Objective： To evaluate the effects of polymorphisms in TLR7 and TLRS（as potential candidate genes） on asthma risk and asthma-related phenotypes. Methods： We consecutively recruited 318 unrelated adult asthmatic pa...Objective： To evaluate the effects of polymorphisms in TLR7 and TLRS（as potential candidate genes） on asthma risk and asthma-related phenotypes. Methods： We consecutively recruited 318 unrelated adult asthmatic patients and 352 healthy volunteers from the same area of southeast China. Genotyping of each selected SNP was performed using multiplex PCR in conjunction with tagged array single base extension technology. We conducted case-control and case-only association studies between the selected SNPs in TLR7 and TLR8 and asthma or asthma-related phenotypes. Results： The T allele of rs5935436 SNP in TLR7 was protective from developing asthma in males （adjusted ORs = 0.126, 95% CIs = 0.016-0.995）. The CT/TT genotype of rs5935436 was less frequent in female asthmatics with allergic rhinitis （adjusted ORs = 0.18, 95% CIs = 0.04-0.90）. The homozygote AA of rs3761623 and GG of rs3764880 were positively associated with lower FEV1% and asthma severity in female asthmatics. These results were confirmed by haplotype analysis. Conclusion：TLR7 and TLR8 polymorphisms may play an important role in the pathogenesis of asthma that is gender-dependent. This could be clinically useful, both for identifying patients at risk of asthma and for preventing its occurrence.展开更多
While repurposed drugs came in handy earlier in the wake of the coronavirus disease 2019(COVID-19)pandemic,vaccination has been considered a more sustainable approach.The recent spikes have been linked to“double,”“...While repurposed drugs came in handy earlier in the wake of the coronavirus disease 2019(COVID-19)pandemic,vaccination has been considered a more sustainable approach.The recent spikes have been linked to“double,”“triple,”and even multi-mutant variants,thus renewing calls for deeper structural and functional insights of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)as a lead to rationale design of therapeutics,vaccines,and point-of-care diagnostics.There is a repertoire of findings from the earliest SARS-CoV-2 molecular mimicry to evade host immunity cum host immune responses to the role of the viral glycocalyx in modulating the susceptibility and severity of infection through attraction and repulsive interactions.Recently,molecular studies of some viral components that aid infection in the face of vaccination seem unending.In addition,the wave of infections and the attendant case fatality ratios have necessitated the need for emergency use authorizations for COVID-19 vaccines and in vitro diagnostics.This review provides key updates of SARS-CoV-2,current antigenic and formulation strategies,with emergency use authorizations considerations for future vaccine candidates and diagnostics.We also premise that despite the difficulty in modeling and analyzing glycans,understanding and exploiting their roles in the SARS-CoV-2 architecture is fundamental to glycan-based COVID-19 vaccines devoid of inconsistent clinical outcomes.展开更多
基金supported by grants from the National Natural Science Foundation of China 30400191 and 30570797
文摘Objective： To evaluate the effects of polymorphisms in TLR7 and TLRS（as potential candidate genes） on asthma risk and asthma-related phenotypes. Methods： We consecutively recruited 318 unrelated adult asthmatic patients and 352 healthy volunteers from the same area of southeast China. Genotyping of each selected SNP was performed using multiplex PCR in conjunction with tagged array single base extension technology. We conducted case-control and case-only association studies between the selected SNPs in TLR7 and TLR8 and asthma or asthma-related phenotypes. Results： The T allele of rs5935436 SNP in TLR7 was protective from developing asthma in males （adjusted ORs = 0.126, 95% CIs = 0.016-0.995）. The CT/TT genotype of rs5935436 was less frequent in female asthmatics with allergic rhinitis （adjusted ORs = 0.18, 95% CIs = 0.04-0.90）. The homozygote AA of rs3761623 and GG of rs3764880 were positively associated with lower FEV1% and asthma severity in female asthmatics. These results were confirmed by haplotype analysis. Conclusion：TLR7 and TLR8 polymorphisms may play an important role in the pathogenesis of asthma that is gender-dependent. This could be clinically useful, both for identifying patients at risk of asthma and for preventing its occurrence.
文摘While repurposed drugs came in handy earlier in the wake of the coronavirus disease 2019(COVID-19)pandemic,vaccination has been considered a more sustainable approach.The recent spikes have been linked to“double,”“triple,”and even multi-mutant variants,thus renewing calls for deeper structural and functional insights of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)as a lead to rationale design of therapeutics,vaccines,and point-of-care diagnostics.There is a repertoire of findings from the earliest SARS-CoV-2 molecular mimicry to evade host immunity cum host immune responses to the role of the viral glycocalyx in modulating the susceptibility and severity of infection through attraction and repulsive interactions.Recently,molecular studies of some viral components that aid infection in the face of vaccination seem unending.In addition,the wave of infections and the attendant case fatality ratios have necessitated the need for emergency use authorizations for COVID-19 vaccines and in vitro diagnostics.This review provides key updates of SARS-CoV-2,current antigenic and formulation strategies,with emergency use authorizations considerations for future vaccine candidates and diagnostics.We also premise that despite the difficulty in modeling and analyzing glycans,understanding and exploiting their roles in the SARS-CoV-2 architecture is fundamental to glycan-based COVID-19 vaccines devoid of inconsistent clinical outcomes.
