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
Recently,Tian et al.published a research paper with significant breakthroughs in Cell[1].The study found that targeting the signalling pathways named Serpine2-lowdensity lipoprotein receptor-related protein 1(Lrp1)and...Recently,Tian et al.published a research paper with significant breakthroughs in Cell[1].The study found that targeting the signalling pathways named Serpine2-lowdensity lipoprotein receptor-related protein 1(Lrp1)and ectonucleoside triphosphate diphosphohydrolase 1(CD39)-adenosine A_(3)receptor(A_(3)AR)is a promising strategy for the treatment of vascular dementia.The Serpine2-Lrp1 signalling pathway primarily exerts its therapeutic effects on myelin regeneration by regulating the differentiation of oligodendrocyte precursor cells.Serpine2 is a secretory serine protease inhibitor regulates proteolytic homeostasis.It may also bind to cell surface receptors such as Lrp1 to directly activate signalling pathways.As a transmembrane glycoprotein receptor,Lrpl mediates the endocytic clearance of ligands.展开更多
Tajikistan represents a core region of the biodiversity hotspot in Central Asian mountains and has exceptional vascular plant diversity.However,the species diversity of the country faces urgent conservation challenges...Tajikistan represents a core region of the biodiversity hotspot in Central Asian mountains and has exceptional vascular plant diversity.However,the species diversity of the country faces urgent conservation challenges.There has been a lack of a comprehensive and multidimensional assessment to inform strategic conservation planning.Therefore,this study integrated 4 key biodiversity indices including species richness(SR),phylogenetic diversity(PD),threatened species richness(TSR),and endemic species richness(ESR)to map species diversity distribution patterns,identify conservation gaps,and elucidate their effects of climatic factors.This study revealed that species diversity shows a clear trend of decreasing from the western region to the eastern region of Tajikistan.The central–western mountains(specifically the Gissar-Darvasian and Zeravshanian regions)emerge as irreplaceable biodiversity hotspots.However,we found a severe spatial mismatch between these priority areas and the existing protected areas(PAs).Protection coverage for all hotspots was alarmingly low,ranging from 31.00%to 38.00%.Consequently,a critical 64.80%of integrated priority areas fall outside of the current PAs,representing a major conservation gap.This study identified precipitation seasonality and isothermality as the principal drivers,collectively explaining over 50.00%of the diversity variation and suggesting high vulnerability to hydrological shifts.Furthermore,we detected significant geographic sampling bias in the public biodiversity databases,with the most critical hotspot being systematically under-sampled.This study provides a robust scientific basis for conservation action,highlighting the urgent need to strategically expand PAs in the under-protected southwestern region and to mitigate critical sampling gaps through targeted data digitization and field surveys.These measures are indispensable for securing Tajikistan’s unique biodiversity and achieving the Kunming-Montreal Global Biodiversity Framework Target 3(“30×30 Protection”).展开更多
AIM:To explore the repeatability,reproducibility,and agreement in the measurement of the choroidal vascularity index(CVI)for different swept-source optical coherence tomography(OCT)devices and between OCT and OCT angi...AIM:To explore the repeatability,reproducibility,and agreement in the measurement of the choroidal vascularity index(CVI)for different swept-source optical coherence tomography(OCT)devices and between OCT and OCT angiography(OCTA)images.METHODS:Two swept-source OCT imaging systems,VG200I and Topcon DRI OCT Triton,were used to capture OCT and OCTA images in triplicate.The first and third images were taken by one operator,and the second image was taken by another operator.The built-in software was used to calculate the CVI from the OCTA images(CVI-OCTA),and a custom-designed algorithm was used to calculate the CVI from the OCT images(CVI-OCT).Repeatability and reproducibility were assessed with the intraclass correlation coefficient(ICC),and agreement between devices and between OCT and OCTA were evaluated with Bland-Altman analysis.RESULTS:Sixty-eight eyes from 35 adults(17 females)were included in the analysis.The average age of the participants was 23.6±2.3y,with an average spherical equivalent refraction of-3.08±2.47 D and an average AL of 25.21±1.20 mm.Both OCT devices demonstrated high repeatability and reproducibility in measuring the CVI-OCTA(all ICCs>0.894 across five choroidal regions)and CVI-OCT(all ICCs>0.838).Furthermore,the between-device agreement in measuring the CVI-OCT was good[mean difference(MD)ranging from-2.32%to-3.07%],but that in measuring the CVI-OCTA was poor(MD,1.48%to-7.43%).Additionally,the between-imaging agreement(CVI-OCTA versus CVI-OCT)was poor for both devices(Triton,MD,6.05%to 12.68%;VG200I,MD,6.67%to 12.09%).CONCLUSION:Both OCT devices and the two analytical methods demonstrate good stability.The inter-device consistency of CVI-OCT is good,while the inter-device consistency of CVI-OCTA and the consistency between the two analytical methods in the same device are both poor.展开更多
AIM:To investigate the changes of retinal vascular parameters and retinal layer thickness in patients with multiple sclerosis(MS).METHODS:This single-centered case-control study was performed on a MS group of 42 patie...AIM:To investigate the changes of retinal vascular parameters and retinal layer thickness in patients with multiple sclerosis(MS).METHODS:This single-centered case-control study was performed on a MS group of 42 patients diagnosed with MS and a control group of 43 healthy hospital staff matched in terms of age and sex at Iran University,department of neurology and ophthalmology from March 2020 to March 2021.The ophthalmic parameters of each patient were recorded,and optical coherence tomography was used to evaluate the retinal thickness in the layers.RESULTS:This study enrolled a total of 85 participants,with a mean age of 40.44±11.52 years,including 61 females(72%).The control group consisted of 43 individuals with a mean age of 39.49±11.07 years,while the MS group comprised 42 participants with a mean age of 41.40±12.01 years.The mean disease duration in the MS group was 8.45±6.04 a.The thickness of the ganglion cell layer in the right eye was significantly lower in the MS group compared to the control group(P=0.034).In addition,except for the left nasal sector(P=0.106),the mean peripapillary neurofibrillation in all examined sectors were significantly lower in the MS group than in the control group(P<0.05).The average vessel density in both the deep and superficial capillary plexuses across all regions of both eyes was lower in the MS group than in the control group,with all comparisons for the superficial capillary plexus showing statistical significance(P<0.05 for all except the left nasal sector).CONCLUSION:The thickness of the retina of patients with MS is significantly reduced.Therefore,optical coherence tomography results can be used as a reliable tool to evaluate disease progression and prognosis in MS patients.展开更多
This study aims to develop a novel,cost-effective method for fabricating silicone vascular phantoms(SVPs)using"chewy candy"as a dissolvable core material.The study explores the feasibility of using chewy can...This study aims to develop a novel,cost-effective method for fabricating silicone vascular phantoms(SVPs)using"chewy candy"as a dissolvable core material.The study explores the feasibility of using chewy candy to create detailed and intricate vascular models for clinical applications.The chewy candy,an amorphous material,was manually extruded to form vascular models of varying diameters.These models were embedded in a silicone mixture,which was then cured.The chewy candy was subsequently dissolved,leaving behind hollow silicone vascular channels.The SVPs were evaluated for their morphological accuracy and functionality through laser speckle contrast imaging.The SVPs successfully replicated vascular channels with consistent diameters,demonstrating minimal variation across different regions.Functional evaluation using laser speckle contrast imaging revealed distinct flow dynamics in Y-shaped and H-shaped SVPs,highlighting the potential for these phantoms to simulate realistic fluid dynamics in vascular systems.This study presents a simple,time-saving,and innovative approach to fabricating complex 3D SVPs using chewy candy.This method offers a viable alternative to traditional fabrication techniques,with potential applications in various biomedical fields.展开更多
Alzheimer’s disease(AD)is the most common form of dementia,affecting over 50 million people worldwide.This figure is projected to nearly double every 20 years,reaching 82 million by 2030 and 152 million by 2050(Alzhe...Alzheimer’s disease(AD)is the most common form of dementia,affecting over 50 million people worldwide.This figure is projected to nearly double every 20 years,reaching 82 million by 2030 and 152 million by 2050(Alzheimer’s Disease International).The apolipoproteinε4(APOE4)allele is the strongest genetic risk factor for late-onset AD(after age 65 years).Apolipoprotein E,a lipid transporter,exists in three variants:ε2,ε3,andε4.APOEε2(APOE2)is protective against AD,APOEε3(APOE3)is neutral,while APOE4 significantly increases the risk.Individuals with one copy of APOE4 have a 4-fold greater risk of developing AD,and those with two copies face an 8-fold risk compared to non-carriers.Even in cognitively normal individuals,APOE4 carriers exhibit brain metabolic and vascular deficits decades before amyloid-beta(Aβ)plaques and neurofibrillary tau tangles emerge-the hallmark pathologies of AD(Reiman et al.,2001,2005;Thambisetty et al.,2010).Notably,studies have demonstrated reduced glucose uptake,or hypometabolism,in brain regions vulnerable to AD in asymptomatic middle-aged APOE4 carriers,long before clinical symptoms arise(Reiman et al.,2001,2005).展开更多
Chronic cerebral hypoperfusion can lead to neuronal necrosis,trigger inflammatory responses,promote white matter damage,and ultimately result in cognitive impairment.Consequently,chronic cerebral hypoperfusion is an i...Chronic cerebral hypoperfusion can lead to neuronal necrosis,trigger inflammatory responses,promote white matter damage,and ultimately result in cognitive impairment.Consequently,chronic cerebral hypoperfusion is an important factor influencing the onset and progression of vascular dementia.The myelin sheath is a critical component of white matter,and damage and repair of the white matter are closely linked to myelin sheath integrity.This article reviews the role of microglia in vascular dementia,focusing on their effects on myelin sheaths and the potential therapeutic implications.The findings suggest that ischemia and hypoxia cause disruption of the blood-brain barrier and activate microglia,which may worsen blood-brain barrier damage through the release of matrix-degrading enzymes.Microglia-mediated metabolic reprogramming is recognized as an important driver of inflammation.Damage to the blood-brain barrier and subsequent inflammation can lead to myelin injury and accelerate the progression of vascular dementia.Early activation of microglia is a protective response that contributes to the maintenance of blood-brain barrier integrity through sensing,debris-clearing,and defensive mechanisms.However,prolonged activation can trigger a shift in microglia toward the pro-inflammatory M1 phenotype,resulting in myelin damage and cognitive impairment.Triggering receptor expressed on myeloid cells 2 and triggering receptor expressed on myeloid cells 1 have been identified as potential biomarkers for vascular dementia,as both are closely linked to cognitive decline.Although effective clinical treatments for myelin damage in the central nervous system are currently lacking,researchers are actively working to develop targeted therapies.Several drugs,including nimodipine,dopaminergic agents,simvastatin,biotin,and quetiapine,have been evaluated for clinical use in treating microglial and myelin damage.Future research will face challenges in developing targeted therapeutic strategies for vascular dementia,requiring further investigation into the timing,duration,and specific mechanisms of microglial activation,as well as the exploration of new drug combinations and additional therapeutic targets.展开更多
Neuroinflammation is a key process in the pathogenesis of various neurodegenerative diseases,such as multiple sclerosis(MS),Alzheimer's disease,and traumatic brain injury.Even for disorders historically unrelated ...Neuroinflammation is a key process in the pathogenesis of various neurodegenerative diseases,such as multiple sclerosis(MS),Alzheimer's disease,and traumatic brain injury.Even for disorders historically unrelated to neuroinflammation,such as Alzheimer's disease,it is now shown to precede pathological protein aggregations.展开更多
The rise of the aging population parallels the rapidly increasing cases of neurological disorders. This puts pressure on scientists and physicians to find novel methods that can prevent and treat neurodegeneration. Th...The rise of the aging population parallels the rapidly increasing cases of neurological disorders. This puts pressure on scientists and physicians to find novel methods that can prevent and treat neurodegeneration. The brain is made up of a complex network of different cell types that work in tandem to maintain systemic homeostasis.展开更多
Vascular cognitive impairment and dementia is a debilitating neurological disorder caused by chronic cerebral hypoperfusion,for which no effective causative treatments are currently available.Intermittent hypoxia has ...Vascular cognitive impairment and dementia is a debilitating neurological disorder caused by chronic cerebral hypoperfusion,for which no effective causative treatments are currently available.Intermittent hypoxia has been shown to enhance cerebral blood flow in mice,but its efficacy in a model of vascular cognitive impairment and dementia remains unclear.In this study,we established a mouse model of vascular cognitive impairment and dementia by bilateral carotid artery stenosis.Intermittent hypoxia was induced before and after this stenosis.We found that intermittent hypoxia increased cerebral blood flow,oxygen saturation,and microcirculation in the prefrontal cortex and hippocampus in the model mice,without causing neurovascular damage.Additionally,intermittent hypoxia significantly improved cognitive function in the mouse model of vascular cognitive impairment and dementia,with perconditioning showing greater efficacy than preconditioning.Improvements in cerebral microcirculation and blood flow were positively correlated with cognitive recovery.Even in a mouse model of vascular cognitive impairment and dementia with comorbidities induced by a high-fat,high-fructose diet,intermittent hypoxic perconditioning demonstrated protective effects on cognitive function.Proteomic analysis indicated that mitochondrial protection is a key mechanism,particularly through upregulating NDUFB8 expression and increasing the activity of mitochondrial complex I.These findings suggest that intermittent hypoxia is a potential non-invasive strategy for the prevention and treatment of vascular cognitive impairment and dementia.展开更多
Background Studies showed that arterial elasticity changes appear earlier than any structural changes, therefore, its accurate evaluation could be applied at early stage to prevent disease. Echo-tracking（E-tracking）...Background Studies showed that arterial elasticity changes appear earlier than any structural changes, therefore, its accurate evaluation could be applied at early stage to prevent disease. Echo-tracking（E-tracking） technique can track the wall motion trajectory in real-time, calculate the change in vascular diameter automatically, and assessment of vascular stiffness and flexibility directly. This article aims to assess the change of elasticity of carotid artery after hormone therapy （HT） using Echo-tracking technology. Methods Echotracking was used to evaluate the carotid elastic moduli, such as the pressure-strain elastic modulus （Ep）, stiffness parameter （β）, arterial compliance （AC）, pulse wave conducting velocity （PWVβ） and augmentation index （AI） by Aloka α10 color Doppler ultrasound diagnosis system. Results Ep,β and PWVβ in HT group were significantly lower than those in the control group （P 〈 0.01）, while AC was obviously higher than the control group （P 〈 0.01）. E2 was negatively related to β, Ep and PWVβ （r = -0.607, r = -0.573, r = -0.574, P 〈 0.001）, while positively related to AC （r = 0.574, P 〈 0.001）; endothelial-dependent dilatation （EDD） was negatively related to β, Ep and PWVβ （r = -0.521, r = -0.411, r = -0.456, P 〈 0.001）, while positively related to AC （r = 0.443, P 〈 0.001）; But IMT was positively related to β, Ep and PWVβ（r = 0.553, r = 0.444, r = 0.529, P 〈 0.001）, while negatively related to AC （r = -0.400, P 〈 0.001）. Conclusions Arterial stiffness increases and compliance decreases in menopausal women. As EDD decreases arterial elasticity recedes, and HT can improve arterial elasticity. E-tracking technology can discover the early changes in arterial stiffness effectively and it is more sensitive in finding out the changes of stiffness in early atherosclerosis than IMT of carotid artery.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
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
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
Objective:This study aimed to observe the effects of xiusanzhen acupuncture(olfactory three-needling therapy)on the behavior,hippocampal histopathology and microglial(MG)activation of rats with vascular dementia(VD),a...Objective:This study aimed to observe the effects of xiusanzhen acupuncture(olfactory three-needling therapy)on the behavior,hippocampal histopathology and microglial(MG)activation of rats with vascular dementia(VD),and to assess the role of the trigeminal nerve.Methods:Sprague-Dawley(SD)rats were randomly assigned to the sham-operation,model,xiusanzhen,and trigeminal neurotomy groups(n=15 per group).Bilateral common carotid artery ligation was performed to prepare the VD models.Models of trigeminal neurotomy were prepared through the excision of the frontal nerve and infraorbital nerve.Xiusanzhen acupuncture was delivered via electric stimulation.The acupoints selected were bilateral“Yingxiang(LI20)”and“Yintang(EX-HN3)”,and the stimulation parameters were as follows:disperse-dense wave,at a frequency of 2/15HZ and intensity of 1 mA.The course of treatment was once daily,with one course lasting five days,followed by an interval of two days,yielding a total of four courses.Behavioral changes were detected using the Morris water maze,changes in histomorphology in the hippocampal CA1 region were determined with hematoxylin and eosin(HE)staining,and MG activation in the hippocampal CA1 region was detected using immunofluorescence.Results:The escape latency:From days 3 to 5,the escape latency was higher in the model group compared to the sham-operation group(P<0.05),but was lower in the xiusanzhen group compared to the model and trigeminal neurotomy groups(P<0.05).The frequency for platform crossing and swimming distance:both were reduced in the model group compared to the sham-operation group(P<0.01);and were elevated in the xiusanzhen group compared to the model group and trigeminal neurotomy group(P<0.01).Hippocampal pathomorphological changes:In the sham-operation group,the morphological structure and nucleoli were well-defined;in the model group and the trigeminal neurotomy group,cell numbers were reduced and karyopyknosis increased;while in the xiusanzhen group,the cell numbers were elevated and karyopyknosis was reduced compared with the model group.MG:the positive rate was higher in the model group compared to the sham-operation group(P<0.05);lower in the xiusanzhen group compared to the model group(P<0.05);and higher in the trigeminal neurotomy group compared to the xiusanzhen group(P<0.05).Conclusion:Xiusanzhen acupuncture attenuates cognitive impairment in VD rats,inhibits MG activation,and reduces hippocampal tissue damage.Its effects depend on the structural integrity of the trigeminal nerve.展开更多
Subretinal fibrosis is the end-stage sequelae of neovascular age-related macular degeneration.It causes local damage to photoreceptors,retinal pigment epithelium,and choroidal vessels,which leads to permanent central ...Subretinal fibrosis is the end-stage sequelae of neovascular age-related macular degeneration.It causes local damage to photoreceptors,retinal pigment epithelium,and choroidal vessels,which leads to permanent central vision loss of patients with neovascular age-related macular degeneration.The pathogenesis of subretinal fibrosis is complex,and the underlying mechanisms are largely unknown.Therefore,there are no effective treatment options.A thorough understanding of the pathogenesis of subretinal fibrosis and its related mechanisms is important to elucidate its complications and explore potential treatments.The current article reviews several aspects of subretinal fibrosis,including the current understanding on the relationship between neovascular age-related macular degeneration and subretinal fibrosis;multimodal imaging techniques for subretinal fibrosis;animal models for studying subretinal fibrosis;cellular and non-cellular constituents of subretinal fibrosis;pathophysiological mechanisms involved in subretinal fibrosis,such as aging,infiltration of macrophages,different sources of mesenchymal transition to myofibroblast,and activation of complement system and immune cells;and several key molecules and signaling pathways participating in the pathogenesis of subretinal fibrosis,such as vascular endothelial growth factor,connective tissue growth factor,fibroblast growth factor 2,platelet-derived growth factor and platelet-derived growth factor receptor-β,transforming growth factor-βsignaling pathway,Wnt signaling pathway,and the axis of heat shock protein 70-Toll-like receptors 2/4-interleukin-10.This review will improve the understanding of the pathogenesis of subretinal fibrosis,allow the discovery of molecular targets,and explore potential treatments for the management of subretinal fibrosis.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
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
The Qinghai-Tibet Plateau(QTP)is the highest and one of the most extensive plateaus in the world.Investigating naturalized non-native plant species composition,phylogenetic relationships among naturalized plant specie...The Qinghai-Tibet Plateau(QTP)is the highest and one of the most extensive plateaus in the world.Investigating naturalized non-native plant species composition,phylogenetic relationships among naturalized plant species,and phylogenetic relationships between native and naturalized plant species on the plateau is of great importance.Here,we analyze a comprehensive dataset including all species of native and naturalized vascular plants known to occur in the core part of the QTP.We use net relatedness index(NRI)and nearest taxon index(NTI),which reflect deep and shallow evolutionary histories,respectively,to quantify phylogenetic relatedness among angiosperm species.The QTP included in this study(1,448,815 km^(2))has 9086 and 314 species of native and naturalized non-native vascular plants,respectively.We find that the naturalized angiosperm species are phylogenetically clustered with respect to the species pool including all native and naturalized angiosperm species on the QTP included in this study,regardless of whether NRI or NTI is used.For the eight regions within the QTP included in this study,NRI and NTI of naturalized angiosperms are positive in seven regions with respect to their respective regional species pools,reflecting phylogenetic clustering.Thus,naturalized angiosperm species are a phylogenetically clustered subset of all angiosperm species on the QTP,regardless of whether the studied plateau as a whole or its constituent regions are considered.展开更多
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support from the Sichuan Science and Technology Program(2024JDHJ0043 and 2025YFHZ0121).
文摘Recently,Tian et al.published a research paper with significant breakthroughs in Cell[1].The study found that targeting the signalling pathways named Serpine2-lowdensity lipoprotein receptor-related protein 1(Lrp1)and ectonucleoside triphosphate diphosphohydrolase 1(CD39)-adenosine A_(3)receptor(A_(3)AR)is a promising strategy for the treatment of vascular dementia.The Serpine2-Lrp1 signalling pathway primarily exerts its therapeutic effects on myelin regeneration by regulating the differentiation of oligodendrocyte precursor cells.Serpine2 is a secretory serine protease inhibitor regulates proteolytic homeostasis.It may also bind to cell surface receptors such as Lrp1 to directly activate signalling pathways.As a transmembrane glycoprotein receptor,Lrpl mediates the endocytic clearance of ligands.
基金the Chinese Academy of Sciences Research Center for Ecology and Environment of Central Asia(RCEECA),the construction and joint research for the China-Tajikistan“Belt and Road”Joint Laboratory on Biodiversity Conservation and Sustainable Use(2024YFE0214200)the Shanghai Cooperation Organization Partnership and International Technology Cooperation Plan of Science and Technology Projects(2023E01018,2025E01056)the Chinese Academy of Sciences President’s International Fellowship Initiative(PIFI)(2024VBC0006).
文摘Tajikistan represents a core region of the biodiversity hotspot in Central Asian mountains and has exceptional vascular plant diversity.However,the species diversity of the country faces urgent conservation challenges.There has been a lack of a comprehensive and multidimensional assessment to inform strategic conservation planning.Therefore,this study integrated 4 key biodiversity indices including species richness(SR),phylogenetic diversity(PD),threatened species richness(TSR),and endemic species richness(ESR)to map species diversity distribution patterns,identify conservation gaps,and elucidate their effects of climatic factors.This study revealed that species diversity shows a clear trend of decreasing from the western region to the eastern region of Tajikistan.The central–western mountains(specifically the Gissar-Darvasian and Zeravshanian regions)emerge as irreplaceable biodiversity hotspots.However,we found a severe spatial mismatch between these priority areas and the existing protected areas(PAs).Protection coverage for all hotspots was alarmingly low,ranging from 31.00%to 38.00%.Consequently,a critical 64.80%of integrated priority areas fall outside of the current PAs,representing a major conservation gap.This study identified precipitation seasonality and isothermality as the principal drivers,collectively explaining over 50.00%of the diversity variation and suggesting high vulnerability to hydrological shifts.Furthermore,we detected significant geographic sampling bias in the public biodiversity databases,with the most critical hotspot being systematically under-sampled.This study provides a robust scientific basis for conservation action,highlighting the urgent need to strategically expand PAs in the under-protected southwestern region and to mitigate critical sampling gaps through targeted data digitization and field surveys.These measures are indispensable for securing Tajikistan’s unique biodiversity and achieving the Kunming-Montreal Global Biodiversity Framework Target 3(“30×30 Protection”).
基金Supported by the National Key Research and Development Program of China(No.2022YFC3502503)the Medical and Health Science and Technology Project of the Zhejiang Provincial Health Commission of China(No.2022PY072).
文摘AIM:To explore the repeatability,reproducibility,and agreement in the measurement of the choroidal vascularity index(CVI)for different swept-source optical coherence tomography(OCT)devices and between OCT and OCT angiography(OCTA)images.METHODS:Two swept-source OCT imaging systems,VG200I and Topcon DRI OCT Triton,were used to capture OCT and OCTA images in triplicate.The first and third images were taken by one operator,and the second image was taken by another operator.The built-in software was used to calculate the CVI from the OCTA images(CVI-OCTA),and a custom-designed algorithm was used to calculate the CVI from the OCT images(CVI-OCT).Repeatability and reproducibility were assessed with the intraclass correlation coefficient(ICC),and agreement between devices and between OCT and OCTA were evaluated with Bland-Altman analysis.RESULTS:Sixty-eight eyes from 35 adults(17 females)were included in the analysis.The average age of the participants was 23.6±2.3y,with an average spherical equivalent refraction of-3.08±2.47 D and an average AL of 25.21±1.20 mm.Both OCT devices demonstrated high repeatability and reproducibility in measuring the CVI-OCTA(all ICCs>0.894 across five choroidal regions)and CVI-OCT(all ICCs>0.838).Furthermore,the between-device agreement in measuring the CVI-OCT was good[mean difference(MD)ranging from-2.32%to-3.07%],but that in measuring the CVI-OCTA was poor(MD,1.48%to-7.43%).Additionally,the between-imaging agreement(CVI-OCTA versus CVI-OCT)was poor for both devices(Triton,MD,6.05%to 12.68%;VG200I,MD,6.67%to 12.09%).CONCLUSION:Both OCT devices and the two analytical methods demonstrate good stability.The inter-device consistency of CVI-OCT is good,while the inter-device consistency of CVI-OCTA and the consistency between the two analytical methods in the same device are both poor.
文摘AIM:To investigate the changes of retinal vascular parameters and retinal layer thickness in patients with multiple sclerosis(MS).METHODS:This single-centered case-control study was performed on a MS group of 42 patients diagnosed with MS and a control group of 43 healthy hospital staff matched in terms of age and sex at Iran University,department of neurology and ophthalmology from March 2020 to March 2021.The ophthalmic parameters of each patient were recorded,and optical coherence tomography was used to evaluate the retinal thickness in the layers.RESULTS:This study enrolled a total of 85 participants,with a mean age of 40.44±11.52 years,including 61 females(72%).The control group consisted of 43 individuals with a mean age of 39.49±11.07 years,while the MS group comprised 42 participants with a mean age of 41.40±12.01 years.The mean disease duration in the MS group was 8.45±6.04 a.The thickness of the ganglion cell layer in the right eye was significantly lower in the MS group compared to the control group(P=0.034).In addition,except for the left nasal sector(P=0.106),the mean peripapillary neurofibrillation in all examined sectors were significantly lower in the MS group than in the control group(P<0.05).The average vessel density in both the deep and superficial capillary plexuses across all regions of both eyes was lower in the MS group than in the control group,with all comparisons for the superficial capillary plexus showing statistical significance(P<0.05 for all except the left nasal sector).CONCLUSION:The thickness of the retina of patients with MS is significantly reduced.Therefore,optical coherence tomography results can be used as a reliable tool to evaluate disease progression and prognosis in MS patients.
基金supported by the Regional Innovation System&Education(RISE)program through the Gangwon RISE Center,funded by the Ministry of Education(MOE)and the Gangwon State(G.S.),Republic of Korea(2025-RISE-10-006).
文摘This study aims to develop a novel,cost-effective method for fabricating silicone vascular phantoms(SVPs)using"chewy candy"as a dissolvable core material.The study explores the feasibility of using chewy candy to create detailed and intricate vascular models for clinical applications.The chewy candy,an amorphous material,was manually extruded to form vascular models of varying diameters.These models were embedded in a silicone mixture,which was then cured.The chewy candy was subsequently dissolved,leaving behind hollow silicone vascular channels.The SVPs were evaluated for their morphological accuracy and functionality through laser speckle contrast imaging.The SVPs successfully replicated vascular channels with consistent diameters,demonstrating minimal variation across different regions.Functional evaluation using laser speckle contrast imaging revealed distinct flow dynamics in Y-shaped and H-shaped SVPs,highlighting the potential for these phantoms to simulate realistic fluid dynamics in vascular systems.This study presents a simple,time-saving,and innovative approach to fabricating complex 3D SVPs using chewy candy.This method offers a viable alternative to traditional fabrication techniques,with potential applications in various biomedical fields.
基金supported by National Institute on Aging(NIH-NIA)R01AG054459(to ALL).
文摘Alzheimer’s disease(AD)is the most common form of dementia,affecting over 50 million people worldwide.This figure is projected to nearly double every 20 years,reaching 82 million by 2030 and 152 million by 2050(Alzheimer’s Disease International).The apolipoproteinε4(APOE4)allele is the strongest genetic risk factor for late-onset AD(after age 65 years).Apolipoprotein E,a lipid transporter,exists in three variants:ε2,ε3,andε4.APOEε2(APOE2)is protective against AD,APOEε3(APOE3)is neutral,while APOE4 significantly increases the risk.Individuals with one copy of APOE4 have a 4-fold greater risk of developing AD,and those with two copies face an 8-fold risk compared to non-carriers.Even in cognitively normal individuals,APOE4 carriers exhibit brain metabolic and vascular deficits decades before amyloid-beta(Aβ)plaques and neurofibrillary tau tangles emerge-the hallmark pathologies of AD(Reiman et al.,2001,2005;Thambisetty et al.,2010).Notably,studies have demonstrated reduced glucose uptake,or hypometabolism,in brain regions vulnerable to AD in asymptomatic middle-aged APOE4 carriers,long before clinical symptoms arise(Reiman et al.,2001,2005).
基金supported by the Natural Science Foundation of Beijing,No.7232279(to XW)the National Natural Science Foundation of China,No.U21A20400(to QW)Key Project of Beijing University of Chinese Medicine,Nos.2022-JYB-JBZR-004(to XW),2024-JYB-JBZD-043(to CL).
文摘Chronic cerebral hypoperfusion can lead to neuronal necrosis,trigger inflammatory responses,promote white matter damage,and ultimately result in cognitive impairment.Consequently,chronic cerebral hypoperfusion is an important factor influencing the onset and progression of vascular dementia.The myelin sheath is a critical component of white matter,and damage and repair of the white matter are closely linked to myelin sheath integrity.This article reviews the role of microglia in vascular dementia,focusing on their effects on myelin sheaths and the potential therapeutic implications.The findings suggest that ischemia and hypoxia cause disruption of the blood-brain barrier and activate microglia,which may worsen blood-brain barrier damage through the release of matrix-degrading enzymes.Microglia-mediated metabolic reprogramming is recognized as an important driver of inflammation.Damage to the blood-brain barrier and subsequent inflammation can lead to myelin injury and accelerate the progression of vascular dementia.Early activation of microglia is a protective response that contributes to the maintenance of blood-brain barrier integrity through sensing,debris-clearing,and defensive mechanisms.However,prolonged activation can trigger a shift in microglia toward the pro-inflammatory M1 phenotype,resulting in myelin damage and cognitive impairment.Triggering receptor expressed on myeloid cells 2 and triggering receptor expressed on myeloid cells 1 have been identified as potential biomarkers for vascular dementia,as both are closely linked to cognitive decline.Although effective clinical treatments for myelin damage in the central nervous system are currently lacking,researchers are actively working to develop targeted therapies.Several drugs,including nimodipine,dopaminergic agents,simvastatin,biotin,and quetiapine,have been evaluated for clinical use in treating microglial and myelin damage.Future research will face challenges in developing targeted therapeutic strategies for vascular dementia,requiring further investigation into the timing,duration,and specific mechanisms of microglial activation,as well as the exploration of new drug combinations and additional therapeutic targets.
基金supported by FWO(Fonds voor Wetenschappelijk Onderzoek),grant number G07562NFWO(to BB)。
文摘Neuroinflammation is a key process in the pathogenesis of various neurodegenerative diseases,such as multiple sclerosis(MS),Alzheimer's disease,and traumatic brain injury.Even for disorders historically unrelated to neuroinflammation,such as Alzheimer's disease,it is now shown to precede pathological protein aggregations.
文摘The rise of the aging population parallels the rapidly increasing cases of neurological disorders. This puts pressure on scientists and physicians to find novel methods that can prevent and treat neurodegeneration. The brain is made up of a complex network of different cell types that work in tandem to maintain systemic homeostasis.
基金supported by the Beijing Nova Program,Nos.20230484436,Z211100002121038the Chinese Institutes for Medical Research,No.CX23YQ01+1 种基金the NationalNatural Science Foundation of China,Nos.32100925,82027802Beijing-Tianjin-Hebei Basic Research Cooperation Project,No.22JCZXJC00190(all to XJand JL).
文摘Vascular cognitive impairment and dementia is a debilitating neurological disorder caused by chronic cerebral hypoperfusion,for which no effective causative treatments are currently available.Intermittent hypoxia has been shown to enhance cerebral blood flow in mice,but its efficacy in a model of vascular cognitive impairment and dementia remains unclear.In this study,we established a mouse model of vascular cognitive impairment and dementia by bilateral carotid artery stenosis.Intermittent hypoxia was induced before and after this stenosis.We found that intermittent hypoxia increased cerebral blood flow,oxygen saturation,and microcirculation in the prefrontal cortex and hippocampus in the model mice,without causing neurovascular damage.Additionally,intermittent hypoxia significantly improved cognitive function in the mouse model of vascular cognitive impairment and dementia,with perconditioning showing greater efficacy than preconditioning.Improvements in cerebral microcirculation and blood flow were positively correlated with cognitive recovery.Even in a mouse model of vascular cognitive impairment and dementia with comorbidities induced by a high-fat,high-fructose diet,intermittent hypoxic perconditioning demonstrated protective effects on cognitive function.Proteomic analysis indicated that mitochondrial protection is a key mechanism,particularly through upregulating NDUFB8 expression and increasing the activity of mitochondrial complex I.These findings suggest that intermittent hypoxia is a potential non-invasive strategy for the prevention and treatment of vascular cognitive impairment and dementia.
文摘Background Studies showed that arterial elasticity changes appear earlier than any structural changes, therefore, its accurate evaluation could be applied at early stage to prevent disease. Echo-tracking（E-tracking） technique can track the wall motion trajectory in real-time, calculate the change in vascular diameter automatically, and assessment of vascular stiffness and flexibility directly. This article aims to assess the change of elasticity of carotid artery after hormone therapy （HT） using Echo-tracking technology. Methods Echotracking was used to evaluate the carotid elastic moduli, such as the pressure-strain elastic modulus （Ep）, stiffness parameter （β）, arterial compliance （AC）, pulse wave conducting velocity （PWVβ） and augmentation index （AI） by Aloka α10 color Doppler ultrasound diagnosis system. Results Ep,β and PWVβ in HT group were significantly lower than those in the control group （P 〈 0.01）, while AC was obviously higher than the control group （P 〈 0.01）. E2 was negatively related to β, Ep and PWVβ （r = -0.607, r = -0.573, r = -0.574, P 〈 0.001）, while positively related to AC （r = 0.574, P 〈 0.001）; endothelial-dependent dilatation （EDD） was negatively related to β, Ep and PWVβ （r = -0.521, r = -0.411, r = -0.456, P 〈 0.001）, while positively related to AC （r = 0.443, P 〈 0.001）; But IMT was positively related to β, Ep and PWVβ（r = 0.553, r = 0.444, r = 0.529, P 〈 0.001）, while negatively related to AC （r = -0.400, P 〈 0.001）. Conclusions Arterial stiffness increases and compliance decreases in menopausal women. As EDD decreases arterial elasticity recedes, and HT can improve arterial elasticity. E-tracking technology can discover the early changes in arterial stiffness effectively and it is more sensitive in finding out the changes of stiffness in early atherosclerosis than IMT of carotid artery.
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.
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 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 Natural Science Foundation of China Young Scientists Fund:82004480。
文摘Objective:This study aimed to observe the effects of xiusanzhen acupuncture(olfactory three-needling therapy)on the behavior,hippocampal histopathology and microglial(MG)activation of rats with vascular dementia(VD),and to assess the role of the trigeminal nerve.Methods:Sprague-Dawley(SD)rats were randomly assigned to the sham-operation,model,xiusanzhen,and trigeminal neurotomy groups(n=15 per group).Bilateral common carotid artery ligation was performed to prepare the VD models.Models of trigeminal neurotomy were prepared through the excision of the frontal nerve and infraorbital nerve.Xiusanzhen acupuncture was delivered via electric stimulation.The acupoints selected were bilateral“Yingxiang(LI20)”and“Yintang(EX-HN3)”,and the stimulation parameters were as follows:disperse-dense wave,at a frequency of 2/15HZ and intensity of 1 mA.The course of treatment was once daily,with one course lasting five days,followed by an interval of two days,yielding a total of four courses.Behavioral changes were detected using the Morris water maze,changes in histomorphology in the hippocampal CA1 region were determined with hematoxylin and eosin(HE)staining,and MG activation in the hippocampal CA1 region was detected using immunofluorescence.Results:The escape latency:From days 3 to 5,the escape latency was higher in the model group compared to the sham-operation group(P<0.05),but was lower in the xiusanzhen group compared to the model and trigeminal neurotomy groups(P<0.05).The frequency for platform crossing and swimming distance:both were reduced in the model group compared to the sham-operation group(P<0.01);and were elevated in the xiusanzhen group compared to the model group and trigeminal neurotomy group(P<0.01).Hippocampal pathomorphological changes:In the sham-operation group,the morphological structure and nucleoli were well-defined;in the model group and the trigeminal neurotomy group,cell numbers were reduced and karyopyknosis increased;while in the xiusanzhen group,the cell numbers were elevated and karyopyknosis was reduced compared with the model group.MG:the positive rate was higher in the model group compared to the sham-operation group(P<0.05);lower in the xiusanzhen group compared to the model group(P<0.05);and higher in the trigeminal neurotomy group compared to the xiusanzhen group(P<0.05).Conclusion:Xiusanzhen acupuncture attenuates cognitive impairment in VD rats,inhibits MG activation,and reduces hippocampal tissue damage.Its effects depend on the structural integrity of the trigeminal nerve.
基金supported by grants from National Key R&D Program of China,No.2023YFC2506100(to JZ)the National Natural Science Foundation of China,No.82171062(to JZ).
文摘Subretinal fibrosis is the end-stage sequelae of neovascular age-related macular degeneration.It causes local damage to photoreceptors,retinal pigment epithelium,and choroidal vessels,which leads to permanent central vision loss of patients with neovascular age-related macular degeneration.The pathogenesis of subretinal fibrosis is complex,and the underlying mechanisms are largely unknown.Therefore,there are no effective treatment options.A thorough understanding of the pathogenesis of subretinal fibrosis and its related mechanisms is important to elucidate its complications and explore potential treatments.The current article reviews several aspects of subretinal fibrosis,including the current understanding on the relationship between neovascular age-related macular degeneration and subretinal fibrosis;multimodal imaging techniques for subretinal fibrosis;animal models for studying subretinal fibrosis;cellular and non-cellular constituents of subretinal fibrosis;pathophysiological mechanisms involved in subretinal fibrosis,such as aging,infiltration of macrophages,different sources of mesenchymal transition to myofibroblast,and activation of complement system and immune cells;and several key molecules and signaling pathways participating in the pathogenesis of subretinal fibrosis,such as vascular endothelial growth factor,connective tissue growth factor,fibroblast growth factor 2,platelet-derived growth factor and platelet-derived growth factor receptor-β,transforming growth factor-βsignaling pathway,Wnt signaling pathway,and the axis of heat shock protein 70-Toll-like receptors 2/4-interleukin-10.This review will improve the understanding of the pathogenesis of subretinal fibrosis,allow the discovery of molecular targets,and explore potential treatments for the management of subretinal fibrosis.
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.
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.
基金supported by grants from the Second Tibetan Plateau Scientific Expedition and Research(STEP)program(2019QZKK0502)the Strategic Priority Research Program of Chinese Academy of Sciences(XDA20050203)+4 种基金the National Natural Science Foundation of China-Yunnan joint fund to support key projects(U1802232)the Major Program for Basic Research Project of Yunnan Province(202101BC070002)the Yunnan Young&Elite Talents Project(YNWR-QNBJ-2019-033)the Ten Thousand Talents Program of Yunnan Province(202005AB160005)the Chinese Academy of Sciences“Light of West China”Program.
文摘The Qinghai-Tibet Plateau(QTP)is the highest and one of the most extensive plateaus in the world.Investigating naturalized non-native plant species composition,phylogenetic relationships among naturalized plant species,and phylogenetic relationships between native and naturalized plant species on the plateau is of great importance.Here,we analyze a comprehensive dataset including all species of native and naturalized vascular plants known to occur in the core part of the QTP.We use net relatedness index(NRI)and nearest taxon index(NTI),which reflect deep and shallow evolutionary histories,respectively,to quantify phylogenetic relatedness among angiosperm species.The QTP included in this study(1,448,815 km^(2))has 9086 and 314 species of native and naturalized non-native vascular plants,respectively.We find that the naturalized angiosperm species are phylogenetically clustered with respect to the species pool including all native and naturalized angiosperm species on the QTP included in this study,regardless of whether NRI or NTI is used.For the eight regions within the QTP included in this study,NRI and NTI of naturalized angiosperms are positive in seven regions with respect to their respective regional species pools,reflecting phylogenetic clustering.Thus,naturalized angiosperm species are a phylogenetically clustered subset of all angiosperm species on the QTP,regardless of whether the studied plateau as a whole or its constituent regions are considered.
