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.

Protocol to study the effects of AMPK-mTOR/PINK-Parkin dual signaling pathways on the formation of coronary heart disease showing blood stasis symptom pattern based on traditional Chinese medicine theory of“heart governing blood and vessels”

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.

The importance of laminin at the blood-brain barrier

The blood-brain barrier is a unique property of central nervous system blood vessels that protects sensitive central nervous system cells from potentially harmful blood components.The mechanistic basis of this barrier is found at multiple levels,including the adherens and tight junction proteins that tightly bind adjacent endothelial cells and the influence of neighboring pericytes,microglia,and astrocyte endfeet.In addition,extracellular matrix components of the vascular basement membrane play a critical role in establishing and maintaining blood-brain barrier integrity,not only by providing an adhesive substrate for blood-brain barrier cells to adhere to,but also by providing guidance cues that strongly influence vascular cell behavior.The extracellular matrix protein laminin is one of the most abundant components of the basement membrane,and several lines of evidence suggest that it plays a key role in directing blood-brain barrier behavior.In this review,we describe the basic structure of laminin and its receptors,the expression patterns of these molecules in central nervous system blood vessels and how they are altered in disease states,and most importantly,how genetic deletion of different laminin isoforms or their receptors reveals the contribution of these molecules to blood-brain barrier function and integrity.Finally,we discuss some of the important unanswered questions in the field and provide a“to-do”list of some of the critical outstanding experiments.

Advances in the differentiation of pluripotent stem cells into vascular cells

Blood vessels constitute a closed pipe system distributed throughout the body,transporting blood from the heart to other organs and delivering metabolic waste products back to the lungs and kidneys.Changes in blood vessels are related to many disorders like stroke,myocardial infarction,aneurysm,and diabetes,which are important causes of death worldwide.Translational research for new appro-aches to disease modeling and effective treatment is needed due to the huge socio-economic burden on healthcare systems.Although mice or rats have been widely used,applying data from animal studies to human-specific vascular physiology and pathology is difficult.The rise of induced pluripotent stem cells(iPSCs)provides a reliable in vitro resource for disease modeling,regenerative medicine,and drug discovery because they carry all human genetic information and have the ability to directionally differentiate into any type of human cells.This review summarizes the latest progress from the establishment of iPSCs,the strategies for differentiating iPSCs into vascular cells,and the in vivo trans-plantation of these vascular derivatives.It also introduces the application of these technologies in disease modeling,drug screening,and regenerative medicine.Additionally,the application of high-tech tools,such as omics analysis and high-throughput sequencing,in this field is reviewed.

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.

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.

The development of blood-retinal barrier during the interaction of astrocytes with vascular wall cells

Astrocytes are intimately involved in the formation and development of retinal vessels. Astrocyte dysfunction is a major cause of blood-retinal barrier injury and other retinal vascular diseases. In this study, the development of the retinal vascular system and the formation of the blood-ret-inal barrier in mice were investigated using immunolfuorescence staining, gelatin-ink perfusion, and transmission electron microscopy. The results showed that the retinal vascular system of mice develops from the optic disc after birth, and radiates out gradually to cover the entire retina, taking the papilla optica as the center. First, the superifcial vasculature is formed on the inner retinal layer;then, the vasculature extends into the inner and outer edges of the retinal inner nuclear layer, forming the deep vasculature that is parallel to the superifcial vasculature. The blood-retinal barrier is mainly composed of endothelium, basal lamina and the end-feet of astrocytes, which become mature during mouse development. Initially, the naive endothelial cells were immature with few organelles and many microvilli. The basal lamina was uniform in thickness, and the glial end-feet surrounded the outer basal lamina incompletely. In the end, the blood-retinal barrier matures with smooth endothelia connected through tight junctions, rela-tively thin and even basal lamina, and relatively thin glial cell end-feet. These ifndings indicate that the development of the vasculature in the retina follows the rules of“center to periphery”and“superifcial layer to deep layers”. Its development and maturation are spatially and tempo-rally consistent with the functional performance of retinal neurons and photosensitivity. The blood-retinal barrier gradually becomes mature via the process of interactions between astro-cytes and blood vessel cells.

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.

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.

Molecular events in the jaw vascular unit:A traditional review of the mechanisms involved in inflammatory jaw bone diseases

Inflammatory jaw bone diseases are common in stomatology,including periodontitis,peri-implantitis,medication-related osteonecrosis of the jaw,radiation osteomyelitis of the jaw,age-related osteoporosis,and other specific infections.These diseases may lead to tooth loss and maxillofacial deformities,severely affecting patients'quality of life.Over the years,the reconstruction of jaw bone deficiency caused by inflammatory diseases has emerged as a medical and socioeconomic challenge.Therefore,exploring the pathogenesis of inflammatory diseases associated with jaw bones is crucial for improving prognosis and developing new targeted therapies.Accumulating evidence indicates that the integrated bone formation and dysfunction arise from complex interactions among a network of multiple cell types,including osteoblast-associated cells,immune cells,blood vessels,and lymphatic vessels.However,the role of these different cells in the inflammatory process and the'rules'with which they interact are still not fully understood.Although many investigations have focused on specific pathological processes and molecular events in inflammatory jaw diseases,few articles offer a perspective of integration.Here,we review the changes and mechanisms of various cell types in inflammatory jaw diseases,with the hope of providing insights to drive future research in this field.

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.

Anti-cancer,Anti-inflammatory,Antioxidant and Other Pharmacological Effects of Wedelactone and Their Molecular Mechanisms

Wedelolide is a coumarin-like active substance extracted from Ecliptae Herba.It not only has pharmacological effects of anti-pulmonary fibrosis,anti-arthritis,blood vessel protection and liver protection,but also effectively inhibits the proliferation of cancer cells and induces apoptosis of cancer cells,thereby delaying the further development of malignant tumors.In this paper,the pharmacological effects and mechanisms of wedelactone were reviewed to lay a foundation for further study and clinical application of wedelactone.

COMPUTATIONAL TECHNIQUE FOR FLOW IN BLOODVESSELS WITH POROUS EFFECTS

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.

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.

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.

Three-dimensional morphological and fluorescent imaging of zebrafish with a continuous-rotational light-sheet microscope

Light-sheet fluorescence microscopy(LSFM)has been widely used to image the three-dimensional(3D)structures and functions of various millimeter-size bio-specimen such as zebrafish.However,the sample adsorption and scattering cause shading of the light-sheet illumination,preventing the even 3D image of thick samples.Herein,we report a continuous-rotational light-sheet microscope(CR-LSM)that enables simultaneous 3D bright-field and fluorescence imaging.With a high-accuracy rotational stage,CR-LSM records the outline projections and the fluorescent images of the sample at multiple rotation angles.Then,3D morphology and fluorescent structure were reconstructed with a developed algorithm.Using CR-LSM,zebrafish’s whole-fish contour and blood vessel structures were obtained simultaneously.

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.

Analysis of the rogue waves in the blood based on the high-order NLS equations with variable coefficients

The research of rogue waves is an advanced field which has important practical and theoretical significances in mathematics,physics,biological fluid mechanics,oceanography,etc.Using the reductive perturbation theory and long wave approximation,the equations governing the movement of blood vessel walls and the flow of blood are transformed into high-order nonlinear Schrodinger(NLS)equations with variable coefficients.The third-order nonlinear Schrodinger equation is degenerated into a completely integrable Sasa–Satsuma equation(SSE)whose solutions can be used to approximately simulate the real rogue waves in the vessels.For the first time,we discuss the conditions for generating rogue waves in the blood vessels and effects of some physiological parameters on the rogue waves.Based on the traveling wave solutions of the fourth-order nonlinear Schrodinger equation,we analyze the effects of the higher order terms and the initial deformations of the blood vessel on the wave propagation and the displacement of the tube wall.Our results reveal that the amplitude of the rogue waves are proportional to the initial stretching ratio of the tube.The high-order nonlinear and dispersion terms lead to the distortion of the wave,while the initial deformation of the tube wall will influence the wave amplitude and wave steepness.

Fabrication and data harvesting of casting sample of rat liver blood vessels

BACKGROUND: The configuration and course of liver blood vessels (LBVs) are involved in the study of patho-genesis of hepatic diseases including liver cirrhosis, tissue engineering of the liver and surgical treatment of diseases of the liver and gallbladder. In the study of vascularization in tissue engineering of the liver in particular, the work we should do is to get the anatomy data of LBVs for computer-aided reconstruction of digital model of LBVs. In doing so, the casting sample of rat liver blood vessels (RLBVs) is fabricated and the data of each section of the sample is harvested. METHODS: Liquid polymer preparation (8%-10%), which was made of chlorinated poly vinyl chloride ( CPVC) as a solute, acetone as solvent and pigment, was injected into the RLBVs of 40 rats. Once acetone evaporated, the preparation solidified. When the cells and connective tissue were dissolved by hydrochloric acid, a casting sample of RLBV was left. The sample was embedded in paraffin and cut into sections. The data of each section of RLBVs was collected by digital camera. RESULTS: In 36 rats, the casting sample of RLBVs was made successfully by this method. The diameter of the hepatic arteries varied from 0. 8 to 0.2 mm, the portal veins from 2.0 to 0.1 mm, and the hepatic veins from 2.2 to 0.2 mm. In each rat, about 150 photographs of the sections of RLBVs were taken. CONCLUSION: The method described above is feasible for getting experimental data for computer-aided reconstruction of the digital model of RLBVs.