We examined a new method for visualization of the primo vascular system in the rat brain involving lateral ventricle injection of trypan blue. Results showed that the primo vascular system in the lateral ventricles an...We examined a new method for visualization of the primo vascular system in the rat brain involving lateral ventricle injection of trypan blue. Results showed that the primo vascular system in the lateral ventricles and arachnoid mater of the brain were preferentially stained relative to blood vessels and fascia. The primo-vessels along blood vessels in the brain were clearly exhibited. In addition, the primo vascular system was evident between the fourth ventricle and the quadrigeminal cistern. Our experimental findings indicate that this new technique of lateral ventricle injection of trypan blue can visualize the primo vascular system in lateral ventricles and arachnoid mater of rats in situ.展开更多
Endothelial cells arranged on the vessel lumen are constantly stimulated by blood flow,blood pressure and pressureinduced cyclic stretch.These stimuli are sensed through mechanical sensory structures and converted int...Endothelial cells arranged on the vessel lumen are constantly stimulated by blood flow,blood pressure and pressureinduced cyclic stretch.These stimuli are sensed through mechanical sensory structures and converted into a series of functional responses through mechanotransduction pathways.The process will eventually affect vascular health.Therefore,there has been an urgent need to establish in vitro endothelial biomechanics and mechanobiology of models,which reproduce three-dimensional structure vascular system.In recent years,the rapid development in microfluidic technology makes it possible to replicate the key structural and functionally biomechanical characteristics of vessels.Here,we summarized the progress of microfluidic chips used for the investigation of endothelial biomechanics and mechanobiology of the vascular system.Firstly,we elucidated the contribution of shear stress and circumferential stress,to vascular physiology.Then,we reviewed some applications using microfluidic technology in angiogenesis and vasculogenesis,endothelial permeability and mechanotransduction,as well as the blood-brain barrier under these physical forces.Finally,we discussed the future obstacles in terms of the development and application of microfluidic vascular chips.展开更多
Ketone bodies have emerged as central mediators of metabolic health,and multiple beneficial effects of a ketogenic diet,impacting metabolism,neuronal pathologies and,to a certain extent,tumorigenesis,have been reporte...Ketone bodies have emerged as central mediators of metabolic health,and multiple beneficial effects of a ketogenic diet,impacting metabolism,neuronal pathologies and,to a certain extent,tumorigenesis,have been reported both in animal models and clinical research.Ketone bodies,endogenously produced by the liver,act pleiotropically as metabolic intermediates,signaling molecules,and epigenetic modifiers.The endothelium and the vascular system are central regulators of the organism’s metabolic state and become dysfunctional in cardiovascular disease,atherosclerosis,and diabetic micro-and macrovascular complications.As physiological circulating ketone bodies can attain millimolar concentrations,the endothelium is the first-line cell lineage exposed to them.While in diabetic ketoacidosis high ketone body concentrations are detrimental to the vasculature,recent research revealed that ketone bodies in the low millimolar range may exert beneficial effects on endothelial cell(EC)functioning by modulating the EC inflammatory status,senescence,and metabolism.Here,we review the long-held evidence of detrimental cardiovascular effects of ketoacidosis as well as the more recent evidence for a positive impact of ketone bodies—at lower concentrations—on the ECs metabolism and vascular physiology and the subjacent cellular and molecular mechanisms.We also explore arising controversies in the field and discuss the importance of ketone body concentrations in relation to their effects.At low concentration,endogenously produced ketone bodies upon uptake of a ketogenic diet or supplemented ketone bodies(or their precursors)may prove beneficial to ameliorate endothelial function and,consequently,pathologies in which endothelial damage occurs.展开更多
Although aortic aneurysms are the most common type encountered clinically, they do not span the entire spectrum of possible aneurysms of the cardiovascular system. As cross sectional imaging techniques with cardiac co...Although aortic aneurysms are the most common type encountered clinically, they do not span the entire spectrum of possible aneurysms of the cardiovascular system. As cross sectional imaging techniques with cardiac computed tomography and cardiac magnetic resonance imaging continue to improve and becomes more commonplace, once rare cardiovascular aneurysms are being encountered at higher rates. In this review, a series of uncommon, yet clinically important, cardiovascular aneurysms will be presented with review of epidemiology, clinical presentation and complications, imaging features and relevant differential diagnoses, and aneurysm management.展开更多
AIM:To investigate the morphological characteristics of retinal vessels in patients with different severity of diabetic retinopathy(DR)and in patients with or without diabetic macular edema(DME).METHODS:The 239 eyes o...AIM:To investigate the morphological characteristics of retinal vessels in patients with different severity of diabetic retinopathy(DR)and in patients with or without diabetic macular edema(DME).METHODS:The 239 eyes of DR patients and 100 eyes of healthy individuals were recruited for the study.The severity of DR patients was graded as mild,moderate and severe non-proliferative diabetic retinopathy(NPDR)according to the international clinical diabetic retinopathy(ICDR)disease severity scale classification,and retinal vascular morphology was quantitatively analyzed in ultra-wide field images using RU-net and transfer learning methods.The presence of DME was determined by optical coherence tomography(OCT),and differences in vascular morphological characteristics were compared between patients with and without DME.RESULTS:Retinal vessel segmentation using RU-net and transfer learning system had an accuracy of 99%and a Dice metric of 0.76.Compared with the healthy group,the DR group had smaller vessel angles(33.68±3.01 vs 37.78±1.60),smaller fractal dimension(Df)values(1.33±0.05 vs 1.41±0.03),less vessel density(1.12±0.44 vs 2.09±0.36)and fewer vascular branches(206.1±88.8 vs 396.5±91.3),all P<0.001.As the severity of DR increased,Df values decreased,P=0.031.No significant difference between the DME and non-DME groups were observed in vascular morphological characteristics.CONCLUSION:In this study,an artificial intelligence retinal vessel segmentation system is used with 99%accuracy,thus providing with relatively satisfactory performance in the evaluation of quantitative vascular morphology.DR patients have a tendency of vascular occlusion and dropout.The presence of DME does not compromise the integral retinal vascular pattern.展开更多
Mimicking vascular systems in living beings,designers have realized microvascular composites to achieve thermal regulation and other functionalities,such as electromagnetic modulation,sensing,and healing.Such material...Mimicking vascular systems in living beings,designers have realized microvascular composites to achieve thermal regulation and other functionalities,such as electromagnetic modulation,sensing,and healing.Such material systems avail circulating fluids through embedded vasculatures to accomplish the mentioned functionalities that benefit various aerospace,military,and civilian applications.Although heat transfer is a mature field,control of thermal characteristics in synthetic microvascular systems via circulating fluids is new,and a theoretical underpinning is lacking.What will benefit designers are predictive mathematical models and an in-depth qualitative understanding of vascular-based active cooling/heating.So,the central focus of this paper is to address the remarked knowledge gap.First,we present a reduced-order model with broad applicability,allowing the inlet temperature to differ from the ambient temperature.Second,we apply mathematical analysis tools to this reduced-order model and reveal many heat transfer properties of fluid-sequestered vascular systems.We derive point-wise properties(minimum,maximum,and comparison principles)and global properties(e.g.,bounds on performance metrics such as the mean surface temperature and thermal efficiency).These newfound results deepen our understanding of active cooling/heating and propel the perfecting of thermal regulation systems.展开更多
The aim of this review is to present and compare the various animal models of vascularized nerve grafts described in the literature as well as to summarize preclinical evidence for superior functional results compared...The aim of this review is to present and compare the various animal models of vascularized nerve grafts described in the literature as well as to summarize preclinical evidence for superior functional results compared to non-vascularized free nerve grafts. We also will present the state of the art on prefabricated vascularized nerve grafts. A systematic literature review on vascularized nerve graft models was conducted via the retrieval with the Pub Med database on March 30, 2019. Data on the animal, nerve, and vascularization model, the recipient bed, the evaluation time points and methods, and the results of the study results were extracted and analyzed from selected articles. The rat sciatic nerve was the most popular model for vascularized nerve grafts, followed by the rabbit;however, rabbit models allow for longer nerve grafts, which are suitable for translational evaluation, and produced more cautious results on the superiority of vascularized nerve grafts. Compared to free nerve grafts, vascularized nerve grafts have better early but similar long-term results, especially in an avascular bed. There are few studies on avascular receiving beds and prefabricated nerve grafts. The clinical translation potential of available animal models is limited, and current experimental knowledge cannot fully support that the differences between vascularized nerve grafts and free nerve grafts yield a clinical advantage that justifies the complexity of the procedure.展开更多
Background: Elevated Fontan pressure (FP) alone cannot fully predict clinical outcomes. We hypothesized thathemodynamic profiling using a cardiac index (CI)-systemic vascular resistance (SVR) plot could characterize c...Background: Elevated Fontan pressure (FP) alone cannot fully predict clinical outcomes. We hypothesized thathemodynamic profiling using a cardiac index (CI)-systemic vascular resistance (SVR) plot could characterize clinicalfeatures and predict the prognosis of post-Fontan patients. Methods: We included post-Fontan patients whounderwent cardiac catheterization at age < 10 years. Patients were classified into four categories: A, CI ≥ 3, SVRindex (SVRI) ≥ 20;B, CI < 3, SVRI ≥ 20;C, CI ≥ 3, SVRI < 20;and D, CI < 3, SVRI < 20. The primary outcome wasfreedom from the combined endpoint: new onset of protein-losing enteropathy or plastic bronchitis, heart transplant,and death. Clinical and hemodynamic variables and freedom from the endpoint were compared betweenthe hemodynamic categories and outcome predictors were evaluated. Results: Eighty-three patients wereincluded. Median follow-up was 5.3 years. Category A/B/C/D consisted of 4/15/53/11 patients, respectively. Allthe patients in category A were New York Heart Association I/II and had a significantly lower pulmonary vascularresistance index (PVRI). Patients in category C had lower pulmonary/systemic blood flow. Patients in category Dhad a higher PVRI and had the poorest freedom from the endpoint (44% at 5 years). Elevated FP and category Dwere outcome predictors. Conclusions: CI-SVR plots was a novel adjunctive method for Fontan hemodynamicprofiling.展开更多
Background Vascular hyporeactivity and leakage are key pathophysiologic features that produce multi-organ damage upon sepsis.We hypothesized that pericytes,a group of pluripotent cells that maintain vascular integrity...Background Vascular hyporeactivity and leakage are key pathophysiologic features that produce multi-organ damage upon sepsis.We hypothesized that pericytes,a group of pluripotent cells that maintain vascular integrity and tension,are protective against sepsis via regulating vascular reactivity and permeability.Methods We conducted a series of in vivo experiments using wild-type(WT),platelet-derived growth factor receptor-β(PDGFR-β)-Cre+mT/mG transgenic mice and Tie2-Cre+Cx43^(flox/flox)mice to examine the relative contribution of pericytes in sepsis,either induced by cecal ligation and puncture(CLP)or lipopolysaccharide(LPS)challenge.In a separate set of experiments with Sprague-Dawley(SD)rats,pericytes were depleted using CP-673451,a selective PDGFR-βinhibitor,at a dosage of 40 mg/(kg·d)for 7 consecutive days.Cultured pericytes,vascular endothelial cells(VECs)and vascular smooth muscle cells(VSMCs)were used for mechanistic investigations.The effects of pericytes and pericyte-derived microvesicles(PCMVs)and candidate miRNAs on vascular reactivity and barrier function were also examined.Results CLP and LPS induced severe injury/loss of pericytes,vascular hyporeactivity and leakage(P<0.05).Transplantation with exogenous pericytes protected vascular reactivity and barrier function via microvessel colonization(P<0.05).Cx43 knockout in either pericytes or VECs reduced pericyte colonization in microvessels(P<0.05).Additionally,PCMVs transferred miR-145 and miR-132 to VSMCs and VECs,respectively,exerting a protective effect on vascular reactivity and barrier function after sepsis(P<0.05).miR-145 primarily improved the contractile response of VSMCs by activating the sphingosine kinase 2(Sphk2)/sphingosine-1-phosphate receptor(S1PR)1/phosphorylation of myosin light chain 20 pathway,whereas miR-132 effectively improved the barrier function of VECs by activating the Sphk2/S1PR2/zonula occludens-1 and vascular endothelial-cadherin pathways.Conclusions Pericytes are protective against sepsis through regulating vascular reactivity and barrier function.Possible mechanisms include both direct colonization of microvasculature and secretion of PCMVs.展开更多
Three-dimensional(3D)printing and bioprinting have come into view for a plannable and standardizable generation of implantable tissue-engineered constructs that can substitute native tissues and organs.These tissue-en...Three-dimensional(3D)printing and bioprinting have come into view for a plannable and standardizable generation of implantable tissue-engineered constructs that can substitute native tissues and organs.These tissue-engineered structures are intended to integrate with the patient’s body.Vascular tissue engineering(TE)is relevant in TE because it supports the sustained oxygenization and nutrition of all tissue-engineered constructs.Bioinks have a specific role,representingthenecessarymedium for printability and vascular cell growth.This review aims to understand the requirements for the design of vascular bioinks.First,an in-depth analysis of vascular cell interaction with their native environment must be gained.A physiological bioink suitable for a tissue-engineered vascular graft(TEVG)must not only ensure good printability but also induce cells to behave like in a native vascular vessel,including self-regenerative and growth functions.This review describes the general structure of vascular walls with wall-specific cell and extracellular matrix(ECM)components and biomechanical properties and functions.Furthermore,the physiological role of vascular ECM components for their interaction with vascular cells and the mode of interaction is introduced.Diverse currently available or imaginable bioinks are described from physiological matrix proteins to nonphysiologically occurring but natural chemical compounds useful for vascular bioprinting.The physiological performance of these bioinks is evaluated with regard to biomechanical properties postprinting,with a view to current animal studies of 3D printed vascular structures.Finally,the main challenges for further bioink development,suitable bioink components to create a self-assembly bioink concept,and future bioprinting strategies are outlined.These concepts are discussed in terms of their suitability to be part of a TEVG with a high potential for later clinical use.展开更多
Dear Editor,Three dimensional(3D)bioprinted extracellular matrix(ECM)can be used to provide both biochemical and biophysical cues to direct mesenchymal stem cells(MSCs)differentiation,and then differentiated cells wer...Dear Editor,Three dimensional(3D)bioprinted extracellular matrix(ECM)can be used to provide both biochemical and biophysical cues to direct mesenchymal stem cells(MSCs)differentiation,and then differentiated cells were isolated for implantation in vivo using surgical procedures.However,the reduced cell activity after cell isolation from 3D constructs and low cell retention in injured sites limit its application[1].Methacrylated gelatin(GelMA)hydrogel has the advantage of fast crosslinking,which could resemble complex architectures of tissue construct in vivo[2].Here,we adopted a noninvasive bioprinting procedure to imitate the regenerative microenvironment that could simultaneously direct the sweat gland(SG)and vascular differentiation from MSCs and ultimately promote the replacement of glandular tissue in situ(Fig.1a).展开更多
Adequate vascularization is a critical determinant for the successful construction and clinical implementation of complex organotypic tissue models. Currently, low cell and vessel density and insufficient vascular mat...Adequate vascularization is a critical determinant for the successful construction and clinical implementation of complex organotypic tissue models. Currently, low cell and vessel density and insufficient vascular maturation make vascularized organotypic tissue construction difficult,greatly limiting its use in tissue engineering and regenerative medicine. To address these limitations, recent studies have adopted pre-vascularized microtissue assembly for the rapid generation of functional tissue analogs with dense vascular networks and high cell density. In this article, we summarize the development of module assembly-based vascularized organotypic tissue construction and its application in tissue repair and regeneration, organ-scale tissue biomanufacturing, as well as advanced tissue modeling.展开更多
Blood vessels constitute a closed pipe system distributed throughout the body,transporting blood from the heart to other organs and delivering metabolic waste products back to the lungs and kidneys.Changes in blood ve...Blood vessels constitute a closed pipe system distributed throughout the body,transporting blood from the heart to other organs and delivering metabolic waste products back to the lungs and kidneys.Changes in blood vessels are related to many disorders like stroke,myocardial infarction,aneurysm,and diabetes,which are important causes of death worldwide.Translational research for new appro-aches to disease modeling and effective treatment is needed due to the huge socio-economic burden on healthcare systems.Although mice or rats have been widely used,applying data from animal studies to human-specific vascular physiology and pathology is difficult.The rise of induced pluripotent stem cells(iPSCs)provides a reliable in vitro resource for disease modeling,regenerative medicine,and drug discovery because they carry all human genetic information and have the ability to directionally differentiate into any type of human cells.This review summarizes the latest progress from the establishment of iPSCs,the strategies for differentiating iPSCs into vascular cells,and the in vivo trans-plantation of these vascular derivatives.It also introduces the application of these technologies in disease modeling,drug screening,and regenerative medicine.Additionally,the application of high-tech tools,such as omics analysis and high-throughput sequencing,in this field is reviewed.展开更多
Synthetic vascular grafts suitable for small-diameter arteries(<6 mm) are in great need.However,there are still no commercially available small-diameter vascular grafts(SDVGs) in clinical practice due to thrombosis...Synthetic vascular grafts suitable for small-diameter arteries(<6 mm) are in great need.However,there are still no commercially available small-diameter vascular grafts(SDVGs) in clinical practice due to thrombosis and stenosis after in vivo implantation.When designing SDVGs,many studies emphasized reendothelization but ignored the importance of reconstruction of the smooth muscle layer(SML).To facilitate rapid SML regeneration,a high-resolution 3D printing method was used to create a novel bilayer SDVG with structures and mechanical properties mimicking natural arteries.Bioinspired by the collagen alignment of SML,the inner layer of the grafts had larger pore sizes and high porosity to accelerate the infiltration of cells and their circumferential alignment,which could facilitate SML reconstruction for compliance restoration and spontaneous endothelialization.The outer layer was designed to induce fibroblast recruitment by low porosity and minor pore size and provide SDVG with sufficient mechanical strength.One month after implantation,the arteries regenerated by 3D-printed grafts exhibited better pulsatility than electrospun grafts,with a compliance(8.9%) approaching that of natural arteries(11.36%) and significantly higher than that of electrospun ones(1.9%).The 3D-printed vascular demonstrated a three-layer structure more closely resembling natural arteries while electrospun grafts showed incomplete endothelium and immature SML.Our study shows the importance of SML reconstruction during vascular graft regeneration and provides an effective strategy to reconstruct blood vessels through 3D-printed structures rapidly.展开更多
Background:Circular RNAs(circRNAs)have been recognized as significant regulators of pulmonary hypertension(PH);however,the differential expression and function of circRNAs in different vascular cells under hypoxia rem...Background:Circular RNAs(circRNAs)have been recognized as significant regulators of pulmonary hypertension(PH);however,the differential expression and function of circRNAs in different vascular cells under hypoxia remain unknown.Here,we identified co-differentially expressed circRNAs and determined their putative roles in the proliferation of pulmonary artery smooth muscle cells(PASMCs),pulmonary microvascular endothelial cells(PMECs),and pericytes(PCs)under hypoxia.Methods:Whole transcriptome sequencing was performed to analyze the differential expression of circRNAs in three different vascular cell types.Bioinformatic analysis was used to predict their putative biological function.Quantitative real-time polymerase chain reaction,Cell Counting Kit-8,and EdU Cell Proliferation assays were carried out to determine the role of circular postmeiotic segregation 1(circPMS1)as well as its potential sponge mechanism in PASMCs,PMECs,and PCs.Results:PASMCs,PMECs,and PCs exhibited 16,99,and 31 differentially expressed circRNAs under hypoxia,respectively.CircPMS1 was upregulated in PASMCs,PMECs,and PCs under hypoxia and enhanced the proliferation of vascular cells.CircPMS1may upregulate DEP domain containing 1(DEPDC1)and RNA polymerase II subunit D expression by targeting microRNA-432-5p(miR-432-5p)in PASMCs,upregulate MAX interactor 1(MXI1)expression by targeting miR-433-3p in PMECs,and upregulate zinc finger AN1-type containing 5(ZFAND5)expression by targeting miR-3613-5p in PCs.Conclusions:Our results suggest that circPMS1 promotes cell proliferation through the miR-432-5p/DEPDC1 or miR-432-5p/POL2D axis in PASMCs,through the miR-433-3p/MXI1 axis in PMECs,and through the miR-3613-5p/ZFAND5 axis in PCs,which provides putative targets for the early diagnosis and treatment of PH.展开更多
With an increase in global aging,the number of people affected by cerebrovascular diseases is also increasing,and the incidence of vascular dementia-closely related to cerebrovascular risk-is increasing at an epidemic...With an increase in global aging,the number of people affected by cerebrovascular diseases is also increasing,and the incidence of vascular dementia-closely related to cerebrovascular risk-is increasing at an epidemic rate.However,few therapeutic options exist that can markedly improve the cognitive impairment and prognosis of vascular dementia patients.Similarly in Alzheimer’s disease and other neurological disorders,synaptic dysfunction is recognized as the main reason for cognitive decline.Nitric oxide is one of the ubiquitous gaseous cellular messengers involved in multiple physiological and pathological processes of the central nervous system.Recently,nitric oxide has been implicated in regulating synaptic plasticity and plays an important role in the pathogenesis of vascular dementia.This review introduces in detail the emerging role of nitric oxide in physiological and pathological states of vascular dementia and summarizes the diverse effects of nitric oxide on different aspects of synaptic dysfunction,neuroinflammation,oxidative stress,and blood-brain barrier dysfunction that underlie the progress of vascular dementia.Additionally,we propose that targeting the nitric oxide-sGC-cGMP pathway using certain specific approaches may provide a novel therapeutic strategy for vascular dementia.展开更多
Peripheral nerve injuries induce a severe motor and sensory deficit. Since the availability of autologous nerve transplants for nerve repair is very limited, alternative treatment strategies are sought, including the ...Peripheral nerve injuries induce a severe motor and sensory deficit. Since the availability of autologous nerve transplants for nerve repair is very limited, alternative treatment strategies are sought, including the use of tubular nerve guidance conduits(tNGCs). However, the use of tNGCs results in poor functional recovery and central necrosis of the regenerating tissue, which limits their application to short nerve lesion defects(typically shorter than 3 cm). Given the importance of vascularization in nerve regeneration, we hypothesized that enabling the growth of blood vessels from the surrounding tissue into the regenerating nerve within the tNGC would help eliminate necrotic processes and lead to improved regeneration. In this study, we reported the application of macroscopic holes into the tubular walls of silk-based tNGCs and compared the various features of these improved silk^(+) tNGCs with the tubes without holes(silk^(–) tNGCs) and autologous nerve transplants in an 8-mm sciatic nerve defect in rats. Using a combination of micro-computed tomography and histological analyses, we were able to prove that the use of silk^(+) tNGCs induced the growth of blood vessels from the adjacent tissue to the intraluminal neovascular formation. A significantly higher number of blood vessels in the silk^(+) group was found compared with autologous nerve transplants and silk^(–), accompanied by improved axon regeneration at the distal coaptation point compared with the silk^(–) tNGCs at 7 weeks postoperatively. In the 15-mm(critical size) sciatic nerve defect model, we again observed a distinct ingrowth of blood vessels through the tubular walls of silk^(+) tNGCs, but without improved functional recovery at 12 weeks postoperatively. Our data proves that macroporous tNGCs increase the vascular supply of regenerating nerves and facilitate improved axonal regeneration in a short-defect model but not in a critical-size defect model. This study suggests that further optimization of the macroscopic holes silk^(+) tNGC approach containing macroscopic holes might result in improved grafting technology suitable for future clinical use.展开更多
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
Background:Mufangji tang(MFJT)is composed of Ramulus Cinnamomi,Radix Ginseng,Cocculus orbiculatus(Linn.)DC.,and Gypsum.In clinical settings,MFJT has been effectively employed in addressing a range of respiratory disor...Background:Mufangji tang(MFJT)is composed of Ramulus Cinnamomi,Radix Ginseng,Cocculus orbiculatus(Linn.)DC.,and Gypsum.In clinical settings,MFJT has been effectively employed in addressing a range of respiratory disorders,notably including pulmonary arterial hypertension(PAH).However,the mechanism of action of MFJT on PAH remains unknown.Methods:In this study,a monocrotaline-induced PAH rat model was established and treated with MFJT.The therapeutic effects of MFJT on PAH rat model were evaluated.Network pharmacology was conducted to screen the possible targets for MFJT on PAH,and the molecular docking between the main active components and the core targets was carried out.The key targets identified from network pharmacology were tested.Results:Results showed significant therapeutic effects of MFJT on PAH rat model.Analysis of network pharmacology revealed several potential targets related to apoptosis,inflammation,oxidative stress,and vascular remodeling.Molecular docking showed that the key components were well docked with the core targets.Further experimental validation results that MFJT treatment induced apoptosis(downregulated Bcl-2 levels and upregulated Bax levels in lung tissue),inhibited inflammatory response and oxdative stress(decreased the levels of IL-1β,TNF-α,inducible NOS,and malondialdehyde,and increased the levels of endothelial nitric oxide synthase,nitric oxide,glutathione and superoxide dismutase),reduced the proliferation of pulmonary arterial smooth muscle cells(downregulated ET-1 andβ-catenin levels and ERK1/2 phosphorylation,increased GSK3βlevels).Conclusion:Our study revealed MFJT treatment could alleviate PAH in rats via induction of apoptosis,inhibition of inflammation and oxidative stress,and the prevention of vascular remodeling.展开更多
Background:Porto-sinusoidal vascular disease(PSVD)and portal vein thrombosis(PVT)are causes of portal hypertension characterized respectively by an intrahepatic and a pre-hepatic obstacle to the flow in the portal sys...Background:Porto-sinusoidal vascular disease(PSVD)and portal vein thrombosis(PVT)are causes of portal hypertension characterized respectively by an intrahepatic and a pre-hepatic obstacle to the flow in the portal system.As PVT may be a consequence of PSVD,in PVT patients at presentation,a pre-existing PSVD should be suspected.In these patients the identification of an underlying PSVD would have relevant implication regarding follow-up and therapeutic management,but it could be challenging.In this setting ultrasonography may be valuable in differential diagnosis.The aim of the study was to use ultrasonography to identify parameters to discriminate between PSVD and“pure”PVT and then to suspect PVT secondary to a pre-existing PSVD.Methods:Fifty-three patients with histologically proven PSVD and forty-eight patients affected by chronic PVT were enrolled and submitted to abdominal ultrasonography with elastography by acoustic radiation force impulse(ARFI).Results:ARFI was higher and superior mesenteric vein(SMV)diameter was wider in PSVD patients than in PVT patients.Thus,a prognostic score was obtained as linear combinations of the two parameters with a good discrimination capacity between PSVD and PVT(the area under the curve=0.780;95%confidence interval:0.690-0.869).Conclusions:A score based on ARFI and SMV diameter may be useful to suspect an underlying PSVD in patients with PVT and to identify a subgroup of patients to be submitted to liver biopsy.展开更多
基金the National Natural Science Foundation of China for Youths (General Program),No.30801464the National Basic Research Program of China (973 Program),No.2007CB512705the GIST Systems Biology Program of Korea in 2010
文摘We examined a new method for visualization of the primo vascular system in the rat brain involving lateral ventricle injection of trypan blue. Results showed that the primo vascular system in the lateral ventricles and arachnoid mater of the brain were preferentially stained relative to blood vessels and fascia. The primo-vessels along blood vessels in the brain were clearly exhibited. In addition, the primo vascular system was evident between the fourth ventricle and the quadrigeminal cistern. Our experimental findings indicate that this new technique of lateral ventricle injection of trypan blue can visualize the primo vascular system in lateral ventricles and arachnoid mater of rats in situ.
基金supported by the National Natural Science Research Foundation of China(61533016,11827803,31971244,31570947,11772036,11421202 and U20A20390)the National Key Research and Development Program of China(2016YFC1102202 and 2016YFC1101101)Beijing Natural Science Foundation(4194079)and the 111 Project(B13003).
文摘Endothelial cells arranged on the vessel lumen are constantly stimulated by blood flow,blood pressure and pressureinduced cyclic stretch.These stimuli are sensed through mechanical sensory structures and converted into a series of functional responses through mechanotransduction pathways.The process will eventually affect vascular health.Therefore,there has been an urgent need to establish in vitro endothelial biomechanics and mechanobiology of models,which reproduce three-dimensional structure vascular system.In recent years,the rapid development in microfluidic technology makes it possible to replicate the key structural and functionally biomechanical characteristics of vessels.Here,we summarized the progress of microfluidic chips used for the investigation of endothelial biomechanics and mechanobiology of the vascular system.Firstly,we elucidated the contribution of shear stress and circumferential stress,to vascular physiology.Then,we reviewed some applications using microfluidic technology in angiogenesis and vasculogenesis,endothelial permeability and mechanotransduction,as well as the blood-brain barrier under these physical forces.Finally,we discussed the future obstacles in terms of the development and application of microfluidic vascular chips.
基金Supported by Polish National Science Centre,Project Grant NCN Harmonia,No.2019/30/M/NZ3/00682NAWA/Campusfrance Polonium,No.PPN/X/RJ/1876/2019.
文摘Ketone bodies have emerged as central mediators of metabolic health,and multiple beneficial effects of a ketogenic diet,impacting metabolism,neuronal pathologies and,to a certain extent,tumorigenesis,have been reported both in animal models and clinical research.Ketone bodies,endogenously produced by the liver,act pleiotropically as metabolic intermediates,signaling molecules,and epigenetic modifiers.The endothelium and the vascular system are central regulators of the organism’s metabolic state and become dysfunctional in cardiovascular disease,atherosclerosis,and diabetic micro-and macrovascular complications.As physiological circulating ketone bodies can attain millimolar concentrations,the endothelium is the first-line cell lineage exposed to them.While in diabetic ketoacidosis high ketone body concentrations are detrimental to the vasculature,recent research revealed that ketone bodies in the low millimolar range may exert beneficial effects on endothelial cell(EC)functioning by modulating the EC inflammatory status,senescence,and metabolism.Here,we review the long-held evidence of detrimental cardiovascular effects of ketoacidosis as well as the more recent evidence for a positive impact of ketone bodies—at lower concentrations—on the ECs metabolism and vascular physiology and the subjacent cellular and molecular mechanisms.We also explore arising controversies in the field and discuss the importance of ketone body concentrations in relation to their effects.At low concentration,endogenously produced ketone bodies upon uptake of a ketogenic diet or supplemented ketone bodies(or their precursors)may prove beneficial to ameliorate endothelial function and,consequently,pathologies in which endothelial damage occurs.
文摘Although aortic aneurysms are the most common type encountered clinically, they do not span the entire spectrum of possible aneurysms of the cardiovascular system. As cross sectional imaging techniques with cardiac computed tomography and cardiac magnetic resonance imaging continue to improve and becomes more commonplace, once rare cardiovascular aneurysms are being encountered at higher rates. In this review, a series of uncommon, yet clinically important, cardiovascular aneurysms will be presented with review of epidemiology, clinical presentation and complications, imaging features and relevant differential diagnoses, and aneurysm management.
基金Supported by Zhejiang Medical Health Science and Technology Project(No.2023KY490).
文摘AIM:To investigate the morphological characteristics of retinal vessels in patients with different severity of diabetic retinopathy(DR)and in patients with or without diabetic macular edema(DME).METHODS:The 239 eyes of DR patients and 100 eyes of healthy individuals were recruited for the study.The severity of DR patients was graded as mild,moderate and severe non-proliferative diabetic retinopathy(NPDR)according to the international clinical diabetic retinopathy(ICDR)disease severity scale classification,and retinal vascular morphology was quantitatively analyzed in ultra-wide field images using RU-net and transfer learning methods.The presence of DME was determined by optical coherence tomography(OCT),and differences in vascular morphological characteristics were compared between patients with and without DME.RESULTS:Retinal vessel segmentation using RU-net and transfer learning system had an accuracy of 99%and a Dice metric of 0.76.Compared with the healthy group,the DR group had smaller vessel angles(33.68±3.01 vs 37.78±1.60),smaller fractal dimension(Df)values(1.33±0.05 vs 1.41±0.03),less vessel density(1.12±0.44 vs 2.09±0.36)and fewer vascular branches(206.1±88.8 vs 396.5±91.3),all P<0.001.As the severity of DR increased,Df values decreased,P=0.031.No significant difference between the DME and non-DME groups were observed in vascular morphological characteristics.CONCLUSION:In this study,an artificial intelligence retinal vessel segmentation system is used with 99%accuracy,thus providing with relatively satisfactory performance in the evaluation of quantitative vascular morphology.DR patients have a tendency of vascular occlusion and dropout.The presence of DME does not compromise the integral retinal vascular pattern.
文摘Mimicking vascular systems in living beings,designers have realized microvascular composites to achieve thermal regulation and other functionalities,such as electromagnetic modulation,sensing,and healing.Such material systems avail circulating fluids through embedded vasculatures to accomplish the mentioned functionalities that benefit various aerospace,military,and civilian applications.Although heat transfer is a mature field,control of thermal characteristics in synthetic microvascular systems via circulating fluids is new,and a theoretical underpinning is lacking.What will benefit designers are predictive mathematical models and an in-depth qualitative understanding of vascular-based active cooling/heating.So,the central focus of this paper is to address the remarked knowledge gap.First,we present a reduced-order model with broad applicability,allowing the inlet temperature to differ from the ambient temperature.Second,we apply mathematical analysis tools to this reduced-order model and reveal many heat transfer properties of fluid-sequestered vascular systems.We derive point-wise properties(minimum,maximum,and comparison principles)and global properties(e.g.,bounds on performance metrics such as the mean surface temperature and thermal efficiency).These newfound results deepen our understanding of active cooling/heating and propel the perfecting of thermal regulation systems.
文摘The aim of this review is to present and compare the various animal models of vascularized nerve grafts described in the literature as well as to summarize preclinical evidence for superior functional results compared to non-vascularized free nerve grafts. We also will present the state of the art on prefabricated vascularized nerve grafts. A systematic literature review on vascularized nerve graft models was conducted via the retrieval with the Pub Med database on March 30, 2019. Data on the animal, nerve, and vascularization model, the recipient bed, the evaluation time points and methods, and the results of the study results were extracted and analyzed from selected articles. The rat sciatic nerve was the most popular model for vascularized nerve grafts, followed by the rabbit;however, rabbit models allow for longer nerve grafts, which are suitable for translational evaluation, and produced more cautious results on the superiority of vascularized nerve grafts. Compared to free nerve grafts, vascularized nerve grafts have better early but similar long-term results, especially in an avascular bed. There are few studies on avascular receiving beds and prefabricated nerve grafts. The clinical translation potential of available animal models is limited, and current experimental knowledge cannot fully support that the differences between vascularized nerve grafts and free nerve grafts yield a clinical advantage that justifies the complexity of the procedure.
文摘Background: Elevated Fontan pressure (FP) alone cannot fully predict clinical outcomes. We hypothesized thathemodynamic profiling using a cardiac index (CI)-systemic vascular resistance (SVR) plot could characterize clinicalfeatures and predict the prognosis of post-Fontan patients. Methods: We included post-Fontan patients whounderwent cardiac catheterization at age < 10 years. Patients were classified into four categories: A, CI ≥ 3, SVRindex (SVRI) ≥ 20;B, CI < 3, SVRI ≥ 20;C, CI ≥ 3, SVRI < 20;and D, CI < 3, SVRI < 20. The primary outcome wasfreedom from the combined endpoint: new onset of protein-losing enteropathy or plastic bronchitis, heart transplant,and death. Clinical and hemodynamic variables and freedom from the endpoint were compared betweenthe hemodynamic categories and outcome predictors were evaluated. Results: Eighty-three patients wereincluded. Median follow-up was 5.3 years. Category A/B/C/D consisted of 4/15/53/11 patients, respectively. Allthe patients in category A were New York Heart Association I/II and had a significantly lower pulmonary vascularresistance index (PVRI). Patients in category C had lower pulmonary/systemic blood flow. Patients in category Dhad a higher PVRI and had the poorest freedom from the endpoint (44% at 5 years). Elevated FP and category Dwere outcome predictors. Conclusions: CI-SVR plots was a novel adjunctive method for Fontan hemodynamicprofiling.
基金supported by the Key Projects and Innovation Group of National Natural Science Foundation of China(81830065),the Innovation Groups of NSFC(81721001),and the Young Scientists Fund(82102279).
文摘Background Vascular hyporeactivity and leakage are key pathophysiologic features that produce multi-organ damage upon sepsis.We hypothesized that pericytes,a group of pluripotent cells that maintain vascular integrity and tension,are protective against sepsis via regulating vascular reactivity and permeability.Methods We conducted a series of in vivo experiments using wild-type(WT),platelet-derived growth factor receptor-β(PDGFR-β)-Cre+mT/mG transgenic mice and Tie2-Cre+Cx43^(flox/flox)mice to examine the relative contribution of pericytes in sepsis,either induced by cecal ligation and puncture(CLP)or lipopolysaccharide(LPS)challenge.In a separate set of experiments with Sprague-Dawley(SD)rats,pericytes were depleted using CP-673451,a selective PDGFR-βinhibitor,at a dosage of 40 mg/(kg·d)for 7 consecutive days.Cultured pericytes,vascular endothelial cells(VECs)and vascular smooth muscle cells(VSMCs)were used for mechanistic investigations.The effects of pericytes and pericyte-derived microvesicles(PCMVs)and candidate miRNAs on vascular reactivity and barrier function were also examined.Results CLP and LPS induced severe injury/loss of pericytes,vascular hyporeactivity and leakage(P<0.05).Transplantation with exogenous pericytes protected vascular reactivity and barrier function via microvessel colonization(P<0.05).Cx43 knockout in either pericytes or VECs reduced pericyte colonization in microvessels(P<0.05).Additionally,PCMVs transferred miR-145 and miR-132 to VSMCs and VECs,respectively,exerting a protective effect on vascular reactivity and barrier function after sepsis(P<0.05).miR-145 primarily improved the contractile response of VSMCs by activating the sphingosine kinase 2(Sphk2)/sphingosine-1-phosphate receptor(S1PR)1/phosphorylation of myosin light chain 20 pathway,whereas miR-132 effectively improved the barrier function of VECs by activating the Sphk2/S1PR2/zonula occludens-1 and vascular endothelial-cadherin pathways.Conclusions Pericytes are protective against sepsis through regulating vascular reactivity and barrier function.Possible mechanisms include both direct colonization of microvasculature and secretion of PCMVs.
文摘Three-dimensional(3D)printing and bioprinting have come into view for a plannable and standardizable generation of implantable tissue-engineered constructs that can substitute native tissues and organs.These tissue-engineered structures are intended to integrate with the patient’s body.Vascular tissue engineering(TE)is relevant in TE because it supports the sustained oxygenization and nutrition of all tissue-engineered constructs.Bioinks have a specific role,representingthenecessarymedium for printability and vascular cell growth.This review aims to understand the requirements for the design of vascular bioinks.First,an in-depth analysis of vascular cell interaction with their native environment must be gained.A physiological bioink suitable for a tissue-engineered vascular graft(TEVG)must not only ensure good printability but also induce cells to behave like in a native vascular vessel,including self-regenerative and growth functions.This review describes the general structure of vascular walls with wall-specific cell and extracellular matrix(ECM)components and biomechanical properties and functions.Furthermore,the physiological role of vascular ECM components for their interaction with vascular cells and the mode of interaction is introduced.Diverse currently available or imaginable bioinks are described from physiological matrix proteins to nonphysiologically occurring but natural chemical compounds useful for vascular bioprinting.The physiological performance of these bioinks is evaluated with regard to biomechanical properties postprinting,with a view to current animal studies of 3D printed vascular structures.Finally,the main challenges for further bioink development,suitable bioink components to create a self-assembly bioink concept,and future bioprinting strategies are outlined.These concepts are discussed in terms of their suitability to be part of a TEVG with a high potential for later clinical use.
基金supported by the Science Fund for National Defense Distinguished Young Scholars(2022-JCJQ-ZQ-016)the Key Basic Research Projects of the Foundation Strengthening Plan(2022-JCJQZD-096-00)+2 种基金the National Key Research and Development Program of China(2022YFA1104604)the National Natural Science Foundation of China(32000969)the Key Support Program for Growth Factor Research(SZYZ-TR-03).
文摘Dear Editor,Three dimensional(3D)bioprinted extracellular matrix(ECM)can be used to provide both biochemical and biophysical cues to direct mesenchymal stem cells(MSCs)differentiation,and then differentiated cells were isolated for implantation in vivo using surgical procedures.However,the reduced cell activity after cell isolation from 3D constructs and low cell retention in injured sites limit its application[1].Methacrylated gelatin(GelMA)hydrogel has the advantage of fast crosslinking,which could resemble complex architectures of tissue construct in vivo[2].Here,we adopted a noninvasive bioprinting procedure to imitate the regenerative microenvironment that could simultaneously direct the sweat gland(SG)and vascular differentiation from MSCs and ultimately promote the replacement of glandular tissue in situ(Fig.1a).
文摘Adequate vascularization is a critical determinant for the successful construction and clinical implementation of complex organotypic tissue models. Currently, low cell and vessel density and insufficient vascular maturation make vascularized organotypic tissue construction difficult,greatly limiting its use in tissue engineering and regenerative medicine. To address these limitations, recent studies have adopted pre-vascularized microtissue assembly for the rapid generation of functional tissue analogs with dense vascular networks and high cell density. In this article, we summarize the development of module assembly-based vascularized organotypic tissue construction and its application in tissue repair and regeneration, organ-scale tissue biomanufacturing, as well as advanced tissue modeling.
文摘Blood vessels constitute a closed pipe system distributed throughout the body,transporting blood from the heart to other organs and delivering metabolic waste products back to the lungs and kidneys.Changes in blood vessels are related to many disorders like stroke,myocardial infarction,aneurysm,and diabetes,which are important causes of death worldwide.Translational research for new appro-aches to disease modeling and effective treatment is needed due to the huge socio-economic burden on healthcare systems.Although mice or rats have been widely used,applying data from animal studies to human-specific vascular physiology and pathology is difficult.The rise of induced pluripotent stem cells(iPSCs)provides a reliable in vitro resource for disease modeling,regenerative medicine,and drug discovery because they carry all human genetic information and have the ability to directionally differentiate into any type of human cells.This review summarizes the latest progress from the establishment of iPSCs,the strategies for differentiating iPSCs into vascular cells,and the in vivo trans-plantation of these vascular derivatives.It also introduces the application of these technologies in disease modeling,drug screening,and regenerative medicine.Additionally,the application of high-tech tools,such as omics analysis and high-throughput sequencing,in this field is reviewed.
基金sponsored by the National Natural Science Foundation of China (Nos.52235007, 52325504, T2121004)Zhejiang Province Natural Science Foundation of China under Grant No.LQ23H090012, LQ22H180001the Science and Technology of Medicine and Health program of Zhejiang Province (No.2023RC028)。
文摘Synthetic vascular grafts suitable for small-diameter arteries(<6 mm) are in great need.However,there are still no commercially available small-diameter vascular grafts(SDVGs) in clinical practice due to thrombosis and stenosis after in vivo implantation.When designing SDVGs,many studies emphasized reendothelization but ignored the importance of reconstruction of the smooth muscle layer(SML).To facilitate rapid SML regeneration,a high-resolution 3D printing method was used to create a novel bilayer SDVG with structures and mechanical properties mimicking natural arteries.Bioinspired by the collagen alignment of SML,the inner layer of the grafts had larger pore sizes and high porosity to accelerate the infiltration of cells and their circumferential alignment,which could facilitate SML reconstruction for compliance restoration and spontaneous endothelialization.The outer layer was designed to induce fibroblast recruitment by low porosity and minor pore size and provide SDVG with sufficient mechanical strength.One month after implantation,the arteries regenerated by 3D-printed grafts exhibited better pulsatility than electrospun grafts,with a compliance(8.9%) approaching that of natural arteries(11.36%) and significantly higher than that of electrospun ones(1.9%).The 3D-printed vascular demonstrated a three-layer structure more closely resembling natural arteries while electrospun grafts showed incomplete endothelium and immature SML.Our study shows the importance of SML reconstruction during vascular graft regeneration and provides an effective strategy to reconstruct blood vessels through 3D-printed structures rapidly.
基金Central University Basic Research Fund of China,Grant/Award Number:22120220562National Natural Science Foundation of China,Grant/Award Number:81870044+1 种基金Natural Science Foundation of Shanghai,Grant/Award Number:201409004100 and 21ZR1453800Shanghai Pulmonary Hospital,Grant/Award Number:FKLY20005 and fkzr2320。
文摘Background:Circular RNAs(circRNAs)have been recognized as significant regulators of pulmonary hypertension(PH);however,the differential expression and function of circRNAs in different vascular cells under hypoxia remain unknown.Here,we identified co-differentially expressed circRNAs and determined their putative roles in the proliferation of pulmonary artery smooth muscle cells(PASMCs),pulmonary microvascular endothelial cells(PMECs),and pericytes(PCs)under hypoxia.Methods:Whole transcriptome sequencing was performed to analyze the differential expression of circRNAs in three different vascular cell types.Bioinformatic analysis was used to predict their putative biological function.Quantitative real-time polymerase chain reaction,Cell Counting Kit-8,and EdU Cell Proliferation assays were carried out to determine the role of circular postmeiotic segregation 1(circPMS1)as well as its potential sponge mechanism in PASMCs,PMECs,and PCs.Results:PASMCs,PMECs,and PCs exhibited 16,99,and 31 differentially expressed circRNAs under hypoxia,respectively.CircPMS1 was upregulated in PASMCs,PMECs,and PCs under hypoxia and enhanced the proliferation of vascular cells.CircPMS1may upregulate DEP domain containing 1(DEPDC1)and RNA polymerase II subunit D expression by targeting microRNA-432-5p(miR-432-5p)in PASMCs,upregulate MAX interactor 1(MXI1)expression by targeting miR-433-3p in PMECs,and upregulate zinc finger AN1-type containing 5(ZFAND5)expression by targeting miR-3613-5p in PCs.Conclusions:Our results suggest that circPMS1 promotes cell proliferation through the miR-432-5p/DEPDC1 or miR-432-5p/POL2D axis in PASMCs,through the miR-433-3p/MXI1 axis in PMECs,and through the miR-3613-5p/ZFAND5 axis in PCs,which provides putative targets for the early diagnosis and treatment of PH.
基金supported by the National Key R&D Program of China,No.2019YFE0121200(to LQZ)the National Natural Science Foundation of China,Nos.82325017(to LQZ),82030032(to LQZ),82261138555(to DL)+2 种基金the Natural Science Foundation of Hubei Province,No.2022CFA004(to LQZ)the Natural Science Foundation of Jiangxi Province,No.20224BAB206040(to XZ)Research Project of Cognitive Science and Transdisciplinary Studies Center of Jiangxi Province,No.RZYB202201(to XZ).
文摘With an increase in global aging,the number of people affected by cerebrovascular diseases is also increasing,and the incidence of vascular dementia-closely related to cerebrovascular risk-is increasing at an epidemic rate.However,few therapeutic options exist that can markedly improve the cognitive impairment and prognosis of vascular dementia patients.Similarly in Alzheimer’s disease and other neurological disorders,synaptic dysfunction is recognized as the main reason for cognitive decline.Nitric oxide is one of the ubiquitous gaseous cellular messengers involved in multiple physiological and pathological processes of the central nervous system.Recently,nitric oxide has been implicated in regulating synaptic plasticity and plays an important role in the pathogenesis of vascular dementia.This review introduces in detail the emerging role of nitric oxide in physiological and pathological states of vascular dementia and summarizes the diverse effects of nitric oxide on different aspects of synaptic dysfunction,neuroinflammation,oxidative stress,and blood-brain barrier dysfunction that underlie the progress of vascular dementia.Additionally,we propose that targeting the nitric oxide-sGC-cGMP pathway using certain specific approaches may provide a novel therapeutic strategy for vascular dementia.
基金supported by the Lorenz B?hler Fonds,#2/19 (obtained by the Neuroregeneration Group,Ludwig Boltzmann Institute for Traumatology)the City of Vienna project ImmunTissue,MA23#30-11 (obtained by the Department Life Science Engineering,University of Applied Sciences Technikum Wien)。
文摘Peripheral nerve injuries induce a severe motor and sensory deficit. Since the availability of autologous nerve transplants for nerve repair is very limited, alternative treatment strategies are sought, including the use of tubular nerve guidance conduits(tNGCs). However, the use of tNGCs results in poor functional recovery and central necrosis of the regenerating tissue, which limits their application to short nerve lesion defects(typically shorter than 3 cm). Given the importance of vascularization in nerve regeneration, we hypothesized that enabling the growth of blood vessels from the surrounding tissue into the regenerating nerve within the tNGC would help eliminate necrotic processes and lead to improved regeneration. In this study, we reported the application of macroscopic holes into the tubular walls of silk-based tNGCs and compared the various features of these improved silk^(+) tNGCs with the tubes without holes(silk^(–) tNGCs) and autologous nerve transplants in an 8-mm sciatic nerve defect in rats. Using a combination of micro-computed tomography and histological analyses, we were able to prove that the use of silk^(+) tNGCs induced the growth of blood vessels from the adjacent tissue to the intraluminal neovascular formation. A significantly higher number of blood vessels in the silk^(+) group was found compared with autologous nerve transplants and silk^(–), accompanied by improved axon regeneration at the distal coaptation point compared with the silk^(–) tNGCs at 7 weeks postoperatively. In the 15-mm(critical size) sciatic nerve defect model, we again observed a distinct ingrowth of blood vessels through the tubular walls of silk^(+) tNGCs, but without improved functional recovery at 12 weeks postoperatively. Our data proves that macroporous tNGCs increase the vascular supply of regenerating nerves and facilitate improved axonal regeneration in a short-defect model but not in a critical-size defect model. This study suggests that further optimization of the macroscopic holes silk^(+) tNGC approach containing macroscopic holes might result in improved grafting technology suitable for future clinical use.
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.
基金supported by the Qingdao Medical Research Guidance Plan(2020-WJZD049).
文摘Background:Mufangji tang(MFJT)is composed of Ramulus Cinnamomi,Radix Ginseng,Cocculus orbiculatus(Linn.)DC.,and Gypsum.In clinical settings,MFJT has been effectively employed in addressing a range of respiratory disorders,notably including pulmonary arterial hypertension(PAH).However,the mechanism of action of MFJT on PAH remains unknown.Methods:In this study,a monocrotaline-induced PAH rat model was established and treated with MFJT.The therapeutic effects of MFJT on PAH rat model were evaluated.Network pharmacology was conducted to screen the possible targets for MFJT on PAH,and the molecular docking between the main active components and the core targets was carried out.The key targets identified from network pharmacology were tested.Results:Results showed significant therapeutic effects of MFJT on PAH rat model.Analysis of network pharmacology revealed several potential targets related to apoptosis,inflammation,oxidative stress,and vascular remodeling.Molecular docking showed that the key components were well docked with the core targets.Further experimental validation results that MFJT treatment induced apoptosis(downregulated Bcl-2 levels and upregulated Bax levels in lung tissue),inhibited inflammatory response and oxdative stress(decreased the levels of IL-1β,TNF-α,inducible NOS,and malondialdehyde,and increased the levels of endothelial nitric oxide synthase,nitric oxide,glutathione and superoxide dismutase),reduced the proliferation of pulmonary arterial smooth muscle cells(downregulated ET-1 andβ-catenin levels and ERK1/2 phosphorylation,increased GSK3βlevels).Conclusion:Our study revealed MFJT treatment could alleviate PAH in rats via induction of apoptosis,inhibition of inflammation and oxidative stress,and the prevention of vascular remodeling.
基金This study was approved by Ethical Committee of The Sapienza University of Rome(5068/2018).
文摘Background:Porto-sinusoidal vascular disease(PSVD)and portal vein thrombosis(PVT)are causes of portal hypertension characterized respectively by an intrahepatic and a pre-hepatic obstacle to the flow in the portal system.As PVT may be a consequence of PSVD,in PVT patients at presentation,a pre-existing PSVD should be suspected.In these patients the identification of an underlying PSVD would have relevant implication regarding follow-up and therapeutic management,but it could be challenging.In this setting ultrasonography may be valuable in differential diagnosis.The aim of the study was to use ultrasonography to identify parameters to discriminate between PSVD and“pure”PVT and then to suspect PVT secondary to a pre-existing PSVD.Methods:Fifty-three patients with histologically proven PSVD and forty-eight patients affected by chronic PVT were enrolled and submitted to abdominal ultrasonography with elastography by acoustic radiation force impulse(ARFI).Results:ARFI was higher and superior mesenteric vein(SMV)diameter was wider in PSVD patients than in PVT patients.Thus,a prognostic score was obtained as linear combinations of the two parameters with a good discrimination capacity between PSVD and PVT(the area under the curve=0.780;95%confidence interval:0.690-0.869).Conclusions:A score based on ARFI and SMV diameter may be useful to suspect an underlying PSVD in patients with PVT and to identify a subgroup of patients to be submitted to liver biopsy.