Ferulic acid reduces inflammatory response induced by radiation through Sirt1-NLRP3 pathway

Objective:A model of inflammatory damage was induced by radiation to investigate whether ferulic acid(FA)can reduce the inflammatory response through the Sirt1-NLRP3 inflammatory pathway.This will help discover radiation-protective drugs and elucidate the molecular mechanisms related to radiation-induced inflammatory damage.Methods:A mouse model of radiation-induced immunoinflammatory injury was established to verify the anti-inflammatory effects of FA in vivo.C57BL/6J mice were randomly divided into six groups,and 5 Gy whole-body irradiation was used for modeling.Mice were administered a gastric solvent,amifostine,or 25,50,or 100 mg/kg FA daily for 12 days,consecutively,before irradiation.The serum of mice was collected 24 hour after irradiation to observe the content of inflammatory factors interleukin(IL)-1β,IL-18,IL-6,and tumor necrosis factor(TNF)-α.The spleen and thymus tissues of mice were weighed and the organ index was calculated for pathological testing and immunofluorescence detection.Results:FA reduced the radiation-induced decrease in the spleen and thymus indices.FA significantly reduced the secretion of inflammatory factors in the serum and reversed the radiation-induced reduction in lymphocytes in the spleen and thymus of mice.FA activated Sirt1 and inhibited the expression of the NLRP3 inflammasome to alleviate the inflammatory response.Conclusions:FA reduced radiation-induced inflammation in animals,possibly by activating Sirt1 and reducing nucleotide oligomerization domain(NOD)-like receptor thermal protein domain associated protein 3(NLRP3)inflammasome expression,thereby reducing the secretion of inflammatory factors.

Safety and immunogenicity of COVID-19 vaccine ZF2001 in Chinese aged 60 years and older

The coronavirus disease 2019(COVID-19)pandemic remains a significant global health challenge.Older adults are the population at high risk of developing severe COVID-19 or death[1–3].To date,dozens of vaccines for prototype severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)have received emergency use authorization or conditional marketing approval in many countries[4].ZF2001,a protein subunit vaccine comprising two copies of tandem receptor-binding domain(RBD)from prototype SARS-CoV-2(HB-02 strain)[5,6],has demonstrated safety and immunogenicity in populations aged 3–17 and 18–59 after three doses of vaccination[7,8].Moreover,it has shown good efficacy in the prevention of symptomatic COVID-19 caused by infections from the alpha,kappa,and delta variants after a six-month follow-up for adults beyond 18 years of age in a phase 3 trial[9].ZF2001 was safe and well-tolerated in a large cohort of adults(R18 years of age),and the incidence of adverse events was lower among the participants 60 years of age or older than among those aged 18–59[9].However,its durability and immunogenicity in individuals 60 years of age and older have not been reported and need further investigation.Here,we reported the phase 1 trial of ZF2001 in adults aged 60 or older in China to determine the safety,tolerability,and immunogenicity of ZF2001 in older populations after short(1 month)-and long(6 months)-term follow-up.Moreover,we conducted a post-hoc analysis of serum samples to assess their neutralization capacity against omicron variants.