Sepsis-induced liver injury(SILI)is an important cause of septicemia deaths.BaWeiBaiDuSan(BWBDS)was extracted from a formula of Panax ginseng C.A.Meyer,Lilium brownie F.E.Brown ex Miellez var.viridulum Baker,Polygonat...Sepsis-induced liver injury(SILI)is an important cause of septicemia deaths.BaWeiBaiDuSan(BWBDS)was extracted from a formula of Panax ginseng C.A.Meyer,Lilium brownie F.E.Brown ex Miellez var.viridulum Baker,Polygonatum sibiricum Delar.ex Redoute,Lonicera japonica Thunb.,Hippophae rhamnoides Linn.,Amygdalus Communis Vas,Platycodon grandiflorus(Jacq.)A.DC.,and Cortex Phelloderdri.Herein,we investigated whether the BWBDS treatment could reverse SILI by the mechanism of modulating gut microbiota.BWBDS protected mice against SILI,which was associated with promoting macrophage anti-inflammatory activity and enhancing intestinal integrity.BWBDS selectively promoted the growth of Lactobacillus johnsonii(L.johnsonii)in cecal ligation and puncture treated mice.Fecal microbiota transplantation treatment indicated that gut bacteria correlated with sepsis and was required for BWBDS anti-sepsis effects.Notably,L.johnsonii significantly reduced SILI by promoting macrophage anti-inflammatory activity,increasing interleukin-10+M2 macrophage production and enhancing intestinal integrity.Furthermore,heat inactivation L.johnsonii(HI-L.johnsonii)treatment promoted macrophage anti-inflammatory activity and alleviated SILI.Our findings revealed BWBDS and gut microbiota L.johnsonii as novel prebiotic and probiotic that may be used to treat SILI.The potential underlying mechanism was at least in part,via L.johnsonii-dependent immune regulation and interleukin-10+M2 macrophage production.展开更多
Acute lung injury(ALI),as a common clinical emergency,is pulmonary edema and diffuse lung infiltration caused by inflammation.The lack of non-invasive alert strategy,resulting in failure to carry out preventive treatm...Acute lung injury(ALI),as a common clinical emergency,is pulmonary edema and diffuse lung infiltration caused by inflammation.The lack of non-invasive alert strategy,resulting in failure to carry out preventive treatment,means high mortality and poor prognosis.Stimulator of interferon genes(STING)is a key molecular biomarker of innate immunity in response to inflammation,but there is still a lack of STING-targeted strategy.In this study,a novel STING-targeted PET tracer,[~(18)F]FBTA,was labeled with high radiochemical yield(79.7±4.3%)and molar activity(32.5±2.9 GBq/μmol).We confirmed that[~(18)F]FBTA has a strong STING binding affinity(K_d=26.86±6.79 nmol/L)and can be used for PET imaging in ALI mice to alert early lung inflammation and to assess the efficacy of drug therapy.Our STING-targeted strategy also reveals that[~(18)F]FBTA can trace ALI before reaching the computed tomography(CT)diagnostic criteria,and demonstrates its better specificity and distribution than[~(18)F]fluorodeoxyglucose([~(18)F]FDG).展开更多
The authors regret that there were some picture errors in Fig.7C and Supporting Information Fig.S10B owing to the negligence of the picture typesetting and careless mistakes.In Fig.7C,the H&E picture of PBS+Lipo+C...The authors regret that there were some picture errors in Fig.7C and Supporting Information Fig.S10B owing to the negligence of the picture typesetting and careless mistakes.In Fig.7C,the H&E picture of PBS+Lipo+CLP group was the inverted picture of CLP group in Fig.5G.In Fig.7C,the H&E picture of Clo-Lipo+CLP group was zoom-in picture of L johnsoni+CLP group in Fig.8F.In Fig.SI0B,the H&E picture of ileum in CLP group was zoom-in picture of Anti-IL-10R+CLP group in Fig.S11C.The authors revise the H&E picture of liver in PBS+Lipo+CLP group and the H&E picture of liver in Clo-Lipo+CLP group in Fig.7C.Also,the H&E picture of ileum in CLP group of Fig.S10B have been revised.The correct figures are presented as below.展开更多
基金funded by regular grants and joint grant(File No.0096/2018/A3,0111/2020/A3 and 0056/2020/AMJ)Dr.Neher’s Biophysics Laboratory for Innovative Drug Discovery(File No.001/2020/ALC)+4 种基金supported by the Macao Science and Technology Development Fundsupported by 2020 Young Qihuang Scholar funded by the National Administration of Traditional Chinese Medicinesupported by National Natural Science Foundation of China(82025036)supported by the Start-up Research Grant of University of Macao(SRG2022-00020-FHS,China)the Faculty of Health Science,University of Macao(Macao,China).
文摘Sepsis-induced liver injury(SILI)is an important cause of septicemia deaths.BaWeiBaiDuSan(BWBDS)was extracted from a formula of Panax ginseng C.A.Meyer,Lilium brownie F.E.Brown ex Miellez var.viridulum Baker,Polygonatum sibiricum Delar.ex Redoute,Lonicera japonica Thunb.,Hippophae rhamnoides Linn.,Amygdalus Communis Vas,Platycodon grandiflorus(Jacq.)A.DC.,and Cortex Phelloderdri.Herein,we investigated whether the BWBDS treatment could reverse SILI by the mechanism of modulating gut microbiota.BWBDS protected mice against SILI,which was associated with promoting macrophage anti-inflammatory activity and enhancing intestinal integrity.BWBDS selectively promoted the growth of Lactobacillus johnsonii(L.johnsonii)in cecal ligation and puncture treated mice.Fecal microbiota transplantation treatment indicated that gut bacteria correlated with sepsis and was required for BWBDS anti-sepsis effects.Notably,L.johnsonii significantly reduced SILI by promoting macrophage anti-inflammatory activity,increasing interleukin-10+M2 macrophage production and enhancing intestinal integrity.Furthermore,heat inactivation L.johnsonii(HI-L.johnsonii)treatment promoted macrophage anti-inflammatory activity and alleviated SILI.Our findings revealed BWBDS and gut microbiota L.johnsonii as novel prebiotic and probiotic that may be used to treat SILI.The potential underlying mechanism was at least in part,via L.johnsonii-dependent immune regulation and interleukin-10+M2 macrophage production.
基金the National Natural Science Foundation of China Youth Program(82202207)the Department of Science and Technology of Guangdong Province(2018B030322006,China)+1 种基金the Science and Technology Project Grant of Zhuhai(ZH22036201210067PWC,China)the Scientific Research Project Traditional Chinese Medicine Bureau of Guangdong Province(202106080515386340,China)。
文摘Acute lung injury(ALI),as a common clinical emergency,is pulmonary edema and diffuse lung infiltration caused by inflammation.The lack of non-invasive alert strategy,resulting in failure to carry out preventive treatment,means high mortality and poor prognosis.Stimulator of interferon genes(STING)is a key molecular biomarker of innate immunity in response to inflammation,but there is still a lack of STING-targeted strategy.In this study,a novel STING-targeted PET tracer,[~(18)F]FBTA,was labeled with high radiochemical yield(79.7±4.3%)and molar activity(32.5±2.9 GBq/μmol).We confirmed that[~(18)F]FBTA has a strong STING binding affinity(K_d=26.86±6.79 nmol/L)and can be used for PET imaging in ALI mice to alert early lung inflammation and to assess the efficacy of drug therapy.Our STING-targeted strategy also reveals that[~(18)F]FBTA can trace ALI before reaching the computed tomography(CT)diagnostic criteria,and demonstrates its better specificity and distribution than[~(18)F]fluorodeoxyglucose([~(18)F]FDG).
文摘The authors regret that there were some picture errors in Fig.7C and Supporting Information Fig.S10B owing to the negligence of the picture typesetting and careless mistakes.In Fig.7C,the H&E picture of PBS+Lipo+CLP group was the inverted picture of CLP group in Fig.5G.In Fig.7C,the H&E picture of Clo-Lipo+CLP group was zoom-in picture of L johnsoni+CLP group in Fig.8F.In Fig.SI0B,the H&E picture of ileum in CLP group was zoom-in picture of Anti-IL-10R+CLP group in Fig.S11C.The authors revise the H&E picture of liver in PBS+Lipo+CLP group and the H&E picture of liver in Clo-Lipo+CLP group in Fig.7C.Also,the H&E picture of ileum in CLP group of Fig.S10B have been revised.The correct figures are presented as below.
