BACKGROUND Peripheral arterial disease(PAD)has become one of the leading causes of disability and death in diabetic patients.Restoring blood supply to the hindlimbs,especially by promoting arteriogenesis,is currently ...BACKGROUND Peripheral arterial disease(PAD)has become one of the leading causes of disability and death in diabetic patients.Restoring blood supply to the hindlimbs,especially by promoting arteriogenesis,is currently the most effective strategy,in which endothelial cells play an important role.Tongxinluo(TXL)has been widely used for the treatment of cardio-cerebrovascular diseases and extended for diabetes-related vascular disease.AIM To investigate the effect of TXL on diabetic PAD and its underlying mechanisms.METHODS An animal model of diabetic PAD was established by ligating the femoral artery of db/db mice.Laser Doppler imaging and micro-computed tomography(micro-CT)were performed to assess the recovery of blood flow and arteriogenesis.Endothelial cell function related to arteriogenesis and cellular pyroptosis was assessed using histopathology,Western blot analysis,enzyme-linked immunosorbent assay and real-time polymerase chain reaction assays.In vitro,human vascular endothelial cells(HUVECs)and human vascular smooth muscle cells(VSMCs)were pretreated with TXL for 4 h,followed by incubation in high glucose and hypoxia conditions to induce cell injury.Then,indicators of HUVEC pyroptosis and function,HUVECVSMC interactions and the migration of VSMCs were measured.RESULTS Laser Doppler imaging and micro-CT showed that TXL restored blood flow to the hindlimbs and enhanced arteriogenesis.TXL also inhibited endothelial cell pyroptosis via the reactive oxygen species/nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3/Caspase-1/GSDMD signaling pathway.In addition,TXL restored endothelial cell functions,including maintaining the balance of vasodilation,acting as a barrier to reduce inflammation,and enhancing endothelial-smooth muscle cell interactions through the Jagged-1/Notch-1/ephrin-B2 signaling pathway.Similar results were observed in vitro.CONCLUSION TXL has a pro-arteriogenic effect in the treatment of diabetic PAD,and the mechanism may be related to the inhibition of endothelial cell pyroptosis,restoration of endothelial cell function and promotion of endothelial cell-smooth muscle cell interactions.展开更多
A highly stable and luminescent metal-organic framework(LMOF) with layered structure,namely,C6H4N5OZn(1) has been successfully achieved and fully characterized by single crystal X-ray diffraction,powder X-ray diffract...A highly stable and luminescent metal-organic framework(LMOF) with layered structure,namely,C6H4N5OZn(1) has been successfully achieved and fully characterized by single crystal X-ray diffraction,powder X-ray diffractions,fluorescence titration and thermogravimetry.This blue-light emitting compound 1 exhibit outstanding stability and can detect Fe3+ and Cu2+ in water specifically,presenting potential application in the field of fluorescent probe technology.Fluorescence titration experiments indicate that the detection of Fe3+ ions by 1 is more significant than that of Cu2+ ions in terms of Ksv value.Furthermore,guest-assisted exfoliation of layered MOF 1 is efficiently carried out through ether O—H hydrogen bond or π…π interactions between the layered host structure and intercalated guest molecules(4,4’-oxybisbenzoic acid and triphenylamine).Tyndal scattering was observed in the suspensions of obtained MOF nanosheets.This study shows that the compound 1 with unique metal ion sensing properties can be applied as a probe material in water pollution treatment field,but also opens up the opportunity for synthesizing luminescent MONs through the "bottom-up" guest intercalation methodology.展开更多
基金Supported by The Hebei Province Natural Science Foundation,No. H2019106062Key R&D Plan of Hebei Provincial Department of Science and Technology,No. 223777155DResearch Project of Hebei Provincial Administration of Traditional Chinese Medicine,No. 2023179
文摘BACKGROUND Peripheral arterial disease(PAD)has become one of the leading causes of disability and death in diabetic patients.Restoring blood supply to the hindlimbs,especially by promoting arteriogenesis,is currently the most effective strategy,in which endothelial cells play an important role.Tongxinluo(TXL)has been widely used for the treatment of cardio-cerebrovascular diseases and extended for diabetes-related vascular disease.AIM To investigate the effect of TXL on diabetic PAD and its underlying mechanisms.METHODS An animal model of diabetic PAD was established by ligating the femoral artery of db/db mice.Laser Doppler imaging and micro-computed tomography(micro-CT)were performed to assess the recovery of blood flow and arteriogenesis.Endothelial cell function related to arteriogenesis and cellular pyroptosis was assessed using histopathology,Western blot analysis,enzyme-linked immunosorbent assay and real-time polymerase chain reaction assays.In vitro,human vascular endothelial cells(HUVECs)and human vascular smooth muscle cells(VSMCs)were pretreated with TXL for 4 h,followed by incubation in high glucose and hypoxia conditions to induce cell injury.Then,indicators of HUVEC pyroptosis and function,HUVECVSMC interactions and the migration of VSMCs were measured.RESULTS Laser Doppler imaging and micro-CT showed that TXL restored blood flow to the hindlimbs and enhanced arteriogenesis.TXL also inhibited endothelial cell pyroptosis via the reactive oxygen species/nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3/Caspase-1/GSDMD signaling pathway.In addition,TXL restored endothelial cell functions,including maintaining the balance of vasodilation,acting as a barrier to reduce inflammation,and enhancing endothelial-smooth muscle cell interactions through the Jagged-1/Notch-1/ephrin-B2 signaling pathway.Similar results were observed in vitro.CONCLUSION TXL has a pro-arteriogenic effect in the treatment of diabetic PAD,and the mechanism may be related to the inhibition of endothelial cell pyroptosis,restoration of endothelial cell function and promotion of endothelial cell-smooth muscle cell interactions.
基金financially supported by the National Natural Science Foundation of China(No.21671084)NSF of Jiangsu Province(No.BK20131244)+5 种基金Six talent peaks project in Jiangsu Province(No.2014-XCL-008)the Qing Lan Project of Jiangsu Provincethe Innovation Program of Graduate Students in JiangsuProvince(No.KYLX16-0508)a Project Funded by the Priority Academic Program Development of Jiangsu Higher Education InstitutionInnovation Program for Graduate Student from Jiangsu University of Science and Technology(No.YCX15S-19)the Foundation of Jiangsu Educational Committee(No.16KJB430011)。
文摘A highly stable and luminescent metal-organic framework(LMOF) with layered structure,namely,C6H4N5OZn(1) has been successfully achieved and fully characterized by single crystal X-ray diffraction,powder X-ray diffractions,fluorescence titration and thermogravimetry.This blue-light emitting compound 1 exhibit outstanding stability and can detect Fe3+ and Cu2+ in water specifically,presenting potential application in the field of fluorescent probe technology.Fluorescence titration experiments indicate that the detection of Fe3+ ions by 1 is more significant than that of Cu2+ ions in terms of Ksv value.Furthermore,guest-assisted exfoliation of layered MOF 1 is efficiently carried out through ether O—H hydrogen bond or π…π interactions between the layered host structure and intercalated guest molecules(4,4’-oxybisbenzoic acid and triphenylamine).Tyndal scattering was observed in the suspensions of obtained MOF nanosheets.This study shows that the compound 1 with unique metal ion sensing properties can be applied as a probe material in water pollution treatment field,but also opens up the opportunity for synthesizing luminescent MONs through the "bottom-up" guest intercalation methodology.