Umbilical Cord Vein Research Articles

Serotonin and cyclic sleep organization in healthy full-term newborns

Relevance: The growth of neuropsychiatric diseases caused by perinatal pathology indicates the need to study the biochemical markers of brain damage in the newborn for the timely prevention of adverse consequences. Serotonin in early ontogenesis provides intensive development of neuronal structures and cortical networks involved in the mechanisms of formation of cyclic sleep organization a fine criterion of morphofunctional development of the brain.
 aim: The aim of the work is to study the content of serotonin in healthy full-term newborns in comparison with the quantitative and qualitative characteristics of the electropoligraphic sleep pattern.
 Material and methods: 84 healthy newborns were examined, which, depending on the gestational age, were divided into 3 groups: I 37 weeks (20 people), II 38 weeks (24 people), III 39-40 weeks (40 people). The content of serotonin in platelet-rich plasma of blood from the umbilical cord vein and in platelet suspension prepared from venous blood taken from mothers and children on the first day of life and again on day 5 was determined by high-performance liquid chromatography with electrochemical detection. A quantitative and qualitative analysis of the sleep electropoligram was performed 7-12 hours after birth.
 Results: The content of serotonin in platelet-rich plasma in umbilical cord blood in children does not depend on the method of birth, is 2 times lower than in the venous blood of mothers (0.379 0.116 microns/l, versus 0.756 0.200 microns/l, but there is a high correlation between the indicators (r = 0.8, p 0.05). At the gestational age of 39-40 weeks, the level of serotonin in platelet-rich plasma and in venous blood platelets is significantly higher than in those born at 37 weeks. In the latter, the increase in the content of serotonin in platelets continues after birth (at day 1, 0.539 0.149 nM/109 Tr, and on day 5 0.846 0.094 nM/109 Tr; p 0.05), whereas the indicators for those born at 39-40 weeks of pregnancy. They do not change (0.797 0.190 nM/109 Tr and 0.749 0.142 nM/109 Tr, respectively). A significant increase in the content of serotonin in the platelet-rich plasma and in the platelets of the child in the period from 37 to 39 weeks, both during intrauterine development and in the first days of life, correlates with an increase in the representation of the orthodox phase in the sleep cycle.
 Conclusion: The general pattern of changes in serotonin content and cyclic sleep organization in the early neonatal period in healthy newborns, depending on gestational age, indicates the possibility of using the obtained standard values of serotonin as a biochemical marker of functional brain development.

Major Reservoir for Heparin-Releasable TFPIα (Tissue Factor Pathway Inhibitor α) Is Extracellular Matrix.

[Figure: see text].

Extracellular matrix (ECM)-derived bioinks designed to foster vasculogenesis and neurite outgrowth: Characterization and bioprinting

The field of bioprinting has shown a tremendous development in recent years, focusing on the development of advanced in vitro models and on regeneration approaches. In this scope, the lack of suitable biomaterials that can be efficiently formulated as printable bioinks, while supporting specific cellular events, is currently considered as one of the main limitations in the field. Indeed, extracellular matrix (ECM)-derived biomaterials formulated to enable printability and support cellular response, for instance via integrin binding, are eagerly awaited in the field of bioprinting. Several bioactive laminin sequences, including peptides such as YIGSR and IKVAV, have been identified to promote endothelial cell attachment and/or neurite outgrowth and guidance, respectively. Here, we show the development of two distinct bioinks, designed to foster vasculogenesis or neurogenesis, based on methacrylated collagen and hyaluronic acid (CollMA and HAMA, respectively), both relevant ECM-derived polymers, and on their combination with cysteine-flanked laminin-derived peptides. Using this strategy, it was possible to optimize the bioink printability, by tuning CollMA and HAMA concentration and ratio, and modulate their bioactivity, through adjustments in the cell-active peptide sequence spatial density, without compromising cell viability. We demonstrated that cell-specific bioinks could be customized for the bioprinting of both human umbilical vein cord endothelial cells (HUVECs) or adult rat sensory neurons from the dorsal root ganglia, and could stimulate both vasculogenesis and neurite outgrowth, respectively. This approach holds great potential as it can be tailored to other cellular models, due to its inherent capacity to accommodate different peptide compositions and to generate complex peptide mixtures and/or gradients.

946 Fetal blood gases after in utero carbon dioxide insufflation for percutaneous fetoscopic spina bifida repair

Prenatal repair of open spina bifida (OSB) via the percutaneous fetoscopic approach does not require maternal laparotomy, hysterotomy, or exteriorization of the uterus. This technique does require intrauterine carbon dioxide (CO2) insufflation for surgical manipulation of the fetus. There is limited data on the physiological effects of CO2 insufflation on human fetuses and no data using the entirely percutaneous fetoscopic surgical technique. Our aim was to examine the effects of CO2 insufflation on fetal blood gases after percutaneous fetoscopic OSB repair. Prospective study of patients that underwent percutaneous fetoscopic OSB repair from 2/2019 to 7/2020. Fetal cordocentesis of the umbilical vein was performed in cases with favorable access to the umbilical cord. The umbilical vein cord blood samples were obtained under ultrasound guidance immediately at the conclusion of the OSB repair. Simultaneous maternal arterial blood gas samples were also obtained. Results are reported as median (range). Of 20 patients who underwent percutaneous fetoscopic OSB repair, 7 patients (35%) underwent fetal blood sampling. Gestational age at time of surgery was 27.4 (24.0 – 27.9) weeks and operative time was 183 (156 – 251) minutes. The CO2 exposure time was 122 (57 – 146) minutes with maximum pressure of 13.5 (12.0 – 15.0) mmHg. Fetal umbilical vein results were: pH 7.346 (7.301 – 7.387), pO2 56.2 (47.1 – 99.9) mmHg, pCO2 43.8 (36.2 – 53.0) mmHg, HCO3 23.9 (20.1 – 25.6) mmol/l and base excess (BE) -2.2 (-4.5 – -0.4) mmol/l. The lowest fetal pH recorded was 7.301. Simultaneous maternal arterial blood gas results were: pH 7.370 (7.284 – 7.420), pO2 187.5 (124.4 – 405.2) mmHg, pCO2 36.6 (30.7 – 46.0) mmHg, HCO3 21.3 (18.0 – 22.8) mmol/l and BE -3.2 (-5.9 – -1.8) mmol/l. After prolonged CO2 insufflation of the uterus, the fetal umbilical vein pH remained within normal range, above levels associated with fetal acidosis.

Impaired validity of the new FIGO and Swedish CTG classification templates to identify fetal acidosis in the first stage of labor

Introduction Cardiotocography (CTG) is the main method of intrapartum fetal surveillance. In 2015 a new guideline was introduced by the International Federation of Gynecology and Obstetrics (FIGO), FIGO-15. In Sweden it was adjusted to SWE-17, replacing the previous national template, SWE-09. This study, conducted at one university hospital and one regional hospital in southern Sweden, evaluated the diagnostic validity of these three templates to detect fetal acidosis during the first stage of labor. Material and methods A total of 73 neonates with pH <7.1 in umbilical cord artery or vein at cesarean delivery during the first stage of labor were identified retrospectively. For each acidotic neonate, three non-acidemic neonates, with a pH ≥7.2 in cord artery and vein, and Apgar scores ≥9 at five and ten minutes, in all 219 neonates, were selected. The CTG tracings before birth in acidemic neonates, and tracings at the same cervical dilatation in the non-acidemic neonates, were independently assessed by three professionals from the obstetric staff, blinded to group and clinical data. Based on their categorizations of the included variables (baseline, variability, accelerations, decelerations and contraction rate), each CTG tracing was systematically classified according to the three templates. The sensitivity and specificity to identify acidemia by the classification pathological were determined for each template. Interobserver agreement in the assessments of tracings as pathological or not was analyzed, using free-marginal Kappa index. Results The sensitivity for patterns classified as pathological to identify acidemia was similar for FIGO-15 (71%) and SWE-17 (77%, p = .13), and the specificity was 97% for both. SWE-09 had a significantly higher sensitivity (95%, p < .001) albeit with a lower specificity (90%, p < .001) than the other two templates. Among acidemic neonates, the fraction of tracings classified as normal was higher with SWE-17 (9.6%) than with SWE-09 (0%; p = .01) and FIGO-15 (1.4%; p = .06). For tracings from neonates with acidemia, agreement for three independent assessors was strong (κ 0.85) with SWE-09, and weak for FIGO-15 (κ 0.47), and SWE-17 (κ 0.51). For tracings from neonates without acidemia, the agreement was almost perfect for FIGO-15 (κ 0.91), strong withSWE-17 (κ 0.90) and moderate with SWE-09 (κ 0.78). Conclusions The ability of FIGO-15 and SWE-17 to identify fetal acidosis is considered insufficient. The combination of a high sensitivity and a high specificity makes SWE-09 the most discriminatory template during the first stage of labor.

Iron Homeostasis in Full Term, Normal Birthweight Gambian Neonates Over the First Week of Life

Background: Human neonates elicit a profound hypoferremia to protect against bacterial and fungal sepsis on their first day of life. We examined the transience of this effect by measuring iron and its chaperone proteins, inflammatory and hematological parameters over the first post-partum week. Methods: We prospectively studied term (>37 completed gestational weeks), normal weight (>2500g) newborns at Kanifing General Hospital, The Gambia. Blood was sampled from the umbilical cord vein (CDV) and artery (CDA). Neonatal venous blood was sampled at 6-24h (V1) in all babies who were then randomized to a second blood draw at 25-80h (V2), 81-136h (V3) or 137-192h (V4). Hepcidin, serum iron, transferrin saturation, transferrin, haptoglobin, CRP, AGP, sTfR, ferritin, TIBC, UIBC and full blood count were assayed. Findings: 278 neonates (54.3% males, gestational age 39.4±1.3wk, birth weight 3299±368g) were enrolled. We confirmed the profound early post-natal decrease in serum iron (CDV=22.7±7.0µmol/L to V1=7.3±4.3µmol/L, P<0.0001) and TSAT (50.2±16.7% to 14.4±6.1%, P<0.0001). Both variables increased steadily to reach 16.5±3.9µmol/L and 36.7±9.2% at V4 (P for trend <0.0001 for each). Hepcidin increased rapidly after birth (CDV=19.4±14.4ng/ml to V1=38.9±23.9ng/ml, P<0.0001) then dipped before rising again by V4. Inflammatory markers increased from V1 onwards. Network analysis revealed a disconnect between the correlations observed in CDV and V2-V4 and those in V1. Surprisingly, serum iron and TSAT were only weakly influenced by hepcidin. Interpretations: This data shows that the rapid anti-infective post-natal hypoferremia in human neonates is transient. The later rise in serum iron despite very high hepcidin indicates hepcidin resistance possibly caused by macrophage saturation with iron released from degradation of fetal erythrocytes. Pharmacological prolongation of hypoferremia might offer an ancillary tool in the armoury against antimicrobial resistance, but would need to overcome or circumvent the hepcidin. Funding: Bill & Melinda Gates Foundation (OPP1152353). Trial Registration: clinicaltrials.gov (NCT03353051). Registration date: November 27, 2017. Declaration of Interest: The authors declare that they have no competing interests. Ethical Approval: The trial was approved by the Medical Research Council Unit The Gambia at London School of Hygiene and Tropical Medicine (MRCG at LSHTM) Scientific Coordinating Committee, the Joint Gambia Government/MRC Ethics Committee (SCC1525) and the London School of Hygiene and Tropical Medicine Ethics Committee (Ref:14316) and conducted according to Good Clinical Practice (GCP) standards. All participants gave written, informed consent.

Preliminary report on partial pressure changes of oxygen and carbon dioxide in umbilical artery and vein before and after the first breath in Chinese neonates II-The personalized analysis of partial pressure of oxygen and carbon dioxide difference between umbilical artery and vein at same time in same newborn

Objective: In order to explore the mechanism of neonatal spontaneous breathing, the difference of oxygen and carbon dioxide between umbilical cord arteries and veins before the start of spontaneous breathing after birth has been analyzed among people. In this part, the related information is analyzed individually. Methods: After all fetal parents signed the informed consent before birth, and before the newborn was born and did not breathe, the umbilical cord was exposed as quickly as possible, and the heparinized arterial indwelling needle was inserted into the umbilical artery and umbilical vein in the direction of newborn and placenta, and then blood was taken continuously. Although dozens of mothers were selected,but only 3 cases were collected from Pua and Puv blood samplers at the same time for blood gas analysis and determination, and the differences and dynamic changes of umbilical vein and umbilical artery were calculated and analyzed. Results: In all 3 none spontaneous breathing newborns,PuvO2 was significantly higher than PuaO2 at the same time (P<0.01), with an average difference of (24.17±7.09) mmHg; while PuvCO2 was significantly lower than PuaCO2 (all P<0.01), with an average difference of (-7.67±3.70) mmHg.The difference of Puv-uaO2 was significantly higher than those of Puv-uaCO2 (P<0.05). Conclusion: PuaO2 decreases gradually with time (heartbeat frequency) before spontaneous breathing after the delivered fetus as a newborn, and it induces the first inhalation to start spontaneous breathing when it reaches the threshold of triggering breathing.

MicroRNA-128 Confers Anti-Endothelial Adhesion and Anti-Migration Properties to Counteract Highly Metastatic Cervical Cancer Cells' Migration in a Parallel-Plate Flow Chamber.

Despite the distant metastasis of cervical cancer cells being a prominent cause of mortality, neither the metastasis capacity nor the in vitro conditions mimicking adhesion of cervical cancer cells to endothelial cells have been fully elucidated. Circulating metastatic cancer cells undergo transendothelial migration and invade normal organs in distant metastasis; however, the putative molecular mechanism remains largely uncertain. In this study, we describe the use of an in vitro parallel-plate flow chamber to simulate the dynamic circulation stress on cervical cancer cells and elucidate their vascular adhesion and metastasis. We isolate the viable and shear stress-resistant (SSR) cervical cancer cells for mechanistic studies. Remarkably, the identified SSR-HeLa and SSR-CaSki exhibited high in vitro adhesive and metastatic activities. Hence, a consistently suppressed miR-128 level was revealed in SSR cell clones compared to those of parental wild-type (WT) cells. Overexpressed miR-128 attenuated SSR-HeLa cells’ adherence to human umbilical cord vein endothelial cells (HUVECs); in contrast, suppressed miR-128 efficiently augmented the static adhesion capacity in WT-HeLa and WT-CaSki cells. Hence, amplified miR-128 modestly abolished in vitro SSR-augmented HeLa and CaSki cell movement, whereas reduced miR-128 aggravated the migration speed in a time-lapse recording assay in WT groups. Consistently, the force expression of miR-128 alleviated the SSR-enhanced HeLa and CaSki cell mobility in a wound healing assay. Notably, miR-128 mediated SSR-enhanced HeLa and CaSki cells’ adhesion and metastasis through suppressed ITGA5, ITGB5, sLex, CEACAM-6, MMP9, and MMP23 transcript levels. Our data provide evidence suggesting that miR-128 is a promising microRNA that prevented endothelial cells’ adhesion and transendothelial migration to contribute to the SSR-enhanced adhesion and metastasis progression under a parallel-plate flow chamber system. This indicates that the nucleoid-based miR-128 strategy may be an attractive therapeutic strategy to eliminate tumor cells resistant to circulation shear flow, prevent vascular adhesion, and preclude subsequent transendothelial metastasis.

4-hexylresorcinol-induced protein expression changes in human umbilical cord vein endothelial cells as determined by immunoprecipitation high-performance liquid chromatography.

4-Hexylresorcinol (4HR) is used as a food preservative and an ingredient of toothpaste and cosmetics. The present study was performed using 233 antisera to determine the changes in protein expression induced by 4HR in human umbilical cord vein endothelial cells (HUVECs), and evaluated the 4HR-induced effects in comparison with previous results (Kim et al., 2019). Similar to RAW 264.7 cells, 4HR-treated HUVECs showed decreases in the expression of the proliferation-related proteins, cMyc/MAX/MAD network proteins, p53/RB and Wnt/β-catenin signaling, and they showed inactivation of DNA transcription and protein translation compared to the untreated controls. 4HR upregulated growth factors (TGF-β1, β2, β3, SMAD2/3, SMAD4, HGF-α, Met, IGF-1) and RAS signaling proteins (RAF-B, p38, p-p38, p-ERK-1, and Rab-1), and induced stronger expression of the cellular protection-, survival-, and differentiation-related proteins in HUVECs than in RAW 264.7 cells. 4HR suppressed NFkB signaling in a manner that suggests potential anti-inflammatory and wound healing effects by reducing M1 macrophage polarization and increasing M2 macrophage polarization in both cells. 4HR-treated HUVECs tended to increase the ER stress mediators by upregulating eIF2AK3, ATF4, ATF6, lysozyme, and LC3 and downregulating eIF2α and GADD153 (CHOP), resulting in PARP-1/AIF-mediated apoptosis. These results indicate that 4HR has similar effects on the protein expression of HUVECs and RAW 264.7 cells, but their protein expression levels differ according to cell types. The 4HR-treated cells showed global protein expression characteristic of anticancer and wound healing effects, which could be alleviated simultaneously by other proteins exerting opposite functions. These results suggest that although 4HR has similar effects on the global protein expression of HUVECs and RAW 264.7 cells, the 4HR-induced molecular interferences in those cells are complex enough to produce variable protein expression, leading different cell functions. Moreover, HUVECs have stronger wound healing potential to overcome the impact induced by 4HR than RAW 264.7 cells.

Effect of anthocyanin-rich sour cherry extract on the level of IL-8 in LPS-induced endothelial cell

The anthocyanin content of the Hungarian sour cherry is remarkable. Nutraceutical and pharmaceutical effects of the anthocyanins and their role in disease prevention have been studied extensively. Endothelial cells are involved in the pathogenesis of several inflammatory diseases. The objective of this work was to investigate pure sour cherry extract on human umbilical cord vein endothelial cells (HUVECs) as an inflammatory model. HUVECs were treated with 100 ng/mL lipopolysaccharide (LPS) and 50 mg/mL sour cherry extract or M199 medium as control. The optimal concentration range of the sour cherry extract was investigated and selected based on MTT assay measuring the conversion of the tetrazolium salt to formazan by mitochondrial dehydrogenases. The level of interleukine-8 (IL-8), a pro-inflammatory cytokine, was measured in Luminex MagPlex assay. LPS treatment significantly increased the secretion of IL-8. The pure sour cherry extract was able to attenuate this increment indicating the potent anti-inflammatory effect of pure sour cherry extract. Our results emphasize that pure sour cherry extract could reduce the LPS-induced inflammatory response thereby may improve endothelial dysfunction.

Histological Study of Human Umbilical Cord in Diabetic Pregnant Females

Background: The umbilical cord (UC) is the lifeline between the fetus and placenta. It allows gas and nutrient exchange. Diabetes mellitus is the most common metabolic disorder that occurs during pregnancy, it has complications on both mother and fetus. The changes in the structure of UC with diabetes may have effect on the viability of the fetus.Aim of the Work: Is to study the effect of gestational diabetes on the histological structure of UC.Patients and Methods: The umbilical cord biopsies were collected immediately after delivery from 30 full term pregnant women, 15 normal pregnant females (Control group), and 15 pregnant women had gestational diabetes (Diabetic group). Informed written consent was taken from all pregnant women sharing in this study. These biopsies were processed for light and electron microscopic studies. Also morphometric and statistical analysis for the data were done.Results: Light microscopic study of diabetic UC samples showed degeneration of Wharton’s jelly fibers with formation of honey comb like empty spaces. Erosion of endothelial cells lined the umbilical vessels; with separation of their smooth muscle fibers were observed. There were degeneration of collagen fibers and decrease amount of elastic fibers in the wall of umbilical vessels. Morphometric studies showed significant decrease in the intima and media thickness in diabetic UC arteries compared to UC control arteries. The UC vein of diabetic samples showed significant dilatation of the lumen and thinner wall compared to that of control group.Conclusion: The present study proved that gestational diabetes has many injurious effects on histological structure of UC.

Developmental programming in human umbilical cord vein endothelial cells following fetal growth restriction

BackgroundFetal growth restriction (FGR) is associated with an increased susceptibility for various noncommunicable diseases in adulthood, including cardiovascular and renal disease. During FGR, reduced uteroplacental blood flow, oxygen and nutrient supply to the fetus are hypothesized to detrimentally influence cardiovascular and renal programming. This study examined whether developmental programming profiles, especially related to the cardiovascular and renal system, differ in human umbilical vein endothelial cells (HUVECs) collected from pregnancies complicated by placental insufficiency-induced FGR compared to normal growth pregnancies. Our approach, involving transcriptomic profiling by RNA-sequencing and gene set enrichment analysis focused on cardiovascular and renal gene sets and targeted DNA methylation assays, contributes to the identification of targets underlying long-term cardiovascular and renal diseases.ResultsGene set enrichment analysis showed several downregulated gene sets, most of them involved in immune or inflammatory pathways or cell cycle pathways. seven of the 22 significantly upregulated gene sets related to kidney development and four gene sets involved with cardiovascular health and function were downregulated in FGR (n = 11) versus control (n = 8). Transcriptomic profiling by RNA-sequencing revealed downregulated expression of LGALS1, FPR3 and NRM and upregulation of lincRNA RP5-855F14.1 in FGR compared to controls. DNA methylation was similar for LGALS1 between study groups, but relative hypomethylation of FPR3 and hypermethylation of NRM were present in FGR, especially in male offspring. Absolute differences in methylation were, however, small.ConclusionThis study showed upregulation of gene sets related to renal development in HUVECs collected from pregnancies complicated by FGR compared to control donors. The differentially expressed gene sets related to cardiovascular function and health might be in line with the downregulated expression of NRM and upregulated expression of lincRNA RP5-855F14.1 in FGR samples; NRM is involved in cardiac remodeling, and lincRNAs are correlated with cardiovascular diseases. Future studies should elucidate whether the downregulated LGALS1 and FPR3 expressions in FGR are angiogenesis-modulating regulators leading to placental insufficiency-induced FGR or whether the expression of these genes can be used as a biomarker for increased cardiovascular risk. Altered DNA methylation might partly underlie FPR3 and NRM differential gene expression differences in a sex-dependent manner.

Human umbilical cord mesenchymal stem cells improve morphometric and histopathologic changes of cyclophosphamide-injured ovarian follicles in mouse model of premature ovarian failure

BackgroundMesenchymal stem cells have restorative effects on premature ovarian failure (POF). The aim of this study was to investigate the effects of human umbilical cord vein MSCs (hUCV-MSCs) on follicular quantitative parameters and histological changes of ovaries in the cyclophosphamide (CTX)-induced POF in mice. Materials and methodsC57BL/6 mice were divided into three groups (10 mice in each group). In the control group, phosphate-buffered saline (PBS) was injected via tail vein following 15 days injection of PBS intraperitoneally (IP). In the CTX group, CTX was administered IP for 15 days and then PBS was injected via tail vein. In the CTX + hUCV-MSCs group, following CTX administration, single dose of the 1 × 106 of hUCV-MSCs were injected into tail vein. H&E, trichrome and PAS staining as well as TUNEL assay were performed on the ovaries tissue sections. The number of follicles, follicular quantitative parameters and apoptotic index were obtained. The serum levels of estradiol and FSH were measured in the mice. ResultsIn the CTX + hUCV-MSCs group, degenerative changes were decreased and follicular quantitative parameters increased in the ovarian follicles compared to the CTX group. In this group number of follicles was increased, apoptotic index was decreased, estradiol and FSH levels were decreased and increased, respectively, all of them improved compared to the CTX group. The mean percentage areas of collagen fibers content were decreased compared to the CTX group. ConclusionResults showed that, hUCV-MSCs administration increases follicular quantitative parameters and improve degenerative changes in the follicles following CTX injury.

Effect of Anthocyanin-Rich Extract of Sour Cherry for Hyperglycemia-Induced Inflammatory Response and Impaired Endothelium-Dependent Vasodilation.

Diabetes mellitus (DM)-related morbidity and mortality are steadily rising worldwide, affecting about half a billion people worldwide. A significant proportion of diabetic cases are in the elderly, which is concerning given the increasing aging population. Proper nutrition is an important component in the effective management of diabetes in the elderly. A plethora of active substances of plant origin exhibit potency to target the pathogenesis of diabetes mellitus. The nutraceutical and pharmaceutical effects of anthocyanins have been extensively studied. In this study, the effect of Hungarian sour cherry, which is rich in anthocyanins, on hyperglycemia-induced endothelial dysfunction was tested using human umbilical cord vein endothelial cells (HUVECs). HUVECs were maintained under both normoglycemic (5 mM) and hyperglycemic (30 mM) conditions with or without two concentrations (1.50 ng/µL) of anthocyanin-rich sour cherry extract. Hyperglycemia-induced oxidative stress and inflammatory response and damaged vasorelaxation processes were investigated by evaluating the level of reactive oxygen species (ROS) and gene expression of four proinflammatory cytokines, namely, tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), interleukin-8 (IL-8), and interleukin-1α (IL-1α), as well as the gene expression of nitric oxide synthase (NOS) endothelin-1 (ET-1) and endothelin-converting enzyme-1 (ECE-1). It was found that hyperglycemia-induced oxidative stress was significantly suppressed by anthocyanin-rich sour cherry extract in a concentration-dependent manner. The gene expression of the tested proinflammatory cytokines increased under hyperglycemic conditions but was significantly reduced by both 1 and 50 ng/µL anthocyanin-rich sour cherry extract. Further, although increased ET-1 and ECE-1 expression due to hyperglycemia was reduced by anthocyanin-rich sour cherry extract, NOS expression was increased by the extract. Collectively, these data suggest that anthocyanin-rich sour cherry extract could alleviate hyperglycemia-induced endothelial dysfunction due to its antioxidant, anti-inflammatory, and vasorelaxant effects.

Biochemical Research of the Effects of Essential Oil Obtained from the Fruit of Myrtus communis L. on Cell Damage Associated with Lipopolysaccharide-Induced Endotoxemia in a Human Umbilical Cord Vein Endothelial Cells.

The aim of this study to investigate the potential effects of essential oils and compounds obtained from MC fruit on sepsis induced endothelial cell damage in human umbilical cord vein endothelial cells (HUVECs) at molecular and cellular levels on in vitro sepsis model. A sepsis model was induced by the application of LPS. The HUVEC treatment groups were as follows: control, LPS, MC, MC plus LPS, 1.8 cineole, 1.8 cineole plus LPS, α-pinene, α-pinene plus LPS, α-terpineol, and α-terpineol plus LPS. Following the treatments, cell proliferation was analyzed using the xCELLigence® system. The mRNA expression of various cytokines [tumor necrosis factor (TNF-α), interleukin-1β (IL-1β), and IL-6] and endothelial nitric oxide (eNOS) were determined by quantitative polymerase chain reaction (qPCR) analysis. The 1.8 cineole and α-pinene treatments at specific doses showed toxic effects on α-terpineine, although it did not result in a change in the cellular index as compared with that of the control group. The application of LPS to HUVECs led to a significant decrease in the cellular index, depending on the treatment time. It did not correct the decreased cell index of MC plus LPS and α-terpineol plus LPS groups as compared with that of the LPS-only group. The 1.8 cineole plus LPS treatment and α-pinene plus LPS treatment significantly increased the cell index as compared with that of the LPS-only treatment, and the cell index in these groups was closer to that of the control. According to the results of the qPCR analysis, neither the MC-only treatment nor the α-terpineol-only treatment significantly reduced cellular damage caused by LPS-induced increases in TNF-α, IL-1β, IL-6, and eNOS mRNA expression. However, both the 1.8 cineole treatment and α-pinene treatments significantly decreased TNF-α, IL-1β, IL-6, and eNOS mRNA expression induced by LPS. Volatile oil obtained from MC fruit and the MC compound α-terpineol had no effect on the decreased cell index and increased cytokine response due to LPS-induced endothelial cell damage. However, 1.8 cineole and α-pinene, other major components of MC fruit, ameliorated LPS-induced damage in HUVECs at cellular and biomolecular levels (TNF-α, IL-1β, IL-6, and eNOS).

Plasma amino acid pools in the umbilical cord artery show lower 15N natural isotope abundance relative to the maternal venous pools

ABSTRACT 15N natural isotope abundance (NIA) is systematically higher in infants’ hair than in that of their mothers at birth. This study aimed to investigate this difference in plasma pools. We compared 15N NIA values for plasma amino acid (AA) pools (free + protein-bound) in the umbilical cord artery (UCA) and vein (UCV) and in the maternal vein (MV) at birth. This preliminary study included 7 mother–infant dyads. Whole plasma was treated (HCl) to hydrolyze protein. Following derivatization, AAs were separated using gas chromatography and compound-specific 15N NIA values were measured on-line using an isotope ratio monitoring mass spectrometer. 15N NIA plasma AA pools in the UCA and UCV were highly correlated to the MV, r 2 > 0.89 and r 2 > 0.88 (both P < 10−4) respectively. The full model found a significant effect of sampling compartment (P = 0.02) and AA type (P < 0.0001) on 15N NIA plasma AA values. 15N NIA plasma AA was 0.74 ‰ higher (P = 0.01) in the MV than in the UCA. This study indicates that a decrease in 15N NIA for plasma AA pools occurs in the fetal–placental unit. Trial registration: ClinicalTrials.gov identifier: NCT00607061.

Cobalt-containing bioactive glass mimics vascular endothelial growth factor A and hypoxia inducible factor 1 function.

Bioactive glasses (BGs) have shown great potential for tissue regeneration and their composition flexibility allows the incorporation of different ions with physiological activities and therapeutic properties in the glass network. Among the many ions that could be incorporated, cobalt (Co) is a significant one, as it mimics hypoxia, triggering the formation of new blood vessels by the vascular endothelial growth factor A (VEGFA), due to the stabilizing effect on the hypoxia inducible factor 1 subunit alpha (HIF1A), an activator of angiogenesis-related genes, and is therefore of great interest for tissue engineering applications. However, despite its promising properties, the effects of glasses incorporated with Co on angiogenesis, through human umbilical cord vein endothelial cells (HUVECs) studies, need to be further investigated. Therefore, this work aimed to evaluate the biocompatibility and angiogenic potential of a new sol-gel BG, derived from the SiO2 -CaO-P2 O5 -CoO system. The structural evaluation showed the predominance of an amorphous glass structure, and the homogeneous presence of cobalt in the samples was confirmed. in vitro experiments showed that Co-containing glasses did not affect the viability of HUVECs, stimulated the formation of tubes and the gene expression of HIF1A and VEGFA. in vivo experiments showed that Co-containing glasses stimulated VEGFA and HIF1A expression in blood vessels and cell nuclei, respectively, in the deep dermis layer of the dorsal region of rats, featuring considerable local stimulation of the angiogenesis process due to Co-release. Co-containing glasses showed therapeutic effect, and Co incorporation is a promising strategy for obtaining materials with superior angiogenesis properties for tissue engineering applications.

Interactome of miRNAs and transcriptome of human umbilical cord endothelial cells exposed to short-term simulated microgravity

Adaptation of humans in low gravity conditions is a matter of utmost importance when efforts are on to a gigantic leap in human space expeditions for tourism and formation of space colonies. In this connection, cardiovascular adaptation in low gravity is a critical component of human space exploration. Deep high-throughput sequencing approach allowed us to analyze the miRNA and mRNA expression profiles in human umbilical cord vein endothelial cells (HUVEC), cultured under gravity (G), and stimulated microgravity (MG) achieved with a clinostat. The present study identified totally 1870 miRNAs differentially expressed in HUVEC under MG condition when compared to the cells subjected to unitary G conditions. The functional association of identified miRNAs targeting specific mRNAs revealed that miRNAs, hsa-mir-496, hsa-mir-151a, hsa-miR-296-3p, hsa-mir-148a, hsa-miR-365b-5p, hsa-miR-3687, hsa-mir-454, hsa-miR-155-5p, and hsa-miR-145-5p differentially regulated the genes involved in cell adhesion, angiogenesis, cell cycle, JAK-STAT signaling, MAPK signaling, nitric oxide signaling, VEGF signaling, and wound healing pathways. Further, the q-PCR based experimental studies of upregulated and downregulated miRNA and mRNAs demonstrate that the above reported miRNAs influence the cell proliferation and vascular functions of the HUVEC in MG conditions effectively. Consensus on the interactome results indicates restricted fluctuations in the transcriptome of the HUVEC exposed to short-term MG that could lead to higher levels of endothelial functions like angiogenesis and vascular patterning.

Fabrication of Stiffness Gradients of GelMA Hydrogels Using a 3D Printed Micromixer.

Many properties in both healthy and pathological tissues are highly influenced by the mechanical properties of the extracellular matrix. Stiffness gradient hydrogels are frequently used for exploring these complex relationships in mechanobiology. In this study, the fabrication of a simple, cost-efficient, and versatile system is reported for creation of stiffness gradients from photoactive hydrogels like gelatin-methacryloyl (GelMA). The setup includes syringe pumps for gradient generation and a 3D printed microfluidic device for homogenous mixing of GelMA precursors with different crosslinker concentration. The stiffness gradient is investigated by using rheology. A co-culture consisting of human adipose tissue-derived mesenchymal stem cells (hAD-MSCs) and human umbilical cord vein endothelial cells (HUVECs) is encapsulated in the gradient construct. It is possible to locate the stiffness ranges at which the studied cells displayed specific spreading morphology and migration rates. With the help of the described system, variable mechanical gradient constructs can be created and optimal 3D cell culture conditions can be experientially identified.

Anti-angiogenic effects of testis-specific gene antigen 10 on primary endothelial cells.

Growing evidence indicates the antitumor and antiangiogenesis activities of testis-specific gene antigen 10 (TSGA10). However, the underlying mechanisms and precise role of TSGA10 in angiogenesis are still elusive. In this study, we isolated human umbilical cord vein endothelial cells (HUVECs) and stably transfected with pcDNA3.1 carrying TSGA10 coding sequence. We demonstrated that TSGA10 over-expression significantly decreases HUVEC tubulogenesis and interconnected capillary network formation. HUVECs over-expressing TSGA10 exhibited a significant decrease in migration and proliferation rates. TSGA10 over-expression markedly decreased expression of angiogenesis-related genes, including VEGF-A, VEGFR-2, Ang-1, Ang-2, and Tie-2. Our ELISA results showed the decrease in VEGF-A mRNA expression level is associated with a significant decrease in its protein secretion. Additionally, over-expressing TSGA10 decreased expression levels of marker genes of cell migration (MMP-2, MMP-9, and SDF-1a) and proliferation (PCNA and Ki-67. Furthermore, ERK-1 and AKT phosphorylation significantly reduced in HUVECs over-expressing TSGA10. Our findings suggest a potent anti-angiogenesis activity of TSGA10 in HUVECs through down-regulation of ERK and AKT signalling pathways, and may provide therapeutic benefits for the management of different pathological angiogenesis.