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.

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.

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.

Electro-acupuncture at Conception and Governor vessels and transplantation of umbilical cord bloodderived mesenchymal stem cells for treating cerebral ischemia/reperfusion injury

Mesenchymal stem cell transplantation is a novel means of treating cerebral ischemia/reper- fusion, and can promote angiogenesis and neurological functional recovery. Acupuncture at Conception and Governor vessels also has positive effects as a treatment for cerebral ischemia/ reperfusion. Therefore, we hypothesized that electro-acupuncture at Conception and Governor vessels plus mesenchymal stem cell transplantation may have better therapeutic effects on the promotion of angiogenesis and recovery of neurological function than either treatment alone. In the present study, human umbilical cord blood-derived mesenchymal stem cells were isolated, cultured, identified and intracranially transplanted into the striatum and subcortex of rats at 24 hours following cerebral ischemia/reperfusion. Subsequently, rats were electro-acupunctured at Conception and Governor vessels at 24 hours after transplantation. Modified neurological severity scores and immunohistochemistry findings revealed that the combined interventions of electro-acupuncture and mesenchymal stem cell transplantation clearly improved neurological impairment and up-regulated vascular endothelial growth factor expression around the isch- emic focus. The combined intervention provided a better outcome than mesenchymal stem cell transplantation alone. These findings demonstrate that electro-acupuncture at Conception and Governor vessels and mesenchymal stem cell transplantation have synergetic effects on promot- ing neurological function recovery and angiogenesis in rats after cerebral ischemia/reperfusion.

Influence of folic acid and vitamin B12 combined therapy on plasma Hcy, inflammatory factor levels and blood vessels endothelial function in patients with vascular dementia and type H hypertension

Objective:To investigate influence of folic acid and vitamin B12 combined therapy on plasma homocysteine (Hcy) level, blood vessels endothelial function and inflammatory factors in patients with vascular dementia and type H hypertension.Methods:100 cases of patients with vascular dementia and type H hypertension accorded with the inclusion criteria were selected as research objects. They were randomly divided as the control group and the therapeutic group, 50 cases each. For control group, Enalapril tablets were administered by mouth for treatment. For therapeutic group, folic acid and vitamin B12 treatment were provided on the basis of treatment for control group. Treatments were continued for 12 weeks. Plasma Hcy levels, inflammatory factors [(interleukin-6 (IL-6), interleukin-8 (IL-8) and hypersensitive C reaction protein (hs-CRP)], blood vessels endothelial function indexes variation in patients before and after treatment were observed and detected.Results:Plasma Hcy, IL-6, IL-8 and hs-CRP levels in two groups of patients after treatment were significantly decreased comparing with the same group before treatment, and the above index levels in therapeutic group after treatment were significantly lower than control group (P<0.05);For comparison of blood vessels endothelial function indexes in the patients, NO levels in two groups after treatment were increased in various degrees, and endothelin-1 (ET-1) were decreased. The differences between levels of the two indexes in therapeutic group before and after treatment were significant, and levels after treatment in therapeutic group were significantly better than in control group (P<0.05). While variations of the differences in control group before and after treatment were not significant (P>0.05);After treatment, diastolic pressure and systolic pressure in the two groups of patients were significantly improved comparing with before treatment (P<0.05). However, after treatment, the differences of levels between therapeutic group and control group were not significant (P>0.05). MMSE score in therapeutic group after treatment was significantly higher than before treatment, and significantly higher than in control group (P<0.05).Conclusions: Combined therapy of folic acid and vitamin B12 for treating vascular dementia with type H hypertension could effectively decrease plasma Hcy and inflammatory factor levels, and improve blood vessels endothelial function and dementia degree on patients. It has certain clinical value which deserves to be promoted.

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.

Blood-brain barrier pathology in cerebral small vessel disease

Cerebral small vessel disease is a neurological disease that affects the brain microvasculature and which is commonly observed among the elderly.Although at first it was considered innocuous,small vessel disease is nowadays regarded as one of the major vascular causes of dementia.Radiological signs of small vessel disease include small subcortical infarcts,white matter magnetic resonance imaging hyperintensities,lacunes,enlarged perivascular spaces,cerebral microbleeds,and brain atrophy;however,great heterogeneity in clinical symptoms is observed in small vessel disease patients.The pathophysiology of these lesions has been linked to multiple processes,such as hypoperfusion,defective cerebrovascular reactivity,and blood-brain barrier dysfunction.Notably,studies on small vessel disease suggest that blood-brain barrier dysfunction is among the earliest mechanisms in small vessel disease and might contribute to the development of the hallmarks of small vessel disease.Therefore,the purpose of this review is to provide a new foundation in the study of small vessel disease pathology.First,we discuss the main structural domains and functions of the blood-brain barrier.Secondly,we review the most recent evidence on blood-brain barrier dysfunction linked to small vessel disease.Finally,we conclude with a discussion on future perspectives and propose potential treatment targets and interventions.

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.

DISPLACEMENT WAVE OF THE BLOOD VESSEL——A MECHANICAL MODEL

According to clinical observations and model experiment,we have developed a theoretical mod- el and obtained its mathematical equations to investigate the displacement wave of the blood vessel.The waveform and its occurrence criterion have been obtained by using perturbation theory and numerical method. The present study suggests that the displacement wave is associated with the blood velocity waveform and the machanical behaviour of the blood vessel,but not with the pressure waveform.The clinical criterion is in agreement with the observations.

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.

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.

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.

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.

Altered Calcium Handling in Peripheral Nerve Terminals and Blood Vessels in Spontaneously Hypertensive Rats

The present study was designed to clarify the roles of N-type and P/Q-type calcium channels in the increased sympathetic activity of spontaneously hypertensive rats (SHR/Izm). We also tested in SHR/Izm the contribution to increased vascular tone of α1A adrenoceptor-linked L-type calcium channels and α1B receptor-mediated calcium mobilization from the sarcoplasmic reticulum. Methods: Six-week-old SHR/Izm and Wistar-Kyoto rats (WKY/Izm) were used. A superior mesenteric arterial preparation was electrically stimulated before and after treatment with ω-conotoxin GVIa (N-type calcium channel blocker [CgTX]) and ω-agatoxinIVa (P/Q-type calcium channel blocker [AgaTX]). Pressor response to norepinephrine was measured before and after treatment with the α1A blocker WB-4101 and the α1B blocker chloroethyl clonidine (CEC). To determine the intracellular calcium store size, the effects of ryanodine on pressor response and caffeine-induced vascular contraction were also tested. Results: Norepinephrine overflow evoked by electrical stimulation was increased in SHR/Izm. CgTX but not AgaTX suppressed the increased NE overflow in SHR/Izm. WB-4101 suppressed the pressor response to norepinephrine in SHR/Izm but not WKY/Izm rats. CEC had no effects on pressor response to norepinephrine in both types of rats. Caffeine-induced contraction to a high potassium-induced maximal contraction ratio was reduced in SHR/Izm. The effect of ryanodine on pressor response was reduced in SHR/Izm. Conclusion: N-type calcium channels but not P/Q-type calcium channels play an important role in the increased sympathetic tone in SHR/ Izm. Although α1A adrenoceptor-linked L-type calcium channels contribute to the increased vascular tone, the intracellular calcium store size was reduced in SHR/Izm.

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.

APPLICATION OF DOPPLER OPTICAL COHERENCE TOMOGRAPHY IN RHEOLOGICAL STUDIES:BLOOD FLOW AND VESSELS MECHANICAL PROPERTIES EVALUATION

Doppler Optical Coherence Tomography(DOCT)is a noninvasive optical diagnostic technique,which is well suited for the quantitative mapping of microflow velocity profiles and the analysis of flow-vessel interactions.The noninvasive imaging and quantitative analysis of blood flow in the complex-structured vascular bed is required in many biomedical applications,including those where the determination of mechanical properties of vessels or the knowledge of the mechanic interactions between the flow and the housing medium plays a key role.The change of microvessel wall elasticity could be a potential indicator of cardiovascular disease at the very early stage,whilst monitoring the blood flow dynamics and associated temporal and spatial variations in vessel’s wall shear stress could help predicting the possible rupture of atherosclerotic plaques.The results of feasibility studies of application of DOCT for the evaluation of mechanical properties of elastic vessel model are presented.The technique has also been applied for imaging of sub-cranial rat blood flow in vivo.

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.

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.