Vascular medicine in the 21st century:Embracing comprehensive vasculature evaluation and multidisciplinary treatment

The field of vascular medicine has undergone a profound transformation in the 21st century,transforming our approach to assessment and treatment.Athero-sclerosis,a complex inflammatory disease that affects medium and large arteries,presents a major challenge for researchers and healthcare professionals.This condition,characterized by arterial plaque formation and narrowing,poses sub-stantial challenges to vascular health at individual,national,and global scales.Its repercussions are far-reaching,with clinical outcomes including ischemic heart disease,ischemic stroke,and peripheral arterial disease—conditions with esca-lating global prevalence.Early detection of vascular changes caused by athero-sclerosis is crucial in preventing these conditions,reducing morbidity,and averting mortality.This article underscored the imperative of adopting a holistic approach to grappling with the intricacies,trajectories,and ramifications of atherosclerosis.It stresses the need for a thorough evaluation of the vasculature and the implementation of a multidisciplinary treatment approach.By consi-dering the entire vascular system,healthcare providers can explore avenues for prevention,early detection,and effective management of this condition,ultima-tely leading to improved patient outcomes.We discussed current practices and proposed new directions made possible by emerging diagnostic modalities and treatment strategies.Additionally,we considered healthcare expenditure,resour-ce allocation,and the transformative potential of new innovative treatments and technologies.

The association between retinal vasculature changes and stroke:a literature review and Meta-analysis

AIM： To determine the association between retinal vasculature changes and stroke.METHODS： MEDLINE and EMBASE were searched for relevant human studies to September 2015 that investigated the association between retinal vasculature changes and the prevalence or incidence of stroke; the studies were independently examined for their qualities. Data on clinical characteristics and calculated summary odds ratios （ORs） were extracted for associations between retinal microvascular abnormalities and stroke, including stroke subtypes where possible, and adjusted for key variables. RESULTS： Nine cases were included in the study comprising 20 659 patients, 1178 of whom were stroke patients. The retinal microvascular morphological markers used were hemorrhage, microaneurysm, vessel caliber, arteriovenous nicking, and fractal dimension. OR of retinal arteriole narrowing and retinal arteriovenous nicking and stroke was 1.42 and 1.91, respectively, indicating that a small-caliber retinal arteriole and retinal arteriovenous nicking were associated with stroke. OR of retinal hemorrhage and retinal microaneurysm and stroke was 3.21 and 3.83, respectively, indicating that retinal microvascular lesions were highly associated with stroke. Results also showed that retinal fractal dimension reduction was associated with stroke （OR： 2.28 for arteriole network, OR： 1.80 for venular network）.CONCLUSION： Retinal vasculature changes have a specific relationship to stroke, which is promising evidence for the prediction of stroke using computerized retinal vessel analysis.

Outcomes of secondary sulcus intraocular lens implantation in unilateral anterior persistent fetal vasculature

AIM: To evaluate the surgical results of sulcus intraocular lens(IOL) implantation in children with unilateral anterior persistent fetal vasculature(PFV) underwent primary vitrectomy combined with lensectomy and preservation of the peripheral anterior capsule.METHODS: Twenty-two eyes of 22 children with unilateral anterior PFV who underwent sulcus secondary IOL implantation were analyzed. Main outcome measures were preoperative and postoperative visual acuity, and complications both intraoperatively and postoperatively. RESULTS: Review of 22 consecutive patients identified best-corrected visual acuity(BCVA) improvement from 1.37±0.84 to 0.73±0.57 logarithm of the minimal angle of resolution(logMAR) after IOL implantation(P<0.001) with a mean follow-up was 16.55±5.86 mo. Average age at secondary IOL implantation was 41.05±15.41 mo. Three eyes(13.64%) achieved BCVA of 0.3 logMAR at the final visit. Transient intraocular pressure rise(4 eyes; 18.18%), postoperative increased inflammation(3 eyes; 13.64%) and postoperative hypotony(2 eyes; 9.09%) were common complications.CONCLUSION: Properly preservation of the anterior lens capsule during the primary surgery facilitated secondary sulcus IOL implantation in pediatric patients with anterior PFV, with favorable postoperative visual outcomes and compatible percentage of complications.

A Feature Selection Strategy to Optimize Retinal Vasculature Segmentation

Diabetic retinopathy (DR) is a complication of diabetesmellitus thatappears in the retina. Clinitians use retina images to detect DR pathologicalsigns related to the occlusion of tiny blood vessels. Such occlusion brings adegenerative cycle between the breaking off and the new generation of thinnerand weaker blood vessels. This research aims to develop a suitable retinalvasculature segmentation method for improving retinal screening proceduresby means of computer-aided diagnosis systems. The blood vessel segmentationmethodology relies on an effective feature selection based on SequentialForward Selection, using the error rate of a decision tree classifier in theevaluation function. Subsequently, the classification process is performed bythree alternative approaches: artificial neural networks, decision trees andsupport vector machines. The proposed methodology is validated on threepublicly accessible datasets and a private one provided by Hospital Sant Joanof Reus. In all cases we obtain an average accuracy above 96% with a sensitivityof 72% in the blood vessel segmentation process. Compared with the state-ofthe-art, our approach achieves the same performance as other methods thatneed more computational power.Our method significantly reduces the numberof features used in the segmentation process from 20 to 5 dimensions. Theimplementation of the three classifiers confirmed that the five selected featureshave a good effectiveness, independently of the classification algorithm.

Outcomes of small gauge pars plicata vitrectomy for patients with persistent fetal vasculature:a report of 105 cases

AIM：To evaluate the surgical outcomes in eyes with persistent fetal vasculatures（PFV） managed by small gauge pars plicata vitrectomy.METHODS：Consecutive patients with PFV treated by small gauge pars plicata vitrectomy at Beijing Tongren Eye Center between January 2010 and January 2013 were retrospectively reviewed.RESULTS：A total of 118 eyes of 105 patients with PFV were included and undergone small gauge pars plicata vitrectomy,of which 84（71.2%） eyes had lensectomy and 16（13.6%） eyes had lens aspiration and immediate intraocular lens implantation.The percentage of sutured scleral incision of 23 gauge vitrectomy（71.7%,33/46） was higher than that of the 25 gauge vitrectomy（18.1%,13/72）.At last follow-up,visual acuity remained stable in 34 eyes（28.8%） and improved in 84 eyes（71.2%）.Age at surgery（less than 2 y）,anterior type of PFV,and immediate IOL implantation were associated with postoperative improved visual acuity.Sixty five（55.1%） eyes had retinal detachment preoperatively,among which 33（50.8%,33/65） eyes had retinal reattachment or partial retinal reattachment.CONCLUSION：The results suggest that cases with PFV have a potential for developing good visual acuity after small gauge pars plicata vitrectomy with favorable anatomic outcomes and acceptable rate of serious surgical complications.

Impact of vasculature damage on the outcome of spinal cord injury:a novel collagenase-induced model may give new insights into the mechanisms involved

The deleterious effect of vasculature damage on the outcome of spinal cord injury has long been recognized, and numerous clinical studies have shown that the presence of hemorrhage into the spinal cord is directly associated with a poorer neurological outcome. Vascular damage leads to de- creased blood flow to the cord and the release of potentially toxic blood-borne components. Here we consider the mechanisms that may be contributing to hemorrhage-induced damage and discuss the utility of a new model of spinal cord hemorrhage, which was urgently required as most of our current understanding has been extrapolated from intracerebral hemorrhage studies.

Pathological abnormalities in splenic vasculature in non-cirrhotic portal hypertension:Its relevance in the management of portal hypertension

BACKGROUND Portal hypertension(PH)is associated with changes in vascular structure and function of the portosplenomesenteric system(PSMS).This is referred to as portal hypertensive vasculopathy.Pathological abnormalities of PSMS has been described in the literature for cirrhotic patients.Raised portal pressure and hyperdynamic circulation are thought to be the underlying cause of this vasculopathy.In view of this,it is expected that pathological changes in splenic and portal vein similar to those reported in cirrhotic patients with PH may also be present in patients with non-cirrhotic PH(NCPH).AIM To investigate pathological abnormalities of splenic vein in patients with NCPH,and suggest its possible implications in the management of PH.METHODS A prospective observational study was performed on 116 patients with NCPH[Extrahepatic portal vein obstruction(EHPVO):53 and non-cirrhotic portal fibrosis(NCPF):63]who underwent proximal splenorenal shunt(PSRS),interposition shunt or splenectomy with devascularization in JIPMER,Pondicherry,India,a tertiary level referral center,between 2011-2016.All patients were evaluated by Doppler study of PSMS,computed tomography portovenogram and upper gastrointestinal endoscopy.An acoustic resonance forced impulse(ARFI)scan and abdomen ultrasound were done for all cases to exclude cirrhosis.Intraoperative and histopathological assessment of the harvested splenic vein was performed in all.The study group was divided into delayed and early presentation based on the median duration of symptoms(i.e.108 mo).RESULTS The study group comprising of 116 patients[77(66%)females and 39(34%)males]with NCPH had a median age of 22 years.Median duration of symptoms was 108 mo.The most common presentation in both EHPVO and NCPF patients was upper gastrointestinal bleeding(hematemesis and melena).The ARFI scan revealed a median score of 1.2(1.0-1.8)m/s for EHPVO and 1.5(0.9-2.8)m/s for NCPF.PSRS was performed in 84 patients(two of whom underwent interposition PSRS using a 10 mm Dacron graft);splenoadrenal shunt in 9;interposition mesocaval shunt in 5;interposition 1st jejunal to caval shunt in 1 patient and devascularization with splenectomy in 17 patients.Median presplenectomy portal pressure was 25(range:15-51)mm Hg.In 77%cases,the splenic vein was abnormal upon intraoperative assessment.Under macroscopic examination,wall thickening was observed in 108(93%),venous thrombosis in 32(28%)and vein wall calcification in 27(23%)cases.Upon examination under a surgical magnification loupe,21(18%)patients had intimal defects in the splenic vein.Histopathological examination of veins was abnormal in all cases.Medial hypertrophy was noted in nearly all patients(107/116),while intimal fibrosis was seen in 30%.Ninety one percent of patients with intimal fibrosis also had venous thrombosis.Vein wall calcification was found in 22%,all of whom had intimal fibrosis and venous thrombosis.The proportion of patients with pathological abnormalities in the splenic vein were significantly greater in the delayed presentation group as compared to the early presentation group.CONCLUSION Pathological changes in the splenic vein similar to those in cirrhotic patients with PH are noted in NCPH.We recommend that PH in NCPH be treated as systemic and pulmonary hypertension equivalent in the gastrointestinal tract,and that early aggressive therapy be initiated to reduce portal pressure and hemodynamic stress to avoid potential lethal effects.

Role of Smad4 from ocular surface ectoderm in retinal vasculature development

●AIM:To investigate how signals from lens regulate retinal vascular development and neovascularization.●METHODS:Le-Cre transgenic mouse line was employed to inactivate Smad4 in the surface ectoderm selectively.Standard histological and whole-mount retina staining were employed to reveal morphological changes of retinal vasculature in Smad4 defective eye.cDNA microarray and subsequent analyses were conducted to investigate the molecular mechanism underlying the vascular phenotype.Quantitative polymerase chain reaction(qPCR)was carried out to verify the microarrays results.●RESULTS:We found that inactivation of Smad4 specifically on surface ectoderm leads to a variety of retinal vasculature anomalies.Microarray analyses and qPCR revealed that Sema3 c,Sema3 e,Nrp1,Tie1,Sox7,Sox17,and Sox18 are significantly affected in the knockout retinas at different developmental stages,suggesting that ocular surface ectoderm-derived Smad4 can signal to the retina and regulates various angiogenic signaling in the retina.●CONCLUSION:Our data suggest that the cross-talk between ocular surface ectoderm and retina is important for retinal vasculature development,and Smad4 regulates various signaling associated with sprouting angiogenesis,vascular remodeling and maturation in the retina of mice.

Quantitative analysis of retinal vasculature in normal eyes using ultra-widefield fluorescein angiography

AIM:To quantify the area and density of retinal vascularity by ultra-widefield fluorescein angiography(UWFA).METHODS:In a retrospective study,UWFA images were obtained using an ultra-widefield imaging device in 42 normal eyes of 42 patients.Central and peripheral steered images were used to define the edge of retinal vasculature by a certified grader.The length from the center of the optic disc to the edge of retinal vascularity(RVL)in each quadrant and the total retinal vascular perfusion area(RVPA)were determined by the grader using OptosAdvance software.The density of retinal vascularity(RVD)was quantified in different zones of central-steered images using Image J software.RESULTS:Among 42 healthy eyes,the values for mean RVL in each quadrant were 19.007±0.781 mm(superior),18.467±0.869 mm(inferior),17.738±0.622 mm(nasal)and 24.241±1.336 mm(temporal).The mean RVPA was 1140.117±73.825 mm^(2).The mean RVD of the total retina was 4.850%±0.638%.RVD varied significantly between different retina zones(P<0.001),and significant differences existed in the RVD values for total retinal area in patients over 50 years old compared to those under 50 years old(P=0.033).No gender difference was found.CONCLUSION:The UWFA device can be a promising tool for analyzing the overall retinal vasculature and may provide a better understanding of retinal vascular morphology in normal eyes.Aging may be related to lower RVD.

Ocular development in children with unilateral congenital cataract and persistent fetal vasculature

AIM: To investigate the ocular development of patients who had unilateral congenital cataract(CC) combined with persistent fetal vasculature(PFV).METHODS: This cross-sectional, observational study included patients who had unilateral CC and PFV and those with isolated unilateral CC.Axial length(AL), keratometry, anterior chamber depth(ACD), lens thickness, and vitreous length were obtained.The ocular biometric parameters of the affected eyes of patients with CC and PFV were compared with the fellow eyes and with the affected eyes of patients with isolated CC.RESULTS: A total of 110 patients were included and divided into 4 groups: group 1(18 patients with CC and PFV, <24 mo), group 2(22 patients with CC and PFV, ≥24 mo), group 3(35 patients with CC, <24 mo), and group 4(35 patients with CC, ≥24 mo).The ALs of the affected eyes were shorter than those of the fellow eyes in group 1(20.02±1.06 vs 20.66±0.63 mm, P=0.025).While the ALs of the affected eyes were longer than those of the fellow eyes in group 2(23.18±2.00 vs 22.31±1.06 mm, P=0.044) and group 4(22.64±1.80 vs 22.02±1.01 mm, P=0.033).The keratometries of the affected eyes were steeper than those of the fellow eyes in group 2(44.78±1.66 vs 43.83±1.38 D,P=0.041) and group 4(43.76±1.91 vs 43.34±1.46 D, P=0.043).No difference of ACDs between two eyes was found in all groups(all P>0.05).CONCLUSION: Compared with the fellow eyes, the ALs of the eyes with unilateral CC and PFV are shorter in patients younger than 24 mo and longer in those older than 24 mo;the keratometries of the eyes with unilateral CC and PFV are steeper in patients older than 24 mo and similar with those younger than 24 mo.These findings provide further understanding of ocular development in patients with both CC and PFV.

Engineered Vasculature for Organ-on-a-Chip Systems

Organ-on-a-chip technology,a promising three-dimensional(3D)dynamic culture method,ensures accu-rate and efficient cell culture and has great potential for replacing animal models in preclinical testing.The circulatory system,the most abundant organ in the human body,plays a crucial role in oxygen exchange and mass transfer,which is the determining factor for the survival of tissues and organs.Thus,it is essential to integrate the circulatory system into an organ-on-a-chip to recreate tissue and organ microenvironments and physiological functions.This review discusses the synergy between the vasculature and the emerging organ-on-a-chip technology,which offers even better possibilities of dupli-cating physiology and disease characteristics.In addition,we review the different steps of a vascularized organ-on-a-chip fabrication process,including structure fabrication and tissue construction using differ-ent biofabrication strategies.Finally,we outline the applicability of this technology in the fascinating and fast-developing field of organ and tumor culture.

Changes in the peripapillary vasculature and macular thickness after cataract surgery using two phacoemulsification systems with optical coherence tomography angiography

AIM:To assess the changes in the peripapillary vasculature and macular thickness after cataract surgery using two phacoemulsification systems with optical coherence tomography angiography(OCTA).METHODS:Fifty-two eyes of 52 patients with agerelated cataract were randomized into two groups for phacoemulsification:Infiniti group(26 patients)using the Infiniti phacoemulsification system with gravity-fluidics and Centurion group(26 patients)using the Centurion phacoemulsification system with active-fluidics.The peripapillary vessel density(PVD)and macular thickness were examined using OCTA at baseline and at 1d,1 and 3mo after cataract surgery.RESULTS:In the Infiniti group,the PVD was significantly reduced at 1d after the cataract surgery(P<0.001).However,the retinal nerve fiber layer(RNFL)thickness showed no significant change during the follow-up.Change in PVD 1d postoperatively was significantly negatively correlated to the cumulative dissipated energy(CDE),estimated fluid usage(EFU),effective phacoemulsification time(EPT),intraocular pressure(IOP),and total operating time(TOT;P<0.05).The macular thickness was significantly increased in all regions after the cataract surgery(P<0.05).However,no significant changes were found in the macular vessel density(VD)during the follow-up(P>0.05).In the Centurion group,the VD and thickness in the optic papilla and macula did not significantly change in all regions during the follow-up(all P>0.05).The best-corrected visual acuity(BCVA)significantly improved in both groups postoperatively(P<0.001).CONCLUSION:Using the Infiniti phacoemulsification system,OCTA provides a promising analysis of retinal vascular alterations,demonstrating a reduction of the PVD and an increase in the macular thickness.The Centurion phacoemulsification system can provide better retinal vasculature preservation during cataract surgery.

Biomechanical forces in atherosclerosis-susceptible and -resistant regions of human vasculature differentially regulate endothelial vaso-protective phenotypes

Introduction Atherosclerosis is a potentially life-threatening disease of large arteries that is strongly associated with systemic risk factors such as hypercholesterolemia,hypertension,smoking,and diabetes. However,atherosclerosis develops as a

Comparative Anatomy of the Vasculature of the Dog (Canis familiaris) and Domestic Cat (Felis catus) Paw Pad

The microvasculature of footpads in the dog and domestic cat was investigated using histology and scanning electron microscopy of corrosion casts. Methylmethacrylate resin vascular casts for scanning electron microscopy, Indian ink injected whole mount and histological specimens were each prepared, in a series of 16 limbs of 4 adult dogs and 12 limbs of 3 adult domestic cats. The network of blood vessels in the dog paw pad appears to have an intricate pattern, especially with regard to venous outflow forming a peri-arterial venous network. Numerous arteriovenous anastomoses (AVAs) were found in the canine dermis. While, that of the domestic cat had less complex vascular pattern in the footpad without the peri-arterial venous network. AVAs were observed sporadically in the feline dermis. The peri-arterial venous network in the paw pad formed a countercurrent heat exchanger in dogs. When the foot pad is exposed to a cold environment in dogs, the countercurrent heat exchanger serves to prevent heat loss by re-circulating heat back to the body core, adopting an inhospitable environment. AVAs also play a role in regulating the body temperature. A lack of the peri-arterial venous network and few AVAs appear to make felines more prone to suffer from a cold condition than canines.

Evaluating the role of herg potassium-channel protein in the development of heart and vasculature

The role of human ether a-go-go related gene(hERG) in electrically excitable cells has long been known.hERG currents IKr contribute to the re-polarisation phase 3 of the cardiac action potential. Mutations of this channel causes long QT syndrome. N629D hERG mutation(GFGN to GFGD) alters the pore selectivity signature sequence.N629D was over-expressed, via adenoviral gene transfer,in car-diomyocytes derived from mouse embryonic stem cells,the "IKr" showed outward rectification and an inward tail current,while WT IKr showed inward rectification and a positive tail current.N629D "IKr" phenotype also altered resting membrane potential and caused arrhythmia.Since hERG was reported to express in early stage of cardiogenesis,the role of the ERG potassium channel in cardiac development was elaborated in an in vivo model of a homozygous. The hERG N629D mutation was introduced into the orthologous mouse gene,mERG,by homologous recombination in mouse embryonic stem cells. N629D/N629D homozygous mutation results in embryonic lethality(died by E11.5).The mutation displayed defect cardiac morphogenesis including altered looping architecture,poorly developed bulbus cordis,and distorted aortic sac and branchial arches. N629D/N629D myocytes from embryonic day 9.5 embryos manifested complete loss of IKr function, depolarized resting potential,prolonged action potential duration(LQT),failure to repolarize,and propensity to oscillatory arrhythmias.Because deletion of transcription factor Hand2 produces apoptosis in similar regions and with a similar final developmental phenotype,Hand2 expression was evaluated. Robust decrease in Hand2 expression was observed in the secondary heart field in N629D/N629D embryos. mERG protein expression in the developing embryonic heart is not homogeneous.The protein expression is exaggerated in the right ventricle and in the outflow tract.N629D/N629D embryos manifest extensive apoptosis particularly in the first branchial arch and the facial region.Given that cells from the branchial arch populate the outflow tract,the early apoptosis,in the branchial arch and facial region would prevent those cells from contributing to the development of the outflow tract in N629D/N629D hearts.The working model is that the Hand2 expres- sion is down regulated in N629D/N629D embryonic right ventricle and outflow tract because progenitor cells that populate the outflow tract undergo apoptosis while in the facial region and branchial arch. Thus tissues that would be expected to express Hand2 are absent,simply because those structures fail to develop.N629D/N629D embryos also displayed defects in both extraembryonic and intraem-bryonic vasculature.Yolk sac from N629D/N629D homozygous embryos revealed primary vascular networks formed,while they failed to remodel into more complex vascular structures,unlike wild-type yolk sacs at E9.5 N629D/N629D embryo yolk sacs at E9.5 display absence of visible vessels.Intraembry-onic vessels in the mutant showed less complex branching in comparison with the normal vessels structure in WT embryo,dorsal aorta exhibited abnormally formation and small lumens.Whole mount in situ hybridization displayed hERG was also expressed in E9.5 yolk sac and dorsal aorta.Immunofluorescence showed the co-localization of hERG and Cd31 and smooth muscle actin in E10.5. The role of hERG protein in the development of vasculature is further evaluated by using Cre-loxP-based mouse model for tissue specific hERG mutation expression.

Active molecule-based theranostic agents for tumor vasculature normalization and antitumor efficacy

Tumor vascular normalization has emerged as a promising strategy for synergistic therapy recently.Based on the strategy of“fluorescence turn on-controllable release”,a novel bifunctional candidate was con-structed based on previous developed vascular normalization inducer QDAU5,which could self-assemble to form functional enzyme infrared QDAU5 nanoparticles(FEIRQ NPs).Subsequently,biological evaluation demonstrated that the FEIRQ NPs could induce ferroptosis,endoplasmic reticulum stress,and antigen pre-conditioning and maturation of dendritic cells and CD8^(+)T cells,leading to excellent antitumor efficacy in the absence of cytotoxic drugs.Additionally,FEIRQ NPs show high fluorescence intensity upon expo-sure to theβ-galactosidase(β-Gal)enzyme expressed in ovarian cancer,enabling real-time monitoring of therapeutic effects.Overall,our findings suggest a prospering strategy to early diagnosis and efficient therapy for ovarian cancer without cytotoxicity.

Imaging of human parafoveal area with large field of view in adaptive optics line scanning ophthalmoscope

The parafoveal area,with its high concentration of photoreceptors andfine retinal capillaries,is crucial for central vision and often exhibits early signs of pathological changes.The current adaptive optics scanning laser ophthalmoscope(AOSLO)provides an excellent tool to acquire accurate and detailed information about the parafoveal area with cellular resolution.However,limited by the scanning speed of two-dimensional scanning,thefield of view(FOV)in the AOSLO system was usually less than or equal to 2,and the stitching for the parafoveal area required dozens of images,which was time-consuming and laborious.Unfortunately,almost half of patients are unable to obtain stitched images because of their poorfixation.To solve this problem,we integrate AO technology with the line-scan imaging method to build an adaptive optics line scanning ophthalmoscope(AOLSO)system with a larger FOV.In the AOLSO,afocal spherical mirrors in pairs are nonplanar arranged and the distance and angle between optical elements are optimized to minimize the aberrations,two cylinder lenses are orthogonally placed before the imaging sensor to stretch the point spread function(PSF)for sufficiently digitizing light energy.Captured human retinal images show the whole parafoveal area with 55FOV,60 Hz frame rate and cellular resolutions.Take advantage of the 5FOV of the AOLSO,only 9 frames of the retina are captured with several minutes to stitch a montage image with an FOV of 99,in which photoreceptor counting is performed within approximately 5eccentricity.The AOLSO system not only provides cellular resolution but also has the capability to capture the parafoveal region in a single frame,which offers great potential for noninvasive studying of the parafoveal area.

Non-invasive delivery of levodopa-loaded nanoparticles to the brain via lymphatic vasculature to enhance treatment of Parkinson’s disease

Levodopa(L-DOPA),a precursor of dopamine,is commonly prescribed for the treatment of the Parkinson’s disease(PD).However,oral administration of levodopa results in a high level of homocysteine in the peripheral circulation,thereby elevating the risk of cardiovascular disease,and limiting its clinical application.Here,we report a non-invasive method to deliver levodopa to the brain by delivering L-DOPA-loaded sub-50 nm nanoparticles via brain-lymphatic vasculature.The hydrophilic L-DOPA was successfully encapsulated into nanoparticles of tannic acid(TA)/polyvinyl alcohol(PVA)via hydrogen bonding using the flash nanocomplexation(FNC)process,resulting in a high L-DOPA-loading capacity and uniform size in a scalable manner.Pharmacodynamics analysis in a PD rat model demonstrated that the levels of dopamine and tyrosine hydroxylase,which indicate the dopaminergic neuron functions,were increased by 2-and 4-fold,respectively.Movement disorders and cerebral oxidative stress of the rats were significantly improved.This formulation exhibited a high degree of biocompatibility as evidenced by lack of induced inflammation or other pathological changes in major organs.This antioxidative and drug-delivery platform administered through the brain-lymphatic vasculature shows promise for clinical treatment of the PD.

Constructing biomimetic liver models through biomaterials and vasculature engineering

The occurrence of various liver diseases can lead to organ failure of the liver,which is one of the leading causes of mortality worldwide.Liver tissue engineering see the potential for replacing liver transplantation and drug toxicity studies facing donor shortages.The basic elements in liver tissue engineering are cells and biomaterials.Both mature hepatocytes and differentiated stem cells can be used as themain source of cells to construct spheroids and organoids,achieving improved cell function.To mimic the extracellular matrix(ECM)environment,biomaterials need to be biocompatible and bioactive,which also help support cell proliferation and differentiation and allow ECM deposition and vascularized structures formation.In addition,advancedmanufacturing approaches are required to construct the extracellular microenvironment,and it has been proved that the structured three-dimensional culture system can help to improve the activity of hepatocytes and the characterization of specific proteins.In summary,we review biomaterials for liver tissue engineering,including natural hydrogels and synthetic polymers,and advanced processing techniques for building vascularized microenvironments,including bioassembly,bioprinting and microfluidic methods.We then summarize the application fields including transplant and regeneration,disease models and drug cytotoxicity analysis.In the end,we put the challenges and prospects of vascularized liver tissue engineering.

AN ULTRASTRUCTURAL STUDY ON THE EARLY EFFECTS OF PHOTODYNAMIC THERAPY ON MICROVASCULATURE OF TUMORS AND NORMAL ORGANS IN MICE

Photodynamic therapy (PDT)is a new, promising therapeutic modality in cancer treatment. However, the mechanism of its tumoricidal effect has not been fully understood. There is increasing evidence that the disruption of tumor blood flow with subsequent tissue anoxia mainly leads to cellular death after PDT. However, the events leading to the observed changes in blood flow have not been defined. It is well known that an intact