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.

Blood Vessel Segmentation with Classification Model for Diabetic Retinopathy Screening

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.

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.

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.

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.

Endothelial cells and blood vessels are major targets for COVID-19-induced tissue injury and spreading to various organs

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.

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.

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.

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.

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.

Curvelet Transform Based on Edge Preserving Filter for Retinal Blood Vessel Segmentation

Segmentation of vessel in retinal fundus images is a primary step for the clinical identification for specific eye diseases.Effective diagnosis of vascular pathologies from angiographic images is thus a vital aspect and generally depends on segmentation of vascular structure.Although various approaches for retinal vessel segmentation are extensively utilized,however,the responses are lower at vessel’s edges.The curvelet transform signifies edges better than wavelets,and hence convenient for multiscale edge enhancement.The bilateral filter is a nonlinear filter that is capable of providing effective smoothing while preserving strong edges.Fast bilateral filter is an advanced version of bilateral filter that regulates the contrast while preserving the edges.Therefore,in this paper a fusion algorithm is recommended by fusing fast bilateral filter that can effectively preserve the edge details and curvelet transform that has better capability to detect the edge direction feature and better investigation and tracking of significant characteristics of the image.Afterwards C mean thresholding is used for the extraction of vessel.The recommended fusion approach is assessed on DRIVE dataset.Experimental results illustrate that the fusion algorithm preserved the advantages of the both and provides better result.The results demonstrate that the recommended method outperforms the traditional approaches.

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-

Effects of intrauterine infection in different periods on the placenta and endometrial blood vessel formation of pregnant mice and the growth and development of fetal rats

Objective:To investigate the effects of intrauterine infection in different periods on the placenta and endometrial blood vessel formation of pregnant rats and the growth and development of fetal rats.Methods:According to the random number table method,32 pregnant rats were divided into the early infection group,the mid-term infection group,the late infection group and the control group,with 8 rats in each group.On the 3rd,9th and 15th day of pregnancy,lipopolysaccharide was injected intraperitoneally to construct intrauterine infection models.The pregnant rats in the control group were intraperitoneally injected with the same dose of 0.9%sodium chloride solution.On the 18th day of pregnancy,the inflammatory factors[interleukin-6(IL-6),tumor necrosis factor-(TNF-)],the blood vessel density of placenta and endometrium in the placental tissues of pregnant rats,dead fetus+absorbed fetus,the inflammatory factors IL-6,TNF-and oxidation reaction indicators[malondialdehyde(MDA)and myeloperoxidase(MPO)]in the fetal rat lung and brain tissues were detected.Results:The changing trend of IL-6 and TNF-levels in the placental tissues of pregnant rats with intrauterine infection in different periods was:the control group<the late infection group<the mid-term infection group<the early infection group,the differences were statistically significant(p<.05).The changing trend of fetal rat weight,placental weight and placental coefficient in the intrauterine infection groups in different periods was:the control group>the late infection group>the mid-term infection group>the early infection group,the differences were statistically significant(p<.05).The blood vessel density of placenta and endometrium,the mean number of fetuses,brain coefficient and lung coefficient in the late infection group were significantly increased in comparison with the early infection group and the mid-term infection group.The total number and the ratio of dead fetus+absorbed fetus,the levels of IL-6,TNF-,MDA and MPO in brain and lung tissues were significantly reduced,and the differences were statistically significant(p<.05).The blood vessel density of placenta and endometrium,brain coefficient and lung coefficient of pregnant rats in the mid-term infection group were significantly increased in comparison with the early infection group,and the differences were statistically significant(p<.05).There was no statistically significant difference in the other indicators between the two groups(p>.05).Conclusions:Intrauterine infection in different periods can inhibit placental and endometrial angiogenesis,and affect the survival rate of fetal rats and the growth and development of brain and lung.The reason may be related to the aggravation of fetal inflammatory responses and oxidative stress.The earlier the intrauterine infection occurs,the severer the adverse effects on the fetal rats will be.

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.

Impact of lymphatic and/or blood vessel invasion in stage Ⅱ gastric cancer

AIM:To determine the prognostic value of lymphatic and/or blood vessel invasion (LBVI) in patients with stage Ⅱ gastric cancer.METHODS:From January 2001 to December 2006,487 patients with histologically confirmed primary gastric adenocarcinoma were diagnosed with stage Ⅱ gastric 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.Clinicopathological findings 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 mo.Stage Ⅱ a cancer was observed in 334 patients,including 268 T3N0,63 T2N1,and three T1N2,and stage Ⅱb was observed in 102 patients,including 49 patients T3N1,51 T2N2,one T1N3,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 LNpositive 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 metastases was detected (LBVI+/LN ,group Ⅱ).In 167 patients (38.3%),LN metastases were found.Among those patients,LBVI was not determined in 96 patients (22.0%) (LBVI /LN+,group Ⅲ),and was determined in 71 patients (16.3%) (LBVI+/LN+,group Ⅳ).Correlation 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 survival 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 LBVInegative 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 Ⅱ gastric cancer patients revealed that LBVI independently affected patient prognosis in LN-negative patients (P = 0.018) but not in LN-positive patients (P = 0.508).CONCLUSION:In LN-negative stage Ⅱ gastric cancer patients,LBVI is an additional independent prognostic marker,and may provide useful information to identify patients with poorer prognosis.

Tissue engineering of blood vessels with endothelial cells differentiated from mouse embryonic stem cells

Endothelial cells (TEC3 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 × l06 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 TEC3 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.

Automated retinal blood vessels segmentation based on simplified PCNN and fast 2D-Otsu algorithm

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.