RESUMEN
INTRODUCTION: Pneumonia is an inflammation-related respiratory infection and chlorogenic acid (CGA) possesses a wide variety of bioactive properties, such as anti-inflammation and anti-bacteria. AIM: This study explored the anti-inflammatory mechanism of CGA in Klebsiella pneumoniae (Kp)-induced rats with severe pneumonia. METHODS: The pneumonia rat models were established by infection with Kp and treated with CGA. Survival rates, bacterial load, lung water content, and cell numbers in the bronchoalveolar lavage fluid were recorded, lung pathological changes were scored, and levels of inflammatory cytokines were determined by enzyme-linked immunosorbent assay. RLE6TN cells were infected with Kp and treated with CGA. The expression levels of microRNA (miR)-124-3p, p38, and mitogen-activated protein kinase (MAPK)-activated protein kinase 2 (MK2) in lung tissues and RLE6TN cells were quantified by real-time quantitative polymerase chain reaction or Western blotting. The binding of miR-124-3p to p38 was validated by the dual-luciferase and RNA pull-down assays. In vitro, the functional rescue experiments were performed using miR-124-3p inhibitor or p38 agonist. RESULTS: Kp-induced pneumonia rats presented high mortality, increased lung inflammatory infiltration and the release of inflammatory cytokines, and enhanced bacterial load, while CGA treatment improved rat survival rates and the above situations. CGA increased miR-124-3p expression, and miR-124-3p inhibited p38 expression and inactivated the p38MAPK pathway. Inhibition of miR-124-3p or activation of the p38MAPK pathway reversed the alleviative effect of CGA on pneumonia in vitro. CONCLUSION: CGA upregulated miR-124-3p expression and inactivated the p38MAPK pathway to downregulate inflammatory levels, facilitating the recovery of Kp-induced pneumonia rats.
Asunto(s)
MicroARNs , Neumonía , Ratas , Animales , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/uso terapéutico , Klebsiella pneumoniae/genética , Ácido Clorogénico/farmacología , Ácido Clorogénico/uso terapéutico , Klebsiella/genética , Klebsiella/metabolismo , MicroARNs/genética , Neumonía/tratamiento farmacológico , Neumonía/microbiología , Citocinas/metabolismo , Antiinflamatorios/farmacologíaRESUMEN
The Omicron EG.5 lineage of SARS-CoV-2 is currently on a trajectory to become the dominant strain. This phase 2 study aims to evaluate the immunogenicity of SCTV01E-2, a tetravalent protein vaccine, with a specific emphasis on its immunogenicity against Omicron EG.5, comparing it with its progenitor vaccine, SCTV01E (NCT05933512). As of 12 September 2023, 429 participants aged ≥18 years were randomized into the groups SCTV01E (N = 215) and SCTV01E-2 (N = 214). Both vaccines showed increases in neutralizing antibody (nAb) against Omicron EG.5, with a 5.7-fold increase and a 9.0-fold increase in the SCTV01E and SCTV01E-2 groups 14 days post-vaccination, respectively. The predetermined statistical endpoints were achieved, showing that the geometric mean titer (GMT) of nAb and the seroresponse rate (SRR) against Omicron EG.5 were significantly higher in the SCTV01E-2 group than in the SCTV01E group. Additionally, SCTV01E and SCTV01E-2 induced a 5.5-fold and a 5.9-fold increase in nAb against XBB.1, respectively. Reactogenicity was generally mild and transient. No vaccine-related serious adverse events (SAEs), adverse events of special interest (AESIs), or deaths were reported. In summary, SCTV01E-2 elicited robust neutralizing responses against Omicron EG.5 and XBB.1 without raising safety concerns, highlighting its potential as a versatile COVID-19 vaccine against SARS-CoV-2 variants.