In the present study,we investigated the changes of the coagulation state,bone microthrombus,microvascular bed and bone density levels in iron accumulation rats.Meanwhile,the effect of anticoagulation therapy on bone ...In the present study,we investigated the changes of the coagulation state,bone microthrombus,microvascular bed and bone density levels in iron accumulation rats.Meanwhile,the effect of anticoagulation therapy on bone mineral density was further investigated.We established two groups:a control(Ctrl)group and an iron intervention(FAC)group.Changes in coagulation function,peripheral blood cell counts,bone microthrombus,bone vessels and bone mineral density were compared between the two groups.We designed the non-treatment group and treatment group to study the changes of bone mineral density by preventing microthrombus formation with the anticoagulant fondaparinux.We found that the fbrinogen and D-dimer contents were significantly higher,whereas the thrombin time(TT)and prothrombin time(PT)were significantly shorter in the FAC group.After ink staining,the microvascular bed in the FAC group was significantly reduced compared with that in the Ctrl group.HE and Martius Scarlet Blue(MSB)staining showed microthrombus in the bone marrow of the iron accumulation rats.Following anticoagulation therapy,the bone microcirculation vascular bed areas in the treatment group rats were significantly increased.Furthermore,the bone mineral density was increased in the treatment group compared with that in the non-treatment group.Through experiments,we found that the blood in iron accumulation rat was relatively hypercoagulable;moreover,there was microthrombus in the bone marrow,and the bone vascular bed was reduced.Additionally,anticoagulation was helpful for improving bone microcirculation,reducing microthrombus and decreasing bone loss.展开更多
Diabetic retinopathy(DR),a leading cause of visual loss,is the result of microvascular damage induced by prolonged hyperglycemia.Numerous studies have revealed the pivotal role of integrins in the pathogenesis of DR,p...Diabetic retinopathy(DR),a leading cause of visual loss,is the result of microvascular damage induced by prolonged hyperglycemia.Numerous studies have revealed the pivotal role of integrins in the pathogenesis of DR,particularly in key processes such as inflammation,vascular leakage,microthrombus formation,and angiogenesis.Consequently,targeting integrins is considered a promising strategy for the treatment of DR.This review focuses on the function of integrins in DR and their potential as therapeutic targets.It describes the molecular mechanisms through which integrins influence DR progression and summarizes the latest outcomes of integrin antagonist-based therapeutic strategies in clinical studies,evaluating their efficacy and potential challenges,which offer promise as novel treatment options for DR.展开更多
Objective:To study the mechanism and significance of pH change in the coronary artery microthrombosis of rats.Methods:After the sodium laurate-induced model of coronary artery microthrombosis of rats was constructed,t...Objective:To study the mechanism and significance of pH change in the coronary artery microthrombosis of rats.Methods:After the sodium laurate-induced model of coronary artery microthrombosis of rats was constructed,the vascular endothelial cells were separated and then cultured in the mediums with different pH values for 24 h.Enzyme linked immunosorbent assay was used to detect the content of von Willebrand factor(vWF) in the medium;while the real-time PCR and western blot assay were used to detect the expression of fibrinogenlike protein 2(FGL2) at the mRNA and protein level.The comprehensive evaluation was performed to discuss the effect of pH change on the coronary artery microthrombosis of rats.Results:The expression level of vWF detected by enzyme linked immunosorbent assay was 336.67±24.95,311.33±14.98,359.67±39.63,354.67±49.01 and 332.00±33.42(pg/mL) respectively;while the expression of vWF in the model group was 570.00±57.94,524.67±57.94,437.00±95.38,415.33±44.38 and 444.67±74.31 respectively.Being cultured under the different pH values,the relative expression level of FGL2 mRNA in the model group was 7.93±0.93,6.70±0.70.5.03±0.32,5.13±0:40 and 5.57±0.83 respectively.Conclusions:The coronary artery microthrombosis of rats can cause the high expression and secretion of vWF.Meanwhile,FGL2 is also up-regulated in the thrombosis and such up-regulation is more significant in the condition with low pH,which indicates that the low-pH condition may be one of factors that contribute to the cardiovascular diseases.展开更多
Calciphylaxis is a rare,progressive disorder characterized by subcutaneous adipose and dermal microvascular calcifications,microthrombi,and endothelial damage.It mainly affects patients with chronic kidney disease(CKD...Calciphylaxis is a rare,progressive disorder characterized by subcutaneous adipose and dermal microvascular calcifications,microthrombi,and endothelial damage.It mainly affects patients with chronic kidney disease(CKD),which is also known as calcific uremic arteriolopathy.Skin biopsy is the gold standard for diagnosis,but it is an invasive procedure.Calciphylaxis frequently results in ischemic and nonhealing ulcerations with a high mortality rate.A multidisciplinary targeted approach is the primary treatment method.Vascular calcification,which is a common complication in patients with CKD,cannot completely explain the rapid progression of calciphylaxis.This article reviews the advances in the epidemiological characteristics,risk factors,and diagnosis,including non-uremic calciphylaxis and visceral calciphylaxis,pathogenesis,associated animal models,and treatment of calciphylaxis.The scarcity of animal models that mimic the clinical presentation of calciphylaxis hampers the understanding of its pathogenesis.The acute effects on progressive vascular injury,including the induction of severe ischemia and inflammatory responses,have been emphasized.Actively listening to the voices of patients and their families and building a multidimensional research system with artificial intelligence technologies based on the specific molecular makeup of calciphylaxis patients will help tailor regenerative treatment strategies.Mesenchymal stem cells(MSCs)may represent a novel therapy for calciphylaxis because of their regenerative effects,inhibition of vascular calcification,anti-infection and immunomodulation properties,and improvement of hypercoagulability.Safe,effective,accessible,and economical MSC strategies guided by biomarkers deserve consideration for the treatment of this devastating disease.展开更多
文摘In the present study,we investigated the changes of the coagulation state,bone microthrombus,microvascular bed and bone density levels in iron accumulation rats.Meanwhile,the effect of anticoagulation therapy on bone mineral density was further investigated.We established two groups:a control(Ctrl)group and an iron intervention(FAC)group.Changes in coagulation function,peripheral blood cell counts,bone microthrombus,bone vessels and bone mineral density were compared between the two groups.We designed the non-treatment group and treatment group to study the changes of bone mineral density by preventing microthrombus formation with the anticoagulant fondaparinux.We found that the fbrinogen and D-dimer contents were significantly higher,whereas the thrombin time(TT)and prothrombin time(PT)were significantly shorter in the FAC group.After ink staining,the microvascular bed in the FAC group was significantly reduced compared with that in the Ctrl group.HE and Martius Scarlet Blue(MSB)staining showed microthrombus in the bone marrow of the iron accumulation rats.Following anticoagulation therapy,the bone microcirculation vascular bed areas in the treatment group rats were significantly increased.Furthermore,the bone mineral density was increased in the treatment group compared with that in the non-treatment group.Through experiments,we found that the blood in iron accumulation rat was relatively hypercoagulable;moreover,there was microthrombus in the bone marrow,and the bone vascular bed was reduced.Additionally,anticoagulation was helpful for improving bone microcirculation,reducing microthrombus and decreasing bone loss.
基金Supported by the Natural Science Foundation of Inner Mongolia,No.2022MS080572022 Autonomous Region Medical and Health Science and Technology Plan Projects,No.202202190.
文摘Diabetic retinopathy(DR),a leading cause of visual loss,is the result of microvascular damage induced by prolonged hyperglycemia.Numerous studies have revealed the pivotal role of integrins in the pathogenesis of DR,particularly in key processes such as inflammation,vascular leakage,microthrombus formation,and angiogenesis.Consequently,targeting integrins is considered a promising strategy for the treatment of DR.This review focuses on the function of integrins in DR and their potential as therapeutic targets.It describes the molecular mechanisms through which integrins influence DR progression and summarizes the latest outcomes of integrin antagonist-based therapeutic strategies in clinical studies,evaluating their efficacy and potential challenges,which offer promise as novel treatment options for DR.
基金supported by Medical Scientific Research Foundation of Guangdong Province(No.A2012242)
文摘Objective:To study the mechanism and significance of pH change in the coronary artery microthrombosis of rats.Methods:After the sodium laurate-induced model of coronary artery microthrombosis of rats was constructed,the vascular endothelial cells were separated and then cultured in the mediums with different pH values for 24 h.Enzyme linked immunosorbent assay was used to detect the content of von Willebrand factor(vWF) in the medium;while the real-time PCR and western blot assay were used to detect the expression of fibrinogenlike protein 2(FGL2) at the mRNA and protein level.The comprehensive evaluation was performed to discuss the effect of pH change on the coronary artery microthrombosis of rats.Results:The expression level of vWF detected by enzyme linked immunosorbent assay was 336.67±24.95,311.33±14.98,359.67±39.63,354.67±49.01 and 332.00±33.42(pg/mL) respectively;while the expression of vWF in the model group was 570.00±57.94,524.67±57.94,437.00±95.38,415.33±44.38 and 444.67±74.31 respectively.Being cultured under the different pH values,the relative expression level of FGL2 mRNA in the model group was 7.93±0.93,6.70±0.70.5.03±0.32,5.13±0:40 and 5.57±0.83 respectively.Conclusions:The coronary artery microthrombosis of rats can cause the high expression and secretion of vWF.Meanwhile,FGL2 is also up-regulated in the thrombosis and such up-regulation is more significant in the condition with low pH,which indicates that the low-pH condition may be one of factors that contribute to the cardiovascular diseases.
基金supported by the National Natural Science Foundation of China(81570666)the Outstanding Young and Middle-Aged Talents Support Program of the First Affiliated Hospital with Nanjing Medical University(Jiangsu Province Hospital)+4 种基金the Clinical Capacity Enhancement Project(JSPH-MA-2023-7)the Specialized Diseases Clinical Research Fund of Jiangsu Province Hospital(XB202403)supported by Jiangsu Provincial Medical Key Discipline(Laboratory)Cultivation Unit(JSDW202206)the ISN Clinical Research Program(18-01-0247)Key Projects of Medical Scientific Research Funded by the Health Commission of Jiangsu Province(K2024005).
文摘Calciphylaxis is a rare,progressive disorder characterized by subcutaneous adipose and dermal microvascular calcifications,microthrombi,and endothelial damage.It mainly affects patients with chronic kidney disease(CKD),which is also known as calcific uremic arteriolopathy.Skin biopsy is the gold standard for diagnosis,but it is an invasive procedure.Calciphylaxis frequently results in ischemic and nonhealing ulcerations with a high mortality rate.A multidisciplinary targeted approach is the primary treatment method.Vascular calcification,which is a common complication in patients with CKD,cannot completely explain the rapid progression of calciphylaxis.This article reviews the advances in the epidemiological characteristics,risk factors,and diagnosis,including non-uremic calciphylaxis and visceral calciphylaxis,pathogenesis,associated animal models,and treatment of calciphylaxis.The scarcity of animal models that mimic the clinical presentation of calciphylaxis hampers the understanding of its pathogenesis.The acute effects on progressive vascular injury,including the induction of severe ischemia and inflammatory responses,have been emphasized.Actively listening to the voices of patients and their families and building a multidimensional research system with artificial intelligence technologies based on the specific molecular makeup of calciphylaxis patients will help tailor regenerative treatment strategies.Mesenchymal stem cells(MSCs)may represent a novel therapy for calciphylaxis because of their regenerative effects,inhibition of vascular calcification,anti-infection and immunomodulation properties,and improvement of hypercoagulability.Safe,effective,accessible,and economical MSC strategies guided by biomarkers deserve consideration for the treatment of this devastating disease.
