RESUMEN
The wide spread of coronavirus disease 2019 (COVID-19) has significantly threatened public health. Human herd immunity induced by vaccination is essential to fight the epidemic. Therefore, highly immunogenic and safe vaccines are necessary to control SARS-CoV-2, whose S protein is the antigenic determinant responsible for eliciting antibodies that prevent viral entry and fusion. In this study, we developed a SARS-CoV-2 DNA vaccine expressing the S protein, named pVAX-S-OP, which was optimized according to the human-origin codon preference and using polyinosinic-polycytidylic acid as an adjuvant. pVAX-S-OP induced specific antibodies and neutralizing antibodies in BALB/c and hACE2 transgenic mice. Furthermore, we observed 1.43-fold higher antibody titers in mice receiving pVAX-S-OP plus adjuvant than in those receiving pVAX-S-OP alone. Interferon gamma production in the pVAX-S-OP-immunized group was 1.58 times (CD3+CD4+IFN-gamma+) and 2.29 times (CD3+CD8+IFN-gamma+) lower than that in the pVAX-S-OP plus adjuvant group but higher than that in the control group. The pVAX-S-OP vaccine was also observed to stimulate a Th1-type immune response. When, hACE2 transgenic mice were challenged with SARS-CoV-2, qPCR detection of N and E genes showed that the viral RNA loads in pVAX-S-OP-immunized mice lung tissues were 104 times and 106 times lower than those of the PBS control group, which shows that the vaccine could reduce the amount of live virus in the lungs of hACE2 mice. In addition, pathological sections showed less lung damage in the pVAX-S-OP-immunized group. Taken together, our results demonstrated that pVAX-S-OP has significant immunogenicity, which provides support for developing SARS-CoV-2 DNA candidate vaccines.
Asunto(s)
COVID-19 , Vacunas de ADN , Animales , Humanos , Ratones , Adyuvantes Inmunológicos , Anticuerpos Neutralizantes , Anticuerpos Antivirales , COVID-19/prevención & control , Inmunidad Celular , Ratones Transgénicos , SARS-CoV-2/genética , Glicoproteína de la Espiga del Coronavirus/genética , Vacunas de ADN/genéticaRESUMEN
The probiotic properties of two selected lactobacilli strains were assessed. L. salivarius and L. plantarum displayed higher hydrophobicity (48% and 54%, resp.) and coaggregation ability with four pathogens (from 7.9% to 57.5%). L. salivarius and L. plantarum had good inhibitory effects on S. aureus (38.2% and 49.5%, resp.) attachment to Caco-2 cells. Live lactobacilli strains and their conditioned media effectively inhibited IL-8 production (<14.6 pg/mL) in TNF-α-induced Caco-2 cells. Antibiotic-treated and the sonicated lactobacilli also maintained inhibitory effects (IL-8 production from 5.0 to 36.3 pg/mL); however, the heat-treated lactobacilli lost their inhibitory effects (IL-8 production from 130.2 to 161.0 pg/mL). These results suggest that both the structural components and the soluble cellular content of lactobacilli have anti-inflammatory effects. We also found that pretreatment of Caco-2 cells with lactobacilli inhibited S. typhimurium-induced IL-8 production (<27.3 pg/mL). However, lactobacilli did not inhibit IL-8 production in Caco-2 cells pretreated with S. typhimurium. These results suggest that the tested lactobacilli strains are appropriate for preventing inflammatory diseases caused by enteric pathogens but not for therapy. In short, L. salivarius and L. plantarum are potential candidates for the development of microbial ecological agents and functional foods.
Asunto(s)
Interleucina-8/biosíntesis , Lactobacillus/metabolismo , Probióticos/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Antiinflamatorios/administración & dosificación , Antiinflamatorios/metabolismo , Células CACO-2 , Humanos , Interleucina-8/metabolismo , Lactobacillus/genética , Probióticos/administración & dosificación , Salmonella/crecimiento & desarrollo , Salmonella/metabolismo , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/crecimiento & desarrolloRESUMEN
<p><b>BACKGROUND</b>Natural disasters have been frequent in recent years. Effective treatment of patients with cardiovascular disease following natural disasters is an unsolved problem. We aimed to develop a novel miniature mobile cardiac catheterization laboratory (Mini Mobile Cath Lab) to provide emergency interventional services for patients with critical cardiovascular disease following natural disasters. A feasibility study was performed by testing the Mini Mobile Cath Lab on dogs with ST-elevation myocardial infarction (STEMI) model in a hypothetical natural-disaster-stricken area.</p><p><b>METHODS</b>The Mini Mobile Cath Lab was transported to the hypothetical natural-disaster-stricken area by truck. Coronary angiography and primary percutaneous coronary intervention (PCI) were performed on six dogs with STEMI model. The transportation and transformation of the Mini Mobile Cath Lab were monitored and its functioning was evaluated through the results of animal experiments.</p><p><b>RESULTS</b>The Mini Mobile Cath Lab could be transported by truck at an average speed of 80 km/h on mountain roads during daytime in the winter, under conditions of light snow (-15°C to -20°C/-68°F to -59°F). The average time required to prepare the Mini Mobile Cath Lab after transportation, in a wetland area, was 30 minutes. Coronary angiography, and primary PCI were performed successfully.</p><p><b>CONCLUSION</b>This preliminary feasibility study of the use of the Mini Mobile Cath Lab for emergency interventional treatment of dogs with STEMI indicated that it may perform well in the rescue of critical cardiovascular disease following natural disasters.</p>
Asunto(s)
Animales , Perros , Angioplastia Coronaria con Balón , Cateterismo Cardíaco , Enfermedades Cardiovasculares , Terapéutica , Angiografía Coronaria , Desastres , Electrocardiografía , Estudios de Factibilidad , Laboratorios , Infarto del Miocardio , TerapéuticaRESUMEN
The catalysis effect of water-soluble calix[4]arene C[4] (calix[4]arene-5,11,17,23-tetrasulfonate) on hydrolysis of ATP in aqueous solution was studied by HPLC. Using laser photolysis and pulse radiolysis, the supramolecular interaction between water-soluble calix[4]arene and ATP was investigated.