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Introduction: Atherosclerosis (AS) is a common cardiovascular disease with a high incidence rate and mortality. Endothelial cell injury and dysfunction are early markers of AS. Oxidative low-density lipoprotein (Ox-LDL) is a key risk factor for the development of AS. Ox-LDL promotes endothelial cell apoptosis and induces inflammation and oxidative stress in endothelial cells. Small non-coding RNAs (sncRNAs) mainly include Piwi-interacting RNAs (piRNAs), small nucleolar RNAs (snoRNAs), small nuclear RNAs (snRNAs), microRNAs (miRNAs) and repeat-associated RNAs. Studies have shown that small non-coding RNAs play an increasingly important role in diseases. Methods: We used ox-LDL to treat rat endothelial cells to simulate endothelial cell injury. The expression changes of sncRNA were analyzed by small RNA high-throughput sequencing, and the expression changes of piRNA, snoRNA, snRNA, miRNA and repeat-associated RNA were verified by quantitative polymerase chain reaction (qPCR). Results: Small RNA sequencing showed that 42 piRNAs were upregulated and 38 piRNAs were downregulated in endothelial cells treated with ox-LDL. PiRNA DQ614630 promoted the apoptosis of endothelial cells. The snoRNA analysis results showed that 80 snoRNAs were upregulated and 68 snoRNAs were downregulated in endothelial cells with ox-LDL treatment, and snoRNA ENSRNOT00000079032.1 inhibited the apoptosis of endothelial cells. For snRNA, we found that 20 snRNAs were upregulated and 26 snRNAs were downregulated in endothelial cells with ox-LDL treatment, and snRNA ENSRNOT00000081005.1 increased the apoptosis of endothelial cells. Analysis of miRNAs indicated that 106 miRNAs were upregulated and 91 miRNAs were downregulated in endothelial cells with ox-LDL treatment, and miRNA rno-novel-136-mature promoted the apoptosis of endothelial cells. The repeat RNA analysis results showed that 4 repeat RNAs were upregulated and 6 repeat RNAs were downregulated in endothelial cells treated with ox-LDL. Discussion: This study first reported the expression changes of sncRNAs in endothelial cells with ox-LDL treatment, which provided new markers for the diagnosis and treatment of endothelial cell injury.
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BACKGROUND: The pandemic of coronavirus disease 2019 (COVID-19) has caused heavy burdens on national healthcare systems. Nirmatrelvir-ritonavir (Paxlovid) may be one of the most promising therapeutic drugs, with reports of up to 89% reduction rates in hospitalization risk and death among patients with mild-to-moderate COVID-19 who are at risk of developing severe disease. However, limited studies have investigated the effects of this class of drugs on viral clearance and length of hospital stay. METHODS: In this study, we retrospectively analyzed the characteristics of patients infected with the Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and investigated the effects of oral nirmatrelvir-ritonavir on viral clearance and length of hospital stay in mild-to-moderate COVID-19 patients at high risk for progression to severe disease. RESULTS: The median SARS-CoV-2 negative conversion time was 16 (13-20) versus 13 (10-16) days (control group versus nirmatrelvir-ritonavir group, p < 0.001), the median length of hospital stay was 13 (10-16) versus 12 (13-14) days (control group versus nirmatrelvir-ritonavir group, p = 0.01), and the SARS-CoV-2 negative conversion time and length of hospital stay were significantly shorter in the nirmatrelvir-ritonavir group than in the control group. When controlling for hypertension, chronic kidney disease, severity status of COVID-19, use of antibiotic agent, and COVID-19 vaccine received, multiple stepwise linear regression analysis showed that nirmatrelvir-ritonavir treatment was negatively associated with the SARS-CoV-2 negative conversion time and length of hospital stay. CONCLUSION: Nirmatrelvir-ritonavir reduces the viral clearance time and length of hospital stay in hospitalized patients with COVID-19. Nirmatrelvir-ritonavir might be a promising drug to reduce the virus load and the heavy burden of healthcare systems.
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COVID-19 , SARS-CoV-2 , Humanos , Tempo de Internação , Ritonavir/uso terapêutico , Vacinas contra COVID-19 , Estudos Retrospectivos , Tratamento Farmacológico da COVID-19RESUMO
The catalytic enantioselective desymmetrizing bromoaminocyclization of prochiral cyclohexa-1,4-dienes has been achieved by using chiral anion phase-transfer catalysis, providing a range of enantioenriched cis-3a-arylhydroindoles bearing an all-carbon quaternary stereocenter in good yields (up to 78%) and excellent enantioselectivities (up to 97% ee). Furthermore, the potential application of this methodology to natural product total synthesis was demonstrated by the asymmetric synthesis of (+)-Mesembrane.
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Background: Metformin, an antidiabetic drug, has been reported to be involved in atherosclerosis (AS). In this study, the effects of metformin on oxidized low-density lipoprotein (Ox-LDL)-induced macrophage apoptosis were investigated, and the mechanisms involved in this process were examined. Methods: qRT-qPCR analysis was performed to detect the expression of miR-34a in macrophage cells. Cell proliferation was determined by MTT assays and colony formation assays. Cell apoptosis was assessed by the detection of apoptotic rate and caspase 3 activity. Western blot analysis was performed to evaluate the expression of Bcl2 protein. Results: Metformin treatment promoted proliferation and suppressed apoptosis in macrophages following the treatment of oxidized low-density lipoprotein (Ox-LDL). Metformin could inhibit miR-34a in macrophages. miR-34a overexpression could reverse the effect of metformin on proliferation and apoptosis in Ox-LDL-treated macrophages. Moreover, metformin could increase the expression of the miR-34a target gene Bcl2. Furthermore, metformin treatment exerted the pro-proliferation and anti-apoptosis effect through regulating Bcl2 expression in Ox-LDL-stimulated macrophages. Conclusion: Metformin facilitated proliferation and inhibited apoptosis of macrophages treated with Ox-LDL through the miR-34a/Bcl2 axis, indicating the potential value of metformin in AS therapy.