Background Human interleukin(IL)-37 is a constituent of the IL-1 family with potent anti-inflammatory and immunosuppressive attributes.It has been demonstrated extensive beneficial effects on various diseases;however,...Background Human interleukin(IL)-37 is a constituent of the IL-1 family with potent anti-inflammatory and immunosuppressive attributes.It has been demonstrated extensive beneficial effects on various diseases;however,its role in the pathogenesis of diabetic cardiomyopathy(DCM)remains unclear.Methods In vivo,DCM mouse model was established with streptozotocin injection and a high-fat diet in WT and cardiac fibroblasts(CFs)specific hIL-37b overexpression mice(IL-37-Tg).In vitro,primary mouse CFs were isolated from the hearts of adult mice and cultured with high levels of glucose and palmitic acid.Cardiac function of the mice was assessed using echocardiography.Masson staining,immunofluorescence,western blot and RT-PCR assays were employed to evaluate the expression of cardiac fibrosis and SOCS3-JAK2-STAT3 signaling pathway-related proteins.Results In this study,we found that CFs specific IL-37-Tg significantly ameliorated cardiac dysfunction and reduced collagen production by inhibiting the JAK2-STAT3 axis,as evidenced by the decreased levels of p-JAK2 and p-STAT3 in the heart of CFs specific IL-37-Tg DCM mice.The beneficial effects of IL-37 were consistently observed in CFs treated with high glucose(HG)and palmitic acid(PA).Moreover,we also discovered that the presence of IL-37 increased the expression of SOCS3,a crucial regulator of JAK/STAT signaling,in DCM mice and HG and PA-treated CFs.Finally,the anti-fibrotic action of IL-37 in HG and PAtreated CFs was abolished when either SOCS3 was genetically knocked down or JAK2/STAT3 was pharmacologically activated.Conclusions Our findings indicate that IL-37 exerts its antifibrotic effect by promoting SOCS3-mediated JAK2-STAT3 inactivation and may be considered as a potential therapeutic agent for DCM.展开更多
The carbonates in the Middle Ordovician Ma_5~5submember of the Majiagou Formation in the northern Ordos Basin are partially to completely dolomitized.Two types of replacive dolomite are distinguished:(1) type 1dol...The carbonates in the Middle Ordovician Ma_5~5submember of the Majiagou Formation in the northern Ordos Basin are partially to completely dolomitized.Two types of replacive dolomite are distinguished:(1) type 1dolomite,which is primarily characterized by microcrystalline(〈30 urn),euhedral to subhedral dolomite crystals,and is generally laminated and associated with gypsumbearing microcrystalline dolomite,and(2) type 2 dolomite,which is composed primarily of finely crystalline(30-100 urn),regular crystal plane,euhedral to subhedral dolomite.The type 2 dolomite crystals are truncated by stylolites,indicating that the type 2 dolomite most likely predated or developed simultaneously with the formation of the stylolites.Stratigraphic,petrographic,and geochemical data indicate that the type 1 dolomite formed from near-surface,low-temperature,and slightly evaporated seawater and that the dolomitizing fluids may have been driven by density differences and elevation-related hydraulic head.The absence of massive depositional evaporites in the dolomitized intervals indicates that dolomitization was driven by the reflux of slightly evaporated seawater.The δ~(18)O values(-7.5 to-6.1 ‰) of type1 dolomite are slightly lower than those of seawaterderived dolomite,suggesting that the dolomite may be related to the recrystallization of dolomite at higher temperatures during burial.The type 2 dolomite has lowerδ~(18)O values(-8.5 to-6.7 ‰) and Sr~(2+) concentration and slightly higher Na~+,Fe~(2+),and Mn~(2+) concentrations and~(87)Sr/~(86)Sr ratios(0.709188-0.709485) than type 1 dolomite,suggesting that the type 2 dolomite precipitated from modified seawater and dolomitic fluids in pore water and that it developed at slightly higher temperatures as a result of shallow burial.展开更多
Coronary artery perforation(CAP)during percutaneous coronary intervention(PCI)is a serious complication associated with significant morbidity and mortality.Its incidence in the general PCI population has been reported...Coronary artery perforation(CAP)during percutaneous coronary intervention(PCI)is a serious complication associated with significant morbidity and mortality.Its incidence in the general PCI population has been reported to range from 0.50%to 0.58%.Meanwhile,in chronic total occlusion(CTO)PCI procedure,the incidence increased to 1.4%−4.4%.[1]Currently,most of CAPs are distally located and related to guidewire,especially hydrophilic guidewire manipulations.[2]To avoid urgent or emergency cardiac surgery,some commonly used techniques include balloon inflations,covered stents,and coil embolization stand as representative options in the treatment of CAP.[3]Despite the availability of treatment approaches,there is still a lack of a standard consensus about the optimal management of this challenging complication.Endovascular pure electrocoagulation is a new approach that has been reported in the management of small vessel hemorrhage disease in cerebrovascular intervention,it can also provide promising results in CAP management.展开更多
基金funded by the National Natural Science Foundation of China(No.81800330)Natural Science Foundation of Shanghai(No.22ZR1414700)Shanghai Pujiang Program(No.21P1401400).
文摘Background Human interleukin(IL)-37 is a constituent of the IL-1 family with potent anti-inflammatory and immunosuppressive attributes.It has been demonstrated extensive beneficial effects on various diseases;however,its role in the pathogenesis of diabetic cardiomyopathy(DCM)remains unclear.Methods In vivo,DCM mouse model was established with streptozotocin injection and a high-fat diet in WT and cardiac fibroblasts(CFs)specific hIL-37b overexpression mice(IL-37-Tg).In vitro,primary mouse CFs were isolated from the hearts of adult mice and cultured with high levels of glucose and palmitic acid.Cardiac function of the mice was assessed using echocardiography.Masson staining,immunofluorescence,western blot and RT-PCR assays were employed to evaluate the expression of cardiac fibrosis and SOCS3-JAK2-STAT3 signaling pathway-related proteins.Results In this study,we found that CFs specific IL-37-Tg significantly ameliorated cardiac dysfunction and reduced collagen production by inhibiting the JAK2-STAT3 axis,as evidenced by the decreased levels of p-JAK2 and p-STAT3 in the heart of CFs specific IL-37-Tg DCM mice.The beneficial effects of IL-37 were consistently observed in CFs treated with high glucose(HG)and palmitic acid(PA).Moreover,we also discovered that the presence of IL-37 increased the expression of SOCS3,a crucial regulator of JAK/STAT signaling,in DCM mice and HG and PA-treated CFs.Finally,the anti-fibrotic action of IL-37 in HG and PAtreated CFs was abolished when either SOCS3 was genetically knocked down or JAK2/STAT3 was pharmacologically activated.Conclusions Our findings indicate that IL-37 exerts its antifibrotic effect by promoting SOCS3-mediated JAK2-STAT3 inactivation and may be considered as a potential therapeutic agent for DCM.
基金supported by the Major National Science and Technology Projects of China (Grant No. 2011ZX05045)Sinopec (Grant No. 34550000-13-FW0403-0010)
文摘The carbonates in the Middle Ordovician Ma_5~5submember of the Majiagou Formation in the northern Ordos Basin are partially to completely dolomitized.Two types of replacive dolomite are distinguished:(1) type 1dolomite,which is primarily characterized by microcrystalline(〈30 urn),euhedral to subhedral dolomite crystals,and is generally laminated and associated with gypsumbearing microcrystalline dolomite,and(2) type 2 dolomite,which is composed primarily of finely crystalline(30-100 urn),regular crystal plane,euhedral to subhedral dolomite.The type 2 dolomite crystals are truncated by stylolites,indicating that the type 2 dolomite most likely predated or developed simultaneously with the formation of the stylolites.Stratigraphic,petrographic,and geochemical data indicate that the type 1 dolomite formed from near-surface,low-temperature,and slightly evaporated seawater and that the dolomitizing fluids may have been driven by density differences and elevation-related hydraulic head.The absence of massive depositional evaporites in the dolomitized intervals indicates that dolomitization was driven by the reflux of slightly evaporated seawater.The δ~(18)O values(-7.5 to-6.1 ‰) of type1 dolomite are slightly lower than those of seawaterderived dolomite,suggesting that the dolomite may be related to the recrystallization of dolomite at higher temperatures during burial.The type 2 dolomite has lowerδ~(18)O values(-8.5 to-6.7 ‰) and Sr~(2+) concentration and slightly higher Na~+,Fe~(2+),and Mn~(2+) concentrations and~(87)Sr/~(86)Sr ratios(0.709188-0.709485) than type 1 dolomite,suggesting that the type 2 dolomite precipitated from modified seawater and dolomitic fluids in pore water and that it developed at slightly higher temperatures as a result of shallow burial.
基金the Scientific Research Staring Foundation of North Huashan Hospital,Fudan University(No.HSBY2017002)the National Natural Science Foundation in China(No.81800330).
文摘Coronary artery perforation(CAP)during percutaneous coronary intervention(PCI)is a serious complication associated with significant morbidity and mortality.Its incidence in the general PCI population has been reported to range from 0.50%to 0.58%.Meanwhile,in chronic total occlusion(CTO)PCI procedure,the incidence increased to 1.4%−4.4%.[1]Currently,most of CAPs are distally located and related to guidewire,especially hydrophilic guidewire manipulations.[2]To avoid urgent or emergency cardiac surgery,some commonly used techniques include balloon inflations,covered stents,and coil embolization stand as representative options in the treatment of CAP.[3]Despite the availability of treatment approaches,there is still a lack of a standard consensus about the optimal management of this challenging complication.Endovascular pure electrocoagulation is a new approach that has been reported in the management of small vessel hemorrhage disease in cerebrovascular intervention,it can also provide promising results in CAP management.