1.Effectiveness and safety of biologics in short-term reaching-standard treatment of moderate to severe atopic dermatitis:a mesh meta analysis
Pingjuan CHEN ; Gaiqiang CAI ; Ruigui LIU ; Yongxian MAI
Chongqing Medicine 2024;53(11):1717-1725
Objective To employ the mesh meta analysis to compare the effectiveness and safety of short-term reaching-standard treatment in the patients with moderate to severe atopic dermatitis among the different biologics.Methods The randomized controlled trials (RCT) were retrieved from the databases of CNKI,Chinese Biomedical Literature Database,Wanfang,VIP,PubMed,Cochrane Library and Embase data-bases.The retrieval time was from the database establishment to August,2023.The related literatures on the biologics for treating moderate to severe atopic dermatitis were collected.The literatures were screened by the inclusion and exclusion standards,the literature quality was evaluated and the data were extracted.Then the mesh meta analysis was performed by using RevMan 5.3 and Stata 16.0 softwares.Results A total of 754 ar-ticles were retrieved,and 11 articles were finally included,involving in 14 RCT with a total sample number of 5528 cases.There were 4 intervention methods,including placebo and 3 kinds of drugs.The drugs were Dupi-lumab,Lebrikizumab and Tralokinumab.The results showed that for each of effectiveness indicator,different medication regimens had different performance,after comprehensively meeting the treatment criteria,Dupri-uliumab was superior to Lebrikizumab,and Lebrikizumab was superior to Tralokinumab.There was no statis-tical difference in adverse reactions between the three drugs and placebo (P>0.05).Conclusion Dupilumab is currently the most effective biologic agent for short-term target treatment,capable of reducing inflamma-tion and improving skin symptoms.Future studies should further evaluate its long-term efficacy and safety to guide clinical application.
2.Carnosic acid inhibits osteoclast differentiation by inhibiting mitochondrial activity
Haishan LI ; Yuheng WU ; Zixuan LIANG ; Shiyin ZHANG ; Zhen ZHANG ; Bin MAI ; Wei DENG ; Yongxian LI ; Yongchao TANG ; Shuncong ZHANG ; Kai YUAN
Chinese Journal of Tissue Engineering Research 2025;29(2):245-253
BACKGROUND:Carnosic acid,a bioactive compound found in rosemary,has been shown to reduce inflammation and reactive oxygen species(ROS).However,its mechanism of action in osteoclast differentiation remains unclear. OBJECTIVE:To investigate the effects of carnosic acid on osteoclast activation,ROS production,and mitochondrial function. METHODS:Primary bone marrow-derived macrophages from mice were extracted and cultured in vitro.Different concentrations of carnosic acid(0,10,15,20,25 and 30 μmol/L)were tested for their effects on bone marrow-derived macrophage proliferation and toxicity using the cell counting kit-8 cell viability assay to determine a safe concentration.Bone marrow-derived macrophages were cultured in graded concentrations and induced by receptor activator of nuclear factor-κB ligand for osteoclast differentiation for 5-7 days.The effects of carnosic acid on osteoclast differentiation and function were then observed through tartrate-resistant acid phosphatase staining,F-actin staining,H2DCFDA probe and mitochondrial ROS,and Mito-Tracker fluorescence detection.Western blot and RT-PCR assays were subsequently conducted to examine the effects of carnosic acid on the upstream and downstream proteins of the receptor activator of nuclear factor-κB ligand-induced MAPK signaling pathway. RESULTS AND CONCLUSION:Tartrate-resistant acid phosphatase staining and F-actin staining showed that carnosic acid dose-dependently inhibited in vitro osteoclast differentiation and actin ring formation in the cell cytoskeleton,with the highest inhibitory effect observed in the high concentration group(30 μmol/L).Carnosic acid exhibited the most significant inhibitory effect during the early stages(days 1-3)of osteoclast differentiation compared to other intervention periods.Fluorescence imaging using the H2DCFDA probe,mitochondrial ROS,and Mito-Tracker demonstrated that carnosic acid inhibited cellular and mitochondrial ROS production while reducing mitochondrial membrane potential,thereby influencing mitochondrial function.The results of western blot and RT-PCR revealed that carnosic acid could suppress the expression of NFATc1,CTSK,MMP9,and C-fos proteins associated with osteoclast differentiation,and downregulate the expression of NFATc1,Atp6vod2,ACP5,CTSK,and C-fos genes related to osteoclast differentiation.Furthermore,carnosic acid enhanced the expression of antioxidant enzyme proteins and reduced the generation of ROS during the process of osteoclast differentiation.Overall,carnosic acid exerts its inhibitory effects on osteoclast differentiation by inhibiting the phosphorylation modification of the P38/ERK/JNK protein and activating the MAPK signaling pathway in bone marrow-derived macrophages.