Human Vein Research Articles

Driver Identification System Using Finger Vein and YOLO Object Detection

Biometrics used to identify people is one of the safest and most convenient identification methods. The hypoxic hemoglobin method can present a human finger vein image for driver identification through infrared ray irradiation. The finger vein image is captured system; with the finger vein image processed using contrast-limited adaptive histogram equalization (CLAHE) and the Gabor filter to obtain a clearer image. The YOLO object detection technology is used to drive identification. The proposed system can be divided into two parts. The first part is the training part, which processes images. A database generates the weight files for external testing. The second part is the testing system. When the driver's finger is placed in the designated photo area a photo will be taken. The photo will be processed and run on Raspberry Pi 4 together with the weight file to identify the driver. The experimental results show that when the database has a large amount of data, the yolov4-tiny-hy recognition rate is comparable to that of YOLOv4. The training time is greatly shortened.

Effects of different preservation methods of human iliac veins.

With the progress of vascular anastomosis technology, the radical resection surgery of cancer combining with vascular resection and reconstruction has been focused by surgeon. As a natural substitute material for blood vessel, vascular allografts have good vascular compliance and histocompatibility. Generally, the donated veins could not be used immediately, and need to be well preserved. So, it is greatly significant to do research in the preservation effects of different preservation methods on veins. In this study, the effects of different preservative methods of human iliac veins were compared and analyzed in terms of cell viability, vascular wall structure and tension resistance. The donated human iliac veins were randomly divided into three groups: Cold Storage Group (4 °C) (CSG), Frozen Storage Group (-186 °C) (FSG)and Fresh Control Group (FCG). Six detection time-points of preservation for 1, 3, 5, 7, 14, 28days were set respectively. There are ten samples in each group and each time-point separately. Survival and apoptosis of vascular cell were evaluated by MTT assay and Tunel fluorescence staining. Tensile test was used to evaluate mechanical properties of vessels. The changes of vascular endothelial cells, smooth muscle cells, collagen fibers and elastic fibers were evaluated by HE staining, Masson staining and EVG staining. Furthermore, the changes of organelles were observed by transmission electron microscope. With the extension of preservation period, the vascular cell viability and tension resistance of two groups decreased, and the apoptotic cells increased gradually. The apoptosis index of CSG was higher than FSG at each time point (P < 0.05). In terms of cell viability, CSG was higher within 3days (P < 0.05), both groups were same between 3 and 14days, and then CSG lower than FSG after 14days (P < 0.05). In terms of tension resistance, CSG was stronger than FSG (P < 0.05) in first 7days, both groups were same in 2nd week, and then CSG was weaker in 4th week (P < 0.05). In terms of vascular wall structure, in CSG, vascular endothelial cells were damaged and shed, smooth muscle cells were edema after 14days, but the cell membrane and intercellular connection were still intact. In 4th week, endothelial cells were completely damaged and shed, the boundary of smooth muscle cell membrane was unclear, intercellular connection was damaged. Moreover, organelles were destroyed and disappeared, perinuclear condensation of chromatin was observed, and some cells had incomplete nuclear membrane or nuclear fragmentation; However, there were no obvious changes in the FSG within 28days. Finally, local exfoliation and destruction of endothelial cells and edema-like changes of organelles were observed; the collagen fibers and elastic fibers of blood vessels in the two groups had no obvious damage and change within 28days. For excised human iliac vein, cold and frozen storage can effectively preserve the cell viability, wall structure and tension resistance of blood vessels. With the extension of preservation time, the related performance of vessels declined in varying degrees. Within first week, the effect of cold storage is better than frozen storage, but frozen storage is significantly better than cold storage after 2weeks.

Optimization of an Ex-Vivo Human Skin/Vein Model for Long-Term Wound Healing Studies: Ground Preparatory Activities for the 'Suture in Space' Experiment Onboard the International Space Station.

This study is preliminary to an experiment to be performed onboard the International Space Station (ISS) and on Earth to investigate how low gravity influences the healing of sutured human skin and vein wounds. Its objective was to ascertain whether these tissue explants could be maintained to be viable ex vivo for long periods of time, mimicking the experimental conditions onboard the ISS. We developed an automated tissue culture chamber, reproducing and monitoring the physiological tensile forces over time, and a culture medium enriched with serelaxin (60 ng/mL) and (Zn(PipNONO)Cl) (28 ng/mL), known to extend viability of explanted organs for transplantation. The results show that the human skin and vein specimens remained viable for more than 4 weeks, with no substantial signs of damage in their tissues and cells. As a further clue about cell viability, some typical events associated with wound repair were observed in the tissue areas close to the wound, namely remodeling of collagen fibers in the papillary dermis and of elastic fibers in the vein wall, proliferation of keratinocyte stem cells, and expression of the endothelial functional markers eNOS and FGF-2. These findings validate the suitability of this new ex vivo organ culture system for wound healing studies, not only for the scheduled space experiment but also for applications on Earth, such as drug discovery purposes.

Cysteine Sulfenylation of Protein Disulfide Isomerase Links Oxidative Stress to Thrombosis

Oxidative stress increases the risk of clinically significant thrombosis in the setting of inflammation, malignancy, infection, and dyslipidemia. Oxidants generated during oxidative stress are prothrombotic; however, the mechanisms by which oxidants induce thrombus formation is poorly understood. Protein disulfide isomerase (PDI) is a thiol isomerase that serves an important role in thrombus formation. It has a domain structure of a-b-b'-a', in which the aand a' domains are catalytic and the b and b' are substrate binding. A flexible x linker is between the b' and a'domains. PDI is uniquely sensitive to oxidative cysteine modification within the CGHC catalytic motif of its a and a'domains. Yet whether PDI cysteine modifications mediates thrombosis in an oxidative environment has not previously been studied. We hypothesized that oxidized PDI links oxidative stress to a prothrombotic phenotype through post-translational modification of proteins. We have previously shown that dyslipidemia promotes hydrogen peroxide generation from platelets and oxidizes proteins. Using hydrogen peroxide as a model oxidant, we found that oxidation of recombinant PDI promoted the loss of free thiols and inhibited reductase activity in a dose-dependent manner (IC50= 3.3 ± 0.12 µM). To understand how free thiols were lost, we used a benzothiazine-based nucleophilic probe, termed BTD, to label sulfenic acid. The transient cysteine sulfenic acid (S-OH) was detected by BTD labeling in wildtype PDI following exposure to hydrogen peroxide, but not in a PDI mutant in which all active site cysteines had been mutated to alanine. PDI exposure to oxidized lipoprotein particles (OxLDL) or 3-morpholinosydnonimine (SIN-1), a peroxynitrite donor, also promoted its sulfenylation. Using single cysteine mutants of PDI to identify the sulfenylation site, we found that Cys56 was preferentially sulfenylated as mutation of this cysteine prevented further labeling of the sulfenic acid probe. To assess whether interdomain interactions influenced sulfenylation, we evaluated BTD labeling in isolated fragments of PDI. Sulfenylation was identified in the a domain, consistent with Cys56 labeling, and was significantly enhanced in the ab fragment, implicating an interaction between the a and b domains in sulfenylation. No labeling was observed in an isolated b'xa' fragment. Further analysis of structural elements revealed that a conserved Arg120 within the a domain regulates Cys56 reactivity. Indeed, mutation of Arg120 to Ala prevented sulfenylation by peroxides compared to the wildtype control. Maleimide labeling showed that sulfenylated PDI is an intermediary that resolves into disulfided PDI. To determine whether this disulfided PDI promotes oxidase activity, we used a denatured and reduced RNAse that refolds when disulfides are transferred from oxidized PDI to the RNAse. PDI oxidized by hydrogen peroxide promoted RNAse refolding, whereas reduced PDI did not. A selective inhibitor of sulfenylation, arsenite, prevented RNAse refolding, indicating that hydrogen peroxide-induced oxidation of PDI proceeds through a sulfenic acid intermediate. Since PDI is secreted from cells, we evaluated whether activated cells release sulfenylated PDI using both human vein endothelial cells (HUVECs) and platelets. Sulfenylated PDI was increased in the cultured media of HUVECs stimulated with thrombin and in the releasate of platelets stimulated via PAR1 or glycoprotein VI. OxLDL exposure sensitizes platelets to activation by low doses of agonists. Inhibition of PDI using a neutralizing antibody inhibited augmentation of platelet aggregation by oxLDL, suggesting that oxidation of PDI by oxLDL promotes platelet activation. The ability of oxLDL to enhance the prothrombotic effect of PDI was tested in vivo in a murine model of laser-induced thrombus formation. Mice were infused with either control IgG or IgG directed at PDI, followed by the infusion of oxLDL. OxLDL significantly enhanced thrombus formation in this model. The effect of oxLDL was inhibited by anti-PDI IgG but not control IgG antibody or buffer, implicating PDI as an effector of oxLDL-augmented thrombus formation. In conclusion, our study demonstrates sulfenylation of PDI and shows that PDI sulfenylation retains PDI oxidase activity. Oxidation of PDI by oxidants such as oxLDL occurs in platelets and in endothelium and promotes thrombosis in the setting of oxidative stress.

Morphology of Biomaterials Affect O-Glycosylation of HUVECs.

Biomaterials have been widely used as substitutes for diseased tissue in surgery and have gained great success and attention. At present, the biocompatibility of biomaterials such as PET woven fabrics is often evaluated both in vitro and in vivo. However, the current experimental methods cannot reveal the relationship between material surfaces and cell adhesion, and few research works have focused on the mechanisms of how the surface morphology of biomaterials affects cell adhesion and proliferation. Thus, it is meaningful to find out how the altered surfaces could affect cell adhesion and growth. In this study, we employed Ar low-temperature plasma treatment technology to create nano-grooves on the warp yarn of PET woven fabrics and seeded human umbellar vein endothelial cells (HUVEC) on these fabrics. We then assessed the O-glycan and N-glycan profiles of the cells grown on different structures of the polyester woven fabrics. The result showed that the surface morphology of polyester woven fabrics could affect the O-glycan profile but not the N-glycan profile of cultured HUVEC. Taken together, the study describes the effects of the surface morphology of biomaterial on the biosynthesis of cellular glycans and may provide new insights into the design and manufacture of biomaterials used as blood vessels based on the expression profiles of O-glycans on cultured cells.

Abstract 15487: Boosting Autophagy for the Reduction of Diabetes-Induced Endothelial Dysfunction

Introduction: Diabetes is one of the main cause of endothelial dysfunction. The molecular mechanisms underlying the effects of hyperglycaemia in endothelial cells still need to be clarified. Autophagy, a stress-responsive and self-renewal mechanism exerts beneficial effects in the cardiovascular system. However, its role in diabetes-induced endothelial dysfunction is unknown. Hypothesis: Endothelial autophagy is impaired in the presence of diabetes and restoration of autophagy may reduce diabetes-induced endothelial damage. Methods: The effects of hyperglycaemia (HG, 30 mM for 6 and 24 hours) on autophagy, mitophagy and endothelial function were evaluated in vitro in human umbilical endothelial cells (HUVEC). Vascular reactivity experiments were performed in mesenteric arteries from wild-type mice (WT) treated with HG and in human saphenous veins from patients with peripheral artery diseases. Autophagy reactivation was carried out through ATG7 overexpression (ATG7ov) or through spermidine (SP) (100 nM), a natural activator of autophagy and inhibitor of p300. Results: HG reduces autophagy (0.6 fold p&lt;0.05) and mitophagy (1.5 fold p&lt;0.001) in endothelial cells. HG also inhibits stress-induced autophagy in cells undergoing hypoxia (0.6 fold p&lt;0.05). ATG7ov rescues apoptosis (0.52 fold p&lt;0.05) and angiogenesis (2.3 fold p&lt;0.05) in HUVEC exposed to HG treatment. We found increased expression of the histone acetyltransferase p300 (2.27 fold p&lt;0.05), a known inhibitor of autophagy. Knockout mice of autophagy (Beclin 1 +/-) show a reduction in endothelial-dependent vasorelaxation compared to WT mice in response to HG (-19.16 % +-4.97 SEM vs -48.39 % +-2.18 SEM p&lt;0.001). Autophagy reactivation through ATG7ov or spermidine rescues endothelial-dependent relaxation in WT mice treated with HG (ATG7ov -62.48 % +-5.16 SEM; SP -63.01 +-3.22 SEM; HG -40.67 % +-3.82 p&lt;0.001). Finally, we demonstrated that SP improves vascular function in human veins (-37.6 % +-12.76 SEM vs -12.52 % +-5.6 SEM p&lt;0.001). Conclusions: The impairment of autophagy in response to diabetes contributes to endothelial dysfunction. Boosting autophagy with natural activators of autophagy may be a suitable intervention to reduce vascular damage in the presence of metabolic stress.

Abstract 15806: The Unique Cellular Ecosystem of the Human Basilic Vein: A Single-Cell Transcriptomic Analysis

Introduction: The cells in veins that contribute to vascular disease have not been fully characterized. This study generated a cellular atlas of the human basilic vein that will help understand vein physiology and pathologies. Methods: Single-cell sequencing of four basilic veins from healthy organ donors. Results: The integrated single-cell profile of 15,747 vein cells revealed 13 populations containing canonical and non-canonical vascular markers. The SMC population represented 16% of cells, of which 8% were purely contractile and the remaining 8% had a modulated phenotype. One cluster of modulated SMCs expressed ECM genes (collagen type IV, FN1, and TNC) while retaining high expression of contractile markers (DES, MYH11, ACTG2). The other SMC cluster had unique expression of CD36, APOE, LPL, and STEAP4, characteristic of lipid-processing cells. Surprisingly, these non-diseased veins contained a high number of resident immune cells, including pro-inflammatory macrophages (9%), CD163- and HMOX1-expressing Mhem-like macrophages (18%), lymphocytes (5%), and small counts of neutrophils (0.3%) and mast cells (0.7%). The adventitial cell populations highlighted the fundamental role of this layer in vascular maintenance, remodeling, and angiogenesis. We found a significant number of vasa vasorum ECs (6.5%) which differentiated from the luminal subpopulation (3.5%) by CD34, KDR, NOTCH4, and ICAM2 expression. There were also two types of fibroblasts. Classical fibroblasts (19%) had high expression of collagen genes, while adipogenic fibroblasts (21%) were characterized by high levels of ECM-interacting fibulins, adipocyte-associated genes (ADH1B, APOD, CXCL14, IGF1), and modulators of angiogenesis (ADM and EFEMP1). CellCall analyses identified 46 overrepresented ligand-receptor communication pathways in all clusters, including CXCL, FGF, IL-6, and complement signaling. Communication between pro-inflammatory macrophages and luminal ECs was the most overrepresented signaling connection. Conclusions: This comprehensive atlas of the human vein will help identify cell subpopulations relevant to venous pathologies, without relying on extrapolations from arterial biology and focusing instead on the uniqueness of vein tissues.

Abstract 13422: Sotagliflozin, a Dual SGLT-1/2 Inhibitor, Modulated Expression of Endothelial Proteins That Inhibit Reactive Oxygen Species During Inflammation Compared With Empagliflozin

Background: Reactive oxygen species (ROS) generated during endothelial cell (EC) dysfunction contributes to progression of atherosclerosis. The SGLT1/2 inhibitor sotagliflozin (sota) reduced atherothrombotic events and hospitalization for worsening heart failure in patients with diabetes (SCORED, SOLOIST). Unlike selective SGLT2 inhibitors, sotagliflozin significantly reduced ischemic events, including myocardial infarction and stroke. We compared the effects of sota and empagliflozin (empa) on expression of ROS signaling proteins in human vein ECs (HUVECs) challenged with interleukin-6 (IL-6) or lipopolysaccharide (LPS). Methods: HUVECs were treated with sota or empa (100 nM) for 30 minutes and the challenged with IL-6 (12 ng/mL) or LPS (100 ng/mL) for 24 hours. Global proteomic analysis was performed using LC/MS to measure relative expression levels of &gt;1,000 proteins. Only significant (p&lt;0.05) changes in expression between treatment groups &gt;1-fold were included in gene set enrichment analysis (GSEA) of biological pathways. Results: Sota significantly changed expression of 166 and 274 proteins in ECs challenged with IL-6 and LPS, respectively. Empa significantly modulated fewer proteins - 122 and 93 proteins - following challenge with IL-6 and LPS, respectively. GSEA revealed that sota, not empa, modulated proteins related to ROS detoxification within the “cellular response to oxidative stress” pathway (GO:0034599) compared to both IL-6 and LPS (pathway adjusted p-values = 0.0016 and 0.036, respectively). Within this pathway, sota increased expression of peroxiredoxin (PRDX) 5 and PRDX6 (1.2 and 1.1-fold) and glutathione peroxidase-1 (GPX1, 1.1-fold) relative to IL-6 alone. Relative to LPS, sota decreased expression GPX1 (1.2-fold), PRDX1 (1.1-fold), and increased thioredoxin (1.1-fold). None of these proteins were modulated significantly by empa. Conclusions: Sota significantly modulated expression of proteins linked to ROS detoxification and signaling in human ECs during inflammation compared to a selective SGLT2 inhibitor. These favorable effects of dual SGLT1/2 inhibition may have implications for inflammation and reduced atherothrombotic risk as demonstrated in outcome trials.

Phosphorylcholine Monoclonal Antibody Therapy Decreases Intraplaque Angiogenesis and Intraplaque Hemorrhage in Murine Vein Grafts.

Phosphorylcholine (PC) is one of the main oxLDL epitopes playing a central role in atherosclerosis, due to its atherogenic and proinflammatory effects. PC can be cleared by natural IgM antibodies and low levels of these antibodies have been associated with human vein graft (VG) failure. Although PC antibodies are recognized for their anti-inflammatory properties, their effect on intraplaque angiogenesis (IPA) and intraplaque hemorrhage (IPH)-interdependent processes contributing to plaque rupture-are unknown. We hypothesized that new IgG phosphorylcholine antibodies (PC-mAb) could decrease vulnerable lesions in murine VGs.Therefore, hypercholesterolemic male ApoE3*Leiden mice received a (donor) caval vein interposition in the carotid artery and weekly IP injections of (5 mg/kg) PCmAb (n = 11) or vehicle (n = 12) until sacrifice at day 28. We found that PCmAb significantly decreased vein graft media (13%), intima lesion (25%), and increased lumen with 32% compared to controls. PCmAb increased collagen content (18%) and decreased macrophages presence (31%). PCmAb resulted in 23% decreased CD163+ macrophages content in vein grafts whereas CD163 expression was decreased in Hb:Hp macrophages. PCmAb significantly lowered neovessel density (34%), EC proliferation and migration with/out oxLDL stimulation. Moreover, PCmAb enhanced intraplaque angiogenic vessels maturation by increasing neovessel pericyte coverage in vivo (31%). Together, this resulted in a 62% decrease in IPH. PCmAb effectively inhibits murine atherosclerotic lesion formation in vein grafts by reducing IPA and IPH via decreased neovessel density and macrophages influx and increased neovessel maturation. PC-mAb therefore holds promise as a new therapeutic approach to prevent vein graft disease.

The effect of lncRNA MIR155HG-modified MSCs and exosome delivery to synergistically attenuate vein graft intimal hyperplasia

BackgroundThe mesenchymal stem cells (MSCs) were used to repair tissue injury. However, the treatment effect was not satisfactory. We investigated whether lncRNA MIR155HG could promote survival and migration of MSCs under oxidative stress, which mimics in vivo environments. Furthermore, we studied the protective effect of exosomes secreted by MSCs transfected with MIR155HG on endothelial cells. This study aimed to determine whether exploiting MSCs and exosomes modified with lncRNA MIR155HG would exert synergistic therapeutic effect to attenuate vein graft intimal hyperplasia more effectively.MethodsLentivirus containing lncRNA MIR155HG overexpressing vector was packaged and used to infect MSCs. Then, CCK-8 assay, flow cytometry, Transwell assay, and Elisa assay were used to assess the functional changes of MSCs with overexpressed MIR155HG (OE-MSCs). Furthermore, the associated pathways were screened by Western blot. MIR155HG-MSCs-derived exosomes (OE-exo) were collected and co-cultured with human umbilicus vein endothelial cell (HUVEC). We validated the protective effect of OE-exo on HUVEC. In vivo, both MSCs and exosomes modified with MIR155HG were injected into a vein graft rat model via tail vein. We observed MSCs homing and intimal hyperplasia of vein graft using a fluorescent microscope and histological stain.ResultsOur study found that lncRNA MIR155HG promoted proliferation, migration, and anti-apoptosis of MSCs. NF-κB pathway took part in the regulation process induced by MIR155HG. OE-exo could enhance the activity and healing ability of HUVEC and reduce apoptosis. In vivo, OE-MSCs had a higher rate of homing to vascular endothelium. The combined treatment with OE-MSCs and OE-exo protected vascular endothelial integrity, reduced inflammatory cell proliferation, and significantly attenuated intimal hyperplasia of vein graft.ConclusionLncRNA MIR155HG could promote the survival and activity of MSCs, and reduce the apoptosis of HUVECs using exosome delivery. Exploiting MSCs and exosomes modified with MIR155HG could attenuate vein graft intimal hyperplasia more effectively and maximize the surgical effect.

Structurally diverse polycyclic polyprenylated acylphloroglucinols with protective effect on human vein endothelial cells injured by high-glucose from Hypericum acmosepalum N. Robson

Hyperacmotone A, a polycyclic polyprenylated acylphloroglucinol (PPAP) with an unprecedented skeleton, along with five undescribed congeners and eleven reported ones, was isolated from Hypericum acmosepalum. Hyperacmotone A possesses a unique monocyclic ring skeleton based on a cyclopent-4-ene-1,3-dione acylphloroglucinol core. Their structures were elucidated by extensive analysis of HRESIMS, NMR, biogenetic pathway, and quantum-chemical calculations. In addition, hypercohone G exhibited significant protective effects on high-glucose-injured HUVECs.

Blood Reflux-Induced Epigenetic Factors HDACs and DNMTs Are Associated with the Development of Human Chronic Venous Disease.

Blood reflux and metabolic regulation play important roles in chronic venous disease (CVD) development. Histone deacetylases (HDACs) and DNA methyltransferases (DNMTs) serve as repressors that inhibit metabolic signaling, which is induced by proatherogenic flow to promote aortic endothelial cell (EC) dysfunction and atherosclerosis. The aim of this study was to elucidate the relationship between blood reflux and epigenetic factors HDACs and DNMTs in CVD. Human varicose veins with different levels of blood reflux versus normal veins with normal venous flow were examined. The results show that HDAC-1, -2, -3, -5, and -7 are overexpressed in the endothelium of varicose veins with blood reflux. Blood reflux-induced HDACs are enhanced in the varicose veins with a longer duration time of blood reflux. In contrast, these HDACs are rarely expressed in the endothelium of the normal vein with normal venous flow. Similar results are obtained for DNMT1 and DNMT3a. Our findings suggest that the epigenetic factors, HDACs and DNMTs, are induced in venous ECs in response to blood reflux but are inhibited in response to normal venous flow. Blood reflux-induced HDACs and DNMTs could inhibit metabolic regulation and promote venous EC dysfunction, which is highly correlated with CVD pathogenesis.

Metallic Nanoparticle-Doped Oxide Semiconductor Film for Bone Tumor Suppression and Bone Regeneration.

Bone implants with the photothermal effect are promising for the treatment of bone tumor defects. Noble metal-based photothermal nanoagents are widely studied for their stable photothermal effect, but they are expensive and difficult to directly grow on implant surfaces. In contrast, non-noble metal photothermal nanoagents are economical but unstable. Herein, to develop a stable and economical photothermal film on bone implants, a Ni nanoparticle-doped oxide semiconductor film was grown in situ on Nitinol via the reduction of Ni-Ti-layered double hydroxides. Ni nanoparticles remained stable in the NiTiO3 structure even when immersed in fluid for 1 month, and thus, the film presented a reliable photothermal effect under near-infrared light irradiation. The film also showed excellent in vitro and in vivo antitumor performance. Moreover, the nanostructure on the film allowed bone differentiation of mouse embryo cells (C3H10T1/2), and the released Ni ions supported the angiogenesis behavior of human vein endothelial cells. Bone implantation experiments further showed the enhancement of osteointegration of the modified Nitinol implant in vivo. This novel multifunctional Nitinol bone implant design offers a promising strategy for the therapy of bone tumor-related defects.

Understanding Cell Model Characteristics-RNA Expression Profiling in Primary and Immortalized Human Mesothelial Cells, and in Human Vein and Microvascular Endothelial Cells.

In vitro studies are essential in pre-clinical research. While choice of cell lines is often driven by handling and cost-effectiveness, in-depth knowledge on specific characteristics is scant. Mesothelial cells, which interact with endothelial cells, are widely used in research, including cancer and drug development, but have not been comprehensively profiled. We therefore performed RNA sequencing of polarized, primary peritoneal (HPMC) and immortalized pleural mesothelial cells (MeT-5A), and compared them to endothelial cells from umbilical vein (HUVEC) and cardiac capillaries (HCMEC). Seventy-seven per cent of 12,760 genes were shared between the 4 cell lines, 1003 were mesothelial and 969 were endothelial cell specific. The transcripts reflected major differences between HPMC and MeT-5A in DNA-related processes, extracellular matrix, migration, proliferation, adhesion, transport, growth factor- and immune response, and between HUVEC and HCMEC in DNA replication, extracellular matrix and adhesion organization. Highly variable shared genes were related to six clusters, cell tissue origin and immortalization, but also cell migration capacity, cell adhesion, regulation of angiogenesis and response to hypoxia. Distinct, cell type specific biological processes were further described by cellular component-, molecular function- and Reactome pathway analyses. We provide crucial information on specific features of the most frequently used mesothelial and endothelial cell lines, essential for appropriate use.

Nondestructive Method for Testing Elasticity of Walls of Human Veins and Arteries

Methods of testing the elasticity of walls of human veins and arteries are considered. The problems that arise when using them are noted. The necessity of developing nondestructive methods for testing the elasticity of the walls of human veins and arteries is substantiated. A technique for monitoring changes in their elasticity using noninvasive methods of pulse wave recording is proposed. The results of comparing data on changes in the elasticity of the walls of veins and arteries obtained using various methods of pulse wave recording and invasive methods are presented. The advantages and disadvantages of the proposed technique using various pulse waves are noted.

Anatomy of the vitelline vein remnant in human embryos and fetuses.

To demonstrate the entire course of the human vitelline vein (VV) in specimens after degeneration of the yolk sac. Sagittal and horizontal histological sections from 8 embryos and 19 fetuses (gestational age approximately 6-12weeks; crown-rump length 11-61mm) were examined. Two types of VV remnants were observed: a long VV on the right superior side of the mesentery of the jejunum (VV1) and a short VV on the left inferior side of the mesentery (VV2). The VV1, observed in 12 specimens, was 20-30 microns in diameter and ran dorsally between the right liver lobe and the jejunum, subsequently merging with an initial superior mesenteric vein on the pancreatic head immediately below the superior portion of the duodenum. The VV2, observed in four specimens, passed dorsally between loops of the ileum on the left side of the mesentery of the ileum and connected to the mesentery. Many of the VVs did not originate from the umbilical cord but suddenly started in the sack of physiological herniation. At 10-12weeks, after herniation, the VVs originated from the umbilicus and were involved by the expanding greater omentum. The right-sided and left-sided VVs seemed to correspond to right and left VV remnants, respectively, and both took an upstream course outside the mesentery of the jejunum and ileum. The right VV upstream portion was likely to disappear later than the left one, but the timing of degeneration varied greatly among individuals, depending on the topographical relationship between the right liver lobe and the jejunum.

Distinct Temporal Pattern of the Prediction of Lumen Remodeling of Lower Extremity Vein Bypass Grafts by Initial Local Hemodynamics.

We predicted human lower extremity vein bypass graft remodeling by hemodynamics. Computed tomography and duplex ultrasound scans of 55 patients were performed at 1week and 1, 6, and 12months post-implantation to obtain wall shear stress (WSS) and oscillatory shear index (OSI) at 1-mm intervals via computational fluid dynamics simulations. Graft remodeling was quantified by computed tomography-measured lumen diameter changes in the early (1week-1month), intermediate (1-6months), and late (6-12months) periods. Linear mixed-effect models were constructed to examine the overall relationship between remodeling and initial hemodynamics using the average data of all cross sections within the same graft. A significant association of graft remodeling with WSS (p < 0.001) and time (p = 0.001) was found; however, the effect size decreased with time (every 2.7 dyne/cm2 increase of WSS was associated with a 0.39, 0.35, 0.002mm diameter increase in the three periods, respectively). The association of remodeling with OSI was significant only in the intermediate period (every 0.1 increase of OSI was associated with a 0.25mm lumen diameter decrease, p = 0.004). Therefore, the association of graft lumen remodeling with local hemodynamics has a distinct temporal pattern; WSS and OSI are predictive of remodeling only in certain postoperative periods.

Generating human artery and vein cells from pluripotent stem cells highlights the arterial tropism of Nipah and Hendra viruses

Stem cell research endeavors to generate specific subtypes of classically defined "cell types." Here, we generate >90% pure human artery or vein endothelial cells from pluripotent stem cells within 3-4days. We specified artery cells by inhibiting vein-specifying signals and vice versa. These cells modeled viral infection of human vasculature by Nipah and Hendra viruses, which are extraordinarily deadly (∼57%-59% fatality rate) and require biosafety-level-4 containment. Generating pure populations of artery and vein cells highlighted that Nipah and Hendra viruses preferentially infected arteries; arteries expressed higher levels of their viral-entry receptor. Virally infected artery cells fused into syncytia containing up to 23 nuclei, which rapidly died. Despite infecting arteries and occupying ∼6%-17% of their transcriptome, Nipah and Hendra largely eluded innate immune detection, minimally eliciting interferon signaling. We thus efficiently generate artery and vein cells, introduce stem-cell-based toolkits for biosafety-level-4 virology, and explore the arterial tropism and cellular effects of Nipah and Hendra viruses.

Development and Preliminary Testing of Porcine Blood-Derived Endothelial-like Cells for Vascular Tissue Engineering Applications: Protocol Optimisation and Seeding of Decellularised Human Saphenous Veins.

Functional endothelial cells (EC) are a critical interface between blood vessels and the thrombogenic flowing blood. Disruption of this layer can lead to early thrombosis, inflammation, vessel restenosis, and, following coronary (CABG) or peripheral (PABG) artery bypass graft surgery, vein graft failure. Blood-derived ECs have shown potential for vascular tissue engineering applications. Here, we show the development and preliminary testing of a method for deriving porcine endothelial-like cells from blood obtained under clinical conditions for use in translational research. The derived cells show cobblestone morphology and expression of EC markers, similar to those seen in isolated porcine aortic ECs (PAEC), and when exposed to increasing shear stress, they remain viable and show mRNA expression of EC markers similar to PAEC. In addition, we confirm the feasibility of seeding endothelial-like cells onto a decellularised human vein scaffold with approximately 90% lumen coverage at lower passages, and show that increasing cell passage results in reduced endothelial coverage.

Triterpenoid saponins from Ilex pubescens promote blood circulation in blood stasis syndrome by regulating sphingolipid metabolism and the PI3K/AKT/eNOS signaling pathway

BackgroundBlood stasis syndrome (BSS) is a severe disorder involving disturbances in glycerophosphocholine metabolism. Ilex pubescens (IP) can regulate the levels of lipids, such as lysophosphatidylcholine (LPC) and lysophosphatidylethanolamine (LPE); however, the main active constituent of IP and its corresponding mechanism in BSS treatment are still unclear. PurposeTo explore the mechanisms by which triterpenoid saponins of IP (IPTS) promote blood circulation using system pharmacology-based approaches. MethodsSprague-Dawley (SD) rat BSS model was prepared by oral administration of IPTS for 7 days followed by adrenaline hydrochloride injection before immersion in ice water. Coagulation parameters in plasma and thromboxane B2 (TXB2), endothelin (ET) and 6-keto-PGF1α in serum were measured. The possible influence on abdominal aortas was evaluated by histopathology assessment. Human vein endothelial cells (HUVECs) were incubated with ox-LDL, and the effects of IPTS on cell viability and LDH release were investigated. UPLC-QTOF-MS/MS was used for metabolic profile analysis of lipid-soluble components in rat plasma and intracellular metabolites in HUVECs. Network pharmacology was used to predict the relevant targets and model pathways of BSS and the main components of IPTS. Molecular docking, molecular dynamics (MD) simulation and biochemical assays were used to predict molecular interactions between the active components of IPTS and target proteins. RT-PCR was used to detect the mRNA level of target proteins. Western blotting and immunohistochemistry (IHC) were used to verify the mechanisms by which IPTS promotes blood circulation in BSS. ResultsIPTS improved blood biochemical function in the process of BSS and played a role in vascular protection and maintenance of the normal morphology of blood vessels. Furthermore, metabolite pathways involved in steroid biosynthesis and sphingolipid metabolism were significantly perturbed. Both metabolomics analysis and network pharmacology results showed that IPTS ameliorates vascular injury and that lipid accumulation may be mediated by PI3K/AKT signaling pathway activation. MD simulation and enzyme inhibitory activity results suggested that the main components of IPTS can form stable complexes with PI3K, AKT and eNOS and that the complexes have significant binding affinity. PI3K, AKT, p-AKT, and eNOS mRNA and protein levels were considerably elevated in the IPTS-treated group. Thus, IPTS protects the vasculature by regulating the PI3K/AKT signaling pathway, activating eNOS and increasing the release of NO. ConclusionA possible mechanism by which IPTS prevents BSS is proposed: IPTS can promote blood circulation by modulating sphingolipid metabolism and activating the PI3K/AKT/eNOS signaling pathways.