L,so as to increase the effect of IFN-α.

Chinese herbal compound affects osteoblast proliferation and bone mineral density / 中国组织工程研究

BACKGROUND:Compound Chinese medicine is a kind of compound drugs with the combination of minerals, plants and animals, which play the multi-target integrated treatment effects in the treatment of bone metabolic disease through various methods. OBJECTIVE:To research the effect of compound traditional Chinese medicine on the proliferation and bone mineral density of osteoblasts, and to explore the pharmacological effect of compound traditional Chinese medicine in the treatment of osteoporosis. METHODS: A retrospective analysis was performed to analyze the effect of some compound traditional Chinese medicines on the proliferation and bone mineral density of osteoblasts that identified in the previous studies, in order to analyze the factors of compound traditional Chinese medicines that can promote the bone formation. The appropriate dose of the drugs that can promote cel proliferation and differentiation and improve the bone mineral density was screened out through the in vitro culture of osteoblasts, and then compared with the results of chemical medicines. RESULTS AND CONCLUSION:Compound traditional Chinese medicines can promote the proliferation and differentiation of osteoblasts and improve the bone mineral density, and have the advantages of ful treatment and less side effect in the treatment of osteoporosis. But the effect of compound traditional Chinese medicines in improving the bone mineral density is less than the chemical drugs. The long-term and large-sample clinical studies should be performed to decrease the risk of osteoporotic fracture.