Repairing the endothelial barrier is essential for maintaining pulmonary fuid balance and regulating leukocyte infiltration during sepsis[1].Tissue kallikrein-related peptidases(KLKs)are secreted serine proteases invo...Repairing the endothelial barrier is essential for maintaining pulmonary fuid balance and regulating leukocyte infiltration during sepsis[1].Tissue kallikrein-related peptidases(KLKs)are secreted serine proteases involved in angiogenesis[2].However,their involvement in regulating endothelial regeneration remains largely unknown.展开更多
Drug development for Alzheimer’s disease is extremely challenging,as demonstrated by the repeated failures of amyloid-β-targeted therapeutics and the controversies surrounding the amyloid-βcascade hypothesis.More r...Drug development for Alzheimer’s disease is extremely challenging,as demonstrated by the repeated failures of amyloid-β-targeted therapeutics and the controversies surrounding the amyloid-βcascade hypothesis.More recently,advances in the development of Lecanemab,an anti-amyloid-βmonoclonal antibody,have shown positive results in reducing brain A burden and slowing cognitive decline in patients with early-stage Alzheimer’s disease in the Phase Ⅲ clinical trial(Clarity Alzheimer’s disease).Despite these promising results,side effects such as amyloid-related imaging abnormalities(ARIA)may limit its usage.ARIA can manifest as ARIA-E(cerebral edema or effusions)and ARIA-H(microhemorrhages or superficial siderosis)and is thought to be caused by increased vascular permeability due to inflammatory responses,leading to leakages of blood products and protein-rich fluid into brain parenchyma.Endothelial dysfunction is an early pathological feature of Alzheimer’s disease,and the blood-brain barrier becomes increasingly leaky as the disease progresses.In addition,APOE4,the strongest genetic risk factor for Alzheimer’s disease,is associated with higher vascular amyloid burden,increased ARIA incidence,and accelerated blood-brain barrier disruptions.These interconnected vascular abnormalities highlight the importance of vascular contributions to the pathophysiology of Alzheimer’s disease.Here,we will closely examine recent research evaluating the heterogeneity of brain endothelial cells in the microvasculature of different brain regions and their relationships with Alzheimer’s disease progression.展开更多
Introduction Fuchs endothelial corneal dystrophy(FECD)is an inherited,degenerative disease of the corneal endothelial cells(CECs).It is characterized by a progressive deterioration of endothelial cells,altered extrace...Introduction Fuchs endothelial corneal dystrophy(FECD)is an inherited,degenerative disease of the corneal endothelial cells(CECs).It is characterized by a progressive deterioration of endothelial cells,altered extracellular matrix(ECM)production,and development of guttae(1,2).The presence of guttae has been shown to significantly impair corneal endothelial function,leading to corneal oedema and visual impairment.展开更多
Axonal remodeling is a critical aspect of ischemic brain repair processes and contributes to spontaneous functional recovery.Our previous in vitro study demonstrated that exosomes/small extracellular vesicles(sEVs)iso...Axonal remodeling is a critical aspect of ischemic brain repair processes and contributes to spontaneous functional recovery.Our previous in vitro study demonstrated that exosomes/small extracellular vesicles(sEVs)isolated from cerebral endothelial cells(CEC-sEVs)of ischemic brain promote axonal growth of embryonic cortical neurons and that microRNA 27a(miR-27a)is an elevated miRNA in ischemic CEC-sEVs.In the present study,we investigated whether normal CEC-sEVs engineered to enrich their levels of miR-27a(27a-sEVs)further enhance axonal growth and improve neurological outcomes after ischemic stroke when compared with treatment with non-engineered CEC-sEVs.27a-sEVs were isolated from the conditioned medium of healthy mouse CECs transfected with a lentiviral miR-27a expression vector.Small EVs isolated from CECs transfected with a scramble vector(Scra-sEVs)were used as a control.Adult male mice were subjected to permanent middle cerebral artery occlusion and then were randomly treated with 27a-sEVs or Scra-sEVs.An array of behavior assays was used to measure neurological function.Compared with treatment of ischemic stroke with Scra-sEVs,treatment with 27a-sEVs significantly augmented axons and spines in the peri-infarct zone and in the corticospinal tract of the spinal grey matter of the denervated side,and significantly improved neurological outcomes.In vitro studies demonstrated that CEC-sEVs carrying reduced miR-27a abolished 27a-sEV-augmented axonal growth.Ultrastructural analysis revealed that 27a-sEVs systemically administered preferentially localized to the pre-synaptic active zone,while quantitative reverse transcription-polymerase chain reaction and Western Blot analysis showed elevated miR-27a,and reduced axonal inhibitory proteins Semaphorin 6A and Ras Homolog Family Member A in the peri-infarct zone.Blockage of the Clathrin-dependent endocytosis pathway substantially reduced neuronal internalization of 27a-sEVs.Our data provide evidence that 27a-sEVs have a therapeutic effect on stroke recovery by promoting axonal remodeling and improving neurological outcomes.Our findings also suggest that suppression of axonal inhibitory proteins such as Semaphorin 6A may contribute to the beneficial effect of 27a-sEVs on axonal remodeling.展开更多
The endothelium modulates vascular homeostasis owing to a variety of vasoconstrictors and vasodilators.Endothelial dysfunction(ED),characterized by impaired vasodilation,inflammation,and thrombosis,triggers future car...The endothelium modulates vascular homeostasis owing to a variety of vasoconstrictors and vasodilators.Endothelial dysfunction(ED),characterized by impaired vasodilation,inflammation,and thrombosis,triggers future cardiovascular(CV)diseases.Chronic kidney disease,a state of chronic inflammation caused by oxidative stress,metabolic abnormalities,infection,and uremic toxins damages the endothelium.ED is also associated with a decline in estimated glomerular filtration rate.After kidney transplantation,endothelial functions undergo immediate but partial restoration,promising graft longevity and enhanced CV health.However,the anticipated CV outcomes do not happen due to various transplant-related and unrelated risk factors for ED,culminating in poor CV health and graft survival.ED in kidney transplant recipients is an underrecognized and poorly studied entity.CV diseases are the leading cause of death among kidney transplant candidates with functioning grafts.ED contributes to the pathogenesis of many of the CV diseases.Various biomarkers and vasoreactivity tests are available to study endothelial functions.With an increasing number of transplants happening every year,and improved graft rejection rates due to the availability of effective immunosuppressants,the focus has now shifted to endothelial protection for the prevention,early recognition,and treatment of CV diseases.展开更多
AIM:To assess the relationship between serological parameters and the prognosis of young patients with retinal vein occlusion(RVO)after intravitreal conbercept injection(IVC).METHODS:This study enrolled 100 young pati...AIM:To assess the relationship between serological parameters and the prognosis of young patients with retinal vein occlusion(RVO)after intravitreal conbercept injection(IVC).METHODS:This study enrolled 100 young patients(≤50 years old)diagnosed with RVO-related macular edema(RVO-ME)who had been undergoing IVC at the 474 Hospital in Xinjiang between January 2022 and October 2023.Patients were categorized into two groups:70 eyes in the effective group and 30 eyes in the ineffective group.The effective group comprised patients exhibiting a visual acuity improvement of≥2 lines at the last follow-up,with resolved ME and central macular thickness(CMT)<300μm.Conversely,the ineffective group included patients with visual acuity improvement of<1 line,persistent ME,and CMT≥300μm at the last follow-up.Serological parameters,including white blood cell count,neutrophil count,lymphocyte count,monocyte count,and mean platelet volume were assessed before treatment.The correlation between bestcorrected visual acuity(BCVA)and neutrophil-to-lymphocyte ratio(NLR),platelet-to-lymphocyte ratio(PLR),systemic immune inflammation index(SII),and systemic immune response index(SIRI)was analyzed.Additionally,the association between these serological parameters and the efficacy of IVC was explored.RESULTS:Three months after treatment,the effective group demonstrated a significant improvement in BCVA from 0.82±0.20 to 0.36±0.10,with a concurrent decrease in CMT from 661.28±163.90 to 200.61±82.45μm(P<0.001).Conversely,the ineffective group exhibited minimal changes in BCVA(0.86±0.25 to 0.82±0.14)and CMT(669.84±164.95 to 492.13±138.67μm,P<0.001).The differences in BCVA and CMT between the two groups were statistically significant(P<0.001).According to subgroup analysis,in patients with central RVO(CRVO),BCVA improved from 0.82±0.23 to 0.49±0.12 in the effective group and from 0.80±0.18 to 0.76±0.22 in the ineffective group(P<0.001).The CMT changes followed a similar pattern.In patients with branch RVO(BRVO),comparable trends in BCVA and CMT changes were observed between the effective and ineffective groups(P<0.001).Additionally,the effective group exhibited higher PLR and SII values than the ineffective group(P<0.05).Further CRVO and BRVO subgroups analysis exhibited consistent PLR and SII value trends.CONCLUSION:Compared to other inflammatory factors,elevated PLR and SII levels before treatment are better predictors of outcomes in young RVO-ME patients undergoing IVC treatment.展开更多
AIM:To determine the therapeutic benefits of fenofibrate(Feno)on the dysfunction of high glucose(HG)-induced human retinal microvascular endothelial cells(HRMECs)and to elucidate the underlying molecular mechanism.MET...AIM:To determine the therapeutic benefits of fenofibrate(Feno)on the dysfunction of high glucose(HG)-induced human retinal microvascular endothelial cells(HRMECs)and to elucidate the underlying molecular mechanism.METHODS:HRMEC dysfunction model was established by 48h glucose(30 mmol/L)treatment and treated with Feno/NOD-like receptor thermal protein domain associated protein 3(NLRP3)inflammasome activator(Nigericin).Cell viability/apoptosis were assessed by cell counting kit-8(CCK-8)/terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay(TUNEL)staining and flow cytometry assays.Levels of apoptosis-(Bcl-2-associated X protein,Bax/B-cell lymphoma 2,Bcl-2),vascular permeability-(vascular endothelial growth factor,VEGF)and inflammasome activation-related proteins(NLRP3/cleaved caspase-1/apoptosis-associated speck-like protein containing a CARD,ASC),as well as inflammatory factors(interleukin,IL-6/IL-1β/tumor necrosis factor,TNF-α/IL-18)were determined with Western blot/enzyme linked immunosorbent assay(ELISA).Cell permeability/reactive oxygen species(ROS)level/superoxide dismutase(SOD)activity/malondialdehyde(MDA)content were assessed by Evans blue staining/2',7'-dichlorodihydrofluorescein diacetate(DCFH-DA)fluorescent probe/SOD kit/MDA kit.RESULTS:HRMEC dysfunction was successfully induced by HG,evidenced by decreased viability(P<0.001),increased apoptosis(P<0.001),permeability(P<0.001),and inflammatory factor levels(P<0.001).Feno treatment significantly ameliorated HG-induced HRMEC dysfunction(P<0.01).Meanwhile,HG induction increased ROS production(P<0.001)and MDA content(P<0.001)in HRMECs,while reducing SOD activity(P<0.001),indicative of oxidative stress.This was,however,abolished by Feno(P<0.05).Moreover,Feno eliminated activation of NLRP3 inflammasomes(P<0.05)in HG-induced HRMECs.Strikingly,activation of NLRP3 inflammasomes partially averted the inhibition of Feno on HG-induced HRMEC dysfunction(P<0.05).CONCLUSION:Feno represses oxidative stress and NLRP3 inflammasome activation,consequently alleviating HG-induced HRMEC dysfunction.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
In patients with Alzheimer’s disease,gamma-glutamyl transferase 5(GGT5)expression has been observed to be downregulated in cerebrovascular endothelial cells.However,the functional role of GGT5 in the development of A...In patients with Alzheimer’s disease,gamma-glutamyl transferase 5(GGT5)expression has been observed to be downregulated in cerebrovascular endothelial cells.However,the functional role of GGT5 in the development of Alzheimer’s disease remains unclear.This study aimed to explore the effect of GGT5 on cognitive function and brain pathology in an APP/PS1 mouse model of Alzheimer’s disease,as well as the underlying mechanism.We observed a significant reduction in GGT5 expression in two in vitro models of Alzheimer’s disease(Aβ_(1-42)-treated hCMEC/D3 and bEnd.3 cells),as well as in the APP/PS1 mouse model.Additionally,injection of APP/PS1 mice with an adeno-associated virus encoding GGT5 enhanced hippocampal synaptic plasticity and mitigated cognitive deficits.Interestingly,increasing GGT5 expression in cerebrovascular endothelial cells reduced levels of both soluble and insoluble amyloid-βin the brains of APP/PS1 mice.This effect may be attributable to inhibition of the expression ofβ-site APP cleaving enzyme 1,which is mediated by nuclear factor-kappa B.Our findings demonstrate that GGT5 expression in cerebrovascular endothelial cells is inversely associated with Alzheimer’s disease pathogenesis,and that GGT5 upregulation mitigates cognitive deficits in APP/PS1 mice.These findings suggest that GGT5 expression in cerebrovascular endothelial cells is a potential therapeutic target and biomarker for Alzheimer’s disease.展开更多
Objective To investigate the structural changes of rat thoracic aorta and changes in expression levels of Bmal1 and cyclins in thoracic aorta endothelial cells following heat stress.Methods Twenty male SD rats were ra...Objective To investigate the structural changes of rat thoracic aorta and changes in expression levels of Bmal1 and cyclins in thoracic aorta endothelial cells following heat stress.Methods Twenty male SD rats were randomized equally into control group and heat stress group.After exposure to 32℃for 2 weeks in the latter group,the rats were examined for histopathological changes and Bmal1 expression in the thoracic aorta using HE staining and immunohistochemistry.In the cell experiments,cultured rat thoracic aortic endothelial cells(RTAECs)were incubated at 40℃for 12 h with or without prior transfection with a Bmal1-specific small interfering RNA(si-Bmal1)or a negative sequence.In both rat thoracic aorta and RTAECs,the expressions of Bmal1,the cell cycle proteins CDK1,CDK4,CDK6,and cyclin B1,and apoptosis-related proteins Bax and Bcl-2 were detected using Western blotting.TUNEL staining was used to detect cell apoptosis in rat thoracic aorta,and the changes in cell cycle distribution and apoptosis in RTAECs were analyzed with flow cytometry.Results Compared with the control rats,the rats exposed to heat stress showed significantly increased blood pressures and lowered heart rate with elastic fiber disruption and increased expressions of Bmal1,cyclin B1 and CDK1 in the thoracic aorta(P<0.05).In cultured RTAECs,heat stress caused significant increase of Bmal1,cyclin B1 and CDK1 protein expression levels,which were obviously lowered in cells with prior si-Bmal1 transfection.Bmal1 knockdown also inhibited heat stress-induced increase of apoptosis in RTAECs as evidenced by decreased expression of Bax and increased expression of Bcl-2.Conclusion Heat stress upregulates Bmal1 expression and causes alterations in expressions of cyclins to trigger apoptosis of rat thoracic aorta endothelial cells,which can be partly alleviated by suppressing Bmal1 expression.展开更多
In the version of the article initially published,in Figure 6,the image of the kidney from mice treated with the CD31-PILs-AUF1 group was inadvertently used.The updated images were listed below.The authors declared th...In the version of the article initially published,in Figure 6,the image of the kidney from mice treated with the CD31-PILs-AUF1 group was inadvertently used.The updated images were listed below.The authors declared that this error does not change any of the descriptions or conclusions in the article.展开更多
Background:Fluorescein is commonly used in ophthalmology for the assessment of ocular surface integrity.There have been limited studies on the effects of fluorescein on corneal endothelial cells.This study aims to ass...Background:Fluorescein is commonly used in ophthalmology for the assessment of ocular surface integrity.There have been limited studies on the effects of fluorescein on corneal endothelial cells.This study aims to assess the effect of the widely used fluorescein dye on human corneal endothelial cells(HCEnCs)in vitro at different concentrations and exposure times.Methods:B4G12,an immortalized human corneal endothelium cell line was cultured on pre-coated tissue culture flask with human endothelial-serum free medium(SFM)supplemented with 10 ng/mL basic fibroblast growth factor(bFGF).The fully confluent B4G12 cell monolayers in 96 well plates were treated with water as control,or fluorescein at various concentrations and exposure times.Cell viability was assessed using two techniques:Alamar Blue assay and cell morphology assessment with an inverted phase-contrast microscopy.Results:Short-term exposure to fluorescein(0.01-0.2%)for up to 30 minutes did not affect cell viability.Continuous fluorescein exposure however significantly reduced the viability of the cells with a notable reduction in cell metabolic activity with fluorescein treatments of 0.001%,0.01% and 0.05% for 1 day(and up to 4 days).Conclusions:Short-term exposure to fluorescein for up to 30 minutes in concentrations commonly used in clinical practice did not affect HCEnC viability.However,fluorescein exposure for longer durations can be detrimental to corneal endothelial cell health.Future studies should evaluate the effects of longer-term fluorescein exposure on endothelial function especially in susceptible patients including the elderly and patients with epithelial defects that enable diffusion of fluorescein towards the endothelium.展开更多
AIM:To assess tomographic changes and subclinical edema detection in Fuchs’endothelial corneal dystrophy(FECD)through Scheimpflug tomography in a group of phakic patients contemplating cataract surgery.METHODS:A retr...AIM:To assess tomographic changes and subclinical edema detection in Fuchs’endothelial corneal dystrophy(FECD)through Scheimpflug tomography in a group of phakic patients contemplating cataract surgery.METHODS:A retrospective study was conducted on 30 phakic eyes from patients diagnosed with FECD but without clinical edema,and 59 phakic eyes from a control group without corneal alterations.Comprehensive ophthalmic examinations were conducted,including slitlamp biomicroscopy,corneal specular microscopy(CSM),and Scheimpflug tomography.RESULTS:The study encompassed 30 phakic eyes with FECD(mean age 59.8±13.1y)and 59 control eyes(mean age 61.3±7.7y).The best-corrected visual acuity was higher in the control group compared to the FECD group[0(0,0.08)vs 0.05(0,0.15)logMAR;P=0.042].CSM revealed significant differences between the FECD and control groups in several parameters:number of analyzed cells(26±13 vs 135±42,P<0.001),cell density(2049±376 vs 2479±225 cells/mm2,P<0.001),mean cell area[463(434,544)vs 397(383,431)μm2;P<0.001],coefficient of variation(54.8%±18.7%vs 41.0%±7.2%,P<0.001),and hexagonal cells[0(0,47%)vs 47%(40%,53%),P<0.001].Although often used as a clinical parameter for detecting edema,central corneal thickness measured by CSM showed no significant difference between the FECD and control groups(530±57 vs 546±30μm,P=0.179).Significant differences were noted in various Pentacam measurements between the groups.Specifically,parameters like loss of parallel isopachs(13 vs 0 eyes,P<0.001),displacement of the thinnest point(11 vs 0 eyes,P<0.001),posterior focal depression(25 vs 7 eyes,P<0.001),and increased light scatter[21.4(17.6;23.9)vs 18.0(16.8,21.8),P=0.01]were significantly more prevalent in FECD eyes,reflecting the presence of subclinical edema and loss of corneal transparency.CONCLUSION:Scheimpflug tomography allows for an objective assessment of FECD,offering the capability to detect subclinical edema at an early stage,monitor disease progression,and serve as a predictor of corneal decompensation following cataract surgery.展开更多
BACKGROUND:The present study aims to investigate whether mannitol facilitates central nervous system(CNS) entry of vancomycin and alleviates methicillin-resistant Staphylococcus aureus(MRSA)intracranial infection.METH...BACKGROUND:The present study aims to investigate whether mannitol facilitates central nervous system(CNS) entry of vancomycin and alleviates methicillin-resistant Staphylococcus aureus(MRSA)intracranial infection.METHODS:Blood-brain barrier(BBB) permeability was assessed by measuring the concentration of sodium fl uorescein(NaF) in the brain tissues of rats and fl uorescein isothiocyanate-dextran(FITC-dextran)in a single-cell layer model.Neutrophil infiltration in the brain tissue,inflammatory cytokine levels in the serum,neurological function,and 7-day survival rates were used to evaluate therapeutic eff ects of mannitol and vancomycin in MRSA-infected rats.Syndecan-1 and fi lamentous actin(F-actin) levels were measured,and the relationship between F-actin and the endothelial glycocalyx layer(EGL) was explored via the depolymerization agent cytochalasin D and the polymerization agent jasplakinolide.RESULTS:Following mannitol administration,the NaF and vancomycin concentrations in the brain tissue increased rapidly within 5 min and remained stable for 30 min,indicating that mannitol increased BBB permeability for 30 min.In vitro,mannitol treatment led to significantly greater FITC-dextran permeation through a single-cell layer compared to controls.In the MRSA intracranial infection model,rats treated with mannitol and vancomycin simultaneously presented less infl ammation,improved neurological function,and increased 7-day survival rate compared to rats treated with vancomycin and mannitol at 10-hour intervals.Further experiments revealed that mannitol decreased the expression of syndecan-1 in brain tissues,which was confi rmed by in vitro experiments showing that mannitol signifi cantly decreased syndecan-1 via F-actin depolymerization.CONCLUSION:Mannitol may enhance the therapeutic effi cacy of vancomycin against intracranial MRSA infection by decreasing the endothelial glycocalyx of the BBB via F-actin depolymerization.展开更多
Liver cancer is the sixth most common cancer and the third leading cause of cancer death worldwide.The predominant type of primary liver cancer is hepatocellular carcinoma(HCC).Tumor vascular endothelial cells(VECs),a...Liver cancer is the sixth most common cancer and the third leading cause of cancer death worldwide.The predominant type of primary liver cancer is hepatocellular carcinoma(HCC).Tumor vascular endothelial cells(VECs),a major component of cells in the microenvironment of HCC,play multifaceted roles in contributing to tumor angiogenesis,proliferation,and migration,as well as therapeutic resistance by attracting myeloid-derived suppressor cells and suppressing cytotoxic CD8 T cell differentiation and function.Recently,Wu et al reported that apatinib,an inhibitor of vascular endothelial growth factor receptor 2,can inhibit tumor VEC glycolysis by regulating phosphatidylinositol 3-kinase/protein kinase B/6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 signaling pathway to suppress HCC progression.With great interest,this editorial paper aims to review the function and key molecular signaling pathways of tumor VECs in HCC initiation and progression and summarize potential treatment options in clinical trials.展开更多
AIM:To compare analysis of the impact of high altitude on corneal endothelial cells,and the prognosis in patients with cataract surgeries.METHODS:Totally 265 plateau patients with cataract surgeries performed between ...AIM:To compare analysis of the impact of high altitude on corneal endothelial cells,and the prognosis in patients with cataract surgeries.METHODS:Totally 265 plateau patients with cataract surgeries performed between January 2019 and July 2022(average altitude=3000 m),and 524 plain patients with cataract surgeries performed between January 2020 and July 2022 were included.The propensity score matching(PSM)method was applied to match the basic information of patients in both regions on a 1:1 basis.Corneal endothelial cell density(ECD),coefficient of variation(CV),hexagonal cell ratio(HEX),duration of surgery,and pre-and postoperative visual acuity(VA)were compared retrospectively,and correlation tests were done.RESULTS:Totally 223 pairs have been matched successfully.The HEX in the plateau group was higher than that in the plain group(61.95%±6.191%vs 44.91%±6.829%,P<0.001).For ECD and CV,no significant differences were observed between both groups(P>0.1).The pre-and postoperative VA of patients with cataract surgeries in the plateau group were lower(1.40±0.610 vs 0.71±0.514,P<0.001&0.68±0.479 vs 0.18±0.259,P<0.001),and the duration of surgery was longer than those in the plain group(27.06±14.900 min vs 16.03±8.033 min,P<0.001).No significant associations were found between the post-operative VA and the corneal endothelial parameters(P>0.05),while the post-operative VA was significantly related to the pre-operative VA and the duration of surgery(P<0.05).CONCLUSION:The relative hypoxic environment of the plateau does not promote the apoptosis of corneal endothelial cells,but may lead to the compensatory increase of their functions.In plateau patients,no significant associations are found between the poor VA and the corneal endothelial functions early after cataract surgeries.展开更多
Nano-plastics,emerging pollutants in the environment,have raised global concern due to their widespread presence in daily life and the potential toxicity to human health.Upon entering human body,nano-plastics can read...Nano-plastics,emerging pollutants in the environment,have raised global concern due to their widespread presence in daily life and the potential toxicity to human health.Upon entering human body,nano-plastics can readily interact with vascular endothelial cells within the bloodstream,potentially leading to endothelial dysfunction.However,our understanding of the toxic impact of nano-plastics on vascular endothelial cells remains insufficient,and the underlying mechanism are yet to be elucidated.This study investigated the toxicological effects of nano-plastics on EA.hy 926 endothelial cells.Exposure to different types of nano-plastics such as polystyrene(PS),amino-modified PS or carboxyl-modified PS,resulted in suppress cell activity,damage to the cell membrane,oxidative stress and significantly inhibit cell migration.RNA sequencing(RNA-seq)and small RNA-seq analyses revealed that numbers of genes and miRNAs were differentially expressed after nano-plastics treatment.CEBPB,a gene within the inflammation-related tumor necrosis factor signaling pathway,was confirmed to be a target of miR-1908-5p,indicating that nano-plastics induced activation of CEBPB might promote inflammatory injury to vascular endothelial cells.These results enhance our understanding of the biological effects of nano-plastics and their potential impact on inflammation injury.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
AIM:To assess the corneal biometric parameters and endothelial cell characteristics in microcornea patients,and exploring their correlations.METHODS:This cross-sectional study included 28 patients of microcornea with ...AIM:To assess the corneal biometric parameters and endothelial cell characteristics in microcornea patients,and exploring their correlations.METHODS:This cross-sectional study included 28 patients of microcornea with uveal coloboma(MCUC),13 patients of microcornea without coloboma(MCNC),and 30 age-matched healthy individuals(the control group).Corneal biometric parameters such as axial length(AL),anterior chamber depth(ACD),and white-to-white corneal diameter(WTW)were measured using the IOL Master.The corneal endothelial cell density(ECD),percentage of hexagonal cells(6A),average cell area(AVE),maximum cell area(MAX),minimum cell area(MIN),cell area standard deviation(SD),and coefficient of variation(CV)were collected by specular microscopy.RESULTS:This study included MCUC and MCNC patients with age-and sex-matched controls.All patients exhibited significantly reduced WTW(MCUC:8.51±0.71 mm;MCNC:9.08±0.42 mm)and worse logMAR BCVA(MCUC 0.62±0.43;MCNC 0.46±0.28)compared to controls(both P<0.001).The ECD was 3106.32±336.80 cells/mm²in the MCUC group and 2906.92±323.53 cells/mm²in the MCNC group,both significantly higher than the control group(2647.43±203.06 cells/mm²,P<0.05).In contrast,the CV,AVE,SD,and ACD in the MCUC and MCNC groups were significantly lower compared to controls(P<0.01).In patients with microcornea,the WTW was negatively correlated with the ECD and 6A,but positively with the CV,MAX,AVE,and SD.The ACD was negatively linked to the ECD,but positively to the AVE.CONCLUSION:The corneal ECD and 6A are increased,while the CV is decreased in patients with microcornea,particularly in those accompanied by uveal coloboma.The ECD and morphology demonstrate close correlations with the WTW and ACD.展开更多
Objective To elucidate the regulatory mechanism of circRNAs in diabetic retinopathy.Methods Next-generation sequencing(NGS)was employed to identify circRNAs that are abnormally expressed in endothe-lial progenitor cel...Objective To elucidate the regulatory mechanism of circRNAs in diabetic retinopathy.Methods Next-generation sequencing(NGS)was employed to identify circRNAs that are abnormally expressed in endothe-lial progenitor cells(EPCs)under hyperglycemia(HG)conditions.The regulatory mechanism and predicted targets of this circRNA were also studied via bioinformatics analysis,luciferase reporter assays,angiogenic differentiation experiments,flow cytometry,and RT-qPCR.Results Circ-astrotactin 1(circ-Astn1)expression was decreased in EPCs under HG conditions,and circ-Astn1 overexpres-sion inhibited HG-induced endothelial damage.The miR-138-5p and silencing information regulator 2 related enzyme 1(SIRT1)were identified as circ-Astn1 downstream targets,which were further verified through luciferase reporter assays.SIRT1 silencing or miR-138-5p overexpression reversed the protective effect of circ-Astn1 on HG-induced endothelial cell dysfunction,as evidenced by increased apoptosis,abnormal vascular differentiation,and inflammatory factor secretion.SIRT1 overexpression reversed miR-138-5p-induced endothelial cell dysfunction under HG conditions.In vivo experiments confirmed that circ-Astnl overexpression promoted skin wound healing through the regulation of SIRT1.Conclusions These findings suggest that circ-Astn1 promotes SIRT1 expression by sponging miR-138-5p.Circ-Astn1 over-expression suppresses HG-induced endothelial cell damage via miR-138-5p/SIRT1 axis.展开更多
基金supported by the National Natural Science Foundation of China(Grant Nos.:32171124,31871156,31971101,32271180,82272229,and 81471852)Hunan Provincial Natural Science Foundation of China(Grant No.:2021JJ31058).
文摘Repairing the endothelial barrier is essential for maintaining pulmonary fuid balance and regulating leukocyte infiltration during sepsis[1].Tissue kallikrein-related peptidases(KLKs)are secreted serine proteases involved in angiogenesis[2].However,their involvement in regulating endothelial regeneration remains largely unknown.
基金supported by the National Natural Science Foundation of China,Nos.82404892(to QY),82061160374(to ZZ)the Science and Technology Development Fund,Macao Special Administrative Region,China,Nos.0023/2020/AFJ,0035/2020/AGJ+2 种基金the University of Macao Research Grant,Nos.MYRG2022-00248-ICMS,MYRG-CRG2022-00010-ICMS(to MPMH)the Natural Science Foundation of Guangdong Province,No.2024A1515012818(to ZZ)the Fundamental Research Funds for the Central Universities,No.21623114(to ZZ).
文摘Drug development for Alzheimer’s disease is extremely challenging,as demonstrated by the repeated failures of amyloid-β-targeted therapeutics and the controversies surrounding the amyloid-βcascade hypothesis.More recently,advances in the development of Lecanemab,an anti-amyloid-βmonoclonal antibody,have shown positive results in reducing brain A burden and slowing cognitive decline in patients with early-stage Alzheimer’s disease in the Phase Ⅲ clinical trial(Clarity Alzheimer’s disease).Despite these promising results,side effects such as amyloid-related imaging abnormalities(ARIA)may limit its usage.ARIA can manifest as ARIA-E(cerebral edema or effusions)and ARIA-H(microhemorrhages or superficial siderosis)and is thought to be caused by increased vascular permeability due to inflammatory responses,leading to leakages of blood products and protein-rich fluid into brain parenchyma.Endothelial dysfunction is an early pathological feature of Alzheimer’s disease,and the blood-brain barrier becomes increasingly leaky as the disease progresses.In addition,APOE4,the strongest genetic risk factor for Alzheimer’s disease,is associated with higher vascular amyloid burden,increased ARIA incidence,and accelerated blood-brain barrier disruptions.These interconnected vascular abnormalities highlight the importance of vascular contributions to the pathophysiology of Alzheimer’s disease.Here,we will closely examine recent research evaluating the heterogeneity of brain endothelial cells in the microvasculature of different brain regions and their relationships with Alzheimer’s disease progression.
文摘Introduction Fuchs endothelial corneal dystrophy(FECD)is an inherited,degenerative disease of the corneal endothelial cells(CECs).It is characterized by a progressive deterioration of endothelial cells,altered extracellular matrix(ECM)production,and development of guttae(1,2).The presence of guttae has been shown to significantly impair corneal endothelial function,leading to corneal oedema and visual impairment.
基金supported by the NIH grants,R01 NS111801(to ZGZ)American Heart Association 16SDG29860003(to YZ)。
文摘Axonal remodeling is a critical aspect of ischemic brain repair processes and contributes to spontaneous functional recovery.Our previous in vitro study demonstrated that exosomes/small extracellular vesicles(sEVs)isolated from cerebral endothelial cells(CEC-sEVs)of ischemic brain promote axonal growth of embryonic cortical neurons and that microRNA 27a(miR-27a)is an elevated miRNA in ischemic CEC-sEVs.In the present study,we investigated whether normal CEC-sEVs engineered to enrich their levels of miR-27a(27a-sEVs)further enhance axonal growth and improve neurological outcomes after ischemic stroke when compared with treatment with non-engineered CEC-sEVs.27a-sEVs were isolated from the conditioned medium of healthy mouse CECs transfected with a lentiviral miR-27a expression vector.Small EVs isolated from CECs transfected with a scramble vector(Scra-sEVs)were used as a control.Adult male mice were subjected to permanent middle cerebral artery occlusion and then were randomly treated with 27a-sEVs or Scra-sEVs.An array of behavior assays was used to measure neurological function.Compared with treatment of ischemic stroke with Scra-sEVs,treatment with 27a-sEVs significantly augmented axons and spines in the peri-infarct zone and in the corticospinal tract of the spinal grey matter of the denervated side,and significantly improved neurological outcomes.In vitro studies demonstrated that CEC-sEVs carrying reduced miR-27a abolished 27a-sEV-augmented axonal growth.Ultrastructural analysis revealed that 27a-sEVs systemically administered preferentially localized to the pre-synaptic active zone,while quantitative reverse transcription-polymerase chain reaction and Western Blot analysis showed elevated miR-27a,and reduced axonal inhibitory proteins Semaphorin 6A and Ras Homolog Family Member A in the peri-infarct zone.Blockage of the Clathrin-dependent endocytosis pathway substantially reduced neuronal internalization of 27a-sEVs.Our data provide evidence that 27a-sEVs have a therapeutic effect on stroke recovery by promoting axonal remodeling and improving neurological outcomes.Our findings also suggest that suppression of axonal inhibitory proteins such as Semaphorin 6A may contribute to the beneficial effect of 27a-sEVs on axonal remodeling.
文摘The endothelium modulates vascular homeostasis owing to a variety of vasoconstrictors and vasodilators.Endothelial dysfunction(ED),characterized by impaired vasodilation,inflammation,and thrombosis,triggers future cardiovascular(CV)diseases.Chronic kidney disease,a state of chronic inflammation caused by oxidative stress,metabolic abnormalities,infection,and uremic toxins damages the endothelium.ED is also associated with a decline in estimated glomerular filtration rate.After kidney transplantation,endothelial functions undergo immediate but partial restoration,promising graft longevity and enhanced CV health.However,the anticipated CV outcomes do not happen due to various transplant-related and unrelated risk factors for ED,culminating in poor CV health and graft survival.ED in kidney transplant recipients is an underrecognized and poorly studied entity.CV diseases are the leading cause of death among kidney transplant candidates with functioning grafts.ED contributes to the pathogenesis of many of the CV diseases.Various biomarkers and vasoreactivity tests are available to study endothelial functions.With an increasing number of transplants happening every year,and improved graft rejection rates due to the availability of effective immunosuppressants,the focus has now shifted to endothelial protection for the prevention,early recognition,and treatment of CV diseases.
基金Supported by Youth Cultivation Research Program of Beijing Road Medical Area,Xinjiang Military Region General Hospital,Xinjiang,China(No.2022jzbj105)Science and Technology Program of Urumqi Municipal Health and Wellness Commission(No.202360).
文摘AIM:To assess the relationship between serological parameters and the prognosis of young patients with retinal vein occlusion(RVO)after intravitreal conbercept injection(IVC).METHODS:This study enrolled 100 young patients(≤50 years old)diagnosed with RVO-related macular edema(RVO-ME)who had been undergoing IVC at the 474 Hospital in Xinjiang between January 2022 and October 2023.Patients were categorized into two groups:70 eyes in the effective group and 30 eyes in the ineffective group.The effective group comprised patients exhibiting a visual acuity improvement of≥2 lines at the last follow-up,with resolved ME and central macular thickness(CMT)<300μm.Conversely,the ineffective group included patients with visual acuity improvement of<1 line,persistent ME,and CMT≥300μm at the last follow-up.Serological parameters,including white blood cell count,neutrophil count,lymphocyte count,monocyte count,and mean platelet volume were assessed before treatment.The correlation between bestcorrected visual acuity(BCVA)and neutrophil-to-lymphocyte ratio(NLR),platelet-to-lymphocyte ratio(PLR),systemic immune inflammation index(SII),and systemic immune response index(SIRI)was analyzed.Additionally,the association between these serological parameters and the efficacy of IVC was explored.RESULTS:Three months after treatment,the effective group demonstrated a significant improvement in BCVA from 0.82±0.20 to 0.36±0.10,with a concurrent decrease in CMT from 661.28±163.90 to 200.61±82.45μm(P<0.001).Conversely,the ineffective group exhibited minimal changes in BCVA(0.86±0.25 to 0.82±0.14)and CMT(669.84±164.95 to 492.13±138.67μm,P<0.001).The differences in BCVA and CMT between the two groups were statistically significant(P<0.001).According to subgroup analysis,in patients with central RVO(CRVO),BCVA improved from 0.82±0.23 to 0.49±0.12 in the effective group and from 0.80±0.18 to 0.76±0.22 in the ineffective group(P<0.001).The CMT changes followed a similar pattern.In patients with branch RVO(BRVO),comparable trends in BCVA and CMT changes were observed between the effective and ineffective groups(P<0.001).Additionally,the effective group exhibited higher PLR and SII values than the ineffective group(P<0.05).Further CRVO and BRVO subgroups analysis exhibited consistent PLR and SII value trends.CONCLUSION:Compared to other inflammatory factors,elevated PLR and SII levels before treatment are better predictors of outcomes in young RVO-ME patients undergoing IVC treatment.
基金Supported by grants from the Tianjin Key Medical Discipline(Specialty)Construction Project(No.TJYXZDXK-037A).
文摘AIM:To determine the therapeutic benefits of fenofibrate(Feno)on the dysfunction of high glucose(HG)-induced human retinal microvascular endothelial cells(HRMECs)and to elucidate the underlying molecular mechanism.METHODS:HRMEC dysfunction model was established by 48h glucose(30 mmol/L)treatment and treated with Feno/NOD-like receptor thermal protein domain associated protein 3(NLRP3)inflammasome activator(Nigericin).Cell viability/apoptosis were assessed by cell counting kit-8(CCK-8)/terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay(TUNEL)staining and flow cytometry assays.Levels of apoptosis-(Bcl-2-associated X protein,Bax/B-cell lymphoma 2,Bcl-2),vascular permeability-(vascular endothelial growth factor,VEGF)and inflammasome activation-related proteins(NLRP3/cleaved caspase-1/apoptosis-associated speck-like protein containing a CARD,ASC),as well as inflammatory factors(interleukin,IL-6/IL-1β/tumor necrosis factor,TNF-α/IL-18)were determined with Western blot/enzyme linked immunosorbent assay(ELISA).Cell permeability/reactive oxygen species(ROS)level/superoxide dismutase(SOD)activity/malondialdehyde(MDA)content were assessed by Evans blue staining/2',7'-dichlorodihydrofluorescein diacetate(DCFH-DA)fluorescent probe/SOD kit/MDA kit.RESULTS:HRMEC dysfunction was successfully induced by HG,evidenced by decreased viability(P<0.001),increased apoptosis(P<0.001),permeability(P<0.001),and inflammatory factor levels(P<0.001).Feno treatment significantly ameliorated HG-induced HRMEC dysfunction(P<0.01).Meanwhile,HG induction increased ROS production(P<0.001)and MDA content(P<0.001)in HRMECs,while reducing SOD activity(P<0.001),indicative of oxidative stress.This was,however,abolished by Feno(P<0.05).Moreover,Feno eliminated activation of NLRP3 inflammasomes(P<0.05)in HG-induced HRMECs.Strikingly,activation of NLRP3 inflammasomes partially averted the inhibition of Feno on HG-induced HRMEC dysfunction(P<0.05).CONCLUSION:Feno represses oxidative stress and NLRP3 inflammasome activation,consequently alleviating HG-induced HRMEC dysfunction.
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 STI2030-Major Projects,No.2021ZD 0201801(to JG)Shanxi Province Basic Research Program,No.20210302123429(to QS).
文摘In patients with Alzheimer’s disease,gamma-glutamyl transferase 5(GGT5)expression has been observed to be downregulated in cerebrovascular endothelial cells.However,the functional role of GGT5 in the development of Alzheimer’s disease remains unclear.This study aimed to explore the effect of GGT5 on cognitive function and brain pathology in an APP/PS1 mouse model of Alzheimer’s disease,as well as the underlying mechanism.We observed a significant reduction in GGT5 expression in two in vitro models of Alzheimer’s disease(Aβ_(1-42)-treated hCMEC/D3 and bEnd.3 cells),as well as in the APP/PS1 mouse model.Additionally,injection of APP/PS1 mice with an adeno-associated virus encoding GGT5 enhanced hippocampal synaptic plasticity and mitigated cognitive deficits.Interestingly,increasing GGT5 expression in cerebrovascular endothelial cells reduced levels of both soluble and insoluble amyloid-βin the brains of APP/PS1 mice.This effect may be attributable to inhibition of the expression ofβ-site APP cleaving enzyme 1,which is mediated by nuclear factor-kappa B.Our findings demonstrate that GGT5 expression in cerebrovascular endothelial cells is inversely associated with Alzheimer’s disease pathogenesis,and that GGT5 upregulation mitigates cognitive deficits in APP/PS1 mice.These findings suggest that GGT5 expression in cerebrovascular endothelial cells is a potential therapeutic target and biomarker for Alzheimer’s disease.
文摘Objective To investigate the structural changes of rat thoracic aorta and changes in expression levels of Bmal1 and cyclins in thoracic aorta endothelial cells following heat stress.Methods Twenty male SD rats were randomized equally into control group and heat stress group.After exposure to 32℃for 2 weeks in the latter group,the rats were examined for histopathological changes and Bmal1 expression in the thoracic aorta using HE staining and immunohistochemistry.In the cell experiments,cultured rat thoracic aortic endothelial cells(RTAECs)were incubated at 40℃for 12 h with or without prior transfection with a Bmal1-specific small interfering RNA(si-Bmal1)or a negative sequence.In both rat thoracic aorta and RTAECs,the expressions of Bmal1,the cell cycle proteins CDK1,CDK4,CDK6,and cyclin B1,and apoptosis-related proteins Bax and Bcl-2 were detected using Western blotting.TUNEL staining was used to detect cell apoptosis in rat thoracic aorta,and the changes in cell cycle distribution and apoptosis in RTAECs were analyzed with flow cytometry.Results Compared with the control rats,the rats exposed to heat stress showed significantly increased blood pressures and lowered heart rate with elastic fiber disruption and increased expressions of Bmal1,cyclin B1 and CDK1 in the thoracic aorta(P<0.05).In cultured RTAECs,heat stress caused significant increase of Bmal1,cyclin B1 and CDK1 protein expression levels,which were obviously lowered in cells with prior si-Bmal1 transfection.Bmal1 knockdown also inhibited heat stress-induced increase of apoptosis in RTAECs as evidenced by decreased expression of Bax and increased expression of Bcl-2.Conclusion Heat stress upregulates Bmal1 expression and causes alterations in expressions of cyclins to trigger apoptosis of rat thoracic aorta endothelial cells,which can be partly alleviated by suppressing Bmal1 expression.
文摘In the version of the article initially published,in Figure 6,the image of the kidney from mice treated with the CD31-PILs-AUF1 group was inadvertently used.The updated images were listed below.The authors declared that this error does not change any of the descriptions or conclusions in the article.
文摘Background:Fluorescein is commonly used in ophthalmology for the assessment of ocular surface integrity.There have been limited studies on the effects of fluorescein on corneal endothelial cells.This study aims to assess the effect of the widely used fluorescein dye on human corneal endothelial cells(HCEnCs)in vitro at different concentrations and exposure times.Methods:B4G12,an immortalized human corneal endothelium cell line was cultured on pre-coated tissue culture flask with human endothelial-serum free medium(SFM)supplemented with 10 ng/mL basic fibroblast growth factor(bFGF).The fully confluent B4G12 cell monolayers in 96 well plates were treated with water as control,or fluorescein at various concentrations and exposure times.Cell viability was assessed using two techniques:Alamar Blue assay and cell morphology assessment with an inverted phase-contrast microscopy.Results:Short-term exposure to fluorescein(0.01-0.2%)for up to 30 minutes did not affect cell viability.Continuous fluorescein exposure however significantly reduced the viability of the cells with a notable reduction in cell metabolic activity with fluorescein treatments of 0.001%,0.01% and 0.05% for 1 day(and up to 4 days).Conclusions:Short-term exposure to fluorescein for up to 30 minutes in concentrations commonly used in clinical practice did not affect HCEnC viability.However,fluorescein exposure for longer durations can be detrimental to corneal endothelial cell health.Future studies should evaluate the effects of longer-term fluorescein exposure on endothelial function especially in susceptible patients including the elderly and patients with epithelial defects that enable diffusion of fluorescein towards the endothelium.
文摘AIM:To assess tomographic changes and subclinical edema detection in Fuchs’endothelial corneal dystrophy(FECD)through Scheimpflug tomography in a group of phakic patients contemplating cataract surgery.METHODS:A retrospective study was conducted on 30 phakic eyes from patients diagnosed with FECD but without clinical edema,and 59 phakic eyes from a control group without corneal alterations.Comprehensive ophthalmic examinations were conducted,including slitlamp biomicroscopy,corneal specular microscopy(CSM),and Scheimpflug tomography.RESULTS:The study encompassed 30 phakic eyes with FECD(mean age 59.8±13.1y)and 59 control eyes(mean age 61.3±7.7y).The best-corrected visual acuity was higher in the control group compared to the FECD group[0(0,0.08)vs 0.05(0,0.15)logMAR;P=0.042].CSM revealed significant differences between the FECD and control groups in several parameters:number of analyzed cells(26±13 vs 135±42,P<0.001),cell density(2049±376 vs 2479±225 cells/mm2,P<0.001),mean cell area[463(434,544)vs 397(383,431)μm2;P<0.001],coefficient of variation(54.8%±18.7%vs 41.0%±7.2%,P<0.001),and hexagonal cells[0(0,47%)vs 47%(40%,53%),P<0.001].Although often used as a clinical parameter for detecting edema,central corneal thickness measured by CSM showed no significant difference between the FECD and control groups(530±57 vs 546±30μm,P=0.179).Significant differences were noted in various Pentacam measurements between the groups.Specifically,parameters like loss of parallel isopachs(13 vs 0 eyes,P<0.001),displacement of the thinnest point(11 vs 0 eyes,P<0.001),posterior focal depression(25 vs 7 eyes,P<0.001),and increased light scatter[21.4(17.6;23.9)vs 18.0(16.8,21.8),P=0.01]were significantly more prevalent in FECD eyes,reflecting the presence of subclinical edema and loss of corneal transparency.CONCLUSION:Scheimpflug tomography allows for an objective assessment of FECD,offering the capability to detect subclinical edema at an early stage,monitor disease progression,and serve as a predictor of corneal decompensation following cataract surgery.
基金supported by the National Natural Science Foundation for Young Scientists of China (grant no.2002074)the Natural Science Foundation of Guangdong Province(2023A1515010267, 2023A1515012665, 2024A1515010073)+1 种基金the China International Medical Foundation Cerebrovascular Disease Youth Innovation Fund (Z-2016-20-2201)the Medical Leading Talents Fund of Guangdong Province (KJ012019430)。
文摘BACKGROUND:The present study aims to investigate whether mannitol facilitates central nervous system(CNS) entry of vancomycin and alleviates methicillin-resistant Staphylococcus aureus(MRSA)intracranial infection.METHODS:Blood-brain barrier(BBB) permeability was assessed by measuring the concentration of sodium fl uorescein(NaF) in the brain tissues of rats and fl uorescein isothiocyanate-dextran(FITC-dextran)in a single-cell layer model.Neutrophil infiltration in the brain tissue,inflammatory cytokine levels in the serum,neurological function,and 7-day survival rates were used to evaluate therapeutic eff ects of mannitol and vancomycin in MRSA-infected rats.Syndecan-1 and fi lamentous actin(F-actin) levels were measured,and the relationship between F-actin and the endothelial glycocalyx layer(EGL) was explored via the depolymerization agent cytochalasin D and the polymerization agent jasplakinolide.RESULTS:Following mannitol administration,the NaF and vancomycin concentrations in the brain tissue increased rapidly within 5 min and remained stable for 30 min,indicating that mannitol increased BBB permeability for 30 min.In vitro,mannitol treatment led to significantly greater FITC-dextran permeation through a single-cell layer compared to controls.In the MRSA intracranial infection model,rats treated with mannitol and vancomycin simultaneously presented less infl ammation,improved neurological function,and increased 7-day survival rate compared to rats treated with vancomycin and mannitol at 10-hour intervals.Further experiments revealed that mannitol decreased the expression of syndecan-1 in brain tissues,which was confi rmed by in vitro experiments showing that mannitol signifi cantly decreased syndecan-1 via F-actin depolymerization.CONCLUSION:Mannitol may enhance the therapeutic effi cacy of vancomycin against intracranial MRSA infection by decreasing the endothelial glycocalyx of the BBB via F-actin depolymerization.
文摘Liver cancer is the sixth most common cancer and the third leading cause of cancer death worldwide.The predominant type of primary liver cancer is hepatocellular carcinoma(HCC).Tumor vascular endothelial cells(VECs),a major component of cells in the microenvironment of HCC,play multifaceted roles in contributing to tumor angiogenesis,proliferation,and migration,as well as therapeutic resistance by attracting myeloid-derived suppressor cells and suppressing cytotoxic CD8 T cell differentiation and function.Recently,Wu et al reported that apatinib,an inhibitor of vascular endothelial growth factor receptor 2,can inhibit tumor VEC glycolysis by regulating phosphatidylinositol 3-kinase/protein kinase B/6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 signaling pathway to suppress HCC progression.With great interest,this editorial paper aims to review the function and key molecular signaling pathways of tumor VECs in HCC initiation and progression and summarize potential treatment options in clinical trials.
文摘AIM:To compare analysis of the impact of high altitude on corneal endothelial cells,and the prognosis in patients with cataract surgeries.METHODS:Totally 265 plateau patients with cataract surgeries performed between January 2019 and July 2022(average altitude=3000 m),and 524 plain patients with cataract surgeries performed between January 2020 and July 2022 were included.The propensity score matching(PSM)method was applied to match the basic information of patients in both regions on a 1:1 basis.Corneal endothelial cell density(ECD),coefficient of variation(CV),hexagonal cell ratio(HEX),duration of surgery,and pre-and postoperative visual acuity(VA)were compared retrospectively,and correlation tests were done.RESULTS:Totally 223 pairs have been matched successfully.The HEX in the plateau group was higher than that in the plain group(61.95%±6.191%vs 44.91%±6.829%,P<0.001).For ECD and CV,no significant differences were observed between both groups(P>0.1).The pre-and postoperative VA of patients with cataract surgeries in the plateau group were lower(1.40±0.610 vs 0.71±0.514,P<0.001&0.68±0.479 vs 0.18±0.259,P<0.001),and the duration of surgery was longer than those in the plain group(27.06±14.900 min vs 16.03±8.033 min,P<0.001).No significant associations were found between the post-operative VA and the corneal endothelial parameters(P>0.05),while the post-operative VA was significantly related to the pre-operative VA and the duration of surgery(P<0.05).CONCLUSION:The relative hypoxic environment of the plateau does not promote the apoptosis of corneal endothelial cells,but may lead to the compensatory increase of their functions.In plateau patients,no significant associations are found between the poor VA and the corneal endothelial functions early after cataract surgeries.
基金supported by the National Natural Science Foundation of China(Key Program,No.U22A20550).
文摘Nano-plastics,emerging pollutants in the environment,have raised global concern due to their widespread presence in daily life and the potential toxicity to human health.Upon entering human body,nano-plastics can readily interact with vascular endothelial cells within the bloodstream,potentially leading to endothelial dysfunction.However,our understanding of the toxic impact of nano-plastics on vascular endothelial cells remains insufficient,and the underlying mechanism are yet to be elucidated.This study investigated the toxicological effects of nano-plastics on EA.hy 926 endothelial cells.Exposure to different types of nano-plastics such as polystyrene(PS),amino-modified PS or carboxyl-modified PS,resulted in suppress cell activity,damage to the cell membrane,oxidative stress and significantly inhibit cell migration.RNA sequencing(RNA-seq)and small RNA-seq analyses revealed that numbers of genes and miRNAs were differentially expressed after nano-plastics treatment.CEBPB,a gene within the inflammation-related tumor necrosis factor signaling pathway,was confirmed to be a target of miR-1908-5p,indicating that nano-plastics induced activation of CEBPB might promote inflammatory injury to vascular endothelial cells.These results enhance our understanding of the biological effects of nano-plastics and their potential impact on inflammation injury.
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 National Natural Science Foundation of China(No.82271052No.82201154)+2 种基金Shandong Provincial Key Research and Development Program(No.2024CXGC010617)Taishan Scholar Program(No.tstp20240858)Educational and Teaching Reform Research Project of Shandong First Medical University(No.XM2024001).
文摘AIM:To assess the corneal biometric parameters and endothelial cell characteristics in microcornea patients,and exploring their correlations.METHODS:This cross-sectional study included 28 patients of microcornea with uveal coloboma(MCUC),13 patients of microcornea without coloboma(MCNC),and 30 age-matched healthy individuals(the control group).Corneal biometric parameters such as axial length(AL),anterior chamber depth(ACD),and white-to-white corneal diameter(WTW)were measured using the IOL Master.The corneal endothelial cell density(ECD),percentage of hexagonal cells(6A),average cell area(AVE),maximum cell area(MAX),minimum cell area(MIN),cell area standard deviation(SD),and coefficient of variation(CV)were collected by specular microscopy.RESULTS:This study included MCUC and MCNC patients with age-and sex-matched controls.All patients exhibited significantly reduced WTW(MCUC:8.51±0.71 mm;MCNC:9.08±0.42 mm)and worse logMAR BCVA(MCUC 0.62±0.43;MCNC 0.46±0.28)compared to controls(both P<0.001).The ECD was 3106.32±336.80 cells/mm²in the MCUC group and 2906.92±323.53 cells/mm²in the MCNC group,both significantly higher than the control group(2647.43±203.06 cells/mm²,P<0.05).In contrast,the CV,AVE,SD,and ACD in the MCUC and MCNC groups were significantly lower compared to controls(P<0.01).In patients with microcornea,the WTW was negatively correlated with the ECD and 6A,but positively with the CV,MAX,AVE,and SD.The ACD was negatively linked to the ECD,but positively to the AVE.CONCLUSION:The corneal ECD and 6A are increased,while the CV is decreased in patients with microcornea,particularly in those accompanied by uveal coloboma.The ECD and morphology demonstrate close correlations with the WTW and ACD.
基金supported by grants from the National Natural Science Foundation of China(No.81770483)Shanghai Tenth Hospital’s improvement plan for NSFC(No.04.03.17.070).
文摘Objective To elucidate the regulatory mechanism of circRNAs in diabetic retinopathy.Methods Next-generation sequencing(NGS)was employed to identify circRNAs that are abnormally expressed in endothe-lial progenitor cells(EPCs)under hyperglycemia(HG)conditions.The regulatory mechanism and predicted targets of this circRNA were also studied via bioinformatics analysis,luciferase reporter assays,angiogenic differentiation experiments,flow cytometry,and RT-qPCR.Results Circ-astrotactin 1(circ-Astn1)expression was decreased in EPCs under HG conditions,and circ-Astn1 overexpres-sion inhibited HG-induced endothelial damage.The miR-138-5p and silencing information regulator 2 related enzyme 1(SIRT1)were identified as circ-Astn1 downstream targets,which were further verified through luciferase reporter assays.SIRT1 silencing or miR-138-5p overexpression reversed the protective effect of circ-Astn1 on HG-induced endothelial cell dysfunction,as evidenced by increased apoptosis,abnormal vascular differentiation,and inflammatory factor secretion.SIRT1 overexpression reversed miR-138-5p-induced endothelial cell dysfunction under HG conditions.In vivo experiments confirmed that circ-Astnl overexpression promoted skin wound healing through the regulation of SIRT1.Conclusions These findings suggest that circ-Astn1 promotes SIRT1 expression by sponging miR-138-5p.Circ-Astn1 over-expression suppresses HG-induced endothelial cell damage via miR-138-5p/SIRT1 axis.
