Objective:To investigate the potential targets and mechanisms of Draconis Sanguis(DS),a valuable traditional Chinese medicine derived from the resin of the palm tree Daemonorops draco Bl(D.Sanguis,Xue Jie),in the trea...Objective:To investigate the potential targets and mechanisms of Draconis Sanguis(DS),a valuable traditional Chinese medicine derived from the resin of the palm tree Daemonorops draco Bl(D.Sanguis,Xue Jie),in the treatment of myocardial infarction(MI).Methods:We explored the potential mechanisms of DS in the treatment of MI using network pharmacology,bioinformatic techniques,and transcriptomic analysis,followed by validation through in vivo and in vitro experiments.Results:Network pharmacology and bioinformatic analyses identified five genes(Fpr1,Glul,Mme,Mmp9,and Pla2g7)as potential targets for MI treatment.Moreover,DS significantly ameliorated cardiac function,inflammatory responses,and MI-induced myocardial fibrosis in vivo.Transcriptomic and bioinformatic analyses identified Pla2g7 as the most critical target in the DS treatment of MI.Molecular docking revealed that the key active ingredient in DS has a strong affinity for this gene.Furthermore,DS reduced the expression of Pla2g7(P=.0009),NLRP3(P=.003),interleukin-18(P<.001),and interleukin-1b(P=.004)mRNAs in vivo.Conclusions:The results indicate that DS can downregulate the expression of Pla2g7 and reduce the inflammatory response.This demonstrates the potential therapeutic target of DS and the mechanism underlying its cardioprotective effects.展开更多
Microtus fortis is the only mammalian host that exhibits intrinsic resistance against Schistosoma japonicum infection.However,the underlying molecular mechanisms of this resistance are not yet known.Here,we perform th...Microtus fortis is the only mammalian host that exhibits intrinsic resistance against Schistosoma japonicum infection.However,the underlying molecular mechanisms of this resistance are not yet known.Here,we perform the first de novo genome assembly of M.fortis,comprehensive gene annotation analysis,and evolution analysis.Furthermore,we compare the recovery rate of schistosomes,pathological changes,and liver transcriptomes between M.fortis and mice at different time points after infection.We observe that the time and type of immune response in M.fortis are different from those in mice.M.fortis activates immune and inflammatory responses on the 10th day post infection,such as leukocyte extravasation,antibody activation,Fc-gamma receptor-mediated phagocytosis,and the interferon signaling cascade,which play important roles in preventing the development of schistosomes.In contrast,an intense immune response occurrs in mice at the late stages of infection and could not eliminate schistosomes.Infected mice suffer severe pathological injury and continuous decreases in cell cycle,lipid metabolism,and other functions.Our findings offer new insights into the intrinsic resistance mechanism of M.fortis against schistosome infection.The genome sequence also provides the basis for future studies of other important traits in M.fortis.展开更多
Chronic subdural hematoma(CSDH)is a disease characterized by capsuled blood products that progressively occupy the intracranial space,causing intracranial hypertension and compression in the brain.CSDH frequently occu...Chronic subdural hematoma(CSDH)is a disease characterized by capsuled blood products that progressively occupy the intracranial space,causing intracranial hypertension and compression in the brain.CSDH frequently occurs in all demographics,especially in the elderly,but the pathogenesis of CSDH remains unclear.In this review,we discuss the origin,development,and current treatment strategies of CSDH.For thefirst time,we analyzed the cellular and molecular compositions of hematoma membranes with a focus on neomembrane formation,a complex early-stage interactive event in hematoma pathogenesis.We hypothesize that in patients with CSDH,dural border cells(DBCs)might be induced to synthesize collagen or serum proteins might accumulate at the dura and arachnoid layers at the site of injury,thereby encapsulating the hemorrhage.Membrane formation may trigger inflammatory responses after subdural hemorrhage,promotingfibroblast-involved extracellular matrix(ECM)deposition and aberrant angiogenesis within the outer membrane.Consequently,ECM deposition and angiogenesis mutually influence each other and are modulated by inflammatory processes.By illustrating the complex and interactive mechanism of neomembrane formation,we aim to provide a novel insight into CSDH pathogenesis and propose directions for future research as well as advancements in treatment strategies for this disease.展开更多
Objective:A model of inflammatory damage was induced by radiation to investigate whether ferulic acid(FA)can reduce the inflammatory response through the Sirt1-NLRP3 inflammatory pathway.This will help discover radiat...Objective:A model of inflammatory damage was induced by radiation to investigate whether ferulic acid(FA)can reduce the inflammatory response through the Sirt1-NLRP3 inflammatory pathway.This will help discover radiation-protective drugs and elucidate the molecular mechanisms related to radiation-induced inflammatory damage.Methods:A mouse model of radiation-induced immunoinflammatory injury was established to verify the anti-inflammatory effects of FA in vivo.C57BL/6J mice were randomly divided into six groups,and 5 Gy whole-body irradiation was used for modeling.Mice were administered a gastric solvent,amifostine,or 25,50,or 100 mg/kg FA daily for 12 days,consecutively,before irradiation.The serum of mice was collected 24 hour after irradiation to observe the content of inflammatory factors interleukin(IL)-1β,IL-18,IL-6,and tumor necrosis factor(TNF)-α.The spleen and thymus tissues of mice were weighed and the organ index was calculated for pathological testing and immunofluorescence detection.Results:FA reduced the radiation-induced decrease in the spleen and thymus indices.FA significantly reduced the secretion of inflammatory factors in the serum and reversed the radiation-induced reduction in lymphocytes in the spleen and thymus of mice.FA activated Sirt1 and inhibited the expression of the NLRP3 inflammasome to alleviate the inflammatory response.Conclusions:FA reduced radiation-induced inflammation in animals,possibly by activating Sirt1 and reducing nucleotide oligomerization domain(NOD)-like receptor thermal protein domain associated protein 3(NLRP3)inflammasome expression,thereby reducing the secretion of inflammatory factors.展开更多
基金the National Natural Science Foundation of China(82222075).
文摘Objective:To investigate the potential targets and mechanisms of Draconis Sanguis(DS),a valuable traditional Chinese medicine derived from the resin of the palm tree Daemonorops draco Bl(D.Sanguis,Xue Jie),in the treatment of myocardial infarction(MI).Methods:We explored the potential mechanisms of DS in the treatment of MI using network pharmacology,bioinformatic techniques,and transcriptomic analysis,followed by validation through in vivo and in vitro experiments.Results:Network pharmacology and bioinformatic analyses identified five genes(Fpr1,Glul,Mme,Mmp9,and Pla2g7)as potential targets for MI treatment.Moreover,DS significantly ameliorated cardiac function,inflammatory responses,and MI-induced myocardial fibrosis in vivo.Transcriptomic and bioinformatic analyses identified Pla2g7 as the most critical target in the DS treatment of MI.Molecular docking revealed that the key active ingredient in DS has a strong affinity for this gene.Furthermore,DS reduced the expression of Pla2g7(P=.0009),NLRP3(P=.003),interleukin-18(P<.001),and interleukin-1b(P=.004)mRNAs in vivo.Conclusions:The results indicate that DS can downregulate the expression of Pla2g7 and reduce the inflammatory response.This demonstrates the potential therapeutic target of DS and the mechanism underlying its cardioprotective effects.
基金This work was supported by the Key Project in the National Science&Technology Pillar Program from the Ministry of Science and Technology(2015BAI09B04)the National Natural Science Foundation of China(31872256,31472188)+2 种基金the National Key Research and Development Program of China(2017YFD0501306)the Science and Technology Service Network Initiative of Chinese Academy of Sciences(KFJ-STS-QYZD-126,ZDBS-SSW-DQC-02)CAS Youth Innovation Promotion Association,and SA-SIBS Scholarship Program.
文摘Microtus fortis is the only mammalian host that exhibits intrinsic resistance against Schistosoma japonicum infection.However,the underlying molecular mechanisms of this resistance are not yet known.Here,we perform the first de novo genome assembly of M.fortis,comprehensive gene annotation analysis,and evolution analysis.Furthermore,we compare the recovery rate of schistosomes,pathological changes,and liver transcriptomes between M.fortis and mice at different time points after infection.We observe that the time and type of immune response in M.fortis are different from those in mice.M.fortis activates immune and inflammatory responses on the 10th day post infection,such as leukocyte extravasation,antibody activation,Fc-gamma receptor-mediated phagocytosis,and the interferon signaling cascade,which play important roles in preventing the development of schistosomes.In contrast,an intense immune response occurrs in mice at the late stages of infection and could not eliminate schistosomes.Infected mice suffer severe pathological injury and continuous decreases in cell cycle,lipid metabolism,and other functions.Our findings offer new insights into the intrinsic resistance mechanism of M.fortis against schistosome infection.The genome sequence also provides the basis for future studies of other important traits in M.fortis.
基金This research was funded by Guangdong Natural Science Foundation(2020A1515010289)Shenzhen Key Medical Discipline Construction Fund(Shenzhen Key Medical Discipline 2020-2024)Shenzhen Science and Technology Innovation Foundation(Shenzhen Technology Key Project JSGG20211029095400001).
文摘Chronic subdural hematoma(CSDH)is a disease characterized by capsuled blood products that progressively occupy the intracranial space,causing intracranial hypertension and compression in the brain.CSDH frequently occurs in all demographics,especially in the elderly,but the pathogenesis of CSDH remains unclear.In this review,we discuss the origin,development,and current treatment strategies of CSDH.For thefirst time,we analyzed the cellular and molecular compositions of hematoma membranes with a focus on neomembrane formation,a complex early-stage interactive event in hematoma pathogenesis.We hypothesize that in patients with CSDH,dural border cells(DBCs)might be induced to synthesize collagen or serum proteins might accumulate at the dura and arachnoid layers at the site of injury,thereby encapsulating the hemorrhage.Membrane formation may trigger inflammatory responses after subdural hemorrhage,promotingfibroblast-involved extracellular matrix(ECM)deposition and aberrant angiogenesis within the outer membrane.Consequently,ECM deposition and angiogenesis mutually influence each other and are modulated by inflammatory processes.By illustrating the complex and interactive mechanism of neomembrane formation,we aim to provide a novel insight into CSDH pathogenesis and propose directions for future research as well as advancements in treatment strategies for this disease.
基金funded by the National Key Research and Development Program(2022YFC3500303)Innovation Team and Talents Cultivation Program of the National Administration of Traditional Chinese Medicine(ZYYCXTD-C-202009)National Natural Science Foundation of China(81873063).
文摘Objective:A model of inflammatory damage was induced by radiation to investigate whether ferulic acid(FA)can reduce the inflammatory response through the Sirt1-NLRP3 inflammatory pathway.This will help discover radiation-protective drugs and elucidate the molecular mechanisms related to radiation-induced inflammatory damage.Methods:A mouse model of radiation-induced immunoinflammatory injury was established to verify the anti-inflammatory effects of FA in vivo.C57BL/6J mice were randomly divided into six groups,and 5 Gy whole-body irradiation was used for modeling.Mice were administered a gastric solvent,amifostine,or 25,50,or 100 mg/kg FA daily for 12 days,consecutively,before irradiation.The serum of mice was collected 24 hour after irradiation to observe the content of inflammatory factors interleukin(IL)-1β,IL-18,IL-6,and tumor necrosis factor(TNF)-α.The spleen and thymus tissues of mice were weighed and the organ index was calculated for pathological testing and immunofluorescence detection.Results:FA reduced the radiation-induced decrease in the spleen and thymus indices.FA significantly reduced the secretion of inflammatory factors in the serum and reversed the radiation-induced reduction in lymphocytes in the spleen and thymus of mice.FA activated Sirt1 and inhibited the expression of the NLRP3 inflammasome to alleviate the inflammatory response.Conclusions:FA reduced radiation-induced inflammation in animals,possibly by activating Sirt1 and reducing nucleotide oligomerization domain(NOD)-like receptor thermal protein domain associated protein 3(NLRP3)inflammasome expression,thereby reducing the secretion of inflammatory factors.
