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.

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.

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.

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.

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.

Reflection-mode photoacoustic microscopy using a hollow focused ultrasound transducer for in vivo imaging of blood vessels

A reflection-mode photoacoustic microscope using a hollow focused ultrasound transducer is developed for highresolution in vivo imaging.A confocal structure of the laser and the ultrasound is used to improve the system resolution.The axial and lateral resolutions of the system are measured to be ～ 32 μm and ～ 58 μm,respectively.Ex vivo and in vivo modes are tested to validate the imaging capability of the photoacoustic microscope.The adjacent vein and artery can be seen clearly from the reconstructed photoacoustic images.The results demonstrate that the reflectionmode photoacoustic microscope can be used for high-resolution imaging of micro-blood vessels,which would be of great benefit for monitoring the neovascularization in tumor angiogenesis.

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.

Hard X-ray in-line outline imaging for blood vessels:first generation synchrotron radiation without contrast agents in vitro

Objective: Phase-contrast X-ray imaging which reduces radiation exposure, is a promising technique for observing the inner structures of biological soft tissues without the aid of contrast agents. The present study intends to depict blood vessels of rabbits and human livers with hard X-ray in-line outline imaging without contrast agents using synchrotron radiation. Methods: All samples were fixed with formalin and sliced into 6 mm sections. The imaging experiments were performed with Fuji-IX80 films on the 4W1A light beam of the first generation synchrotron radiation in Beijing, China. The device of the experiment, which supplies a maximum light spot size of 20×10 mm was similar to that of in-line holography. The photon energy was set at 8 KeV and high quality imagines were obtained by altering the distance between the sample and the film. Results: The trees of rabbit-liver blood vessels and the curved vessels of the cirrhotic human liver were revealed on the images, where vessels < 20 μm in diameter were differentiated. Conclusion: These results show that the blood vessels of liver samples can be revealed by using hard X-ray in-line outline imaging with the first generation synchrotron radiation without contrast agents.

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.

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

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.

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.

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.

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.

Hemodialysis bilayer bionic blood vessels developed by the mechanical stimulation of hepatitis B viral X(HBX)genetransfected hepatic stellate cells

Artificial vascular graft(AVG)fistula is widely used for hemodialysis treatment in patients with renal failure.However,it has poor elasticity and compliance,leading to stenosis and thrombosis.The ideal artificial blood vessel for dialysis should replicate the structure and components of a real artery,which is primarily maintained by collagen in the extracellular matrix(ECM)of arterial cells.Studies have revealed that in hepatitis B virus(HBV)-induced liver fibrosis,hepatic stellate cells(HSCs)become hyperactive and produce excessive ECM fibers.Furthermore,mechanical stimulation can encourage ECM secretion and remodeling of a fiber structure.Based on the above factors,we transfected HSCs with the hepatitis B viral X(HBX)gene for simulating the process of HBV infection.Subsequently,these HBX-HSCs were implanted into a polycaprolactonepolyurethane(PCL-PU)bilayer scaffold in which the inner layer is dense and the outer layer consists of pores,which was mechanically stimulated to promote the secretion of collagen nanofiber from the HBX-HSCs and to facilitate crosslinking with the scaffold.We obtained an ECM-PCL-PU composite bionic blood vessel that could act as access for dialysis after decellularization.Then,the vessel scaffold was implanted into a rabbit’s neck arteriovenous fistula model.It exhibited strong tensile strength and smooth blood flow and formed autologous blood vessels in the rabbit’s body.Our study demonstrates the use of human cells to create biomimetic dialysis blood vessels,providing a novel approach for creating clinical vascular access for dialysis.

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.

Effects of sympathetic histamine on vasomotor responses of blood vessels in rabbit ear to electrical stimulation

Objective To investigate the effects of histamine receptor antagonists on vasoconstriction induced by electrical stimulation （ES） on posterior auricular nerve,and to explore the pre-and post-synaptic effects of sympathetic histamine on the vasomotor responses of vascular smooth muscle in rabbit ear.Methods ES was applied to posterior auricular nerves of the whole rabbit ear at 10 Hz,20 Hz and 40 Hz,respectively.Besides,the whole ear was perfused with different histamine receptor antagonists under constant perfusion pressure,and the changes in the flow rate of perfusate were observed.Results The flow rate of venous outflow was decreased by ES at all the 3 frequencies.The ES-induced vasoconstriction at 20 Hz and 40 Hz could be partly inhibited by H1 receptor antagonist chlorpheniramine （P0.05） .After exhaustion of histamine in mast cells by pretreatment with specific mast cell degranulator compound 48/80,chlorpheniramine could still inhibit the ES-induced flow rate reduction.In contrast,H2 receptor antagonist cimetidine could enhance the 40-Hz ES-induced flow rate reduction （P 0.05） .Moreover,ES-induced vasoconstriction at the 3 frequencies could all be enhanced by H3 receptor antagonist thioperamide （P0.05） .Conclusion Stimulation on the auricular nerve may evoke histamine release from sympathetic nerves rather than from mast cells.Moreover,the functions of sympathetic histamine vary from pre-synaptic modulation to post-synaptic vasoconstriction or vasodilatation,via activation of different histamine receptors.