The degree of nerve regeneration after peripheral nerve injury can be altered by the microenvironment at the site of injury. Stem cells and vascularity are postulated to be a part of a complex pathway that enhances pe...The degree of nerve regeneration after peripheral nerve injury can be altered by the microenvironment at the site of injury. Stem cells and vascularity are postulated to be a part of a complex pathway that enhances peripheral nerve regeneration;however, their interaction remains unexplored. This review aims to summarize current knowledge on this interaction, including various mechanisms through which trophic factors are promoted by stem cells and angiogenesis. Angiogenesis after nerve injury is stimulated by hypoxia, mediated by vascular endothelial growth factor, resulting in the growth of preexisting vessels into new areas. Modulation of distinct signaling pathways in stem cells can promote angiogenesis by the secretion of various angiogenic factors. Simultaneously, the importance of stem cells in peripheral nerve regeneration relies on their ability to promote myelin formation and their capacity to be influenced by the microenvironment to differentiate into Schwann-like cells. Stem cells can be acquired through various sources that correlate to their differentiation potential, including embryonic stem cells, neural stem cells, and mesenchymal stem cells. Each source of stem cells serves its particular differentiation potential and properties associated with the promotion of revascularization and nerve regeneration. Exosomes are a subtype of extracellular vesicles released from cell types and play an important role in cell-to-cell communication. Exosomes hold promise for future transplantation applications, as these vesicles contain fewer membrane-bound proteins, resulting in lower immunogenicity. This review presents pre-clinical and clinical studies that focus on selecting the ideal type of stem cell and optimizing stem cell delivery methods for potential translation to clinical practice. Future studies integrating stem cell-based therapies with the promotion of angiogenesis may elucidate the synergistic pathways and ultimately enhance nerve regeneration.展开更多
Background： Objectives were to examine the effects of selenium （Se） supply and maternal nutritional plane during gestation on mammary gland growth, cellular proliferation, and vascularity at parturition and d 20 of...Background： Objectives were to examine the effects of selenium （Se） supply and maternal nutritional plane during gestation on mammary gland growth, cellular proliferation, and vascularity at parturition and d 20 of lactation. Rambouillet primiparous ewes （n = 84） were allocated to treatments in a 2 x 3 factorial. Factors were dietary Se （adequate Se [ASe, 11.5 μg/kg BW] or high Se [HSe, 77.0 μg/kg BVV]） and nutritional plane （60% IRES], 100% [CON], or 140% [EXC]）. At parturition, lambs were removed and 42 ewes （7/treatment） were necropsied. Remaining ewes were fed a common diet meeting requirements for lactation and mechanically milked twice daily until necropsy on d 20. At both necropsy periods, mammary glands were dissected and tissues harvested. Samples were analyzed for RNA, DNA, and protein content, cell proliferation, and vascularity. Where interactions were present （P 〈 0.05）, least squares means from the highest-order interaction are presented. Results： Final body weight of ewes was least （P 〈 0.002） in RES, intermediate for CON, and greatest for EXC, regardless of stage of the ewe at necropsy （parturition or d 20 of lactation）. In ewes necropsied at parturition, mammary glands were heavier （P = 0.02） in EXC compared to RES, with CON intermediate. Concentration of RNA （rag/g） was decreased （P= 0.01） in EXC compared to CON at parturition. There was a tendency （P= 0.07） for a Se by nutrition interaction in percentage of cells proliferating where ASe-EXC ewes had greater （P_〈 0.02） number of proliferating cells then all other treatments. Mammary vascular area tended （P = 0.08） to be affected by a Se by nutrition interaction where ASe-CON had less （P= 0.007） vascular area than HSe-CON ewes. In ewes necropsied at d 20 of lactation, the number of alveoli per area was decreased （P 〈- 0.05） in RES compared to CON and EXC-fed ewes. Conclusions： Results of this study indicate that proper maternal nutritional plane during gestation is important for mammary gland development, even out to d 20 of lactation.展开更多
Scaphoid fractures,particularly those that occur more proximally,are unreliable in achieving union due to the retrograde blood supply of the scaphoid bone.Vascular compromise is associated with the development of nonu...Scaphoid fractures,particularly those that occur more proximally,are unreliable in achieving union due to the retrograde blood supply of the scaphoid bone.Vascular compromise is associated with the development of nonunions and avascular necrosis of the proximal pole.Due to the tenuous blood supply of the scaphoid,it is imperative that the vascularity be assessed when creating diagnostic and treatment strategies.Early detection of vascular compromise via imaging may signal impending nonunion and allow clinicians to perform interventions that aid in restoring perfusion to the scaphoid.Vascular compromise in the scaphoid presents a diagnostic challenge,in part due to the non-specific findings on plain radiographs and computed tomography.Magnetic resonance imaging techniques have dramatically improved our ability to assess the blood supply to the scaphoid and improve time to intervention.This review aims to summarize these advances and highlights the importance of imaging in assessing vascular compromise in scaphoid nonunion and in reperfusion following surgical intervention.展开更多
AIM:To compare the three-dimensional choroidal vascularity index(CVI)and choroidal thickness between fellow eyes of acute primary angle-closure(F-APAC)and chronic primary angle-closure glaucoma(F-CPACG)and the eyes of...AIM:To compare the three-dimensional choroidal vascularity index(CVI)and choroidal thickness between fellow eyes of acute primary angle-closure(F-APAC)and chronic primary angle-closure glaucoma(F-CPACG)and the eyes of normal controls.METHODS:This study included 37 patients with unilateral APAC,37 with asymmetric CPACG without prior treatment,and 36 healthy participants.Using swept-source optical coherence tomography(SS-OCT),the macular and peripapillary choroidal thickness and three-dimensional CVI were measured and compared globally and sectorally.Pearson’s correlation analysis and multivariate regression models were used to evaluate choroidal thickness or CVI with related factors.RESULTS:The mean subfoveal CVIs were 0.35±0.10,0.33±0.09,and 0.29±0.04,and the mean subfoveal choroidal thickness were 315.62±52.92,306.22±59.29,and 262.69±45.55μm in the F-APAC,F-CPACG,and normal groups,respectively.All macular sectors showed significantly higher CVIs and choroidal thickness in the F-APAC and F-CPACG eyes than in the normal eyes(P<0.05),while there were no significant differences between the F-APAC and F-CPACG eyes.In the peripapillary region,the mean overall CVIs were 0.21±0.08,0.20±0.08,and 0.19±0.05,and the mean overall choroidal thickness were 180.45±54.18,174.82±50.67,and 176.18±37.94μm in the F-APAC,F-CPACG,and normal groups,respectively.There were no significant differences between any of the two groups in all peripapillary sectors.Younger age,shorter axial length,and the F-APAC or F-CPACG diagnosis were significantly associated with higher subfoveal CVI and thicker subfoveal choroidal thickness(P<0.05).CONCLUSION:The fellow eyes of unilateral APAC or asymmetric CPACG have higher macular CVI and choroidal thickness than those of the normal controls.Neither CVI nor choroidal thickness can distinguish between eyes predisposed to APAC or CPACG.A thicker choroid with a higher vascular volume may play a role in the pathogenesis of primary angle-closure glaucoma.展开更多
AIM:To investigate changes in choroidal thickness and vascularity in keratoconus patients treated with corneal crosslinking.METHODS:This study evaluated 28 eyes of 22 patients with keratoconus who underwent corneal cr...AIM:To investigate changes in choroidal thickness and vascularity in keratoconus patients treated with corneal crosslinking.METHODS:This study evaluated 28 eyes of 22 patients with keratoconus who underwent corneal crosslinking.The choroidal thicknesses were evaluated on enhanced depth imaging optical coherence tomography at the preoperative and postoperative 3d,1,and 3mo.Choroidal thickness in the four cardinal quadrants and the fovea were evaluated.The choroidal vascularity index was also calculated.RESULTS:There was no significant difference in central choroidal thickness between the preoperative and postoperative 3d,1mo(P>0.05).There was a significant increase in the 3mo(P=0.034)and a significant decrease in the horizontal choroidal vascularity index on the postoperative 3d(P=0.014),there was no statistically significant change in vertical axes and other visits in horizontal sections(P>0.05).CONCLUSION:This study sheds light on choroidal changes in postoperative corneal crosslinking for keratoconus.While it suggests the procedure’s relative safety for submacular choroid,more extensive research is necessary to confirm these findings and their clinical significance.展开更多
Objective:?The aim of this study is to assess any potential relationship between perifollicular vascularity and occurrence of pregnancy in cases of stimulated IUI cycles using the subjective grading system by 2D trans...Objective:?The aim of this study is to assess any potential relationship between perifollicular vascularity and occurrence of pregnancy in cases of stimulated IUI cycles using the subjective grading system by 2D transvaginal power Doppler ultrasonography.?Design: A prospective cross sectional cohort study. Method: This is a prospective cross-sectional cohort study of 90 stimulated IUI treatment cycles. Selected women were prescribed clomiphene citrate combined with highly purified urinary follicle stimulating hormone. All patients underwent serial transvaginal ultrasound scans starting from day 6 to 7 of the cycle. Perifollicular Doppler blood flows were assessed in dominant follicles ≥18 mm. The patients then were categorized into 3 groups (high vascularity group {G3 & G4}, low vascularity group {G1 & G2} and mixed grades group). Other parameters measured included number of follicles ≥ 18 mm in both ovaries, endometrial thickness and estradiol (E2) level . Human chorionic gonadotropin (hCG) injection 10,000 IU IM was given to the patient when the dominant follicle reached 18 mm in diameter. At that time, the endometrium was evaluated as regards endometrial thickness. IUI was carried out using prepared/“washed” semen (husband). All patients received luteal support in the form of progesterone from day of IUI for 14 days. Serum Β-hCG was estimated 2 weeks after insemination. Results: In this study, from all 90 cases only 8 cases got pregnant with pregnancy rate of 8.88% (6 cases got pregnant in high grade vascularity group;2 cases in mixed grades group and no cases got pregnant?in low grade group). There was statistically significant difference among the 3 groups as regarding?the pregnancy rate (P value = 0.02). There is statistically significant difference in perifollicular resistance index (RI) and pulsatility index (PI) between pregnant and non pregnant cases (P value = 0.016 and 0.047 respectively). In this study, there is no statistically significant difference between pregnant and non pregnant cases as regarding endometrial thickness and E2 level at the day of hCG administration (P value = 0.39 and 0.76 respectively). Conclusion: Perifollicular blood-flow assessment by 2D transvaginal power Doppler is a good predictive for the outcome of stimulated IUI cycles.展开更多
Background:Hemodynamic changes have been observed in patients with Graves’disease.The aim of our study was to evaluate choroidal vascular change using the choroidal vascularity index(CVI)in patients with thyroidassoc...Background:Hemodynamic changes have been observed in patients with Graves’disease.The aim of our study was to evaluate choroidal vascular change using the choroidal vascularity index(CVI)in patients with thyroidassociated ophthalmopathy(TAO).Methods:In this cross-sectional observational study,40 patients affected by TAO were recruited.Forty healthy individuals,matched for age and sex,served as controls.Foveal enhanced-depth imaging optical coherence tomography scans were obtained from all participants.Images were binarized using the ImageJ software and luminal area(LA)and total choroidal area(TCA)were measured.CVI was calculated as the proportion of LA to TCA.The relation between CVI or subfoveal choroidal thickness(SFCT)and clinical activity score,exophthalmometric value,diplopia status,gender,and age was evaluated.Results:CVI was significantly higher in patients with TAO(P=0.004).No significant difference was observed in SFCT(P=0.200)and TCA(P=0.153)comparing TAO patients and healthy controls.LA was significantly higher in TAO group(P=0.045).On multiple regression analysis,CVI was associated with TCA(P=0.043).No association was found between SFCT or CVI and TCA,clinical activity score,exophthalmometric value,Inami value,diplopia status,gender or age(P>0.05).Conclusions:This is the first study that has demonstrated an increase in CVI in eyes with TAO compared with healthy controls and has assessed its association with clinical features.展开更多
Spinal cord injury represents a severe form of central nervous system trauma for which effective treatments remain limited.Microglia is the resident immune cells of the central nervous system,play a critical role in s...Spinal cord injury represents a severe form of central nervous system trauma for which effective treatments remain limited.Microglia is the resident immune cells of the central nervous system,play a critical role in spinal cord injury.Previous studies have shown that microglia can promote neuronal survival by phagocytosing dead cells and debris and by releasing neuroprotective and anti-inflammatory factors.However,excessive activation of microglia can lead to persistent inflammation and contribute to the formation of glial scars,which hinder axonal regeneration.Despite this,the precise role and mechanisms of microglia during the acute phase of spinal cord injury remain controversial and poorly understood.To elucidate the role of microglia in spinal cord injury,we employed the colony-stimulating factor 1 receptor inhibitor PLX5622 to deplete microglia.We observed that sustained depletion of microglia resulted in an expansion of the lesion area,downregulation of brain-derived neurotrophic factor,and impaired functional recovery after spinal cord injury.Next,we generated a transgenic mouse line with conditional overexpression of brain-derived neurotrophic factor specifically in microglia.We found that brain-derived neurotrophic factor overexpression in microglia increased angiogenesis and blood flow following spinal cord injury and facilitated the recovery of hindlimb motor function.Additionally,brain-derived neurotrophic factor overexpression in microglia reduced inflammation and neuronal apoptosis during the acute phase of spinal cord injury.Furthermore,through using specific transgenic mouse lines,TMEM119,and the colony-stimulating factor 1 receptor inhibitor PLX73086,we demonstrated that the neuroprotective effects were predominantly due to brain-derived neurotrophic factor overexpression in microglia rather than macrophages.In conclusion,our findings suggest the critical role of microglia in the formation of protective glial scars.Depleting microglia is detrimental to recovery of spinal cord injury,whereas targeting brain-derived neurotrophic factor overexpression in microglia represents a promising and novel therapeutic strategy to enhance motor function recovery in patients with spinal cord injury.展开更多
Background:Hemodynamic changes have been observed in patients with Graves'disease.The aim of our study was to evaluate choroidal vascular change using the choroidal vascularity index(CVi)in patients with thyroid-a...Background:Hemodynamic changes have been observed in patients with Graves'disease.The aim of our study was to evaluate choroidal vascular change using the choroidal vascularity index(CVi)in patients with thyroid-associated ophthalmopathy(TAO).Methods:In this cross-sectional observational study,40 patients affected by TAO were recruited.Forty healthy individuals,matched for age and sex,served as controls.Foveal enhanced-depth imaging optical coherence tomography scans were obtained from all participants.Images were binarized using the ImageJ software and luminal area(LA)and total choroidal area(TCA)were measured.CVI was calculated as the proportion of LA to TCA.The relation between CVI or subfoveal choroidal thickness(SFCT)and clinical activity score,exophthalmometric value,diplopia status,gender,and age was evaluated.Results:CVI was significantly higher in patients with TAO(P=0.004).No significant difference was observed in SFCT(P=0.200)and TCA(P=0.153)comparing TAO patients and healthy controls.LA was significantly higher in TAO group(P=0.045).On multiple regression analysis,CVI was associated with TCA(P=0.043).No association Was found between SFCT or CVI and TCA,clinical activity score,exophthalmometric value,Inami value,diplopia status,genderorage(P>0.05).Conclusions:This is the first study that has demonstrated an increase in CVI in eyes with TAO compared with healthy controls and has assessed its association with clinical features.展开更多
Ischemic stroke,a frequently occurring form of stroke,is caused by obstruction of cerebral blood flow,which leads to ischemia,hypoxia,and necrosis of local brain tissue.After ischemic stroke,both astrocytes and the bl...Ischemic stroke,a frequently occurring form of stroke,is caused by obstruction of cerebral blood flow,which leads to ischemia,hypoxia,and necrosis of local brain tissue.After ischemic stroke,both astrocytes and the blood–brain barrier undergo morphological and functional transformations.However,the interplay between astrocytes and the blood–brain barrier has received less attention.This comprehensive review explores the physiological and pathological morphological and functional changes in astrocytes and the blood–brain barrier in ischemic stroke.Post-stroke,the structure of endothelial cells and peripheral cells undergoes alterations,causing disruption of the blood–brain barrier.This disruption allows various pro-inflammatory factors and chemokines to cross the blood–brain barrier.Simultaneously,astrocytes swell and primarily adopt two phenotypic states:A1 and A2,which exhibit different roles at different stages of ischemic stroke.During the acute phase,A1 reactive astrocytes secrete vascular endothelial growth factor,matrix metalloproteinases,lipid carrier protein-2,and other cytokines,exacerbating damage to endothelial cells and tight junctions.Conversely,A2 reactive astrocytes produce pentraxin 3,Sonic hedgehog,angiopoietin-1,and other protective factors for endothelial cells.Furthermore,astrocytes indirectly influence blood–brain barrier permeability through ferroptosis and exosomes.In the middle and late(recovery)stages of ischemic stroke,A1 and A2 astrocytes show different effects on glial scar formation.A1 astrocytes promote glial scar formation and inhibit axon growth via glial fibrillary acidic protein,chondroitin sulfate proteoglycans,and transforming growth factor-β.In contrast,A2 astrocytes facilitate axon growth through platelet-derived growth factor,playing a crucial role in vascular remodeling.Therefore,enhancing our understanding of the pathological changes and interactions between astrocytes and the blood–brain barrier is a vital therapeutic target for preventing further brain damage in acute stroke.These insights may pave the way for innovative therapeutic strategies for ischemic stroke.展开更多
Background:The development of materials for cardiovascular surgery that would improve the effectiveness of surgical interventions remains an important task.Surgical intervention during the implantation of vascular pro...Background:The development of materials for cardiovascular surgery that would improve the effectiveness of surgical interventions remains an important task.Surgical intervention during the implantation of vascular prostheses and stents,and the body’s reaction to artificial materials,could lead to chronic inflammation,a local increase in the concentration of proinflammatory factors,and stimulation of unwanted tissue growth.The introduction of nonsteroidal anti-inflammatory drugs into implantable devices could be used to obtain vascular implants that do not induce inflammation and do not induce neointimal tissue outgrowth.Methods:The scaffolds were made by electrospinning from mixtures of polyurethane(PU)with diclofenac(DF).The kinetics of DF release from the scaffolds composed of 3%PU/10%HSA/3%DMSO/DF and 3%PU/DF were studied.The biocompatibility and anti-inflammatory effects of the obtained scaffolds on human gingival fibroblasts and umbilical vein endothelial cells were studied.Results:Both types of scaffolds are characterized by fast DF release.The viability of cells cultured on scaffolds is 2 times worse than that of cells cultured on plastic.The level of the proinflammatory cytokine IL-6 in the culture medium of cells cultured on DF-containing scaffolds was lower than that of cells cultured on scaffolds without DF.Conclusion:The introduction of DF into scaffolds minimizes the inflammation caused by cell reactions to an artificial material.展开更多
Nail changes following upper extremity transplantation(UET)cannot be overlooked as they possess diagnostic and prognostic relevance in allotransplantation of upper limbs.This comprehensive review explores nail and nai...Nail changes following upper extremity transplantation(UET)cannot be overlooked as they possess diagnostic and prognostic relevance in allotransplantation of upper limbs.This comprehensive review explores nail and nail bed related changes encountered in UET recipients in the literature.The differential diagnosis of nail abnormalities in UET includes a wide range of systemic,local and iatrogenic conditions other than immune responses to the allograft.It requires interdisciplinary evaluation by primary transplant surgeons,pathologists,dermatologists and immunologists.The possible underlying mechanisms of nail pathology in UET and the management are discussed.It also underscores the importance of onychodystrophy and need for timely intervention and to improve outcomes in UET recipients.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 brain is the most complex human organ,and commonly used models,such as two-dimensional-cell cultures and animal brains,often lack the sophistication needed to accurately use in research.In this context,human cereb...The brain is the most complex human organ,and commonly used models,such as two-dimensional-cell cultures and animal brains,often lack the sophistication needed to accurately use in research.In this context,human cerebral organoids have emerged as valuable tools offering a more complex,versatile,and human-relevant system than traditional animal models,which are often unable to replicate the intricate architecture and functionality of the human brain.Since human cerebral organoids are a state-of-the-art model for the study of neurodevelopment and different pathologies affecting the brain,this field is currently under constant development,and work in this area is abundant.In this review,we give a complete overview of human cerebral organoids technology,starting from the different types of protocols that exist to generate different human cerebral organoids.We continue with the use of brain organoids for the study of brain pathologies,highlighting neurodevelopmental,psychiatric,neurodegenerative,brain tumor,and infectious diseases.Because of the potential value of human cerebral organoids,we describe their use in transplantation,drug screening,and toxicology assays.We also discuss the technologies available to study cell diversity and physiological characteristics of organoids.Finally,we summarize the limitations that currently exist in the field,such as the development of vasculature and microglia,and highlight some of the novel approaches being pursued through bioengineering.展开更多
Overt and harmful diabetes mellitus(DM)has detrimental effects on individuals and,by extension,the community.Among the microvascular DM complications is diabetic retinopathy(DR).DR may cause irreversible vision deteri...Overt and harmful diabetes mellitus(DM)has detrimental effects on individuals and,by extension,the community.Among the microvascular DM complications is diabetic retinopathy(DR).DR may cause irreversible vision deterioration in cases of poor blood glucose regulation.Changes in vascular permeability are key trigger points for diabetic macular edema(DME),a condition characterized by the accumulation of fluid in the macula.The development of vascular endothelial growth factor(VEGF)pathway inhibitors has provided a pathogenesis-based treatment approach for DME.Optical coherence tomography(OCT)provides highresolution imaging of the anatomy,including the aging of DME and its structural damage,in distinct morphologic subtypes of macular edema,thereby supporting the assessment of macular edema treatment.The availability of repeated OCT monitoring provides clinical reassurance through the treatment.OCT angiography(OCTA)provides retinal blood flow maps with high spatial resolution.The ability promotes an understanding of disease pathogenesis and facilitates the implementation of new therapeutic methods.This review compares the potential of OCT and OCTA in the diagnosis and treatment of DME,as well as their respective therapeutic applications.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
The major aim of stroke therapy is to stimulate brain repair and improve behavioral recovery after cerebral ischemia.One option is to stimulate endogenous neurogenesis in the subventricular zone and direct the newly f...The major aim of stroke therapy is to stimulate brain repair and improve behavioral recovery after cerebral ischemia.One option is to stimulate endogenous neurogenesis in the subventricular zone and direct the newly formed neurons to the damaged area.However,only a small percentage of these neurons survive,and many do not reach the damaged area,possibly because the corpus callosum impedes the migration of subventricular zone-derived stem cells into the lesioned cortex.A second major obstacle to stem cell therapy is the strong inflammatory reaction induced by cerebral ischemia,whereby the associated phagocytic activity of brain macrophages removes both therapeutic cells and/or cell-based drug carriers.To address these issues,neurogenesis was electrically stimulated in the subventricular zone,followed by isolation of proliferating cells,including newly formed neurons,which were subsequently mixed with a nutritional hydrogel.This mixture was then transferred to the stroke cavity of day 14 post-stroke mice.We found that the performance of the treated animals improved in behavioral tests,including novel object,open field,hole board,grooming,and“time-to-feel”adhesive tape tests.Furthermore,immunostaining revealed that the stem cell marker nestin,the neuroepithelial marker Mash1,and the immature neuronal marker doublecortin-positive cells survived in the transplanted area for 2 weeks,possibly due to reduced phagocytic activity and supportive angiogenesis.These results clearly indicate that the transplantation of committed subventricular zone stem cells combined with a protective nutritional gel directly into the infarct cavity after the peak of stroke-induced neuroinflammation represents a feasible approach to improve neurorestoration after cerebral ischemia.展开更多
AIM:To investigate short-term changes in choroidal thickness in response to peripheral myopic defocus induced by two designs of multifocal corneal gas permeable contact lenses(MFGPCL)in young adults.METHODS:Seventeen ...AIM:To investigate short-term changes in choroidal thickness in response to peripheral myopic defocus induced by two designs of multifocal corneal gas permeable contact lenses(MFGPCL)in young adults.METHODS:Seventeen participants,with a mean age of 24.5±4y,underwent choroidal thickness and vascularity index measurements using enhanced depth imaging optical coherence tomography(EDI OCT)at baseline,one day,and one week following MFGPCL wear.Two center-distance MFGPCL designs with similar center zone diameters of 3.0 mm but different peripheral add powers(low add:+1.5 D and high add:+3.0 D)were tested.Each participant was randomly assigned to wear one of the two MFGPCL designs.Measurements of total,luminal,and stromal choroid thickness were obtained in five eccentric regions(6 mm towards the periphery)in all quadrants.RESULTS:Significant thickening in total choroidal thickness were observed after one week of wearing both high add(+10±6µm)and low add(+7±5µm)MFGPCLs,with no statistically significant difference between the two groups(P=0.42).Choroidal thickening was consistent across eccentric regions and quadrants,with no significant differences based on eccentricity or quadrant(all P>0.05).Both lens designs induced choroidal thickening,with no significant difference between them in total choroidal thickness(P=0.18 for quadrants,P=0.51 for eccentric regions).CONCLUSION:Peripheral myopic defocus induced by MFGPCLs lead to significant choroidal thickening,including total,luminal,and stromal components.This study highlights the need for future research to explore the dose-response relationship between peripheral myopic defocus and choroidal thickening,utilizing choroidal response as a potential biomarker.展开更多
文摘The degree of nerve regeneration after peripheral nerve injury can be altered by the microenvironment at the site of injury. Stem cells and vascularity are postulated to be a part of a complex pathway that enhances peripheral nerve regeneration;however, their interaction remains unexplored. This review aims to summarize current knowledge on this interaction, including various mechanisms through which trophic factors are promoted by stem cells and angiogenesis. Angiogenesis after nerve injury is stimulated by hypoxia, mediated by vascular endothelial growth factor, resulting in the growth of preexisting vessels into new areas. Modulation of distinct signaling pathways in stem cells can promote angiogenesis by the secretion of various angiogenic factors. Simultaneously, the importance of stem cells in peripheral nerve regeneration relies on their ability to promote myelin formation and their capacity to be influenced by the microenvironment to differentiate into Schwann-like cells. Stem cells can be acquired through various sources that correlate to their differentiation potential, including embryonic stem cells, neural stem cells, and mesenchymal stem cells. Each source of stem cells serves its particular differentiation potential and properties associated with the promotion of revascularization and nerve regeneration. Exosomes are a subtype of extracellular vesicles released from cell types and play an important role in cell-to-cell communication. Exosomes hold promise for future transplantation applications, as these vesicles contain fewer membrane-bound proteins, resulting in lower immunogenicity. This review presents pre-clinical and clinical studies that focus on selecting the ideal type of stem cell and optimizing stem cell delivery methods for potential translation to clinical practice. Future studies integrating stem cell-based therapies with the promotion of angiogenesis may elucidate the synergistic pathways and ultimately enhance nerve regeneration.
基金supported by National Research Initiative Competitive Grants no.2005-35206-15281 from the USDA Cooperative State ResearchEducation and Extension Service to JSC+1 种基金DARand KAV
文摘Background： Objectives were to examine the effects of selenium （Se） supply and maternal nutritional plane during gestation on mammary gland growth, cellular proliferation, and vascularity at parturition and d 20 of lactation. Rambouillet primiparous ewes （n = 84） were allocated to treatments in a 2 x 3 factorial. Factors were dietary Se （adequate Se [ASe, 11.5 μg/kg BW] or high Se [HSe, 77.0 μg/kg BVV]） and nutritional plane （60% IRES], 100% [CON], or 140% [EXC]）. At parturition, lambs were removed and 42 ewes （7/treatment） were necropsied. Remaining ewes were fed a common diet meeting requirements for lactation and mechanically milked twice daily until necropsy on d 20. At both necropsy periods, mammary glands were dissected and tissues harvested. Samples were analyzed for RNA, DNA, and protein content, cell proliferation, and vascularity. Where interactions were present （P 〈 0.05）, least squares means from the highest-order interaction are presented. Results： Final body weight of ewes was least （P 〈 0.002） in RES, intermediate for CON, and greatest for EXC, regardless of stage of the ewe at necropsy （parturition or d 20 of lactation）. In ewes necropsied at parturition, mammary glands were heavier （P = 0.02） in EXC compared to RES, with CON intermediate. Concentration of RNA （rag/g） was decreased （P= 0.01） in EXC compared to CON at parturition. There was a tendency （P= 0.07） for a Se by nutrition interaction in percentage of cells proliferating where ASe-EXC ewes had greater （P_〈 0.02） number of proliferating cells then all other treatments. Mammary vascular area tended （P = 0.08） to be affected by a Se by nutrition interaction where ASe-CON had less （P= 0.007） vascular area than HSe-CON ewes. In ewes necropsied at d 20 of lactation, the number of alveoli per area was decreased （P 〈- 0.05） in RES compared to CON and EXC-fed ewes. Conclusions： Results of this study indicate that proper maternal nutritional plane during gestation is important for mammary gland development, even out to d 20 of lactation.
文摘Scaphoid fractures,particularly those that occur more proximally,are unreliable in achieving union due to the retrograde blood supply of the scaphoid bone.Vascular compromise is associated with the development of nonunions and avascular necrosis of the proximal pole.Due to the tenuous blood supply of the scaphoid,it is imperative that the vascularity be assessed when creating diagnostic and treatment strategies.Early detection of vascular compromise via imaging may signal impending nonunion and allow clinicians to perform interventions that aid in restoring perfusion to the scaphoid.Vascular compromise in the scaphoid presents a diagnostic challenge,in part due to the non-specific findings on plain radiographs and computed tomography.Magnetic resonance imaging techniques have dramatically improved our ability to assess the blood supply to the scaphoid and improve time to intervention.This review aims to summarize these advances and highlights the importance of imaging in assessing vascular compromise in scaphoid nonunion and in reperfusion following surgical intervention.
基金Supported by the National Natural Science Foundation of China(No.82101087)Shanghai Clinical Research Key Project(No.SHDC2020CR6029).
文摘AIM:To compare the three-dimensional choroidal vascularity index(CVI)and choroidal thickness between fellow eyes of acute primary angle-closure(F-APAC)and chronic primary angle-closure glaucoma(F-CPACG)and the eyes of normal controls.METHODS:This study included 37 patients with unilateral APAC,37 with asymmetric CPACG without prior treatment,and 36 healthy participants.Using swept-source optical coherence tomography(SS-OCT),the macular and peripapillary choroidal thickness and three-dimensional CVI were measured and compared globally and sectorally.Pearson’s correlation analysis and multivariate regression models were used to evaluate choroidal thickness or CVI with related factors.RESULTS:The mean subfoveal CVIs were 0.35±0.10,0.33±0.09,and 0.29±0.04,and the mean subfoveal choroidal thickness were 315.62±52.92,306.22±59.29,and 262.69±45.55μm in the F-APAC,F-CPACG,and normal groups,respectively.All macular sectors showed significantly higher CVIs and choroidal thickness in the F-APAC and F-CPACG eyes than in the normal eyes(P<0.05),while there were no significant differences between the F-APAC and F-CPACG eyes.In the peripapillary region,the mean overall CVIs were 0.21±0.08,0.20±0.08,and 0.19±0.05,and the mean overall choroidal thickness were 180.45±54.18,174.82±50.67,and 176.18±37.94μm in the F-APAC,F-CPACG,and normal groups,respectively.There were no significant differences between any of the two groups in all peripapillary sectors.Younger age,shorter axial length,and the F-APAC or F-CPACG diagnosis were significantly associated with higher subfoveal CVI and thicker subfoveal choroidal thickness(P<0.05).CONCLUSION:The fellow eyes of unilateral APAC or asymmetric CPACG have higher macular CVI and choroidal thickness than those of the normal controls.Neither CVI nor choroidal thickness can distinguish between eyes predisposed to APAC or CPACG.A thicker choroid with a higher vascular volume may play a role in the pathogenesis of primary angle-closure glaucoma.
文摘AIM:To investigate changes in choroidal thickness and vascularity in keratoconus patients treated with corneal crosslinking.METHODS:This study evaluated 28 eyes of 22 patients with keratoconus who underwent corneal crosslinking.The choroidal thicknesses were evaluated on enhanced depth imaging optical coherence tomography at the preoperative and postoperative 3d,1,and 3mo.Choroidal thickness in the four cardinal quadrants and the fovea were evaluated.The choroidal vascularity index was also calculated.RESULTS:There was no significant difference in central choroidal thickness between the preoperative and postoperative 3d,1mo(P>0.05).There was a significant increase in the 3mo(P=0.034)and a significant decrease in the horizontal choroidal vascularity index on the postoperative 3d(P=0.014),there was no statistically significant change in vertical axes and other visits in horizontal sections(P>0.05).CONCLUSION:This study sheds light on choroidal changes in postoperative corneal crosslinking for keratoconus.While it suggests the procedure’s relative safety for submacular choroid,more extensive research is necessary to confirm these findings and their clinical significance.
文摘Objective:?The aim of this study is to assess any potential relationship between perifollicular vascularity and occurrence of pregnancy in cases of stimulated IUI cycles using the subjective grading system by 2D transvaginal power Doppler ultrasonography.?Design: A prospective cross sectional cohort study. Method: This is a prospective cross-sectional cohort study of 90 stimulated IUI treatment cycles. Selected women were prescribed clomiphene citrate combined with highly purified urinary follicle stimulating hormone. All patients underwent serial transvaginal ultrasound scans starting from day 6 to 7 of the cycle. Perifollicular Doppler blood flows were assessed in dominant follicles ≥18 mm. The patients then were categorized into 3 groups (high vascularity group {G3 & G4}, low vascularity group {G1 & G2} and mixed grades group). Other parameters measured included number of follicles ≥ 18 mm in both ovaries, endometrial thickness and estradiol (E2) level . Human chorionic gonadotropin (hCG) injection 10,000 IU IM was given to the patient when the dominant follicle reached 18 mm in diameter. At that time, the endometrium was evaluated as regards endometrial thickness. IUI was carried out using prepared/“washed” semen (husband). All patients received luteal support in the form of progesterone from day of IUI for 14 days. Serum Β-hCG was estimated 2 weeks after insemination. Results: In this study, from all 90 cases only 8 cases got pregnant with pregnancy rate of 8.88% (6 cases got pregnant in high grade vascularity group;2 cases in mixed grades group and no cases got pregnant?in low grade group). There was statistically significant difference among the 3 groups as regarding?the pregnancy rate (P value = 0.02). There is statistically significant difference in perifollicular resistance index (RI) and pulsatility index (PI) between pregnant and non pregnant cases (P value = 0.016 and 0.047 respectively). In this study, there is no statistically significant difference between pregnant and non pregnant cases as regarding endometrial thickness and E2 level at the day of hCG administration (P value = 0.39 and 0.76 respectively). Conclusion: Perifollicular blood-flow assessment by 2D transvaginal power Doppler is a good predictive for the outcome of stimulated IUI cycles.
文摘Background:Hemodynamic changes have been observed in patients with Graves’disease.The aim of our study was to evaluate choroidal vascular change using the choroidal vascularity index(CVI)in patients with thyroidassociated ophthalmopathy(TAO).Methods:In this cross-sectional observational study,40 patients affected by TAO were recruited.Forty healthy individuals,matched for age and sex,served as controls.Foveal enhanced-depth imaging optical coherence tomography scans were obtained from all participants.Images were binarized using the ImageJ software and luminal area(LA)and total choroidal area(TCA)were measured.CVI was calculated as the proportion of LA to TCA.The relation between CVI or subfoveal choroidal thickness(SFCT)and clinical activity score,exophthalmometric value,diplopia status,gender,and age was evaluated.Results:CVI was significantly higher in patients with TAO(P=0.004).No significant difference was observed in SFCT(P=0.200)and TCA(P=0.153)comparing TAO patients and healthy controls.LA was significantly higher in TAO group(P=0.045).On multiple regression analysis,CVI was associated with TCA(P=0.043).No association was found between SFCT or CVI and TCA,clinical activity score,exophthalmometric value,Inami value,diplopia status,gender or age(P>0.05).Conclusions:This is the first study that has demonstrated an increase in CVI in eyes with TAO compared with healthy controls and has assessed its association with clinical features.
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.
文摘Background:Hemodynamic changes have been observed in patients with Graves'disease.The aim of our study was to evaluate choroidal vascular change using the choroidal vascularity index(CVi)in patients with thyroid-associated ophthalmopathy(TAO).Methods:In this cross-sectional observational study,40 patients affected by TAO were recruited.Forty healthy individuals,matched for age and sex,served as controls.Foveal enhanced-depth imaging optical coherence tomography scans were obtained from all participants.Images were binarized using the ImageJ software and luminal area(LA)and total choroidal area(TCA)were measured.CVI was calculated as the proportion of LA to TCA.The relation between CVI or subfoveal choroidal thickness(SFCT)and clinical activity score,exophthalmometric value,diplopia status,gender,and age was evaluated.Results:CVI was significantly higher in patients with TAO(P=0.004).No significant difference was observed in SFCT(P=0.200)and TCA(P=0.153)comparing TAO patients and healthy controls.LA was significantly higher in TAO group(P=0.045).On multiple regression analysis,CVI was associated with TCA(P=0.043).No association Was found between SFCT or CVI and TCA,clinical activity score,exophthalmometric value,Inami value,diplopia status,genderorage(P>0.05).Conclusions:This is the first study that has demonstrated an increase in CVI in eyes with TAO compared with healthy controls and has assessed its association with clinical features.
基金supported by the National Natural Science Foundation of China,No.U21A20400(to QW)the National Natural Science Foundation of China,No.82104560(to CL)+1 种基金the Natural Science Foundation of Beijing,No.7232279(to XW)the Project of Beijing University of Chinese Medicine,Nos.2024-JYB-JBZD-043(to CL),2022-JYB-JBZR-004(to XW)。
文摘Ischemic stroke,a frequently occurring form of stroke,is caused by obstruction of cerebral blood flow,which leads to ischemia,hypoxia,and necrosis of local brain tissue.After ischemic stroke,both astrocytes and the blood–brain barrier undergo morphological and functional transformations.However,the interplay between astrocytes and the blood–brain barrier has received less attention.This comprehensive review explores the physiological and pathological morphological and functional changes in astrocytes and the blood–brain barrier in ischemic stroke.Post-stroke,the structure of endothelial cells and peripheral cells undergoes alterations,causing disruption of the blood–brain barrier.This disruption allows various pro-inflammatory factors and chemokines to cross the blood–brain barrier.Simultaneously,astrocytes swell and primarily adopt two phenotypic states:A1 and A2,which exhibit different roles at different stages of ischemic stroke.During the acute phase,A1 reactive astrocytes secrete vascular endothelial growth factor,matrix metalloproteinases,lipid carrier protein-2,and other cytokines,exacerbating damage to endothelial cells and tight junctions.Conversely,A2 reactive astrocytes produce pentraxin 3,Sonic hedgehog,angiopoietin-1,and other protective factors for endothelial cells.Furthermore,astrocytes indirectly influence blood–brain barrier permeability through ferroptosis and exosomes.In the middle and late(recovery)stages of ischemic stroke,A1 and A2 astrocytes show different effects on glial scar formation.A1 astrocytes promote glial scar formation and inhibit axon growth via glial fibrillary acidic protein,chondroitin sulfate proteoglycans,and transforming growth factor-β.In contrast,A2 astrocytes facilitate axon growth through platelet-derived growth factor,playing a crucial role in vascular remodeling.Therefore,enhancing our understanding of the pathological changes and interactions between astrocytes and the blood–brain barrier is a vital therapeutic target for preventing further brain damage in acute stroke.These insights may pave the way for innovative therapeutic strategies for ischemic stroke.
基金supported by the Russian state-funded project for ICBFM SB RAS(grant number 125012300656-5)。
文摘Background:The development of materials for cardiovascular surgery that would improve the effectiveness of surgical interventions remains an important task.Surgical intervention during the implantation of vascular prostheses and stents,and the body’s reaction to artificial materials,could lead to chronic inflammation,a local increase in the concentration of proinflammatory factors,and stimulation of unwanted tissue growth.The introduction of nonsteroidal anti-inflammatory drugs into implantable devices could be used to obtain vascular implants that do not induce inflammation and do not induce neointimal tissue outgrowth.Methods:The scaffolds were made by electrospinning from mixtures of polyurethane(PU)with diclofenac(DF).The kinetics of DF release from the scaffolds composed of 3%PU/10%HSA/3%DMSO/DF and 3%PU/DF were studied.The biocompatibility and anti-inflammatory effects of the obtained scaffolds on human gingival fibroblasts and umbilical vein endothelial cells were studied.Results:Both types of scaffolds are characterized by fast DF release.The viability of cells cultured on scaffolds is 2 times worse than that of cells cultured on plastic.The level of the proinflammatory cytokine IL-6 in the culture medium of cells cultured on DF-containing scaffolds was lower than that of cells cultured on scaffolds without DF.Conclusion:The introduction of DF into scaffolds minimizes the inflammation caused by cell reactions to an artificial material.
文摘Nail changes following upper extremity transplantation(UET)cannot be overlooked as they possess diagnostic and prognostic relevance in allotransplantation of upper limbs.This comprehensive review explores nail and nail bed related changes encountered in UET recipients in the literature.The differential diagnosis of nail abnormalities in UET includes a wide range of systemic,local and iatrogenic conditions other than immune responses to the allograft.It requires interdisciplinary evaluation by primary transplant surgeons,pathologists,dermatologists and immunologists.The possible underlying mechanisms of nail pathology in UET and the management are discussed.It also underscores the importance of onychodystrophy and need for timely intervention and to improve outcomes in UET recipients.
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.
基金supported by the Grant PID2021-126715OB-IOO financed by MCIN/AEI/10.13039/501100011033 and"ERDFA way of making Europe"by the Grant PI22CⅢ/00055 funded by Instituto de Salud CarlosⅢ(ISCⅢ)+6 种基金the UFIECPY 398/19(PEJ2018-004965) grant to RGS funded by AEI(Spain)the UFIECPY-396/19(PEJ2018-004961)grant financed by MCIN (Spain)FI23CⅢ/00003 grant funded by ISCⅢ-PFIS Spain) to PMMthe UFIECPY 328/22 (PEJ-2021-TL/BMD-21001) grant to LM financed by CAM (Spain)the grant by CAPES (Coordination for the Improvement of Higher Education Personnel)through the PDSE program (Programa de Doutorado Sanduiche no Exterior)to VSCG financed by MEC (Brazil)
文摘The brain is the most complex human organ,and commonly used models,such as two-dimensional-cell cultures and animal brains,often lack the sophistication needed to accurately use in research.In this context,human cerebral organoids have emerged as valuable tools offering a more complex,versatile,and human-relevant system than traditional animal models,which are often unable to replicate the intricate architecture and functionality of the human brain.Since human cerebral organoids are a state-of-the-art model for the study of neurodevelopment and different pathologies affecting the brain,this field is currently under constant development,and work in this area is abundant.In this review,we give a complete overview of human cerebral organoids technology,starting from the different types of protocols that exist to generate different human cerebral organoids.We continue with the use of brain organoids for the study of brain pathologies,highlighting neurodevelopmental,psychiatric,neurodegenerative,brain tumor,and infectious diseases.Because of the potential value of human cerebral organoids,we describe their use in transplantation,drug screening,and toxicology assays.We also discuss the technologies available to study cell diversity and physiological characteristics of organoids.Finally,we summarize the limitations that currently exist in the field,such as the development of vasculature and microglia,and highlight some of the novel approaches being pursued through bioengineering.
文摘Overt and harmful diabetes mellitus(DM)has detrimental effects on individuals and,by extension,the community.Among the microvascular DM complications is diabetic retinopathy(DR).DR may cause irreversible vision deterioration in cases of poor blood glucose regulation.Changes in vascular permeability are key trigger points for diabetic macular edema(DME),a condition characterized by the accumulation of fluid in the macula.The development of vascular endothelial growth factor(VEGF)pathway inhibitors has provided a pathogenesis-based treatment approach for DME.Optical coherence tomography(OCT)provides highresolution imaging of the anatomy,including the aging of DME and its structural damage,in distinct morphologic subtypes of macular edema,thereby supporting the assessment of macular edema treatment.The availability of repeated OCT monitoring provides clinical reassurance through the treatment.OCT angiography(OCTA)provides retinal blood flow maps with high spatial resolution.The ability promotes an understanding of disease pathogenesis and facilitates the implementation of new therapeutic methods.This review compares the potential of OCT and OCTA in the diagnosis and treatment of DME,as well as their respective therapeutic applications.
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 European Union Funding Programme,PNRR,No. 760058(to DMH)the UEFISCDI Project,No. PN-III-P4-IDPCE-2020-059(to APW)
文摘The major aim of stroke therapy is to stimulate brain repair and improve behavioral recovery after cerebral ischemia.One option is to stimulate endogenous neurogenesis in the subventricular zone and direct the newly formed neurons to the damaged area.However,only a small percentage of these neurons survive,and many do not reach the damaged area,possibly because the corpus callosum impedes the migration of subventricular zone-derived stem cells into the lesioned cortex.A second major obstacle to stem cell therapy is the strong inflammatory reaction induced by cerebral ischemia,whereby the associated phagocytic activity of brain macrophages removes both therapeutic cells and/or cell-based drug carriers.To address these issues,neurogenesis was electrically stimulated in the subventricular zone,followed by isolation of proliferating cells,including newly formed neurons,which were subsequently mixed with a nutritional hydrogel.This mixture was then transferred to the stroke cavity of day 14 post-stroke mice.We found that the performance of the treated animals improved in behavioral tests,including novel object,open field,hole board,grooming,and“time-to-feel”adhesive tape tests.Furthermore,immunostaining revealed that the stem cell marker nestin,the neuroepithelial marker Mash1,and the immature neuronal marker doublecortin-positive cells survived in the transplanted area for 2 weeks,possibly due to reduced phagocytic activity and supportive angiogenesis.These results clearly indicate that the transplantation of committed subventricular zone stem cells combined with a protective nutritional gel directly into the infarct cavity after the peak of stroke-induced neuroinflammation represents a feasible approach to improve neurorestoration after cerebral ischemia.
基金Supported by Ongoing Research Funding Program(No.ORF-2025-1160),King Saud University,Riyadh Saudi Arabia.
文摘AIM:To investigate short-term changes in choroidal thickness in response to peripheral myopic defocus induced by two designs of multifocal corneal gas permeable contact lenses(MFGPCL)in young adults.METHODS:Seventeen participants,with a mean age of 24.5±4y,underwent choroidal thickness and vascularity index measurements using enhanced depth imaging optical coherence tomography(EDI OCT)at baseline,one day,and one week following MFGPCL wear.Two center-distance MFGPCL designs with similar center zone diameters of 3.0 mm but different peripheral add powers(low add:+1.5 D and high add:+3.0 D)were tested.Each participant was randomly assigned to wear one of the two MFGPCL designs.Measurements of total,luminal,and stromal choroid thickness were obtained in five eccentric regions(6 mm towards the periphery)in all quadrants.RESULTS:Significant thickening in total choroidal thickness were observed after one week of wearing both high add(+10±6µm)and low add(+7±5µm)MFGPCLs,with no statistically significant difference between the two groups(P=0.42).Choroidal thickening was consistent across eccentric regions and quadrants,with no significant differences based on eccentricity or quadrant(all P>0.05).Both lens designs induced choroidal thickening,with no significant difference between them in total choroidal thickness(P=0.18 for quadrants,P=0.51 for eccentric regions).CONCLUSION:Peripheral myopic defocus induced by MFGPCLs lead to significant choroidal thickening,including total,luminal,and stromal components.This study highlights the need for future research to explore the dose-response relationship between peripheral myopic defocus and choroidal thickening,utilizing choroidal response as a potential biomarker.
