Résumé
Objective @#To explore the role of secreted frizzled ⁃related protein 3 ( sFRP3) , a regulator of the Wnt signaling pathway , in the activation and proliferation of murine cardiac fibroblasts ( CFs ) . @*Methods @#Neonatalmice aged 1 -3 days were obtained for surgical procedures to collect heart tissues. After digestion, CFs were isola.ted and cultured. Transforming growth factor-beta 1 (TGF-β1 ) stimulation was used to induce activation and prolif.eration in CF's after they adhered to the culture dish. Once the model was confirmed, experimental and controlgroups were transfected with sFRP3 overexpression plasmids and empty plasmids for 24 -48 hours. Expression lev.els of sFRP3, Periostin (POSTN), Type I collagen ( Collagen I ), and proliferating cell nuclear antigen ( PCNA) were assessed at the molecular level using Westerm blot and qR'T-PCR. Changes in cell proliferation capacitywere examined using M'TT, CCK-8, and EdU staining methods.@*Results@#In the TGF-β1-induced activation andproliferation model of CFs, compared to the control group, the model group exhibited decreased expression of sFRP3 protein and mRNA , while the expression of activation and proliferation-related proteins PCNA, POSTN, andCollagen I was upregulated. Furthermore, in CFs overexpressing sFRP3 through plasmid transfection, the proteinand mRNA expression of PCNA, POSTN, and Collagen I decreased compared to the empty vector group. MTTCCK-8, and EdU experiments indicated a significant decrease in the proliferative activity of CFs in the sFRP3 over0verexpression of sFRP3 markedly inhibits theexpression group compared to the empty vector group. @*Conclusion@#Overexpression of sFRP3 markedly inhibits theactivation and proliferation of CFs, suggesting that sFRP3 may be a key gene involved in the regulation of CF activation and proliferation.
Résumé
Nerve agents are used in civil wars and terrorist attacks, posing a threat to public safety. Acute exposure to nerve agents such as soman (GD) causes serious brain damage, leading to death due to intense seizures induced by acetylcholinesterase inhibition and neuronal injury resulting from increased excitatory amino-acid levels and neuroinflammation. However, data on the anticonvulsant and neuroprotective efficacies of currently-used countermeasures are limited. Here, we evaluated the potential effects of transient receptor vanilloid 4 (TRPV4) in the treatment of soman-induced status epilepticus (SE) and secondary brain injury. We demonstrated that TRPV4 expression was markedly up-regulated in rat hippocampus after soman-induced seizures. Administration of the TRPV4 antagonist GSK2193874 prior to soman exposure significantly decreased the mortality rate in rats and reduced SE intensity. TRPV4-knockout mice also showed lower incidence of seizures and higher survival rates than wild-type mice following soman exposure. Further in vivo and in vitro experiments demonstrated that blocking TRPV4 prevented NMDA receptor-mediated glutamate excitotoxicity. The protein levels of the NLRP3 inflammasome complex and its downstream cytokines IL-1β and IL-18 increased in soman-exposed rat hippocampus. However, TRPV4 inhibition or deletion markedly reversed the activation of the NLRP3 inflammasome pathway. In conclusion, our study suggests that the blockade of TRPV4 protects against soman exposure and reduces brain injury following SE by decreasing NMDA receptor-mediated excitotoxicity and NLRP3-mediated neuroinflammation. To our knowledge, this is the first study regarding the “dual-switch” function of TRPV4 in the treatment of soman intoxication.
Résumé
OBJECTIVE:To study influential factors for retail chain drugstore undertaking the pharmacy function of community health center based on the perspective of retail chain drugstore pharmacist. METHODS:The stratified sampling method was used to conduct questionnaire survey among pharmacists in retail chain drugstores from Pearl River Delta(Guangzhou,Foshan, Dongguan),eastern Guangdong,western Guangdong and northern Guangdong. Multivariate analysis of variance was performed to study main effects of independent variables,pairwise comparison and interaction,with social demographic characteristics(gender, age,educational level,major,profession at title,working life,location)as independent variables,using fear of workload increase,inadequate pharmaceutical care,lower wages,inadequate electronic prescription acceptance and change in the work model as dependent variable. RESULTS:A total of 242 questionnaires were sent out,involving 239 valid questionnaires with effective recovery rate of 98.8%. The results of multivariate analysis of variance showed that majors of main effect and the interaction between major and professional title affected the fear of increase in the workload;age,education and working years of main effect,and the interaction between age and location affected the fear of inadequate pharmaceutical care;professional title of main effect affected the fear of electronic prescription acceptance;age and location of main effect,and the interactions between age and professional title influenced the fear of change in work model. CONCLUSIONS:It is suggested to strengthen pharmaceutical care and electronic prescription acceptance of pharmaceutical staff in retail chain drugstore,increase the number of professional pharmaceutical staff,allocate pharmaceutical staff reasonably and consider about regional differences.