Hyaluronic acid (HA) is a high molecular weight glycosaminoglycan consisting of alternating D-glucuronic acid and N-acetylglueasamine and plays ex- tremely important roles in many biological processes. In this study...Hyaluronic acid (HA) is a high molecular weight glycosaminoglycan consisting of alternating D-glucuronic acid and N-acetylglueasamine and plays ex- tremely important roles in many biological processes. In this study, we optimized fermentation process for the production of HA by Streptococcus zooepidemicus ATCC35246, including fermentation broth composition and various fermentation parameters. The experimental results showed that the optimal fermentation broth composition was: glucose 45 g/L, yeast extract 10 g/L, tryptone 12 g/L, KH2PO4 2 g/L, K2HPO4 . 3H20 2 g/L, MgSO4 · 7H2O 2 g/L, and (NH4 )2SO4 0.4 g/L. The optimal parameters involved in fermentation was: liquid volume 20%, pH 6. 0, rotation speed 180 r/min, fermentation temperature 35 ℃, fermentation duration 18 h, CTAB concentration 25 mg/L. Under the optimized conditions, the yield of HA was 0. 305 g/L, which was dramatically improved by 43.87% compared to that of 0. 212 g/L before optimization.展开更多
Toll-like receptor 3(TLR3),as an important pattern recognition receptor(PRR),dominates the innate and adaptive immunity regulating many acute and chronic inflammatory diseases.Atherosclerosis is proved as an inflammat...Toll-like receptor 3(TLR3),as an important pattern recognition receptor(PRR),dominates the innate and adaptive immunity regulating many acute and chronic inflammatory diseases.Atherosclerosis is proved as an inflammatory disease,and inflammatory events involved in the entire process of initiation and deterioration.However,the contribution of TLR3 to atherosclerosis remains unclear.Herein,we identified the clinical relevance of TLR3 upregulation and disease processes in human atherosclerosis.Besides,activation of TLR3 also directly led to significant expression of atherogenic chemokines and adhesion molecules.Conversely,silencing TLR3 inhibited the uptake of oxLDL by macrophages and significantly reduced foam cell formation.Given the aberrance in TLR3 functions on atherosclerosis progression,we hypothesized that TLR3 could serve as novel target for clinical atherosclerosis therapy.Therefore,we developed the novel ellipticine derivative SMU-CX24,which specifically inhibited TLR3(IC_(50)=18.87±2.21 nmol/L).In vivo,atherosclerotic burden was alleviated in Western diet fed ApoE^(−/−)mice in response to SMU-CX24 treatment,accompanying notable reductions in TLR3 expression and inflammation infiltration within atherosclerotic lesion.Thus,for the first time,we revealed that pharmacological downregulation of TLR3 with specific inhibitor regenerated inflammatory environment to counteract atherosclerosis progression,thereby proposing a new strategy and probe for atherosclerosis therapy.展开更多
基金Supported by Scientific Research Fund of Sichuan University of Science&Engineering(2011RC12,2014KY02)Scientific Research Foundation of the Education Department of Sichuan Province(15ZA0222)+1 种基金Research Project of Liquor Making Biological Technology and Application of Key Laboratory of Sichuan Province(NJ2013-06)Sichuan Provincial Undergraduate Training Programs for Innovation and Entrepreneurship(201410622021)
文摘Hyaluronic acid (HA) is a high molecular weight glycosaminoglycan consisting of alternating D-glucuronic acid and N-acetylglueasamine and plays ex- tremely important roles in many biological processes. In this study, we optimized fermentation process for the production of HA by Streptococcus zooepidemicus ATCC35246, including fermentation broth composition and various fermentation parameters. The experimental results showed that the optimal fermentation broth composition was: glucose 45 g/L, yeast extract 10 g/L, tryptone 12 g/L, KH2PO4 2 g/L, K2HPO4 . 3H20 2 g/L, MgSO4 · 7H2O 2 g/L, and (NH4 )2SO4 0.4 g/L. The optimal parameters involved in fermentation was: liquid volume 20%, pH 6. 0, rotation speed 180 r/min, fermentation temperature 35 ℃, fermentation duration 18 h, CTAB concentration 25 mg/L. Under the optimized conditions, the yield of HA was 0. 305 g/L, which was dramatically improved by 43.87% compared to that of 0. 212 g/L before optimization.
基金supported by National Natural Science Foundation of China (Nos. 81773558, 82073689 (KC), and 1825702 (HY))National Natural Science Foundation of Guangdong Province (Nos. 2020A151501518, 2018B030312010, China)Science and Technology Program of Guangzhou (No. 201904010380, China)
文摘Toll-like receptor 3(TLR3),as an important pattern recognition receptor(PRR),dominates the innate and adaptive immunity regulating many acute and chronic inflammatory diseases.Atherosclerosis is proved as an inflammatory disease,and inflammatory events involved in the entire process of initiation and deterioration.However,the contribution of TLR3 to atherosclerosis remains unclear.Herein,we identified the clinical relevance of TLR3 upregulation and disease processes in human atherosclerosis.Besides,activation of TLR3 also directly led to significant expression of atherogenic chemokines and adhesion molecules.Conversely,silencing TLR3 inhibited the uptake of oxLDL by macrophages and significantly reduced foam cell formation.Given the aberrance in TLR3 functions on atherosclerosis progression,we hypothesized that TLR3 could serve as novel target for clinical atherosclerosis therapy.Therefore,we developed the novel ellipticine derivative SMU-CX24,which specifically inhibited TLR3(IC_(50)=18.87±2.21 nmol/L).In vivo,atherosclerotic burden was alleviated in Western diet fed ApoE^(−/−)mice in response to SMU-CX24 treatment,accompanying notable reductions in TLR3 expression and inflammation infiltration within atherosclerotic lesion.Thus,for the first time,we revealed that pharmacological downregulation of TLR3 with specific inhibitor regenerated inflammatory environment to counteract atherosclerosis progression,thereby proposing a new strategy and probe for atherosclerosis therapy.