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BackgroundAcute and chronic alcohol abuse have adverse impacts on both the innate and adaptive immune response, which may result in reduced resistance to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection and promote the progression of coronavirus disease 2019 (COVID-19). However, there are no large population-based data evaluating potential causal associations between alcohol consumption and COVID-19. MethodWe conducted a Mendelian randomization study using data from UK Biobank to explore the association between alcohol consumption and risk of SARS-CoV-2 infection and serious clinical outcomes in patients with COVID-19. A total of 12,937 participants aged 50-83 who tested for SARS-CoV-2 between 16 March to 27 July 2020 (12.1% tested positive) were included in the analysis. The exposure factor was alcohol consumption. Main outcomes were SARS-CoV-2 positivity and death in COVID-19 patients. We generated weighted and unweighted allele scores using three genetic variants (rs1229984, rs1260326, and rs13107325) and applied the allele scores as the instrumental variables to assess the effect of alcohol consumption on outcomes. Analyses were conducted separately for white participates with and without obesity. ResultsOf the 12,937 participants, 4,496 were never or infrequent drinkers and 8,441 were frequent drinkers. (including 1,156 light drinkers, 3,795 moderate drinkers, and 3,490 heavy drinkers). Both logistic regression and Mendelian randomization analyses found no evidence that alcohol consumption was associated with risk of SARS-CoV-2 infection in participants either with (OR=0.963, 95%CI 0.800-1.159; q =1.000) or without obesity (OR=0.891, 95%CI 0.755-1.053; q =.319). However, frequent drinking (HR=1.565, 95%CI 1.012-2.419; q =.079), especially heavy drinking (HR=2.071, 95%CI 1.235-3.472; q =.054), was associated with higher risk of death in patients with obesity and COVID-19, but not in patients without obesity. Notably, the risk of death in frequent drinkers with obesity increased slightly with the average amount of alcohol consumed weekly (HR=1.480, 95%CI 1.059-2.069; q =.099). ConclusionsOur findings suggested alcohol consumption may had adverse effects on the progression of COVID-19 in white participants with obesity, but was not associate with susceptibility to SARS-CoV-2 infection.
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To observe the immunogenicity of hPDGF-B immunogens that were synthesized with the fusional expression vector pET28-Trx and to test the suppressive effect of these specific antibodies induced by both of immunogens on proliferation of human HepG2 hepatoma cells. First, we chose 2 antigenic epitopes hPDGF-BΔ103-118aa and hPDGF-BΔ152-167aa from human PDGF-B and inserted these 2 coding regions into the empty vector plasmid pET28-Trx, separately. Second, mice were immunized with purified recombinant proteins to generate polyclonal antibody. Then we intraperitoneally injected mice bearing hepatoma 22 (H22) tumor cells to prepare antibody ascites. ELISA and Western blot were used to detect the titer and the utility of the antibody, respectively. Finally, HepG2 cells were exposed to PDGF-BB protein or anti-PDGF-B ascite antibody in different dilution concentrations groups and the proliferation of HepG2 cells was quantified by CCK8 assay. As the results, we identified mice that could produce high drop of neutralizing antibodies against hPDGF-B induced by both two recombinant proteins. Two anti-PDGF-B ascite antibodies could markedly inhibit the proliferation of HepG2 cells by blocking the stimulating effect of PDGF-BB protein. Our results suggest that Trx-PDGF-B recombinant protein as immunogen provides a new method for the preparation of PDGF-B vaccine, and also a new idea for the treatment of hepatocellular carcinoma in clinical practice.
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ABSTRACT:Objective To validate that relaxin can resist hepatic fibrosis at the cellular level and explore its molecular mechanism in order to provide experimental basis for the treatment of liver cirrhosis.Methods Cultured HSC-T6s were treated with different concentrations (20,50 and 100 ng/mL)of recombinant human relaxin-2 (RLX-2).The proliferation of HSC-T6 was measured by MTT colorimetric assay.The content of type Ⅰcollagen in the cell culture supernatant of each group was detected by ELISA at 48 h of drug intervention;RT-PCR was used to detect the mRNA expressions of CTGF and TGF-β1 in HSC-T6 at 48 h of drug intervention.Results RLX-2 inhibited the proliferation of HSC and reduced type Ⅰ collagen content of HSC cells.It also inhibited the CTGF mRNA expression of HSC,but did not have a significant effect on the expression of TGF-β1 mRNA. Conclusion In the experiment of culturing HSC-T6 in vitro,RLX-2 may play a role in rat liver fibrosis by inhibiting cell proliferation and type Ⅰ collagen and CTGF mRNA expressions.
