There is an urgent need for small-diameter artificial blood vessels in clinic.Physical,chemical and biological factors should be integrated to avoid thrombosis and intimal hyperplasia after implantation and to promote...There is an urgent need for small-diameter artificial blood vessels in clinic.Physical,chemical and biological factors should be integrated to avoid thrombosis and intimal hyperplasia after implantation and to promote successful fabrication of small-diameter artificial blood vessels.From a physical perspective,the internal oriented structures of natural blood vessels plays an important role in guiding the directional growth of cells,improving the blood flow environment,and promoting the regeneration of vascular tissue.In this review,the effects of the oriented structures on cells,including endothelial cells(ECs),smooth muscle cells(SMCs)and stem cells,as well as the effect of the oriented structures on hemodynamics and vascular tissue remodeling and regeneration are introduced.Various forms of oriented structures(fibers,grooves,channels,etc.)and their construction methods are also reviewed.Conclusions and future perspectives are given.It is expected to give some references to relevant researches.展开更多
Biomedical image processing is finding useful in healthcare sector for the investigation,enhancement,and display of images gathered by distinct imaging technologies.Diabetic retinopathy(DR)is an illness caused by diab...Biomedical image processing is finding useful in healthcare sector for the investigation,enhancement,and display of images gathered by distinct imaging technologies.Diabetic retinopathy(DR)is an illness caused by diabetes complications and leads to irreversible injury to the retina blood vessels.Retinal vessel segmentation techniques are a basic element of automated retinal disease screening system.In this view,this study presents a novel blood vessel segmentation with deep learning based classification(BVS-DLC)model forDRdiagnosis using retinal fundus images.The proposed BVS-DLC model involves different stages of operations such as preprocessing,segmentation,feature extraction,and classification.Primarily,the proposed model uses the median filtering(MF)technique to remove the noise that exists in the image.In addition,a multilevel thresholding based blood vessel segmentation process using seagull optimization(SGO)with Kapur’s entropy is performed.Moreover,the shark optimization algorithm(SOA)with Capsule Networks(CapsNet)model with softmax layer is employed for DR detection and classification.Awide range of simulations was performed on the MESSIDOR dataset and the results are investigated interms of different measures.The simulation results ensured the better performance of the proposed model compared to other existing techniques interms of sensitivity,specificity,receiver operating characteristic(ROC)curve,accuracy,and F-score.展开更多
Automated segmentation of blood vessels in retinal fundus images is essential for medical image analysis.The segmentation of retinal vessels is assumed to be essential to the progress of the decision support system fo...Automated segmentation of blood vessels in retinal fundus images is essential for medical image analysis.The segmentation of retinal vessels is assumed to be essential to the progress of the decision support system for initial analysis and treatment of retinal disease.This article develops a new Grasshopper Optimization with Fuzzy Edge Detection based Retinal Blood Vessel Segmentation and Classification(GOFED-RBVSC)model.The proposed GOFED-RBVSC model initially employs contrast enhancement process.Besides,GOAFED approach is employed to detect the edges in the retinal fundus images in which the use of GOA adjusts the membership functions.The ORB(Oriented FAST and Rotated BRIEF)feature extractor is exploited to generate feature vectors.Finally,Improved Conditional Variational Auto Encoder(ICAVE)is utilized for retinal image classification,shows the novelty of the work.The performance validation of the GOFEDRBVSC model is tested using benchmark dataset,and the comparative study highlighted the betterment of the GOFED-RBVSC model over the recent approaches.展开更多
In this study,we aim to combine gene transfection techniques with the modeling methods previously employed by the research group to deeply investigate the corresponding theories of traditional Chinese medicine regard...In this study,we aim to combine gene transfection techniques with the modeling methods previously employed by the research group to deeply investigate the corresponding theories of traditional Chinese medicine regarding“myocardial energy metabolism”and“aortic thrombosis”.Our goal is to elucidate the biological mechanism underlying the occurrence and development of coronary heart disease with blood stasis syndrome from the perspectives of“heart and vessels”and“Qi(in traditional Chinese medicine,it refers to the most fundamental and subtle substances that constitute the human body and maintain life activities.At the same time,it also has the meaning of physiological function.In terms of traditional Chinese medicine,Qi and different words are used together to express different meanings)and blood”.The research content is divided into four modules as follows:1.establishment of an animal model of coronary heart disease with blood stasis syndrome through fibrinogen overexpression.2.Investigation of the mitochondrial quality control system in coronary heart disease with blood stasis syndrome under fibrinogen overexpression.3.Study of platelet autophagy in coronary heart disease with blood stasis syndrome under fibrinogen overexpression.4.Examination of the relationship between the AMPK-mTOR pathway and metabolism in platelet autophagy of coronary heart disease with blood stasis syndrome under fibrinogen overexpression.Ninety-six Sprague Dawley rats will be randomly assigned to the following groups:control group,model group,fibrinogen group and adeno-associated virus group.All rats will undergo a 14-week model construction process,and modern molecular biology methods will be employed to evaluate the model and examine relevant research indicators.The obtained data will be analyzed according to a predefined statistical analysis plan.展开更多
Endothelial cells (TEC_3 cells) derived from mouse embryonic stem (ES) cells were used as seed cells to construct blood vessels. Tissue engineered blood vessels were made by seeding 8 × 10~6 smooth muscle cells (...Endothelial cells (TEC_3 cells) derived from mouse embryonic stem (ES) cells were used as seed cells to construct blood vessels. Tissue engineered blood vessels were made by seeding 8 × 10~6 smooth muscle cells (SMCs) obtained from rabbit arteries onto a sheet of nonwoven polyglycolic acid (PGA) fibers, which was used as a biodegradable polymer scaffold. After being cultured in DMEM medium for 7 days in vitro, SMCs grew well on the PGA fibers, and the cell-PGA sheet was then wrapped around a silicon tube, and implanted subcutaneously into nude mice. After 6～8 weeks, the silicon tube was replaced with another silicon tube in smaller diameter, and then the TEC_3 cells (endothelial cells differentiated from mouse ES cells) were injected inside the engineered vessel tube as the test group. In the control group only culture medium was injected. Five days later, the engineered vessels were harvested for gross observation, histological and immunohistochemical analysis. The preliminary results demonstrated that the SMC-PGA construct could form a tubular structure in 6～8 weeks and PGA fibers were completely degraded. Histological and immunohistochemical analysis of the newly formed tissue revealed a typical blood vessel structure, including a lining of endothelial cells (ECs) on the lumimal surface and the presence of SMC and collagen in the wall. No EC lining was found in the tubes of control group. Therefore, the ECs differentiated from mouse ES cells can serve as seed cells for endothelium lining in tissue engineered blood vessels.展开更多
AIM： To determine the prognostic value of lymphatic and/or blood vessel invasion （LBVI） in patients with stage 11 gastric cancer. METHODS： From January 2001 to December 2006, 487 patients with histologically confi...AIM： To determine the prognostic value of lymphatic and/or blood vessel invasion （LBVI） in patients with stage 11 gastric cancer. METHODS： From January 2001 to December 2006, 487 patients with histologically confirmed primary gas- tric adenocarcinoma were diagnosed with stage 11 gas- tric cancer according to the new 7th edition American Joint Committee on Cancer stage classification at the Department of Gastric Cancer and Soft Tissue Surgery, Fudan University Shanghai Cancer Center. All patients underwent curative gastrectomy with standard lymph node （LN） dissection. Fifty-one patients who died in the postoperative period, due to various complications or other conditions, were excluded. Clinicopathologicalfindings and clinical outcomes were analyzed. Patients were subdivided into four groups according to the status of LBVI and LN metastases. These four patient groups were characterized with regard to age, sex, tumor site, pT category, tumor grading and surgical procedure （subtotal resection vs total resection）, and compared for 5-year overall survival by univariate and multivariate analysis. RESULTS： The study was composed of 320 men and 116 women aged 58.9 ± 11.5 years （range： 23-88 years）. The 5-year overall survival rates were 50.7% and the median survival time was 62 too. Stage Ⅱ a cancer was observed in 334 patients, including 268 T3N0, 63 T2N1, and three TIN2, and stage Ⅱb was observed in 102 patients, including 49 patients T3N1, 51 T2N2, one TIN3, and one T4aN0. The incidence of LBVI was 28.0% in stage II gastric cancer with 19.0% （51/269） and 42.5% （71/167） in LN-negative and LN- positive patients, respectively. In 218 patients （50.0%）, there was neither a histopathologically detectable LBVI nor LN metastases （LBVI-/LN-, group I）; in 51 patients （11.7%）, LBVI with no evidence of LN me- tastases was detected （LBVILN-, group 11）. In 167 patients （38.3%）, LN metastases were found. Among those patients, LBVI was not determined in 96 patients （22.0%） （LBVI-γLN, group Ⅲ）, and was determined in 71 patients （16.3%） （LBVI＋LN＋, group Ⅳ）. Correla- tion analysis showed that N category and the number of positive LNs were significantly associated with the presence of LBVI （P 〈 0.001）. The overall 5-year sur- vival was significantly longer in LN-negative patients compared with LN-positive patients （56.1% vs 42.3%, P = 0.015）. There was a significant difference in the overall 5-year survival between LBVI-positive and LBVI- negative tumors （39.6% vs 54.8%, P = 0.006）. Overall 5-year survival rates in each group were 58.8% （ Ⅰ）, 45.8% （Ⅱ）, 45.7% （Ⅲ） and 36.9% （Ⅳ）, and there was a significant difference in overall survival between the four groups （P=-0.009）. Multivariate analysis in stage 11 gastric cancer patients revealed that LBVI in- dependently affected patient prognosis in LN-negativepatients （P = 0.018） but not in LN-positive patients （P = 0.508）. CONCLUSION： In LN-negative stage 11 gastric cancer patients, LBVI is an additional independent prognostic markeF, and may provide useful information to identify patients with poorer prognosis.展开更多
According to the characteristics of dynamic firing in pulse coupled neural network (PCNN) and regional configuration in retinal blood vessel network, a new method combined with simplified PCNN and fast 2D-Otsu algorit...According to the characteristics of dynamic firing in pulse coupled neural network (PCNN) and regional configuration in retinal blood vessel network, a new method combined with simplified PCNN and fast 2D-Otsu algorithm was proposed for automated retinal blood vessels segmentation. Firstly, 2D Gaussian matched filter was used to enhance the retinal images and simplified PCNN was employed to segment the blood vessels by firing neighborhood neurons. Then, fast 2D-Otsu algorithm was introduced to search the best segmentation results and iteration times with less computation time. Finally, the whole vessel network was obtained via analyzing the regional connectivity. Experiments implemented on the public Hoover database indicate that this new method gets a 0.803 5 true positive rate and a 0.028 0 false positive rate on an average. According to the test results, compared with Hoover algorithm and method of PCNN and 1D-Otsu, the proposed method shows much better performance.展开更多
BACKGROUND The Borrmann classification system is used to describe the macroscopic appearance of advanced gastric cancer,and Borrmann typeⅣdisease is independently associated with a poor prognosis.AIM To evaluate the ...BACKGROUND The Borrmann classification system is used to describe the macroscopic appearance of advanced gastric cancer,and Borrmann typeⅣdisease is independently associated with a poor prognosis.AIM To evaluate the prognostic significance of lymphatic and/or blood vessel invasion(LBVI)combined with the Borrmann type in advanced proximal gastric cancer(APGC).METHODS The clinicopathological and survival data of 440 patients with APGC who underwent curative surgery between 2005 and 2012 were retrospectively analyzed.RESULTS In these 440 patients,LBVI+status was associated with Borrmann typeⅣ,low histological grade,large tumor size,and advanced pT and pN status.The 5-year survival rate of LBVI+patients was significantly lower than that of LBVI– patients,although LBVI was not an independent prognostic factor in the multivariate analysis.No significant difference in the prognosis of patients with Borrmann typeⅢ/LBVI+disease and patients with Borrmann typeⅣdisease was observed.Therefore,we proposed a revised Borrmann typeⅣ(r-BorⅣ)as Borrmann typeⅢplus LBVI+,and found that r-BorⅣwas associated with poor prognosis in patients with APGC,which outweighed the prognostic significance of pT status.CONCLUSION LBVI is related to the prognosis of APGC,but is not an independent prognostic factor.LBVI status can be used to differentiate Borrmann typesⅢandⅣ,and the same approach can be used to treat r-BorⅣand Borrmann typeⅣ.展开更多
Objective Isocitrate dehydrogenase gene(IDH)mutations are associated with tumor angiogenesis and therefore play an important role in glioma management.This study compared the performance of tumor blood vessels counted...Objective Isocitrate dehydrogenase gene(IDH)mutations are associated with tumor angiogenesis and therefore play an important role in glioma management.This study compared the performance of tumor blood vessels counted from contrast-enhanced 3D brain volume(3D-BRAVO)sequence and dynamic contrast-enhanced(DCE)MRI in differentiating IDH1 status in gliomas.Methods Forty-four glioma patients[16 with IDH1 mutant-type(IDH1-MT),28 with IDH1 wild-type(IDH1-WT)]were retrospectively analyzed.A blood vessel entering a tumor was defined as an intratumoral vessel;a blood vessel adjacent to the edge of a tumor was defined as a peritumoral vessel.Combined vessels were defined as the sum of the intratumoral and peritumoral vessels.DCE-derived metrics of tumor were normalized to the contralateral normal-appearing white matter.Results Intratumoral,peritumoral,and combined tumor blood vessels were all significantly different between IDH1-MT and IDH1-WT gliomas,and the range of area under curves(AUCs)was 0.816–0.855.For DCE-derived parameters,cerebral blood volume,cerebral blood flow,mean transit time,and volume transfer constant were significantly different between IDH1-MT and IDH1-WT gliomas,and the range of AUCs was 0.703–0.756.Combined vessels possessed the best performance for identifying IDH1 mutations in gliomas(AUC:0.855,sensitivity:0.857,specificity:0.812,P<0.001).Conclusion The number of tumor blood vessels has comparable diagnostic performance with DCE-derived parameters for differentiating IDH1 mutations and can serve as a potential imaging biomarker to reflect IDH1 mutations in gliomas.展开更多
Background： A major shortcoming in tissue engineered blood vessels （TEBVs） is the lack of healthy and easily attainable smooth muscle cells （SMCs）. Smooth muscle progenitor cells （SPCs）, especially from periphe...Background： A major shortcoming in tissue engineered blood vessels （TEBVs） is the lack of healthy and easily attainable smooth muscle cells （SMCs）. Smooth muscle progenitor cells （SPCs）, especially from peripheral blood, may offer an alternative cell source for tissue engineering involving a less invasive harvesting technique. Methods： SPCs were isolated from 5-ml fresh rat peripheral blood by density-gradient centrifugation and cultured for 3 weeks in endothelial growth medium-2-MV （EGM-2-MV） medium containing platelet-derived growth factoroBB （PDGF BB）. Before seeded on the synthesized scaffold, SPC-derived smooth muscle outgrowth cell （SOC） phenotypes were assessed by immuno-fluorescent staining, Western blot analysis, and reverse transcription polymerase chain reaction （RT-PCR）. The cells were seeded onto the silk fibroin-modified poly（3-hydroxybutyrate-co-3-hydroxyhexanoate） （SF-PHBHHx） scaflblds by 6× 10^4 cells/cm^2 and cultured under the static condition for 3 weeks. The growth and proliferation of the seeded cells on the scaffold were analyzed by 3-（4,5-dimethylthiazol-2-yl）-diphenyltetrazolium bromide （MTT） assay, scanning electron microscope （SEM）, and 4,6-diamidino-2-phenylindole （DAPI） staining. Results： SOCs displayed specific ＂hill and valley＂ morphology, expressed the specific markers of the SMC lineage： smooth muscle （SM） a-actin, calponin and smooth muscle myosin heavy chain （SM MHC） at protein and messenger ribonucleic acid （mRNA） levels. RT-PCR results demonstrate that SOCs also expressed smooth muscle protein 22a （SM22a, a contractile protein, and extracellular matrix components elastin and matrix Gla protein （MGP）, as well as vascular endothelial growth factor （VEGF）. After seeded on the SF-PHBHHx scaffold, the cells showed excellent metabolic activity and proliferation. Conclusion： SPCs isolated from peripheral blood can be differentiated the SMCs in vitro and have an impressive growth potential in the biodegradable synthesized scaffold. Thus, SPCs may be a promising cell sointo urce for constructing TEBVs.展开更多
A geometric model of curved blood vessels is established based on some reasonable hypotheses; the nonlinear motion mechanics model of the curved blood vessel is established according to basic mechanics laws. This mode...A geometric model of curved blood vessels is established based on some reasonable hypotheses; the nonlinear motion mechanics model of the curved blood vessel is established according to basic mechanics laws. This model includes much more physiological factors. It couples the interaction of blood flow with mechanical factors such as the displacement, deformation, strain and stress etc. of the curved blood vessel. It is of great importance for investigating the circulation rules of the cardiovascular system and the nonlinear pulse wave propagation in curved blood vessels.展开更多
According to clinical observations and model experiment,we have developed a theoretical mod- el and obtained its mathematical equations to investigate the displacement wave of the blood vessel.The waveform and its occ...According to clinical observations and model experiment,we have developed a theoretical mod- el and obtained its mathematical equations to investigate the displacement wave of the blood vessel.The waveform and its occurrence criterion have been obtained by using perturbation theory and numerical method. The present study suggests that the displacement wave is associated with the blood velocity waveform and the machanical behaviour of the blood vessel,but not with the pressure waveform.The clinical criterion is in agreement with the observations.展开更多
BACKGROUND In traditional Chinese medicine(TCM),frankincense and myrrh are the main components of the antitumor drug Xihuang Pill.These compounds show anticancer activity in other biological systems.However,whether fr...BACKGROUND In traditional Chinese medicine(TCM),frankincense and myrrh are the main components of the antitumor drug Xihuang Pill.These compounds show anticancer activity in other biological systems.However,whether frankincense and/or myrrh can inhibit the occurrence of hepatocellular carcinoma(HCC)is unknown,and the potential molecular mechanism(s)has not yet been determined.AIM To predict and determine latent anti-HCC therapeutic targets and molecular mechanisms of frankincense and myrrh in vivo.METHODS In the present study,which was based on the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(http://tcmspw.com/tcmsp.php),Universal Protein database(http://www.uniprot.org),GeneCards:The Human Gene Database(http://www.genecards.org/)and Comparative Toxicogenomics Database(http://www.ctdbase.org/),the efficacy of and mechanism by which frankincense and myrrh act as anti-HCC compounds were predicted.The core prediction targets were screened by molecular docking.In vivo,SMMC-7721 human liver cancer cells were transplanted as xenografts into nude mice to establish a subcutaneous tumor model,and two doses of frankincense plus myrrh or one dose of an EGFR inhibitor was administered to these mice continuously for 14 d.The tumors were collected and evaluated:the tumor volume and growth rate were gauged to evaluate tumor growth;hematoxylineosin staining was performed to estimate histopathological changes;immunofluorescence(IF)was performed to detect the expression of CD31,α-SMA and collagen IV;transmission electron microscopy(TEM)was conducted to observe the morphological structure of vascular cells;enzyme-linked immunosorbent assay(ELISA)was performed to measure the levels of secreted HIF-1αand TNF-α;reverse transcription-polymerase chain reaction(RT-qPCR)was performed to measure the mRNA expression of HIF-1α,TNF-α,VEGF and MMP-9;and Western blot(WB)was performed to determine the levels of proteins expressed in the EGFR-mediated PI3K/Akt and MAPK signaling pathways.RESULTS The results of the network pharmacology analysis showed that there were 35 active components in the frankincense and myrrh extracts targeting 151 key targets.The molecular docking analysis showed that both boswellic acid and stigmasterol showed strong affinity for the targets,with the greatest affinity for EGFR.Frankincense and myrrh treatment may play a role in the treatment of HCC by regulating hypoxia responses and vascular system-related pathological processes,such as cytokine-receptor binding,and pathways,such as those involving serine/threonine protein kinase complexes and MAPK,HIF-1 and ErbB signaling cascades.The animal experiment results were verified.First,we found that,through frankincense and/or myrrh treatment,the volume of subcutaneously transplanted HCC tumors was significantly reduced,and the pathological morphology was attenuated.Then,IF and TEM showed that frankincense and/or myrrh treatment reduced CD31 and collagen IV expression,increased the coverage of perivascular cells,tightened the connection between cells,and improved the shape of blood vessels.In addition,ELISA,RT-qPCR and WB analyses showed that frankincense and/or myrrh treatment inhibited the levels of hypoxia-inducible factors,inflammatory factors and angiogenesis-related factors,namely,HIF-1α,TNF-α,VEGF and MMP-9.Furthermore,mechanistic experiments illustrated that the effect of frankincense plus myrrh treatment was similar to that of an EGFR inhibitor with regard to controlling EGFR activation,thereby inhibiting the phosphorylation activity of its downstream targets:the PI3K/Akt and MAPK(ERK,p38 and JNK)pathways.CONCLUSION In summary,frankincense and myrrh treatment targets tumor blood vessels to exert anti-HCC effects via EGFR-activated PI3K/Akt and MAPK signaling pathways,highlighting the potential of this dual TCM compound as an anti-HCC candidate.展开更多
Vascular smooth muscle cell （SMC） differentiation is an important process in vasculogenesis and angio- genesis during embryonic development. The altera- tions in the differentiated state in SMCs contribute to a vari...Vascular smooth muscle cell （SMC） differentiation is an important process in vasculogenesis and angio- genesis during embryonic development. The altera- tions in the differentiated state in SMCs contribute to a variety of major cardiovascular diseases such as atherosclerosis, hypertension, restenosis and vascular aneurysm . A better understanding of the cellular and molecular mechanisms that control SMC differen-tiation is essential to help develop new approaches to both prevent and treat these diseases. Therefore, development of reliable and reproducible in vitro cellular models in order to study the differentiation mechanisms is important although it has been challenging because of intrinsic peculiarities of SMC.展开更多
The β-hydroxybutyrate and β-hydroxyvalerate copolymers( PHBV) /polylactic acid( PLA) is a new biocompatible material,which is developed through bacterial fermentation in vivo systems.The PHBV / PLA material could be...The β-hydroxybutyrate and β-hydroxyvalerate copolymers( PHBV) /polylactic acid( PLA) is a new biocompatible material,which is developed through bacterial fermentation in vivo systems.The PHBV / PLA material could be used to make continuous filaments.However,features of artificial blood vessels,especially small diameter vascular grafts made of PHVB / PLA materials are not known.This research are to evaluate and improve weavability of the PHBV / PLA material, and to explore feasibility of using it in artificial blood vessels.Preliminary results showed that weavability of PHBV / PLV was not good,but its weavability could be improved by using methods of weak chemical,such as sizing.In this research,scanning electron microscope( SEM) was adopted to evaluate weavability of PHBV / PLV after sizing and observe surfaces of yarns and fabrics.Also,in order to set proper parameters in heat settings,differential scanning calorimetry( DSC) was used to identify glass transition temperature.展开更多
A finite element solution for the Navier-Stokes equations for steady flow under the porosity effects through a double branched two-dimensional section of a three-dimensional model of a canine aorta was obtained. The n...A finite element solution for the Navier-Stokes equations for steady flow under the porosity effects through a double branched two-dimensional section of a three-dimensional model of a canine aorta was obtained. The numerical solution involves transforming a physical coordinates to a curvilinear boundary fitted coordinate system.The steady flow,branch flow and shear stress under the porous effects were discussed in detail. The shear stress at the wall was calculated for Reynolds number of 1 000 with branch to main aortic flow rate ratio as a parameter. The results are compared with earlier works involving experimental data and it has been observed that our results are very close to the exact solutions.This work is in fact an improvement of the work of Sharma et al. (2001) in the sense that computational technique is economic and (Reynolds) number is large.展开更多
The coronavirus disease 2019(COVID-19)infected so far over 250 million people and caused the death of over 5 million worldwide.Aging,diabetes,and cardiovascular diseases,conditions with preexisting impaired endothelia...The coronavirus disease 2019(COVID-19)infected so far over 250 million people and caused the death of over 5 million worldwide.Aging,diabetes,and cardiovascular diseases,conditions with preexisting impaired endothelial functions predispose to COVID-19.While respiratory epithelium is the main route of virus entry,the endothelial cells(ECs)lining pulmonary blood vessels are also an integral part of lung injury in COVID-19 patients.COVID-19 not only affects the lungs and respiratory system but also gastrointestinal(GI)tract,liver,pancreas,kidneys,heart,brain,and skin.Blood vessels are likely conduits for the virus dissemination to these distant organs.Importantly,ECs are also critical for vascular regeneration during injury/lesions healing and restoration of vascular network.The World Journal of Gastroenterology has published in last two years over 67 outstanding papers on COVID-19 infection with a focus on the GI tract,liver,pancreas,etc.,however,the role of the endothelial and vascular components as major targets for COVID-19-induced tissue injury,spreading to various organs,and injury healing have not been sufficiently emphasized.In the present article,we focus on these subjects and on current treatments including the most recent oral drugs molnupiravir and paxlovid that show a dramatic,significant efficacy in controlling severe COVID-19 infection.展开更多
There has been an increasing demand for bioengineered blood vessels for utilization in both regenerative medicine and drug screening.However,the availability of a true bioengineered vascular graft remains limited.Thre...There has been an increasing demand for bioengineered blood vessels for utilization in both regenerative medicine and drug screening.However,the availability of a true bioengineered vascular graft remains limited.Three-dimensional(3D)bioprinting presents a potential approach for fabricating blood vessels or vascularized tissue constructs of various architectures and sizes for transplantation and regeneration.In this review,we summarize the basic biology of different blood vessels,as well as 3D bioprinting approaches and bioink designs that have been applied to fabricate vascular and vascularized tissue constructs,with a focus on small-diameter blood vessels.展开更多
BACKGROUND The development of fully functional small diameter vascular grafts requires both a properly defined vessel conduit and tissue-specific cellular populations.Mesenchymal stromal cells(MSCs) derived from the W...BACKGROUND The development of fully functional small diameter vascular grafts requires both a properly defined vessel conduit and tissue-specific cellular populations.Mesenchymal stromal cells(MSCs) derived from the Wharton's Jelly(WJ) tissue can be used as a source for obtaining vascular smooth muscle cells(VSMCs),while the human umbilical arteries(h UAs) can serve as a scaffold for blood vessel engineering.AIM To develop VSMCs from WJ-MSCs utilizing umbilical cord blood platelet lysate.METHODS WJ-MSCs were isolated and expanded until passage(P) 4. WJ-MSCs were properly defined according to the criteria of the International Society for Cell and Gene Therapy. Then, these cells were differentiated into VSMCs with the use of platelet lysate from umbilical cord blood in combination with ascorbic acid,followed by evaluation at the gene and protein levels. Specifically, gene expression profile analysis of VSMCs for ACTA2, MYH11, TGLN, MYOCD, SOX9,NANOG homeobox, OCT4 and GAPDH, was performed. In addition,immunofluorescence against ACTA2 and MYH11 in combination with DAPI staining was also performed in VSMCs. HUAs were decellularized and served as scaffolds for possible repopulation by VSMCs. Histological and biochemical analyses were performed in repopulated h UAs.RESULTS WJ-MSCs exhibited fibroblastic morphology, successfully differentiating into"osteocytes", "adipocytes" and "chondrocytes", and were characterized by positive expression(> 90%) of CD90, CD73 and CD105. In addition, WJ-MSCs were successfully differentiated into VSMCs with the proposed differentiation protocol. VSMCs successfully expressed ACTA2, MYH11, MYOCD, TGLN and SOX9. Immunofluorescence results indicated the expression of ACTA2 and MYH11 in VSMCs. In order to determine the functionality of VSMCs, h UAs were isolated and decellularized. Based on histological analysis, decellularized h UAs were free of any cellular or nuclear materials, while their extracellular matrix retained intact. Then, repopulation of decellularized h UAs with VSMCs was performed for 3 wk. Decellularized h UAs were repopulated efficiently by the VSMCs. Biochemical analysis revealed the increase of total hydroyproline and s GAG contents in repopulated h UAs with VSMCs. Specifically, total hydroxyproline and s GAG content after the 1 st, 2 nd and 3 rd wk was 71 ± 10, 74 ± 9 and 86 ± 8 μg hydroxyproline/mg of dry tissue weight and 2 ± 1, 3 ± 1 and 3 ± 1μg s GAG/mg of dry tissue weight, respectively. Statistically significant differences were observed between all study groups(P<0.05).CONCLUSION VSMCs were successfully obtained from WJ-MSCs with the proposed differentiation protocol. Furthermore, h UAs were efficiently repopulated by VSMCs. Differentiated VSMCs from WJ-MSCs could provide an alternative source of cells for vascular tissue engineering.展开更多
文摘There is an urgent need for small-diameter artificial blood vessels in clinic.Physical,chemical and biological factors should be integrated to avoid thrombosis and intimal hyperplasia after implantation and to promote successful fabrication of small-diameter artificial blood vessels.From a physical perspective,the internal oriented structures of natural blood vessels plays an important role in guiding the directional growth of cells,improving the blood flow environment,and promoting the regeneration of vascular tissue.In this review,the effects of the oriented structures on cells,including endothelial cells(ECs),smooth muscle cells(SMCs)and stem cells,as well as the effect of the oriented structures on hemodynamics and vascular tissue remodeling and regeneration are introduced.Various forms of oriented structures(fibers,grooves,channels,etc.)and their construction methods are also reviewed.Conclusions and future perspectives are given.It is expected to give some references to relevant researches.
基金Ministry of Education in Saudi Arabia for funding this research work through the project number (IFP-2020-66).
文摘Biomedical image processing is finding useful in healthcare sector for the investigation,enhancement,and display of images gathered by distinct imaging technologies.Diabetic retinopathy(DR)is an illness caused by diabetes complications and leads to irreversible injury to the retina blood vessels.Retinal vessel segmentation techniques are a basic element of automated retinal disease screening system.In this view,this study presents a novel blood vessel segmentation with deep learning based classification(BVS-DLC)model forDRdiagnosis using retinal fundus images.The proposed BVS-DLC model involves different stages of operations such as preprocessing,segmentation,feature extraction,and classification.Primarily,the proposed model uses the median filtering(MF)technique to remove the noise that exists in the image.In addition,a multilevel thresholding based blood vessel segmentation process using seagull optimization(SGO)with Kapur’s entropy is performed.Moreover,the shark optimization algorithm(SOA)with Capsule Networks(CapsNet)model with softmax layer is employed for DR detection and classification.Awide range of simulations was performed on the MESSIDOR dataset and the results are investigated interms of different measures.The simulation results ensured the better performance of the proposed model compared to other existing techniques interms of sensitivity,specificity,receiver operating characteristic(ROC)curve,accuracy,and F-score.
文摘Automated segmentation of blood vessels in retinal fundus images is essential for medical image analysis.The segmentation of retinal vessels is assumed to be essential to the progress of the decision support system for initial analysis and treatment of retinal disease.This article develops a new Grasshopper Optimization with Fuzzy Edge Detection based Retinal Blood Vessel Segmentation and Classification(GOFED-RBVSC)model.The proposed GOFED-RBVSC model initially employs contrast enhancement process.Besides,GOAFED approach is employed to detect the edges in the retinal fundus images in which the use of GOA adjusts the membership functions.The ORB(Oriented FAST and Rotated BRIEF)feature extractor is exploited to generate feature vectors.Finally,Improved Conditional Variational Auto Encoder(ICAVE)is utilized for retinal image classification,shows the novelty of the work.The performance validation of the GOFEDRBVSC model is tested using benchmark dataset,and the comparative study highlighted the betterment of the GOFED-RBVSC model over the recent approaches.
基金This work was supported by the National Natural Science Foundation of China(No.81973753 to Jian WX)Hunan Postgraduate Scientific Research Innovation Project(CX 20220781)Hunan University Students’Innovation and Entrepreneurship Training Program(S202210541116).
文摘In this study,we aim to combine gene transfection techniques with the modeling methods previously employed by the research group to deeply investigate the corresponding theories of traditional Chinese medicine regarding“myocardial energy metabolism”and“aortic thrombosis”.Our goal is to elucidate the biological mechanism underlying the occurrence and development of coronary heart disease with blood stasis syndrome from the perspectives of“heart and vessels”and“Qi(in traditional Chinese medicine,it refers to the most fundamental and subtle substances that constitute the human body and maintain life activities.At the same time,it also has the meaning of physiological function.In terms of traditional Chinese medicine,Qi and different words are used together to express different meanings)and blood”.The research content is divided into four modules as follows:1.establishment of an animal model of coronary heart disease with blood stasis syndrome through fibrinogen overexpression.2.Investigation of the mitochondrial quality control system in coronary heart disease with blood stasis syndrome under fibrinogen overexpression.3.Study of platelet autophagy in coronary heart disease with blood stasis syndrome under fibrinogen overexpression.4.Examination of the relationship between the AMPK-mTOR pathway and metabolism in platelet autophagy of coronary heart disease with blood stasis syndrome under fibrinogen overexpression.Ninety-six Sprague Dawley rats will be randomly assigned to the following groups:control group,model group,fibrinogen group and adeno-associated virus group.All rats will undergo a 14-week model construction process,and modern molecular biology methods will be employed to evaluate the model and examine relevant research indicators.The obtained data will be analyzed according to a predefined statistical analysis plan.
基金supported by the national“973”tissue engineering project of China(G1999054300)Shanghai Science and Technology Development Foundation(03DJ14021)
文摘Endothelial cells (TEC_3 cells) derived from mouse embryonic stem (ES) cells were used as seed cells to construct blood vessels. Tissue engineered blood vessels were made by seeding 8 × 10~6 smooth muscle cells (SMCs) obtained from rabbit arteries onto a sheet of nonwoven polyglycolic acid (PGA) fibers, which was used as a biodegradable polymer scaffold. After being cultured in DMEM medium for 7 days in vitro, SMCs grew well on the PGA fibers, and the cell-PGA sheet was then wrapped around a silicon tube, and implanted subcutaneously into nude mice. After 6～8 weeks, the silicon tube was replaced with another silicon tube in smaller diameter, and then the TEC_3 cells (endothelial cells differentiated from mouse ES cells) were injected inside the engineered vessel tube as the test group. In the control group only culture medium was injected. Five days later, the engineered vessels were harvested for gross observation, histological and immunohistochemical analysis. The preliminary results demonstrated that the SMC-PGA construct could form a tubular structure in 6～8 weeks and PGA fibers were completely degraded. Histological and immunohistochemical analysis of the newly formed tissue revealed a typical blood vessel structure, including a lining of endothelial cells (ECs) on the lumimal surface and the presence of SMC and collagen in the wall. No EC lining was found in the tubes of control group. Therefore, the ECs differentiated from mouse ES cells can serve as seed cells for endothelium lining in tissue engineered blood vessels.
文摘AIM： To determine the prognostic value of lymphatic and/or blood vessel invasion （LBVI） in patients with stage 11 gastric cancer. METHODS： From January 2001 to December 2006, 487 patients with histologically confirmed primary gas- tric adenocarcinoma were diagnosed with stage 11 gas- tric cancer according to the new 7th edition American Joint Committee on Cancer stage classification at the Department of Gastric Cancer and Soft Tissue Surgery, Fudan University Shanghai Cancer Center. All patients underwent curative gastrectomy with standard lymph node （LN） dissection. Fifty-one patients who died in the postoperative period, due to various complications or other conditions, were excluded. Clinicopathologicalfindings and clinical outcomes were analyzed. Patients were subdivided into four groups according to the status of LBVI and LN metastases. These four patient groups were characterized with regard to age, sex, tumor site, pT category, tumor grading and surgical procedure （subtotal resection vs total resection）, and compared for 5-year overall survival by univariate and multivariate analysis. RESULTS： The study was composed of 320 men and 116 women aged 58.9 ± 11.5 years （range： 23-88 years）. The 5-year overall survival rates were 50.7% and the median survival time was 62 too. Stage Ⅱ a cancer was observed in 334 patients, including 268 T3N0, 63 T2N1, and three TIN2, and stage Ⅱb was observed in 102 patients, including 49 patients T3N1, 51 T2N2, one TIN3, and one T4aN0. The incidence of LBVI was 28.0% in stage II gastric cancer with 19.0% （51/269） and 42.5% （71/167） in LN-negative and LN- positive patients, respectively. In 218 patients （50.0%）, there was neither a histopathologically detectable LBVI nor LN metastases （LBVI-/LN-, group I）; in 51 patients （11.7%）, LBVI with no evidence of LN me- tastases was detected （LBVILN-, group 11）. In 167 patients （38.3%）, LN metastases were found. Among those patients, LBVI was not determined in 96 patients （22.0%） （LBVI-γLN, group Ⅲ）, and was determined in 71 patients （16.3%） （LBVI＋LN＋, group Ⅳ）. Correla- tion analysis showed that N category and the number of positive LNs were significantly associated with the presence of LBVI （P 〈 0.001）. The overall 5-year sur- vival was significantly longer in LN-negative patients compared with LN-positive patients （56.1% vs 42.3%, P = 0.015）. There was a significant difference in the overall 5-year survival between LBVI-positive and LBVI- negative tumors （39.6% vs 54.8%, P = 0.006）. Overall 5-year survival rates in each group were 58.8% （ Ⅰ）, 45.8% （Ⅱ）, 45.7% （Ⅲ） and 36.9% （Ⅳ）, and there was a significant difference in overall survival between the four groups （P=-0.009）. Multivariate analysis in stage 11 gastric cancer patients revealed that LBVI in- dependently affected patient prognosis in LN-negativepatients （P = 0.018） but not in LN-positive patients （P = 0.508）. CONCLUSION： In LN-negative stage 11 gastric cancer patients, LBVI is an additional independent prognostic markeF, and may provide useful information to identify patients with poorer prognosis.
基金Project (60872081) supported by the National Natural Science Foundation of ChinaProject (50051) supported by the Program for New Century Excellent Talents in UniversityProject (4092034) supported by the Natural Science Foundation of Beijing
文摘According to the characteristics of dynamic firing in pulse coupled neural network (PCNN) and regional configuration in retinal blood vessel network, a new method combined with simplified PCNN and fast 2D-Otsu algorithm was proposed for automated retinal blood vessels segmentation. Firstly, 2D Gaussian matched filter was used to enhance the retinal images and simplified PCNN was employed to segment the blood vessels by firing neighborhood neurons. Then, fast 2D-Otsu algorithm was introduced to search the best segmentation results and iteration times with less computation time. Finally, the whole vessel network was obtained via analyzing the regional connectivity. Experiments implemented on the public Hoover database indicate that this new method gets a 0.803 5 true positive rate and a 0.028 0 false positive rate on an average. According to the test results, compared with Hoover algorithm and method of PCNN and 1D-Otsu, the proposed method shows much better performance.
基金Supported by the Foundation of Innovative Talents in Higher Education of Liaoning Province,No.LR2016043
文摘BACKGROUND The Borrmann classification system is used to describe the macroscopic appearance of advanced gastric cancer,and Borrmann typeⅣdisease is independently associated with a poor prognosis.AIM To evaluate the prognostic significance of lymphatic and/or blood vessel invasion(LBVI)combined with the Borrmann type in advanced proximal gastric cancer(APGC).METHODS The clinicopathological and survival data of 440 patients with APGC who underwent curative surgery between 2005 and 2012 were retrospectively analyzed.RESULTS In these 440 patients,LBVI+status was associated with Borrmann typeⅣ,low histological grade,large tumor size,and advanced pT and pN status.The 5-year survival rate of LBVI+patients was significantly lower than that of LBVI– patients,although LBVI was not an independent prognostic factor in the multivariate analysis.No significant difference in the prognosis of patients with Borrmann typeⅢ/LBVI+disease and patients with Borrmann typeⅣdisease was observed.Therefore,we proposed a revised Borrmann typeⅣ(r-BorⅣ)as Borrmann typeⅢplus LBVI+,and found that r-BorⅣwas associated with poor prognosis in patients with APGC,which outweighed the prognostic significance of pT status.CONCLUSION LBVI is related to the prognosis of APGC,but is not an independent prognostic factor.LBVI status can be used to differentiate Borrmann typesⅢandⅣ,and the same approach can be used to treat r-BorⅣand Borrmann typeⅣ.
基金the National Natural Science Foundation of China(No.81730049 and No.81801666)the Fundamental Research Funds for the Central Universities,HUST(No.2019JYCXJJ044).
文摘Objective Isocitrate dehydrogenase gene(IDH)mutations are associated with tumor angiogenesis and therefore play an important role in glioma management.This study compared the performance of tumor blood vessels counted from contrast-enhanced 3D brain volume(3D-BRAVO)sequence and dynamic contrast-enhanced(DCE)MRI in differentiating IDH1 status in gliomas.Methods Forty-four glioma patients[16 with IDH1 mutant-type(IDH1-MT),28 with IDH1 wild-type(IDH1-WT)]were retrospectively analyzed.A blood vessel entering a tumor was defined as an intratumoral vessel;a blood vessel adjacent to the edge of a tumor was defined as a peritumoral vessel.Combined vessels were defined as the sum of the intratumoral and peritumoral vessels.DCE-derived metrics of tumor were normalized to the contralateral normal-appearing white matter.Results Intratumoral,peritumoral,and combined tumor blood vessels were all significantly different between IDH1-MT and IDH1-WT gliomas,and the range of area under curves(AUCs)was 0.816–0.855.For DCE-derived parameters,cerebral blood volume,cerebral blood flow,mean transit time,and volume transfer constant were significantly different between IDH1-MT and IDH1-WT gliomas,and the range of AUCs was 0.703–0.756.Combined vessels possessed the best performance for identifying IDH1 mutations in gliomas(AUC:0.855,sensitivity:0.857,specificity:0.812,P<0.001).Conclusion The number of tumor blood vessels has comparable diagnostic performance with DCE-derived parameters for differentiating IDH1 mutations and can serve as a potential imaging biomarker to reflect IDH1 mutations in gliomas.
基金supported by Shanghai Science Committee Fund for Key Research Project (No. 04JC14012)Fudan University Med-X Fund, China
文摘Background： A major shortcoming in tissue engineered blood vessels （TEBVs） is the lack of healthy and easily attainable smooth muscle cells （SMCs）. Smooth muscle progenitor cells （SPCs）, especially from peripheral blood, may offer an alternative cell source for tissue engineering involving a less invasive harvesting technique. Methods： SPCs were isolated from 5-ml fresh rat peripheral blood by density-gradient centrifugation and cultured for 3 weeks in endothelial growth medium-2-MV （EGM-2-MV） medium containing platelet-derived growth factoroBB （PDGF BB）. Before seeded on the synthesized scaffold, SPC-derived smooth muscle outgrowth cell （SOC） phenotypes were assessed by immuno-fluorescent staining, Western blot analysis, and reverse transcription polymerase chain reaction （RT-PCR）. The cells were seeded onto the silk fibroin-modified poly（3-hydroxybutyrate-co-3-hydroxyhexanoate） （SF-PHBHHx） scaflblds by 6× 10^4 cells/cm^2 and cultured under the static condition for 3 weeks. The growth and proliferation of the seeded cells on the scaffold were analyzed by 3-（4,5-dimethylthiazol-2-yl）-diphenyltetrazolium bromide （MTT） assay, scanning electron microscope （SEM）, and 4,6-diamidino-2-phenylindole （DAPI） staining. Results： SOCs displayed specific ＂hill and valley＂ morphology, expressed the specific markers of the SMC lineage： smooth muscle （SM） a-actin, calponin and smooth muscle myosin heavy chain （SM MHC） at protein and messenger ribonucleic acid （mRNA） levels. RT-PCR results demonstrate that SOCs also expressed smooth muscle protein 22a （SM22a, a contractile protein, and extracellular matrix components elastin and matrix Gla protein （MGP）, as well as vascular endothelial growth factor （VEGF）. After seeded on the SF-PHBHHx scaffold, the cells showed excellent metabolic activity and proliferation. Conclusion： SPCs isolated from peripheral blood can be differentiated the SMCs in vitro and have an impressive growth potential in the biodegradable synthesized scaffold. Thus, SPCs may be a promising cell sointo urce for constructing TEBVs.
基金Project supported by the National Natural Science Foundation of China(No.19872009)the Foundation of University Key Teachers by the Ministry of Education(No.GG-831-10005-1497)
文摘A geometric model of curved blood vessels is established based on some reasonable hypotheses; the nonlinear motion mechanics model of the curved blood vessel is established according to basic mechanics laws. This model includes much more physiological factors. It couples the interaction of blood flow with mechanical factors such as the displacement, deformation, strain and stress etc. of the curved blood vessel. It is of great importance for investigating the circulation rules of the cardiovascular system and the nonlinear pulse wave propagation in curved blood vessels.
文摘According to clinical observations and model experiment,we have developed a theoretical mod- el and obtained its mathematical equations to investigate the displacement wave of the blood vessel.The waveform and its occurrence criterion have been obtained by using perturbation theory and numerical method. The present study suggests that the displacement wave is associated with the blood velocity waveform and the machanical behaviour of the blood vessel,but not with the pressure waveform.The clinical criterion is in agreement with the observations.
基金the National Natural Science Foundation of China,No.U20A20408(Major Program)and No.82074450(General Program)Natural Science Foundation of Hunan Province,No.2020JJ4066+2 种基金Hunan Province Research and innovation projects for Postgraduates,No.CX20190541Hunan Province"domestic firstclass cultivation discipline"Integrated Traditional Chinese and Western medicine open fund project,No.2018ZXYJH03Hunan University Undergraduate Research Learning and Innovative Experiment Project,No.201609030114.
文摘BACKGROUND In traditional Chinese medicine(TCM),frankincense and myrrh are the main components of the antitumor drug Xihuang Pill.These compounds show anticancer activity in other biological systems.However,whether frankincense and/or myrrh can inhibit the occurrence of hepatocellular carcinoma(HCC)is unknown,and the potential molecular mechanism(s)has not yet been determined.AIM To predict and determine latent anti-HCC therapeutic targets and molecular mechanisms of frankincense and myrrh in vivo.METHODS In the present study,which was based on the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(http://tcmspw.com/tcmsp.php),Universal Protein database(http://www.uniprot.org),GeneCards:The Human Gene Database(http://www.genecards.org/)and Comparative Toxicogenomics Database(http://www.ctdbase.org/),the efficacy of and mechanism by which frankincense and myrrh act as anti-HCC compounds were predicted.The core prediction targets were screened by molecular docking.In vivo,SMMC-7721 human liver cancer cells were transplanted as xenografts into nude mice to establish a subcutaneous tumor model,and two doses of frankincense plus myrrh or one dose of an EGFR inhibitor was administered to these mice continuously for 14 d.The tumors were collected and evaluated:the tumor volume and growth rate were gauged to evaluate tumor growth;hematoxylineosin staining was performed to estimate histopathological changes;immunofluorescence(IF)was performed to detect the expression of CD31,α-SMA and collagen IV;transmission electron microscopy(TEM)was conducted to observe the morphological structure of vascular cells;enzyme-linked immunosorbent assay(ELISA)was performed to measure the levels of secreted HIF-1αand TNF-α;reverse transcription-polymerase chain reaction(RT-qPCR)was performed to measure the mRNA expression of HIF-1α,TNF-α,VEGF and MMP-9;and Western blot(WB)was performed to determine the levels of proteins expressed in the EGFR-mediated PI3K/Akt and MAPK signaling pathways.RESULTS The results of the network pharmacology analysis showed that there were 35 active components in the frankincense and myrrh extracts targeting 151 key targets.The molecular docking analysis showed that both boswellic acid and stigmasterol showed strong affinity for the targets,with the greatest affinity for EGFR.Frankincense and myrrh treatment may play a role in the treatment of HCC by regulating hypoxia responses and vascular system-related pathological processes,such as cytokine-receptor binding,and pathways,such as those involving serine/threonine protein kinase complexes and MAPK,HIF-1 and ErbB signaling cascades.The animal experiment results were verified.First,we found that,through frankincense and/or myrrh treatment,the volume of subcutaneously transplanted HCC tumors was significantly reduced,and the pathological morphology was attenuated.Then,IF and TEM showed that frankincense and/or myrrh treatment reduced CD31 and collagen IV expression,increased the coverage of perivascular cells,tightened the connection between cells,and improved the shape of blood vessels.In addition,ELISA,RT-qPCR and WB analyses showed that frankincense and/or myrrh treatment inhibited the levels of hypoxia-inducible factors,inflammatory factors and angiogenesis-related factors,namely,HIF-1α,TNF-α,VEGF and MMP-9.Furthermore,mechanistic experiments illustrated that the effect of frankincense plus myrrh treatment was similar to that of an EGFR inhibitor with regard to controlling EGFR activation,thereby inhibiting the phosphorylation activity of its downstream targets:the PI3K/Akt and MAPK(ERK,p38 and JNK)pathways.CONCLUSION In summary,frankincense and myrrh treatment targets tumor blood vessels to exert anti-HCC effects via EGFR-activated PI3K/Akt and MAPK signaling pathways,highlighting the potential of this dual TCM compound as an anti-HCC candidate.
基金supported by grants from National Institutes of Health(HL107526,HL119053,and HL123302 to SYC)
文摘Vascular smooth muscle cell （SMC） differentiation is an important process in vasculogenesis and angio- genesis during embryonic development. The altera- tions in the differentiated state in SMCs contribute to a variety of major cardiovascular diseases such as atherosclerosis, hypertension, restenosis and vascular aneurysm . A better understanding of the cellular and molecular mechanisms that control SMC differen-tiation is essential to help develop new approaches to both prevent and treat these diseases. Therefore, development of reliable and reproducible in vitro cellular models in order to study the differentiation mechanisms is important although it has been challenging because of intrinsic peculiarities of SMC.
文摘The β-hydroxybutyrate and β-hydroxyvalerate copolymers( PHBV) /polylactic acid( PLA) is a new biocompatible material,which is developed through bacterial fermentation in vivo systems.The PHBV / PLA material could be used to make continuous filaments.However,features of artificial blood vessels,especially small diameter vascular grafts made of PHVB / PLA materials are not known.This research are to evaluate and improve weavability of the PHBV / PLA material, and to explore feasibility of using it in artificial blood vessels.Preliminary results showed that weavability of PHBV / PLV was not good,but its weavability could be improved by using methods of weak chemical,such as sizing.In this research,scanning electron microscope( SEM) was adopted to evaluate weavability of PHBV / PLV after sizing and observe surfaces of yarns and fabrics.Also,in order to set proper parameters in heat settings,differential scanning calorimetry( DSC) was used to identify glass transition temperature.
文摘A finite element solution for the Navier-Stokes equations for steady flow under the porosity effects through a double branched two-dimensional section of a three-dimensional model of a canine aorta was obtained. The numerical solution involves transforming a physical coordinates to a curvilinear boundary fitted coordinate system.The steady flow,branch flow and shear stress under the porous effects were discussed in detail. The shear stress at the wall was calculated for Reynolds number of 1 000 with branch to main aortic flow rate ratio as a parameter. The results are compared with earlier works involving experimental data and it has been observed that our results are very close to the exact solutions.This work is in fact an improvement of the work of Sharma et al. (2001) in the sense that computational technique is economic and (Reynolds) number is large.
文摘The coronavirus disease 2019(COVID-19)infected so far over 250 million people and caused the death of over 5 million worldwide.Aging,diabetes,and cardiovascular diseases,conditions with preexisting impaired endothelial functions predispose to COVID-19.While respiratory epithelium is the main route of virus entry,the endothelial cells(ECs)lining pulmonary blood vessels are also an integral part of lung injury in COVID-19 patients.COVID-19 not only affects the lungs and respiratory system but also gastrointestinal(GI)tract,liver,pancreas,kidneys,heart,brain,and skin.Blood vessels are likely conduits for the virus dissemination to these distant organs.Importantly,ECs are also critical for vascular regeneration during injury/lesions healing and restoration of vascular network.The World Journal of Gastroenterology has published in last two years over 67 outstanding papers on COVID-19 infection with a focus on the GI tract,liver,pancreas,etc.,however,the role of the endothelial and vascular components as major targets for COVID-19-induced tissue injury,spreading to various organs,and injury healing have not been sufficiently emphasized.In the present article,we focus on these subjects and on current treatments including the most recent oral drugs molnupiravir and paxlovid that show a dramatic,significant efficacy in controlling severe COVID-19 infection.
基金funding from the US National Institutes of Health(R00CA201603,R21EB025270,R21EB026175,R01EB028143)and the Brigham Research Institute.
文摘There has been an increasing demand for bioengineered blood vessels for utilization in both regenerative medicine and drug screening.However,the availability of a true bioengineered vascular graft remains limited.Three-dimensional(3D)bioprinting presents a potential approach for fabricating blood vessels or vascularized tissue constructs of various architectures and sizes for transplantation and regeneration.In this review,we summarize the basic biology of different blood vessels,as well as 3D bioprinting approaches and bioink designs that have been applied to fabricate vascular and vascularized tissue constructs,with a focus on small-diameter blood vessels.
文摘BACKGROUND The development of fully functional small diameter vascular grafts requires both a properly defined vessel conduit and tissue-specific cellular populations.Mesenchymal stromal cells(MSCs) derived from the Wharton's Jelly(WJ) tissue can be used as a source for obtaining vascular smooth muscle cells(VSMCs),while the human umbilical arteries(h UAs) can serve as a scaffold for blood vessel engineering.AIM To develop VSMCs from WJ-MSCs utilizing umbilical cord blood platelet lysate.METHODS WJ-MSCs were isolated and expanded until passage(P) 4. WJ-MSCs were properly defined according to the criteria of the International Society for Cell and Gene Therapy. Then, these cells were differentiated into VSMCs with the use of platelet lysate from umbilical cord blood in combination with ascorbic acid,followed by evaluation at the gene and protein levels. Specifically, gene expression profile analysis of VSMCs for ACTA2, MYH11, TGLN, MYOCD, SOX9,NANOG homeobox, OCT4 and GAPDH, was performed. In addition,immunofluorescence against ACTA2 and MYH11 in combination with DAPI staining was also performed in VSMCs. HUAs were decellularized and served as scaffolds for possible repopulation by VSMCs. Histological and biochemical analyses were performed in repopulated h UAs.RESULTS WJ-MSCs exhibited fibroblastic morphology, successfully differentiating into"osteocytes", "adipocytes" and "chondrocytes", and were characterized by positive expression(> 90%) of CD90, CD73 and CD105. In addition, WJ-MSCs were successfully differentiated into VSMCs with the proposed differentiation protocol. VSMCs successfully expressed ACTA2, MYH11, MYOCD, TGLN and SOX9. Immunofluorescence results indicated the expression of ACTA2 and MYH11 in VSMCs. In order to determine the functionality of VSMCs, h UAs were isolated and decellularized. Based on histological analysis, decellularized h UAs were free of any cellular or nuclear materials, while their extracellular matrix retained intact. Then, repopulation of decellularized h UAs with VSMCs was performed for 3 wk. Decellularized h UAs were repopulated efficiently by the VSMCs. Biochemical analysis revealed the increase of total hydroyproline and s GAG contents in repopulated h UAs with VSMCs. Specifically, total hydroxyproline and s GAG content after the 1 st, 2 nd and 3 rd wk was 71 ± 10, 74 ± 9 and 86 ± 8 μg hydroxyproline/mg of dry tissue weight and 2 ± 1, 3 ± 1 and 3 ± 1μg s GAG/mg of dry tissue weight, respectively. Statistically significant differences were observed between all study groups(P<0.05).CONCLUSION VSMCs were successfully obtained from WJ-MSCs with the proposed differentiation protocol. Furthermore, h UAs were efficiently repopulated by VSMCs. Differentiated VSMCs from WJ-MSCs could provide an alternative source of cells for vascular tissue engineering.
