AIM： To investigate the role of vascular endothelial growth factor （VEGF/and its receptors VEGFR-1 and 2 in the growth and differentiation of gastrointestinal strornal tumors （GISTs）. METHODS： Thirty-three GISTs,...AIM： To investigate the role of vascular endothelial growth factor （VEGF/and its receptors VEGFR-1 and 2 in the growth and differentiation of gastrointestinal strornal tumors （GISTs）. METHODS： Thirty-three GISTs, 15 leiomyomas and 6 schwannomas were examined by immunohistochemistry in this study. RESULTS： VEGF protein was expressed in the cytoplasm of tumor cells, and VEGFRol and 2 were expressed both in the cytoplasm and on the membrane of all tumors. Irnrnunohistochernical staining revealed that 26 GISTs （78.8%）, 9 leiornyornas （60.0%） and 3 schwannornas （50.0%/were positive for VEGF; 24 GISTs （72.7%/, 12 leiornyornas （80.0%） and 4 schwannornas （66.7%） were positive for VEGFR-1; 30 GISTs （90.9%/, 5 leiornyornas （33.3%/and 4 schwannornas （66.7%） were positive for VEGFR-2. VEGFR-2 expression was statistically different between GISTs and leiomyomas （P 〈 0.0001）. However, there was no correlation between the expression of VEGF pathway componenets and the clinical risk categories. CONCLUSION： Our results suggest that the VEGF pathway may play an important role in the differentiation of GISTs, leiomyomas and schwannomas.展开更多
Sodium-glucose cotransporter-2(SGLT-2)inhibitors represent a cutting-edge class of oral antidiabetic therapeutics that operate through selective inhibition of glucose reabsorption in proximal renal tubules,consequentl...Sodium-glucose cotransporter-2(SGLT-2)inhibitors represent a cutting-edge class of oral antidiabetic therapeutics that operate through selective inhibition of glucose reabsorption in proximal renal tubules,consequently augmenting urinary glucose excretion and attenuating blood glucose levels.Extensive clinical investigations have demonstrated their profound cardiovascular efficacy.Parallel basic science research has elucidated the mechanistic pathways through which diverse SGLT-2 inhibitors beneficially modulate pulmonary vascular cells and arterial remodeling.Specifically,these inhibitors exhibit promising potential in enhancing pulmonary vascular endothelial cell function,suppressing pulmonary smooth muscle cell proliferation and migration,reversing pulmonary arterial remodeling,and maintaining hemodynamic equilibrium.This comprehensive review synthesizes current literature to delineate the mechanisms by which SGLT-2 inhibitors enhance pulmonary vascular cell function and reverse pulmonary remodeling,thereby offering novel therapeutic perspectives for pulmonary vascular diseases.展开更多
In this article,we comment on the paper by Kakinuma et al published recently.We focus specifically on the diagnosis of uterine pseudoaneurysm,but we also review other uterine vascular anomalies that may be the cause o...In this article,we comment on the paper by Kakinuma et al published recently.We focus specifically on the diagnosis of uterine pseudoaneurysm,but we also review other uterine vascular anomalies that may be the cause of life-threating hemorrhage and the different causes of uterine pseudoaneurysms.Uterine artery pseudoaneurysm is a complication of both surgical gynecological and nontraumatic procedures.Massive hemorrhage is the consequence of the rupture of the pseudoaneurysm.Uterine artery pseudoaneurysm can develop after obstetric or gynecological procedures,being the most frequent after cesarean or vaginal deliveries,curettage and even during pregnancy.However,there are several cases described unrelated to pregnancy,such as after conization,hysteroscopic surgery or laparoscopic myomectomy.Hemorrhage is the clinical manifestation and it can be life-threatening so suspicion of this vascular lesion is essential for early diagnosis and treatment.However,there are other uterine vascular anomalies that may be the cause of severe hemorrhage,which must be taken into account in the differential diagnosis.Computed tomography angiography and embolization is supposed to be the first therapeutic option in most of them.展开更多
This is a case report of a rare myoma of the anterior vaginal wall that mimicked a paraurethral diverticulum in a postmenopausal woman. Surgical treatment of the lesion was performed via a transvaginal approach withou...This is a case report of a rare myoma of the anterior vaginal wall that mimicked a paraurethral diverticulum in a postmenopausal woman. Surgical treatment of the lesion was performed via a transvaginal approach without complications, and the material was sent for anatomopathological examination, which confirmed the diagnosis of leiomyoma. Vaginal leiomyomas are a rare lineage of tumors at this gynecological site, with just over 300 reports worldwide. Symptoms can range from totally asymptomatic to genitourinary complaints, such as urinary incontinence to dyspareunia. The diagnosis is based on a physical examination and preoperative imaging tests (MRI, transvaginal ultrasound, cystoscopy, computed tomography), but the definitive diagnosis is histopathological analysis of the specimen. The treatment of choice is surgery with complete excision of the lesion, and in 90% of cases, the transvaginal approach is chosen.展开更多
Navigating the intricate and narrow vascular pathways of the body remains a formidable challenge in vascular embolization,often limiting the maneuverability and steerability of traditional catheters.This study,by T.T....Navigating the intricate and narrow vascular pathways of the body remains a formidable challenge in vascular embolization,often limiting the maneuverability and steerability of traditional catheters.This study,by T.T.Xu and co-workers,introduces dual-responsive reconfigurable miniature fiberbots,which are capable of catheter-assisted deployment,navigation,and embolization in vascular systems.Through meticulous design and magnetic control,this work successfully validates a multistage vascular embolization approach in the renal artery of rabbits in vivo.The experiments not only overcome the existing limitations of conventional catheterization techniques but also open new avenues for minimally invasive treatments.展开更多
MANTA vascular closure device is an alternative vascular access closure device that is predominantly designed for large bore arteriotomy procedures.Its implementation to reduce morbidity and mortality following percut...MANTA vascular closure device is an alternative vascular access closure device that is predominantly designed for large bore arteriotomy procedures.Its implementation to reduce morbidity and mortality following percutaneous procedures including peripheral veno-arterial(VA)-extracorporeal membrane oxygenation(ECMO)in critically ill patients with various severe clinical conditions such as refractory cardiogenic shock remains to be under scientific discussion.The use of the MANTA vascular closure device leads to a sufficient reduction in a number of post-decannulation complications such as bleeding,vascular complications,inflammatory reactions and major amputation.Furthermore,the technical success of percutaneous decannulation of VA-ECMO with the MANTA vascular closure device appears to be safe and effective.It has been reported that MANTA vascular closure device exerted a strict similarity with other vascular surgical systems in safe profile regardless of the indication for its utilization.Overall,the immobilized patients achieved a favorable recovery outcome with MANTA including safe decannulation and low risk of vascular complications.The authors suggest the use of pulse wave distal Doppler technology for early detection of these clinically relevant complications.In conclusion,MANTA vascular closure device seems to be safe and effective technical approach to provide low-risk vascular assess for a long time for severe sick individuals.展开更多
Stromal vascular fraction(SVF)is a complex mixture derived from adipose tissue,consisting of a variety of cells.Due to its potential for tissue repair,immunomod-ulation,and support of angiogenesis,SVF represents a pro...Stromal vascular fraction(SVF)is a complex mixture derived from adipose tissue,consisting of a variety of cells.Due to its potential for tissue repair,immunomod-ulation,and support of angiogenesis,SVF represents a promising frontier in regenerative medicine and offers potential therapy for a range of disease condi-tions.In this article,we delve into the mechanisms through which SVF exerts its effects and explore its potential applications in treating both male and female reproductive disorders,including erectile dysfunction,testicular injury,stress urinary incontinence and intrauterine adhesion.展开更多
AIM:To evaluate the role of reactive oxygen speciesendoplasmic reticulum stress(ROS-ERS)in the cellular protection of G protein-coupled receptor 120(GPR120/FFAR4)against high glucose(HG)induced human retinal vascular ...AIM:To evaluate the role of reactive oxygen speciesendoplasmic reticulum stress(ROS-ERS)in the cellular protection of G protein-coupled receptor 120(GPR120/FFAR4)against high glucose(HG)induced human retinal vascular endothelial cell(HRVEC)injury and its underlying mechanisms.METHODS:HRVECs were divided into the control group,GW9508(an agonist of GPR120)group,HG group,and HG+GW9508 group.The cell proliferation and apoptosis were assessed by cell counting kit-8 and annexin V-FITC/PI apoptosis detection kit,respectively.Western blotting analysis was performed to assess the protein expressions of Bax,Bcl-2,activating transcription factor 6(ATF6),PKRlike endoplasmic reticulum kinase(PERK),and inositolrequiring enzyme 1(IRE1).The ROS assay kit was used for the detection of ROS production.Then the cells were transfected with siRNA of GPR120 and the ROS level and protein levels of ATF6,PERK,and IER1 were compared.RESULTS:GW9508 promoted the proliferation of HRVECs,which was significantly reduced by the stimulation of HG.GW9508 remarkably reduced the apoptosis rate of HRVECs under HG and the expression of proapoptotic protein Bax,while increased the expression of antiapoptotic protein Bcl-2.Under HG condition,a significant increase of ROS production was noticed in HRVECs,and GW9508 treatment greatly decreased it.The over-expressions of ERS-related proteins ATF6,PERK,and IER1 under HG were down-regulated by GW9508 treatment.After successfully transfected with siGPR120,the effects of GW9508 on the production of ROS as well as the expressions of ATF6,PERK,and IER1 were reversed.CONCLUSION:GPR120 protects HRVECs against HG induced apoptosis,and suppressing ROS-ERS pathway is one of the mechanisms involved.Activation of GPR120 may be considered as a potential therapeutic target for diabetic retinopathy.展开更多
In regenerative medicine,the isolation of mesenchymal stromal cells(MSCs)from the adipose tissue’s stromal vascular fraction(SVF)is a critical area of study.Our review meticulously examines the isolation process of M...In regenerative medicine,the isolation of mesenchymal stromal cells(MSCs)from the adipose tissue’s stromal vascular fraction(SVF)is a critical area of study.Our review meticulously examines the isolation process of MSCs,starting with the extraction of adipose tissue.The choice of liposuction technique,anatomical site,and immediate processing are essential to maintain cell functionality.We delve into the intricacies of enzymatic digestion,emphasizing the fine-tuning of enzyme concentrations to maximize cell yield while preventing harm.The review then outlines the filtration and centrifugation techniques necessary for isolating a purified SVF,alongside cell viability assessments like flow cytometry,which are vital for confirming the efficacy of the isolated MSCs.We discuss the advantages and drawbacks of using autologous vs allogeneic SVF sources,touching upon immunocompatibility and logistical considerations,as well as the variability inherent in donor-derived cells.Anesthesia choices,the selection between hypo-dermic needles vs liposuction cannulas,and the role of adipose tissue lysers in achieving cellular dissociation are evaluated for their impact on SVF isolation.Centrifugation protocols are also analyzed for their part in ensuring the integrity of the SVF.The necessity for standardized MSC isolation protocols is highlighted,promoting reproducibility and successful clinical application.We encourage ongoing research to deepen the understanding of MSC biology and therapeutic action,aiming to further the field of regenerative medicine.The review concludes with a call for rigorous research,interdisciplinary collaboration,and strict adherence to ethical and regulatory standards to safeguard patient safety and optimize treatment outcomes with MSCs.展开更多
After brain damage,regenerative angiogenesis and neurogenesis have been shown to occur simultaneously in mammals,suggesting a close link between these processes.However,the mechanisms by which these processes interact...After brain damage,regenerative angiogenesis and neurogenesis have been shown to occur simultaneously in mammals,suggesting a close link between these processes.However,the mechanisms by which these processes interact are not well understood.In this work,we aimed to study the correlation between angiogenesis and neurogenesis after a telencephalic stab wound injury.To this end,we used zebrafish as a relevant model of neuroplasticity and brain repair mechanisms.First,using the Tg(fli1:EGFP×mpeg1.1:mCherry)zebrafish line,which enables visualization of blood vessels and microglia respectively,we analyzed regenerative angiogenesis from 1 to 21 days post-lesion.In parallel,we monitored brain cell proliferation in neurogenic niches localized in the ventricular zone by using immunohistochemistry.We found that after brain damage,the blood vessel area and width as well as expression of the fli1 transgene and vascular endothelial growth factor(vegfaa and vegfbb)were increased.At the same time,neural stem cell proliferation was also increased,peaking between 3 and 5 days post-lesion in a manner similar to angiogenesis,along with the recruitment of microglia.Then,through pharmacological manipulation by injecting an anti-angiogenic drug(Tivozanib)or Vegf at the lesion site,we demonstrated that blocking or activating Vegf signaling modulated both angiogenic and neurogenic processes,as well as microglial recruitment.Finally,we showed that inhibition of microglia by clodronate-containing liposome injection or dexamethasone treatment impairs regenerative neurogenesis,as previously described,as well as injury-induced angiogenesis.In conclusion,we have described regenerative angiogenesis in zebrafish for the first time and have highlighted the role of inflammation in this process.In addition,we have shown that both angiogenesis and neurogenesis are involved in brain repair and that microglia and inflammation-dependent mechanisms activated by Vegf signaling are important contributors to these processes.This study paves the way for a better understanding of the effect of Vegf on microglia and for studies aimed at promoting angiogenesis to improve brain plasticity after brain injury.展开更多
With an increase in global aging,the number of people affected by cerebrovascular diseases is also increasing,and the incidence of vascular dementia-closely related to cerebrovascular risk-is increasing at an epidemic...With an increase in global aging,the number of people affected by cerebrovascular diseases is also increasing,and the incidence of vascular dementia-closely related to cerebrovascular risk-is increasing at an epidemic rate.However,few therapeutic options exist that can markedly improve the cognitive impairment and prognosis of vascular dementia patients.Similarly in Alzheimer’s disease and other neurological disorders,synaptic dysfunction is recognized as the main reason for cognitive decline.Nitric oxide is one of the ubiquitous gaseous cellular messengers involved in multiple physiological and pathological processes of the central nervous system.Recently,nitric oxide has been implicated in regulating synaptic plasticity and plays an important role in the pathogenesis of vascular dementia.This review introduces in detail the emerging role of nitric oxide in physiological and pathological states of vascular dementia and summarizes the diverse effects of nitric oxide on different aspects of synaptic dysfunction,neuroinflammation,oxidative stress,and blood-brain barrier dysfunction that underlie the progress of vascular dementia.Additionally,we propose that targeting the nitric oxide-sGC-cGMP pathway using certain specific approaches may provide a novel therapeutic strategy for vascular dementia.展开更多
Peripheral nerve injuries induce a severe motor and sensory deficit. Since the availability of autologous nerve transplants for nerve repair is very limited, alternative treatment strategies are sought, including the ...Peripheral nerve injuries induce a severe motor and sensory deficit. Since the availability of autologous nerve transplants for nerve repair is very limited, alternative treatment strategies are sought, including the use of tubular nerve guidance conduits(tNGCs). However, the use of tNGCs results in poor functional recovery and central necrosis of the regenerating tissue, which limits their application to short nerve lesion defects(typically shorter than 3 cm). Given the importance of vascularization in nerve regeneration, we hypothesized that enabling the growth of blood vessels from the surrounding tissue into the regenerating nerve within the tNGC would help eliminate necrotic processes and lead to improved regeneration. In this study, we reported the application of macroscopic holes into the tubular walls of silk-based tNGCs and compared the various features of these improved silk^(+) tNGCs with the tubes without holes(silk^(–) tNGCs) and autologous nerve transplants in an 8-mm sciatic nerve defect in rats. Using a combination of micro-computed tomography and histological analyses, we were able to prove that the use of silk^(+) tNGCs induced the growth of blood vessels from the adjacent tissue to the intraluminal neovascular formation. A significantly higher number of blood vessels in the silk^(+) group was found compared with autologous nerve transplants and silk^(–), accompanied by improved axon regeneration at the distal coaptation point compared with the silk^(–) tNGCs at 7 weeks postoperatively. In the 15-mm(critical size) sciatic nerve defect model, we again observed a distinct ingrowth of blood vessels through the tubular walls of silk^(+) tNGCs, but without improved functional recovery at 12 weeks postoperatively. Our data proves that macroporous tNGCs increase the vascular supply of regenerating nerves and facilitate improved axonal regeneration in a short-defect model but not in a critical-size defect model. This study suggests that further optimization of the macroscopic holes silk^(+) tNGC approach containing macroscopic holes might result in improved grafting technology suitable for future clinical use.展开更多
BACKGROUND Gastrointestinal(GI)vascular bleeding disorders pose significant clinical challenges due to their complex pathogenesis and varied treatment responses.Despite advancements in diagnostic and therapeutic techn...BACKGROUND Gastrointestinal(GI)vascular bleeding disorders pose significant clinical challenges due to their complex pathogenesis and varied treatment responses.Despite advancements in diagnostic and therapeutic techniques,optimal mana-gement strategies remain elusive,necessitating further research.AIM To assess research trends and clinical advancements in GI vascular bleeding disorders,highlighting key themes and therapeutic progress.METHODS A bibliometric analysis was conducted using the Web of Science Core Collection database,reviewing publications from 2000 to 2024 to identify trends,highfrequency keywords,and key contributions from leading research institutions.In addition,a case study highlighted the effective application of sirolimus in managing colonic angioectasia in a patient with recurrent GI bleeding who had not responded to previous treatments.RESULTS The analysis reviewed 470 scholarly articles from 203 countries,involving 2817 authors across 1502 institutions.The United States led in publication contributions,with strong collaborations with countries like China,England,and Germany.A significant trend was observed in the shift from traditional endoscopic interventions to pharmacological therapies,particularly highlighting the successful use of sirolimus in treating colonic angioectasia. High-frequency keywords such as “angiodysplasia”,“colon”, and “management” were identified, indicating key research themes. The study also noted a growinginterest in drug therapies, as evidenced by the increasing prominence of keywords like “thalidomide” since 2018.CONCLUSIONThis study links bibliometric analysis and clinical insights, highlighting the shift to pharmacological managementin GI vascular bleeding disorders to improve patient outcomes.展开更多
BACKGROUND Liver cirrhosis and portal hypertension(PHT)can lead to lymphatic abnormalities and coagulation dysfunction.Because lymphangiogenesis may relieve liver cirrhosis and PHT,the present study investigated the g...BACKGROUND Liver cirrhosis and portal hypertension(PHT)can lead to lymphatic abnormalities and coagulation dysfunction.Because lymphangiogenesis may relieve liver cirrhosis and PHT,the present study investigated the gene expression alterations in the lymphatic system and the effectiveness of platelet-mediated lymphangiogenesis in improving liver cirrhosis and PHT.AIM To investigate the role of lymphangiogenesis in preclinical PHT models.METHODS Immunohistochemistry and transcriptome sequencing of bile duct ligation(BDL)and control lymphatic samples were conducted to reveal the indicated signaling pathways.Functional enrichment analyses were performed on the differentially expressed genes and hub genes.Adenoviral infection of vascular endothelial growth factor C(VEGF-C),plateletrich plasma(PRP),and VEGF3 receptor(VEGFR)inhibitor MAZ-51 was used as an intervention for the lymphatic system in PHT models.Histology,hemodynamic tests and western blot analyses were performed to demonstrate the effects of lymphatic intervention in PHT patients.RESULTS Lymphangiogenesis was increased in the BDL rat model.Transcriptome sequencing analysis of the extrahepatic lymphatic system revealed its close association with platelet adherence,aggregation,and activation.The role of PHT in the rat model was investigated by activating(PRP)and inhibiting(MAZ-51)the lymphatic system.PRP promoted lymphangiogenesis,which increased lymphatic drainage,alleviated portal pressure,reduced liver fibrosis,inhibited inflammation,inhibited angiogenesis,and suppressed mesenteric artery remodeling.MAZ-51 reversed the above improvements.CONCLUSION Via VEGF-C/VEGFR-3,platelets impede fibrosis,angiogenesis,and mesenteric artery remodeling,ultimately alleviating PHT.Thus,platelet intervention is a therapeutic approach for cirrhosis and PHT.展开更多
Background:Despite the efficacy of absolute ethanol(EtOH),its radiolucency introduces several risks in interventional therapy for treating vascular malformations.This study aims to develop a novel radiopaque ethanol i...Background:Despite the efficacy of absolute ethanol(EtOH),its radiolucency introduces several risks in interventional therapy for treating vascular malformations.This study aims to develop a novel radiopaque ethanol injection(REI)to address this issue.Methods:Iopromide is mixed with ethanol to achieve radiopacity and improve the physicochemical properties of the solution.Overall,82 male New Zealand white rabbits are selected for in vivo radiopacity testing,peripheral vein sclerosis[animals were divided into the following 5 groups(n=6):negative control(NC,saline,0.250 ml/kg),positive control(EtOH,0.250 ml/kg),low-dose REI(L-D REI,0.125 ml/kg),moderate-dose REI(M-D REI,0.250 ml/kg),and highdose REI(H-D REI 0.375 ml/kg)],pharmacokinetic analyses(the blood sample was harvested before injection,5 min,10 min,20 min,40 min,1 h,2 h,4 h,and 8 h after injection in peripheral vein sclerosis experiment),peripheral artery embolization[animals were divided into the following 5 groups(n=3):NC(saline,0.250 ml/kg),positive control(EtOH,0.250 ml/kg),L-D REI(0.125 ml/kg),M-D REI(0.250 ml/kg),and H-D REI(0.375 ml/kg)],kidney transcatheter arterial embolization[animals were divided into the following 4 groups(n=3):positive control(EtOH,0.250 ml/kg),L-D REI(0.125 ml/kg),M-D REI(0.250 ml/kg),and H-D REI(0.375 ml/kg);each healthy kidney was injected with saline as negative control],and biosafety evaluations[animals were divided into the following 5 groups(n=3):NC(0.250 ml/kg),high-dose EtOH(0.375 ml/kg),L-D REI(0.125 ml/kg),M-D REI(0.250 ml/kg),and H-D REI(0.375 ml/kg)].Then,a prospective cohort study involving 6 patients with peripheral venous malformations(VMs)is performed to explore the clinical safety and effectiveness of REI.From Jun 1,2023 to August 31,2023,6 patients[age:(33.3±17.2)years]with lingual VMs received sclerotherapy of REI and 2-month follow-up.Adverse events and serious adverse events were evaluated,whereas the efficacy of REI was determined by both the traceability of the REI under DSA throughout the entire injection and the therapeutic effect 2 months after a single injection.Results:The REI contains 81.4%ethanol(v/v)and 111.3 mg/ml iodine,which can be traced throughout the injection in the animals and patients.The REI also exerts a similar effect as EtOH on peripheral venous sclerosis,peripheral arterial embolization,and renal embolization.Furthermore,the REI can be metabolized at a similar rate compared to EtOH and Ultravist^(®)and did not cause injury to the animals’heart,liver,spleen,lungs,kidneys and brain.No REIrelated adverse effects have occurred during sclerotherapy of VMs,and 4/6 patients(66.7%)have achieved complete response at follow-up.Conclusion:In conclusion,REI is safe,exerts therapeutic effects,and compensates for the radiolucency of EtOH in treating VMs.Trial registration:The clinical trial was registered as No.ChiCTR2300071751 on May 242023.展开更多
Adipose-derived stem cell,one type of mesenchymal stem cells,is a promising approach in treating ischemia-reperfusion injury caused by occlusion of the middle cerebral artery.However,its application has been limited b...Adipose-derived stem cell,one type of mesenchymal stem cells,is a promising approach in treating ischemia-reperfusion injury caused by occlusion of the middle cerebral artery.However,its application has been limited by the complexities of the ischemic microenvironment.Hydrogel scaffolds,which are composed of hyaluronic acid and chitosan,exhibit excellent biocompatibility and biodegradability,making them promising candidates as cell carriers.Vascular endothelial growth factor is a crucial regulatory factor for stem cells.Both hyaluronic acid and chitosan have the potential to make the microenvironment more hospitable to transplanted stem cells,thereby enhancing the therapeutic effect of mesenchymal stem cell transplantation in the context of stroke.Here,we found that vascular endothelial growth factor significantly improved the activity and paracrine function of adipose-derived stem cells.Subsequently,we developed a chitosan-hyaluronic acid hydrogel scaffold that incorporated vascular endothelial growth factor and first injected the scaffold into an animal model of cerebral ischemiareperfusion injury.When loaded with adipose-derived stem cells,this vascular endothelial growth factor–loaded scaffold markedly reduced neuronal apoptosis caused by oxygen-glucose deprivation/reoxygenation and substantially restored mitochondrial membrane potential and axon morphology.Further in vivo experiments revealed that this vascular endothelial growth factor–loaded hydrogel scaffold facilitated the transplantation of adipose-derived stem cells,leading to a reduction in infarct volume and neuronal apoptosis in a rat model of stroke induced by transient middle cerebral artery occlusion.It also helped maintain mitochondrial integrity and axonal morphology,greatly improving rat motor function and angiogenesis.Therefore,utilizing a hydrogel scaffold loaded with vascular endothelial growth factor as a stem cell delivery system can mitigate the adverse effects of ischemic microenvironment on transplanted stem cells and enhance the therapeutic effect of stem cells in the context of stroke.展开更多
Spinal cord injury represents a severe form of central nervous system trauma for which effective treatments remain limited.Microglia is the resident immune cells of the central nervous system,play a critical role in s...Spinal cord injury represents a severe form of central nervous system trauma for which effective treatments remain limited.Microglia is the resident immune cells of the central nervous system,play a critical role in spinal cord injury.Previous studies have shown that microglia can promote neuronal survival by phagocytosing dead cells and debris and by releasing neuroprotective and anti-inflammatory factors.However,excessive activation of microglia can lead to persistent inflammation and contribute to the formation of glial scars,which hinder axonal regeneration.Despite this,the precise role and mechanisms of microglia during the acute phase of spinal cord injury remain controversial and poorly understood.To elucidate the role of microglia in spinal cord injury,we employed the colony-stimulating factor 1 receptor inhibitor PLX5622 to deplete microglia.We observed that sustained depletion of microglia resulted in an expansion of the lesion area,downregulation of brain-derived neurotrophic factor,and impaired functional recovery after spinal cord injury.Next,we generated a transgenic mouse line with conditional overexpression of brain-derived neurotrophic factor specifically in microglia.We found that brain-derived neurotrophic factor overexpression in microglia increased angiogenesis and blood flow following spinal cord injury and facilitated the recovery of hindlimb motor function.Additionally,brain-derived neurotrophic factor overexpression in microglia reduced inflammation and neuronal apoptosis during the acute phase of spinal cord injury.Furthermore,through using specific transgenic mouse lines,TMEM119,and the colony-stimulating factor 1 receptor inhibitor PLX73086,we demonstrated that the neuroprotective effects were predominantly due to brain-derived neurotrophic factor overexpression in microglia rather than macrophages.In conclusion,our findings suggest the critical role of microglia in the formation of protective glial scars.Depleting microglia is detrimental to recovery of spinal cord injury,whereas targeting brain-derived neurotrophic factor overexpression in microglia represents a promising and novel therapeutic strategy to enhance motor function recovery in patients with spinal cord injury.展开更多
BACKGROUND Hepatocellular carcinoma(HCC)is a prevalent and aggressive malignancy in the Chinese population;the severe vascularization by the tumor makes it difficult to cure.The high incidence and poor survival rates ...BACKGROUND Hepatocellular carcinoma(HCC)is a prevalent and aggressive malignancy in the Chinese population;the severe vascularization by the tumor makes it difficult to cure.The high incidence and poor survival rates of this disease indicate the search for new therapeutic alternatives.Apatinib became a drug of choice because it inhibits tyrosine kinase activity,mainly through an effect on vascular endothelial growth factor receptor-2,thereby preventing tumor angiogenesis.This mecha-nism of action makes apatinib effective in the treatment of HCC.METHODS This present study has investigated the effects of HCC cells on VECs,paying particular attention to changes in the glycolytic activity of VECs.The co-culture system established in the present study examined key cellular functions such as extracellular acidification rate and oxygen consumption rate.It also discusses participation of apatinib in the above processes.Core to the findings is the phosphatidylinositol 3-kinase(PI3K)/AKT/6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3(PFKFB3)signaling pathway,emphasizing the function of phosphorylated AKT and its interaction with PFKFB3,an essential regulator of glycolysis.In the investigation,molecular mechanisms by which such a pathway could influence the above VECs functions of proliferation,migration,and tube formation were underlined through coimmunoprecipitation analysis.Besides,supplementary in vivo experiments on nude mice provided additional biological relevance to the obtained results.RESULTS The glycolytic metabolism in VECs co-cultured with HCC cells is highly active,and the increased glycolysis in these endothelial cells accelerates the malignant transformation of HCC cells.Apatinib has been shown to inhibit this glycolytic activity in the VECs.It also hinders the development,multiplication,and movement of these cells while encouraging their programmed cell death.Moreover,biological analysis revealed that apatinib mainly influences VECs by regulating the PI3K/AKT signaling pathway.Subsequent research indicated that apatinib blocks the PI3K/AKT/PFKEB3 pathway,which in turn reduces glycolysis in these cells.CONCLUSION Apatinib influences the glycolytic pathway in the VECs of HCC a through the PI3K/AKT/PFKFB3 signaling pathway.展开更多
Studies have shown that vascular dysfunction is closely related to the pathogenesis of Alzheimer's disease.The middle temporal gyrus region of the brain is susceptible to pronounced impairment in Alzheimer's d...Studies have shown that vascular dysfunction is closely related to the pathogenesis of Alzheimer's disease.The middle temporal gyrus region of the brain is susceptible to pronounced impairment in Alzheimer's disease.Identification of the molecules involved in vascular aberrance of the middle temporal gyrus would support elucidation of the mechanisms underlying Alzheimer's disease and discove ry of novel targets for intervention.We carried out single-cell transcriptomic analysis of the middle temporal gyrus in the brains of patients with Alzheimer's disease and healthy controls,revealing obvious changes in vascular function.CellChat analysis of intercellular communication in the middle temporal gyrus showed that the number of cell interactions in this region was decreased in Alzheimer's disease patients,with altered intercellular communication of endothelial cells and pericytes being the most prominent.Differentially expressed genes were also identified.Using the CellChat results,AUCell evaluation of the pathway activity of specific cells showed that the obvious changes in vascular function in the middle temporal gyrus in Alzheimer's disease were directly related to changes in the vascular endothelial growth factor(VEGF)A-VEGF receptor(VEGFR)2 pathway.AUCell analysis identified subtypes of endothelial cells and pericytes directly related to VEGFA-VEGFR2 pathway activity.Two subtypes of middle temporal gyrus cells showed significant alteration in AD:endothelial cells with high expression of Erb-B2 receptor tyrosine kinase 4(ERBB4^(high))and pericytes with high expression of angiopoietin-like 4(ANGPTL4^(high)).Finally,combining bulk RNA sequencing data and two machine learning algorithms(least absolute shrinkage and selection operator and random forest),four characteristic Alzheimer's disease feature genes were identified:somatostatin(SST),protein tyrosine phosphatase non-receptor type 3(PTPN3),glutinase(GL3),and tropomyosin 3(PTM3).These genes were downregulated in the middle temporal gyrus of patients with Alzheimer's disease and may be used to target the VEGF pathway.Alzheimer's disease mouse models demonstrated consistent altered expression of these genes in the middle temporal gyrus.In conclusion,this study detected changes in intercellular communication between endothelial cells and pericytes in the middle temporal gyrus and identified four novel feature genes related to middle temporal gyrus and vascular functioning in patients with Alzheimer's disease.These findings contribute to a deeper understanding of the molecular mechanisms underlying Alzheimer's disease and present novel treatment targets.展开更多
BACKGROUND Current osteoarthritis(OA)treatments focus on symptom relief without addressing the underlying disease process.In regenerative medicine,current treatments have limitations.In regenerative medicine,more rese...BACKGROUND Current osteoarthritis(OA)treatments focus on symptom relief without addressing the underlying disease process.In regenerative medicine,current treatments have limitations.In regenerative medicine,more research is needed for intra-articular stromal vascular fraction(SVF)injections in OA,including dosage optimization,long-term efficacy,safety,comparisons with other treatments,and mechanism exploration.AIM To compare the efficacy of intra-articular SVF with corticosteroid(ICS)injections in patients with primary knee OA.METHODS The study included 50 patients with Kellgren-Lawrence grades II and III OA.Patients were randomly assigned(1:1)to receive either a single intra-articular SVF injection(group A)or a single intra-articular ICS(triamcinolone)(group B)injection.Patients were followed up at 1,3,6,12,and 24 months.Visual analog score(VAS)and International Knee Documentation Committee(IKDC)scores were administered before the procedure and at all followups.The safety of SVF in terms of adverse and severe adverse events was recorded.Statistical analysis was performed with SPSS Version 26.0,IBM Corp,Chicago,IL,United States.RESULTS Both groups had similar demographics and baseline clinical characteristics.Follow-up showed minor patient loss,resulting in 23 and 24 in groups A and B respectively.Group A experienced a notable reduction in pain,with VAS scores decreasing from 7.7 to 2.4 over 24 months,compared to a minor reduction from 7.8 to 6.2 in Group B.This difference in pain reduction in group A was statistically significant from the third month onwards.Additionally,Group A showed significant improvements in knee functionality,with IKDC scores rising from 33.4 to 83.10,whereas Group B saw a modest increase from 36.7 to 45.16.The improvement in Group A was statistically significant from 6 months and maintained through 24 months.CONCLUSION Our study demonstrated that intra-articular administration of SVF can lead to reduced pain and improved knee function in patients with primary knee OA.More adequately powered,multi-center,double-blinded,randomised clinical trials with longer follow-ups are needed to further establish safety and justify its clinical use.展开更多
文摘AIM： To investigate the role of vascular endothelial growth factor （VEGF/and its receptors VEGFR-1 and 2 in the growth and differentiation of gastrointestinal strornal tumors （GISTs）. METHODS： Thirty-three GISTs, 15 leiomyomas and 6 schwannomas were examined by immunohistochemistry in this study. RESULTS： VEGF protein was expressed in the cytoplasm of tumor cells, and VEGFRol and 2 were expressed both in the cytoplasm and on the membrane of all tumors. Irnrnunohistochernical staining revealed that 26 GISTs （78.8%）, 9 leiornyornas （60.0%） and 3 schwannornas （50.0%/were positive for VEGF; 24 GISTs （72.7%/, 12 leiornyornas （80.0%） and 4 schwannornas （66.7%） were positive for VEGFR-1; 30 GISTs （90.9%/, 5 leiornyornas （33.3%/and 4 schwannornas （66.7%） were positive for VEGFR-2. VEGFR-2 expression was statistically different between GISTs and leiomyomas （P 〈 0.0001）. However, there was no correlation between the expression of VEGF pathway componenets and the clinical risk categories. CONCLUSION： Our results suggest that the VEGF pathway may play an important role in the differentiation of GISTs, leiomyomas and schwannomas.
基金Supported by Science and Technology Department of Yunnan Province-Kunming Medical University,Kunming Medical Joint Special Project-Surface Project,No.202401AY070001-164Yunnan Provincial Clinical Research Center Cardiovascular Diseases-New Technology Research for Development Project for Diagnosis and Treatment Cardiovascular Diseases,No.202102AA310002the Key Technology Research and Device Development Project for Innovative Diagnosis and Treatment of Structural Heart Disease in the Southwest Plateau Region,No.202302AA310045.
文摘Sodium-glucose cotransporter-2(SGLT-2)inhibitors represent a cutting-edge class of oral antidiabetic therapeutics that operate through selective inhibition of glucose reabsorption in proximal renal tubules,consequently augmenting urinary glucose excretion and attenuating blood glucose levels.Extensive clinical investigations have demonstrated their profound cardiovascular efficacy.Parallel basic science research has elucidated the mechanistic pathways through which diverse SGLT-2 inhibitors beneficially modulate pulmonary vascular cells and arterial remodeling.Specifically,these inhibitors exhibit promising potential in enhancing pulmonary vascular endothelial cell function,suppressing pulmonary smooth muscle cell proliferation and migration,reversing pulmonary arterial remodeling,and maintaining hemodynamic equilibrium.This comprehensive review synthesizes current literature to delineate the mechanisms by which SGLT-2 inhibitors enhance pulmonary vascular cell function and reverse pulmonary remodeling,thereby offering novel therapeutic perspectives for pulmonary vascular diseases.
文摘In this article,we comment on the paper by Kakinuma et al published recently.We focus specifically on the diagnosis of uterine pseudoaneurysm,but we also review other uterine vascular anomalies that may be the cause of life-threating hemorrhage and the different causes of uterine pseudoaneurysms.Uterine artery pseudoaneurysm is a complication of both surgical gynecological and nontraumatic procedures.Massive hemorrhage is the consequence of the rupture of the pseudoaneurysm.Uterine artery pseudoaneurysm can develop after obstetric or gynecological procedures,being the most frequent after cesarean or vaginal deliveries,curettage and even during pregnancy.However,there are several cases described unrelated to pregnancy,such as after conization,hysteroscopic surgery or laparoscopic myomectomy.Hemorrhage is the clinical manifestation and it can be life-threatening so suspicion of this vascular lesion is essential for early diagnosis and treatment.However,there are other uterine vascular anomalies that may be the cause of severe hemorrhage,which must be taken into account in the differential diagnosis.Computed tomography angiography and embolization is supposed to be the first therapeutic option in most of them.
文摘This is a case report of a rare myoma of the anterior vaginal wall that mimicked a paraurethral diverticulum in a postmenopausal woman. Surgical treatment of the lesion was performed via a transvaginal approach without complications, and the material was sent for anatomopathological examination, which confirmed the diagnosis of leiomyoma. Vaginal leiomyomas are a rare lineage of tumors at this gynecological site, with just over 300 reports worldwide. Symptoms can range from totally asymptomatic to genitourinary complaints, such as urinary incontinence to dyspareunia. The diagnosis is based on a physical examination and preoperative imaging tests (MRI, transvaginal ultrasound, cystoscopy, computed tomography), but the definitive diagnosis is histopathological analysis of the specimen. The treatment of choice is surgery with complete excision of the lesion, and in 90% of cases, the transvaginal approach is chosen.
基金support from the Hong Kong Research Grants Council(RGC),the Research Fellow Scheme(project no.RFS2122-4S03)the Strategic Topics Grant(project no.STG1/E-401/23-N)+1 种基金Research Impact Fund(project no.R4015-21)We also thank the support from the Multi-scale Medical Robotics Centre(MRC),InnoHK,at the Hong Kong Science Park and the SIAT-CUHK Joint Laboratory of Robotics and Intelligent Systems.
文摘Navigating the intricate and narrow vascular pathways of the body remains a formidable challenge in vascular embolization,often limiting the maneuverability and steerability of traditional catheters.This study,by T.T.Xu and co-workers,introduces dual-responsive reconfigurable miniature fiberbots,which are capable of catheter-assisted deployment,navigation,and embolization in vascular systems.Through meticulous design and magnetic control,this work successfully validates a multistage vascular embolization approach in the renal artery of rabbits in vivo.The experiments not only overcome the existing limitations of conventional catheterization techniques but also open new avenues for minimally invasive treatments.
文摘MANTA vascular closure device is an alternative vascular access closure device that is predominantly designed for large bore arteriotomy procedures.Its implementation to reduce morbidity and mortality following percutaneous procedures including peripheral veno-arterial(VA)-extracorporeal membrane oxygenation(ECMO)in critically ill patients with various severe clinical conditions such as refractory cardiogenic shock remains to be under scientific discussion.The use of the MANTA vascular closure device leads to a sufficient reduction in a number of post-decannulation complications such as bleeding,vascular complications,inflammatory reactions and major amputation.Furthermore,the technical success of percutaneous decannulation of VA-ECMO with the MANTA vascular closure device appears to be safe and effective.It has been reported that MANTA vascular closure device exerted a strict similarity with other vascular surgical systems in safe profile regardless of the indication for its utilization.Overall,the immobilized patients achieved a favorable recovery outcome with MANTA including safe decannulation and low risk of vascular complications.The authors suggest the use of pulse wave distal Doppler technology for early detection of these clinically relevant complications.In conclusion,MANTA vascular closure device seems to be safe and effective technical approach to provide low-risk vascular assess for a long time for severe sick individuals.
文摘Stromal vascular fraction(SVF)is a complex mixture derived from adipose tissue,consisting of a variety of cells.Due to its potential for tissue repair,immunomod-ulation,and support of angiogenesis,SVF represents a promising frontier in regenerative medicine and offers potential therapy for a range of disease condi-tions.In this article,we delve into the mechanisms through which SVF exerts its effects and explore its potential applications in treating both male and female reproductive disorders,including erectile dysfunction,testicular injury,stress urinary incontinence and intrauterine adhesion.
文摘AIM:To evaluate the role of reactive oxygen speciesendoplasmic reticulum stress(ROS-ERS)in the cellular protection of G protein-coupled receptor 120(GPR120/FFAR4)against high glucose(HG)induced human retinal vascular endothelial cell(HRVEC)injury and its underlying mechanisms.METHODS:HRVECs were divided into the control group,GW9508(an agonist of GPR120)group,HG group,and HG+GW9508 group.The cell proliferation and apoptosis were assessed by cell counting kit-8 and annexin V-FITC/PI apoptosis detection kit,respectively.Western blotting analysis was performed to assess the protein expressions of Bax,Bcl-2,activating transcription factor 6(ATF6),PKRlike endoplasmic reticulum kinase(PERK),and inositolrequiring enzyme 1(IRE1).The ROS assay kit was used for the detection of ROS production.Then the cells were transfected with siRNA of GPR120 and the ROS level and protein levels of ATF6,PERK,and IER1 were compared.RESULTS:GW9508 promoted the proliferation of HRVECs,which was significantly reduced by the stimulation of HG.GW9508 remarkably reduced the apoptosis rate of HRVECs under HG and the expression of proapoptotic protein Bax,while increased the expression of antiapoptotic protein Bcl-2.Under HG condition,a significant increase of ROS production was noticed in HRVECs,and GW9508 treatment greatly decreased it.The over-expressions of ERS-related proteins ATF6,PERK,and IER1 under HG were down-regulated by GW9508 treatment.After successfully transfected with siGPR120,the effects of GW9508 on the production of ROS as well as the expressions of ATF6,PERK,and IER1 were reversed.CONCLUSION:GPR120 protects HRVECs against HG induced apoptosis,and suppressing ROS-ERS pathway is one of the mechanisms involved.Activation of GPR120 may be considered as a potential therapeutic target for diabetic retinopathy.
文摘In regenerative medicine,the isolation of mesenchymal stromal cells(MSCs)from the adipose tissue’s stromal vascular fraction(SVF)is a critical area of study.Our review meticulously examines the isolation process of MSCs,starting with the extraction of adipose tissue.The choice of liposuction technique,anatomical site,and immediate processing are essential to maintain cell functionality.We delve into the intricacies of enzymatic digestion,emphasizing the fine-tuning of enzyme concentrations to maximize cell yield while preventing harm.The review then outlines the filtration and centrifugation techniques necessary for isolating a purified SVF,alongside cell viability assessments like flow cytometry,which are vital for confirming the efficacy of the isolated MSCs.We discuss the advantages and drawbacks of using autologous vs allogeneic SVF sources,touching upon immunocompatibility and logistical considerations,as well as the variability inherent in donor-derived cells.Anesthesia choices,the selection between hypo-dermic needles vs liposuction cannulas,and the role of adipose tissue lysers in achieving cellular dissociation are evaluated for their impact on SVF isolation.Centrifugation protocols are also analyzed for their part in ensuring the integrity of the SVF.The necessity for standardized MSC isolation protocols is highlighted,promoting reproducibility and successful clinical application.We encourage ongoing research to deepen the understanding of MSC biology and therapeutic action,aiming to further the field of regenerative medicine.The review concludes with a call for rigorous research,interdisciplinary collaboration,and strict adherence to ethical and regulatory standards to safeguard patient safety and optimize treatment outcomes with MSCs.
基金supported by European Regional Development Funds RE0022527 ZEBRATOX(EU-Région Réunion-French State national counterpart,to Nicolas Diotel and Jean-Loup Bascands).
文摘After brain damage,regenerative angiogenesis and neurogenesis have been shown to occur simultaneously in mammals,suggesting a close link between these processes.However,the mechanisms by which these processes interact are not well understood.In this work,we aimed to study the correlation between angiogenesis and neurogenesis after a telencephalic stab wound injury.To this end,we used zebrafish as a relevant model of neuroplasticity and brain repair mechanisms.First,using the Tg(fli1:EGFP×mpeg1.1:mCherry)zebrafish line,which enables visualization of blood vessels and microglia respectively,we analyzed regenerative angiogenesis from 1 to 21 days post-lesion.In parallel,we monitored brain cell proliferation in neurogenic niches localized in the ventricular zone by using immunohistochemistry.We found that after brain damage,the blood vessel area and width as well as expression of the fli1 transgene and vascular endothelial growth factor(vegfaa and vegfbb)were increased.At the same time,neural stem cell proliferation was also increased,peaking between 3 and 5 days post-lesion in a manner similar to angiogenesis,along with the recruitment of microglia.Then,through pharmacological manipulation by injecting an anti-angiogenic drug(Tivozanib)or Vegf at the lesion site,we demonstrated that blocking or activating Vegf signaling modulated both angiogenic and neurogenic processes,as well as microglial recruitment.Finally,we showed that inhibition of microglia by clodronate-containing liposome injection or dexamethasone treatment impairs regenerative neurogenesis,as previously described,as well as injury-induced angiogenesis.In conclusion,we have described regenerative angiogenesis in zebrafish for the first time and have highlighted the role of inflammation in this process.In addition,we have shown that both angiogenesis and neurogenesis are involved in brain repair and that microglia and inflammation-dependent mechanisms activated by Vegf signaling are important contributors to these processes.This study paves the way for a better understanding of the effect of Vegf on microglia and for studies aimed at promoting angiogenesis to improve brain plasticity after brain injury.
基金supported by the National Key R&D Program of China,No.2019YFE0121200(to LQZ)the National Natural Science Foundation of China,Nos.82325017(to LQZ),82030032(to LQZ),82261138555(to DL)+2 种基金the Natural Science Foundation of Hubei Province,No.2022CFA004(to LQZ)the Natural Science Foundation of Jiangxi Province,No.20224BAB206040(to XZ)Research Project of Cognitive Science and Transdisciplinary Studies Center of Jiangxi Province,No.RZYB202201(to XZ).
文摘With an increase in global aging,the number of people affected by cerebrovascular diseases is also increasing,and the incidence of vascular dementia-closely related to cerebrovascular risk-is increasing at an epidemic rate.However,few therapeutic options exist that can markedly improve the cognitive impairment and prognosis of vascular dementia patients.Similarly in Alzheimer’s disease and other neurological disorders,synaptic dysfunction is recognized as the main reason for cognitive decline.Nitric oxide is one of the ubiquitous gaseous cellular messengers involved in multiple physiological and pathological processes of the central nervous system.Recently,nitric oxide has been implicated in regulating synaptic plasticity and plays an important role in the pathogenesis of vascular dementia.This review introduces in detail the emerging role of nitric oxide in physiological and pathological states of vascular dementia and summarizes the diverse effects of nitric oxide on different aspects of synaptic dysfunction,neuroinflammation,oxidative stress,and blood-brain barrier dysfunction that underlie the progress of vascular dementia.Additionally,we propose that targeting the nitric oxide-sGC-cGMP pathway using certain specific approaches may provide a novel therapeutic strategy for vascular dementia.
基金supported by the Lorenz B?hler Fonds,#2/19 (obtained by the Neuroregeneration Group,Ludwig Boltzmann Institute for Traumatology)the City of Vienna project ImmunTissue,MA23#30-11 (obtained by the Department Life Science Engineering,University of Applied Sciences Technikum Wien)。
文摘Peripheral nerve injuries induce a severe motor and sensory deficit. Since the availability of autologous nerve transplants for nerve repair is very limited, alternative treatment strategies are sought, including the use of tubular nerve guidance conduits(tNGCs). However, the use of tNGCs results in poor functional recovery and central necrosis of the regenerating tissue, which limits their application to short nerve lesion defects(typically shorter than 3 cm). Given the importance of vascularization in nerve regeneration, we hypothesized that enabling the growth of blood vessels from the surrounding tissue into the regenerating nerve within the tNGC would help eliminate necrotic processes and lead to improved regeneration. In this study, we reported the application of macroscopic holes into the tubular walls of silk-based tNGCs and compared the various features of these improved silk^(+) tNGCs with the tubes without holes(silk^(–) tNGCs) and autologous nerve transplants in an 8-mm sciatic nerve defect in rats. Using a combination of micro-computed tomography and histological analyses, we were able to prove that the use of silk^(+) tNGCs induced the growth of blood vessels from the adjacent tissue to the intraluminal neovascular formation. A significantly higher number of blood vessels in the silk^(+) group was found compared with autologous nerve transplants and silk^(–), accompanied by improved axon regeneration at the distal coaptation point compared with the silk^(–) tNGCs at 7 weeks postoperatively. In the 15-mm(critical size) sciatic nerve defect model, we again observed a distinct ingrowth of blood vessels through the tubular walls of silk^(+) tNGCs, but without improved functional recovery at 12 weeks postoperatively. Our data proves that macroporous tNGCs increase the vascular supply of regenerating nerves and facilitate improved axonal regeneration in a short-defect model but not in a critical-size defect model. This study suggests that further optimization of the macroscopic holes silk^(+) tNGC approach containing macroscopic holes might result in improved grafting technology suitable for future clinical use.
基金Air Force Medical Center Youth Talent Program Project,No.22YXQN034Capital Health Development Research Special Project,No.2020-4-5123Beijing Haidian District Health and Wellness Development Scientific Research Cultivation Program,No.HP2021-03-80803.
文摘BACKGROUND Gastrointestinal(GI)vascular bleeding disorders pose significant clinical challenges due to their complex pathogenesis and varied treatment responses.Despite advancements in diagnostic and therapeutic techniques,optimal mana-gement strategies remain elusive,necessitating further research.AIM To assess research trends and clinical advancements in GI vascular bleeding disorders,highlighting key themes and therapeutic progress.METHODS A bibliometric analysis was conducted using the Web of Science Core Collection database,reviewing publications from 2000 to 2024 to identify trends,highfrequency keywords,and key contributions from leading research institutions.In addition,a case study highlighted the effective application of sirolimus in managing colonic angioectasia in a patient with recurrent GI bleeding who had not responded to previous treatments.RESULTS The analysis reviewed 470 scholarly articles from 203 countries,involving 2817 authors across 1502 institutions.The United States led in publication contributions,with strong collaborations with countries like China,England,and Germany.A significant trend was observed in the shift from traditional endoscopic interventions to pharmacological therapies,particularly highlighting the successful use of sirolimus in treating colonic angioectasia. High-frequency keywords such as “angiodysplasia”,“colon”, and “management” were identified, indicating key research themes. The study also noted a growinginterest in drug therapies, as evidenced by the increasing prominence of keywords like “thalidomide” since 2018.CONCLUSIONThis study links bibliometric analysis and clinical insights, highlighting the shift to pharmacological managementin GI vascular bleeding disorders to improve patient outcomes.
基金Supported by the National Natural Science Foundation of China,No.82100639,No.82200630,and No.81970526Postdoctoral Scientific Research Foundation of Shanghai Ninth People’s Hospital,Shanghai Jiao Tong University School of Medicine,No.202401023+3 种基金Clinical Research Program of Ninth People’s Hospital,Shanghai Jiao Tong University School of Medicine,No.JYLJ202124Shanghai Municipal Commission of Health and Family Planning,No.20244Y0195 and No.20234Y0132the Fundamental Research Program Funding of Ninth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine,No.JYZZ162Science Foundation of Xinjiang Uygur Natural Autonomous Region,No.2022D01F17.
文摘BACKGROUND Liver cirrhosis and portal hypertension(PHT)can lead to lymphatic abnormalities and coagulation dysfunction.Because lymphangiogenesis may relieve liver cirrhosis and PHT,the present study investigated the gene expression alterations in the lymphatic system and the effectiveness of platelet-mediated lymphangiogenesis in improving liver cirrhosis and PHT.AIM To investigate the role of lymphangiogenesis in preclinical PHT models.METHODS Immunohistochemistry and transcriptome sequencing of bile duct ligation(BDL)and control lymphatic samples were conducted to reveal the indicated signaling pathways.Functional enrichment analyses were performed on the differentially expressed genes and hub genes.Adenoviral infection of vascular endothelial growth factor C(VEGF-C),plateletrich plasma(PRP),and VEGF3 receptor(VEGFR)inhibitor MAZ-51 was used as an intervention for the lymphatic system in PHT models.Histology,hemodynamic tests and western blot analyses were performed to demonstrate the effects of lymphatic intervention in PHT patients.RESULTS Lymphangiogenesis was increased in the BDL rat model.Transcriptome sequencing analysis of the extrahepatic lymphatic system revealed its close association with platelet adherence,aggregation,and activation.The role of PHT in the rat model was investigated by activating(PRP)and inhibiting(MAZ-51)the lymphatic system.PRP promoted lymphangiogenesis,which increased lymphatic drainage,alleviated portal pressure,reduced liver fibrosis,inhibited inflammation,inhibited angiogenesis,and suppressed mesenteric artery remodeling.MAZ-51 reversed the above improvements.CONCLUSION Via VEGF-C/VEGFR-3,platelets impede fibrosis,angiogenesis,and mesenteric artery remodeling,ultimately alleviating PHT.Thus,platelet intervention is a therapeutic approach for cirrhosis and PHT.
基金supported by the Transverse Research Project of Shanghai Ninth People’s Hospital(JYHX2022007)the Clinical Research Program of Ninth People’s Hospital,Shanghai Jiao Tong University School of Medicine(JYLJ202111).
文摘Background:Despite the efficacy of absolute ethanol(EtOH),its radiolucency introduces several risks in interventional therapy for treating vascular malformations.This study aims to develop a novel radiopaque ethanol injection(REI)to address this issue.Methods:Iopromide is mixed with ethanol to achieve radiopacity and improve the physicochemical properties of the solution.Overall,82 male New Zealand white rabbits are selected for in vivo radiopacity testing,peripheral vein sclerosis[animals were divided into the following 5 groups(n=6):negative control(NC,saline,0.250 ml/kg),positive control(EtOH,0.250 ml/kg),low-dose REI(L-D REI,0.125 ml/kg),moderate-dose REI(M-D REI,0.250 ml/kg),and highdose REI(H-D REI 0.375 ml/kg)],pharmacokinetic analyses(the blood sample was harvested before injection,5 min,10 min,20 min,40 min,1 h,2 h,4 h,and 8 h after injection in peripheral vein sclerosis experiment),peripheral artery embolization[animals were divided into the following 5 groups(n=3):NC(saline,0.250 ml/kg),positive control(EtOH,0.250 ml/kg),L-D REI(0.125 ml/kg),M-D REI(0.250 ml/kg),and H-D REI(0.375 ml/kg)],kidney transcatheter arterial embolization[animals were divided into the following 4 groups(n=3):positive control(EtOH,0.250 ml/kg),L-D REI(0.125 ml/kg),M-D REI(0.250 ml/kg),and H-D REI(0.375 ml/kg);each healthy kidney was injected with saline as negative control],and biosafety evaluations[animals were divided into the following 5 groups(n=3):NC(0.250 ml/kg),high-dose EtOH(0.375 ml/kg),L-D REI(0.125 ml/kg),M-D REI(0.250 ml/kg),and H-D REI(0.375 ml/kg)].Then,a prospective cohort study involving 6 patients with peripheral venous malformations(VMs)is performed to explore the clinical safety and effectiveness of REI.From Jun 1,2023 to August 31,2023,6 patients[age:(33.3±17.2)years]with lingual VMs received sclerotherapy of REI and 2-month follow-up.Adverse events and serious adverse events were evaluated,whereas the efficacy of REI was determined by both the traceability of the REI under DSA throughout the entire injection and the therapeutic effect 2 months after a single injection.Results:The REI contains 81.4%ethanol(v/v)and 111.3 mg/ml iodine,which can be traced throughout the injection in the animals and patients.The REI also exerts a similar effect as EtOH on peripheral venous sclerosis,peripheral arterial embolization,and renal embolization.Furthermore,the REI can be metabolized at a similar rate compared to EtOH and Ultravist^(®)and did not cause injury to the animals’heart,liver,spleen,lungs,kidneys and brain.No REIrelated adverse effects have occurred during sclerotherapy of VMs,and 4/6 patients(66.7%)have achieved complete response at follow-up.Conclusion:In conclusion,REI is safe,exerts therapeutic effects,and compensates for the radiolucency of EtOH in treating VMs.Trial registration:The clinical trial was registered as No.ChiCTR2300071751 on May 242023.
基金supported by a grant from the Excellent Young Scholars Cultivation Project of Fujian Medical University Union Hospital,No.2022XH026(to HC)Joint Funds for the Innovation of Science and Technology in Fujian Province,No.2019Y9058(to XL)the Natural Science Foundation of Fujian Province,No.2020J011017(to XL)。
文摘Adipose-derived stem cell,one type of mesenchymal stem cells,is a promising approach in treating ischemia-reperfusion injury caused by occlusion of the middle cerebral artery.However,its application has been limited by the complexities of the ischemic microenvironment.Hydrogel scaffolds,which are composed of hyaluronic acid and chitosan,exhibit excellent biocompatibility and biodegradability,making them promising candidates as cell carriers.Vascular endothelial growth factor is a crucial regulatory factor for stem cells.Both hyaluronic acid and chitosan have the potential to make the microenvironment more hospitable to transplanted stem cells,thereby enhancing the therapeutic effect of mesenchymal stem cell transplantation in the context of stroke.Here,we found that vascular endothelial growth factor significantly improved the activity and paracrine function of adipose-derived stem cells.Subsequently,we developed a chitosan-hyaluronic acid hydrogel scaffold that incorporated vascular endothelial growth factor and first injected the scaffold into an animal model of cerebral ischemiareperfusion injury.When loaded with adipose-derived stem cells,this vascular endothelial growth factor–loaded scaffold markedly reduced neuronal apoptosis caused by oxygen-glucose deprivation/reoxygenation and substantially restored mitochondrial membrane potential and axon morphology.Further in vivo experiments revealed that this vascular endothelial growth factor–loaded hydrogel scaffold facilitated the transplantation of adipose-derived stem cells,leading to a reduction in infarct volume and neuronal apoptosis in a rat model of stroke induced by transient middle cerebral artery occlusion.It also helped maintain mitochondrial integrity and axonal morphology,greatly improving rat motor function and angiogenesis.Therefore,utilizing a hydrogel scaffold loaded with vascular endothelial growth factor as a stem cell delivery system can mitigate the adverse effects of ischemic microenvironment on transplanted stem cells and enhance the therapeutic effect of stem cells in the context of stroke.
基金supported by the National Natural Science Foundation of China,Nos.82072165 and 82272256(both to XM)the Key Project of Xiangyang Central Hospital,No.2023YZ03(to RM)。
文摘Spinal cord injury represents a severe form of central nervous system trauma for which effective treatments remain limited.Microglia is the resident immune cells of the central nervous system,play a critical role in spinal cord injury.Previous studies have shown that microglia can promote neuronal survival by phagocytosing dead cells and debris and by releasing neuroprotective and anti-inflammatory factors.However,excessive activation of microglia can lead to persistent inflammation and contribute to the formation of glial scars,which hinder axonal regeneration.Despite this,the precise role and mechanisms of microglia during the acute phase of spinal cord injury remain controversial and poorly understood.To elucidate the role of microglia in spinal cord injury,we employed the colony-stimulating factor 1 receptor inhibitor PLX5622 to deplete microglia.We observed that sustained depletion of microglia resulted in an expansion of the lesion area,downregulation of brain-derived neurotrophic factor,and impaired functional recovery after spinal cord injury.Next,we generated a transgenic mouse line with conditional overexpression of brain-derived neurotrophic factor specifically in microglia.We found that brain-derived neurotrophic factor overexpression in microglia increased angiogenesis and blood flow following spinal cord injury and facilitated the recovery of hindlimb motor function.Additionally,brain-derived neurotrophic factor overexpression in microglia reduced inflammation and neuronal apoptosis during the acute phase of spinal cord injury.Furthermore,through using specific transgenic mouse lines,TMEM119,and the colony-stimulating factor 1 receptor inhibitor PLX73086,we demonstrated that the neuroprotective effects were predominantly due to brain-derived neurotrophic factor overexpression in microglia rather than macrophages.In conclusion,our findings suggest the critical role of microglia in the formation of protective glial scars.Depleting microglia is detrimental to recovery of spinal cord injury,whereas targeting brain-derived neurotrophic factor overexpression in microglia represents a promising and novel therapeutic strategy to enhance motor function recovery in patients with spinal cord injury.
基金Supported by the National Natural Science Foundation of China,No.82100542 and No.81802842.
文摘BACKGROUND Hepatocellular carcinoma(HCC)is a prevalent and aggressive malignancy in the Chinese population;the severe vascularization by the tumor makes it difficult to cure.The high incidence and poor survival rates of this disease indicate the search for new therapeutic alternatives.Apatinib became a drug of choice because it inhibits tyrosine kinase activity,mainly through an effect on vascular endothelial growth factor receptor-2,thereby preventing tumor angiogenesis.This mecha-nism of action makes apatinib effective in the treatment of HCC.METHODS This present study has investigated the effects of HCC cells on VECs,paying particular attention to changes in the glycolytic activity of VECs.The co-culture system established in the present study examined key cellular functions such as extracellular acidification rate and oxygen consumption rate.It also discusses participation of apatinib in the above processes.Core to the findings is the phosphatidylinositol 3-kinase(PI3K)/AKT/6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3(PFKFB3)signaling pathway,emphasizing the function of phosphorylated AKT and its interaction with PFKFB3,an essential regulator of glycolysis.In the investigation,molecular mechanisms by which such a pathway could influence the above VECs functions of proliferation,migration,and tube formation were underlined through coimmunoprecipitation analysis.Besides,supplementary in vivo experiments on nude mice provided additional biological relevance to the obtained results.RESULTS The glycolytic metabolism in VECs co-cultured with HCC cells is highly active,and the increased glycolysis in these endothelial cells accelerates the malignant transformation of HCC cells.Apatinib has been shown to inhibit this glycolytic activity in the VECs.It also hinders the development,multiplication,and movement of these cells while encouraging their programmed cell death.Moreover,biological analysis revealed that apatinib mainly influences VECs by regulating the PI3K/AKT signaling pathway.Subsequent research indicated that apatinib blocks the PI3K/AKT/PFKEB3 pathway,which in turn reduces glycolysis in these cells.CONCLUSION Apatinib influences the glycolytic pathway in the VECs of HCC a through the PI3K/AKT/PFKFB3 signaling pathway.
基金supported by the Natural Science Foundation of Shanxi Province,No.20210302123299The Belt and Road Program of Shanxi Province,No.110000261420228002(both to CZ)。
文摘Studies have shown that vascular dysfunction is closely related to the pathogenesis of Alzheimer's disease.The middle temporal gyrus region of the brain is susceptible to pronounced impairment in Alzheimer's disease.Identification of the molecules involved in vascular aberrance of the middle temporal gyrus would support elucidation of the mechanisms underlying Alzheimer's disease and discove ry of novel targets for intervention.We carried out single-cell transcriptomic analysis of the middle temporal gyrus in the brains of patients with Alzheimer's disease and healthy controls,revealing obvious changes in vascular function.CellChat analysis of intercellular communication in the middle temporal gyrus showed that the number of cell interactions in this region was decreased in Alzheimer's disease patients,with altered intercellular communication of endothelial cells and pericytes being the most prominent.Differentially expressed genes were also identified.Using the CellChat results,AUCell evaluation of the pathway activity of specific cells showed that the obvious changes in vascular function in the middle temporal gyrus in Alzheimer's disease were directly related to changes in the vascular endothelial growth factor(VEGF)A-VEGF receptor(VEGFR)2 pathway.AUCell analysis identified subtypes of endothelial cells and pericytes directly related to VEGFA-VEGFR2 pathway activity.Two subtypes of middle temporal gyrus cells showed significant alteration in AD:endothelial cells with high expression of Erb-B2 receptor tyrosine kinase 4(ERBB4^(high))and pericytes with high expression of angiopoietin-like 4(ANGPTL4^(high)).Finally,combining bulk RNA sequencing data and two machine learning algorithms(least absolute shrinkage and selection operator and random forest),four characteristic Alzheimer's disease feature genes were identified:somatostatin(SST),protein tyrosine phosphatase non-receptor type 3(PTPN3),glutinase(GL3),and tropomyosin 3(PTM3).These genes were downregulated in the middle temporal gyrus of patients with Alzheimer's disease and may be used to target the VEGF pathway.Alzheimer's disease mouse models demonstrated consistent altered expression of these genes in the middle temporal gyrus.In conclusion,this study detected changes in intercellular communication between endothelial cells and pericytes in the middle temporal gyrus and identified four novel feature genes related to middle temporal gyrus and vascular functioning in patients with Alzheimer's disease.These findings contribute to a deeper understanding of the molecular mechanisms underlying Alzheimer's disease and present novel treatment targets.
文摘BACKGROUND Current osteoarthritis(OA)treatments focus on symptom relief without addressing the underlying disease process.In regenerative medicine,current treatments have limitations.In regenerative medicine,more research is needed for intra-articular stromal vascular fraction(SVF)injections in OA,including dosage optimization,long-term efficacy,safety,comparisons with other treatments,and mechanism exploration.AIM To compare the efficacy of intra-articular SVF with corticosteroid(ICS)injections in patients with primary knee OA.METHODS The study included 50 patients with Kellgren-Lawrence grades II and III OA.Patients were randomly assigned(1:1)to receive either a single intra-articular SVF injection(group A)or a single intra-articular ICS(triamcinolone)(group B)injection.Patients were followed up at 1,3,6,12,and 24 months.Visual analog score(VAS)and International Knee Documentation Committee(IKDC)scores were administered before the procedure and at all followups.The safety of SVF in terms of adverse and severe adverse events was recorded.Statistical analysis was performed with SPSS Version 26.0,IBM Corp,Chicago,IL,United States.RESULTS Both groups had similar demographics and baseline clinical characteristics.Follow-up showed minor patient loss,resulting in 23 and 24 in groups A and B respectively.Group A experienced a notable reduction in pain,with VAS scores decreasing from 7.7 to 2.4 over 24 months,compared to a minor reduction from 7.8 to 6.2 in Group B.This difference in pain reduction in group A was statistically significant from the third month onwards.Additionally,Group A showed significant improvements in knee functionality,with IKDC scores rising from 33.4 to 83.10,whereas Group B saw a modest increase from 36.7 to 45.16.The improvement in Group A was statistically significant from 6 months and maintained through 24 months.CONCLUSION Our study demonstrated that intra-articular administration of SVF can lead to reduced pain and improved knee function in patients with primary knee OA.More adequately powered,multi-center,double-blinded,randomised clinical trials with longer follow-ups are needed to further establish safety and justify its clinical use.
