Reduction of photodynamic damage of blood vessels in the protected region by(–)-epigallocatechin gallate

Photodynamic therapy(PDT)has been increasingly used in the clinical treatment of neoplastic,inflammatory and infectious skin diseases.However,the generation of reactive oxygen species(ROS)may induce undesired side effects in normal tissue surrounding the treatment lesion,which is a big challenge for the clinical application of PDT.To date,(–)-Epigallocatechin gallate(EGCG)has been widely proposed as an antiangiogenic and antitumor agent for the protection of normal tissue from ROS-mediated oxidative damage.This study evaluates the regulation ability of EGCG for photodynamic damage of blood vessels during hematoporphyrin monomethyl ether(Hemoporfin)-mediated PDT.The quenching rate constants of EGCG for the triplet-state Hemoporfin and photosensitized 1O2 generation are determined to be 6.8×10^(8)M^(−1)S^(−1),respectively.The vasoconstriction of blood vessels in the protected region treated with EGCG hydrogel after PDT is lower than that of the control region treated with pure hydrogel,suggesting an efficiently reduced photodamage of Hemoporfin for blood vessels treated with EGCG.This study indicates that EGCG is an efficient quencher for triplet-state Hemoporfin and 1O2,and EGCG could be potentially used to reduce the undesired photodamage of normal tissue in clinical PDT.

Construction of Oriented Structure in Inner Surface of Small-Diameter Artificial Blood Vessels:A Review

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.

Intelligent Machine Learning Enabled Retinal Blood Vessel Segmentation and Classification

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.

NONLINEAR MOTION MECHANICS MODEL OF CURVED BLOOD VESSEL

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.

A Comparative Study Between Tumor Blood Vessels and Dynamic Contrast-enhanced MRI for Identifying Isocitrate Dehydrogenase Gene 1(IDH1)Mutation Status in Glioma

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.

Frankincense myrrh attenuates hepatocellular carcinoma by regulating tumor blood vessel development through multiple epidermal growth factor receptor-mediated signaling pathways

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.

From nerve to blood vessel:a new role of Olfm2 in smooth muscle differentiation from human embryonic stem cell-derived mesenchymal cells

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.

Differentiation of smooth muscle progenitor cells in peripheral blood and its application in tissue engineered blood vessels

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.

Bioprinting of Small-Diameter Blood Vessels

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.

Weavability of β-Hydroxybutyrate and β-Hydroxyvalerate Copolymers( PHBV ) /PLA Used in Artificial Blood Vessels

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.

Novel Method Employing Accelerated-Oscillated Wave Saline Solutions to Unblock Blood Vessels—Physics and Fluid Dynamics Perspectives and Simulations

This research assesses the speed of blood flow across blood vessels and more specifically the veins in terms of Reynold’s number (laminar flow vs. turbulence flow) and in terms of overall speed of the blood when being injected with high-speed saline particles. The authors propose a novel technique to generate accelerated-waved particles built from saline solution to enable the unblocking of partially-blocked healthy-walled veins, and to restore normal operations of these veins. The novel technique encompasses a pump that accelerates saline solutions into the blood stream of the vein and these oscillated waves break down the fats or deposits inside the veins in order to help the blood to flow freely without any obstruction. This research simulated the vein with blood stream using characteristics of the vein in terms of vein diameter, blood density, venous blood flow, and the viscosity of the blood at the normal body temperature. The speed of the overall blood flow after the injection of the accelerated saline droplet solution was determined as well as the depth of penetration of the accelerated particles in order to cleanse the inside of the vein. Results are promising in terms of not altering significantly the overall speed of the bloodstream and also in terms of efficacy of the length of the vein which is being cleaned using this accelerated particle method.

BLOOD FLOW AND MACROMOLECULAR TRANSPORT IN CURVED BLOOD VESSELS

A numerical analysis of the steady/pulsatile flow and macromolecular （such as LDL and Albumin） transport in curved blood vessels was carried out. The computational results predict that the vortex of the secondary flow is time-dependent in the aortic arch. The concentration of macromolecule concentrates at the region of sharp curve, and the wall concentration at the outer part is higher than that at the inner part. Atherosclerosis and thrombosis are prone to develop in such regions with sharp flow.

Design and Development of PHBV/PLA Artificial Blood Vessels

In the research,a β-hydroxybutyrate and β-hydroxyvalerate copolymer(PHBV)/polylactic acid(PLA)artificial blood vessel was designed and developed,and it was also implanted in vivo for a period of time to observe its biocompatibility and degradation performance.The results showed that the developed PHBV/PLA artificial blood vessel could be used to replace the natural blood vessel,but its degradation rate was too fast and the mechanical supporting force was insufficient.Thus,properties of the PHBV/PLA need to be further improved.

Abnormality of peripheral nerve conduction velocity associated with illness course, symptoms and fasting blood glucose in patients with type 2 diabetes mellitus

BACKGROUND: It has shown that abnormality of peripheral nerve conduction velocity during onset of diabetes mellitus is not related to age and sex, but to symptoms, illness course and level of fasting blood glucose. OBJECTIVE: To measure correlation of abnormality of peripheral nerve conduction velocity with various illness courses, symptoms and levels of fasting blood glucose of patients with type 2 diabetes mellitus. DESIGN: Case analysis. SETTING: Department of Neurology, Central People's Hospital of Huizhou. PARTICIPANTS: A total of 128 patients who were diagnosed as type 2 diabetes mellitus were selected from Central People's Hospital of Huizhou from September 2001 to October 2005. There were 75 males and 53 females aged 32-83 years and the illness course ranged from 1 month to 20 years. METHODS: All 128 patients with type 2 diabetes mellitus received neuro-electrophysiological study and their clinical data were retrospectively analyzed to measure peripheral nerve conduction velocity and fasting blood glucose so as to investigate the correlation of peripheral nerve conduction velocity with clinical symptoms, illness course and levels of fasting blood glucose. MAIN OUTCOME MEASURES: Correlation of peripheral nerve conduction velocity with clinical symptoms, illness course and levels of fasting blood glucose. RESULTS: All 128 patients with type 2 diabetes mellitus were involved in the final analysis. ① Among 128 patients, 114 patients had abnormality of peripheral nerve conduction velocity; 110 patients had clinical symptoms, including 102 patients having abnormality of peripheral nerve conduction velocity; 18 patients did not have clinical symptoms, including 12 patients having abnormality of peripheral nerve conduction velocity. There were significant differences between them (χ 2=8.275, P =0.04). ② Among 128 patients, illness course of 75 patients was equal to or less than 5 years, including 27 patients having abnormality of peripheral nerve conduction velocity; illness course of 53 patients was more than 5 years, including 35 patients having abnormality of peripheral nerve conduction velocity. There were significant differences between them (χ 2=11.469, P =0.003). ③ Among 128 patients, levels of fasting blood glucose of 75 patients was equal to or lower than 11 mmol/L, including 41 patients having abnormality of peripheral nerve conduction velocity; levels of fasting blood glucose of 53 patients was higher than 11 mmol/L, including 38 patients having abnormality of peripheral nerve conduction velocity. There were significant differences between them (χ 2=4.023, P =0.134). CONCLUSION: ① Abnormality of peripheral nerve conduction velocity of patients with type 2 diabetes mellitus is related to illness courses and clinical symptoms. The longer the illness course is, the severer the abnormality of peripheral nerve conduction velocity is. Abnormality of peripheral nerve conduction velocity always occurs on patients who have clinical symptoms. ② Abnormality of peripheral nerve conduction velocity is not related to levels of fasting blood glucose.

A retinal blood vessel extraction algorithm based on CART decision tree and improved AdaBoost

This paper presents a supervised learning algorithm for retinal vascular segmentation based on classification and regression tree (CART) algorithm and improved adptive bosting (AdaBoost). Local binary patterns (LBP) texture features and local features are extracted by extracting,reversing,dilating and enhancing the green components of retinal images to construct a 17-dimensional feature vector. A dataset is constructed by using the feature vector and the data manually marked by the experts. The feature is used to generate CART binary tree for nodes,where CART binary tree is as the AdaBoost weak classifier,and AdaBoost is improved by adding some re-judgment functions to form a strong classifier. The proposed algorithm is simulated on the digital retinal images for vessel extraction (DRIVE). The experimental results show that the proposed algorithm has higher segmentation accuracy for blood vessels,and the result basically contains complete blood vessel details. Moreover,the segmented blood vessel tree has good connectivity,which basically reflects the distribution trend of blood vessels. Compared with the traditional AdaBoost classification algorithm and the support vector machine (SVM) based classification algorithm,the proposed algorithm has higher average accuracy and reliability index,which is similar to the segmentation results of the state-of-the-art segmentation algorithm.

THE DISPLACEMENT WAVE THEORY OF BLOOD VESSEL

On the basis of the medical and mechanical analysis and explanations in this paper the visco-elastic simply supported beam model is proposed to treat the displacement wave of the blood vessels. The relationships between the displacement wave and blood vessel elasticity as well as the viscous dissipation of the blood and blood vessel are obtained. The corresponding relations of such kinds of pulses in the traditional Chinese medicine as smooth pulse, surface pulse and deep pulse to the displacement waves of blood vessels are also found. The computational results are in good agreement with those acquired in the experiments with ultrasonic wave.

ZJC 480 Series Helium-Neon Laser Blood Vessel Internal Exposure Apparatus

The ZJC 480 series helium-neon laser blood vessel internal exposure apparatus was developed by the Changchun Zhongji Photoelectric Co, Ltd. It is used in the treatment of ischemic anoxic cardiovascular and cerebrovascular diseases, nervous system disorders, and respiratory and urinary system disorders. In 1995, the ZJC series was appraised as the "95 State-Grade Key New Product" by the State Science and Tech-

Glioma stem cells and the occurrence of tumor blood vessels

Epithelial glioma is the most common brain cancer,accounting for 35.26%-60.69%of intracranial tumors with an average of 44.69%,and it remains the greatest challenge in the field of neurosurgery.The median survival time of patients with advanced glioma is only 12 to 18 months due to the characteristics of high aggression,and the therapeutic effect was poor though surgery,chemotherapy,and targeted drug therapy being treated.Because of the presence of heterogeneity and the differentiation disorder,only a small number of glioma cells are the source of tumor growth and metastasis,which are highly resistant to traditional treatments.They are deemed as the“seed”tumor cells as they could get rid of the effect of the treatment and reconstruct the organization of tumor.They are also termed as brain tumor stem cell(BTSC)or glioma stem cells(GSCs)since neural stem cells share similar features with them.Recent data reveal that they are directly related with invasion,angiogenesis,tolerance,chemotherapy,recurrence of glioma.Based on the research result by the team,the paper elaborates the characteristics of GSCs and the relationship with the tumor angiogenesis.