Tipos de partos y niveles de oxitocina, cortisol y hormonas tiroideas en plasma del cordón umbilical / Types of deliveries and levels of oxytocin, cortisol and thyroid hormones in umbilical cord plasma

Introducción: La placenta sintetiza y secreta varias hormonas que permiten la regulación del embarazo, el trabajo de parto y la adaptación metabólica materno-fetal. Su comportamiento asociado al tipo de parto puede dar información relevante sobre efectos epigenéticos. Objetivo: Describir el tipo de parto con los niveles de oxitocina, cortisol y hormonas tiroideas en plasma de cordón umbilical al nacer. Método: A 50 mujeres con embarazos principalmente normales se les cuantificaron los niveles neurohormonales en plasma de cordón umbilical, obtenido inmediatamente tras el periodo expulsivo. Los resultados se incorporaron a la base de datos clínicos de cada participante y se analizaron con Stata v.14.0. El protocolo fue aprobado por el comité de ética. Resultados: Hubo 33 partos vaginales (12 espontáneos, 13 acelerados y 8 inducidos) y 17 cesáreas (7 electivas y 10 de urgencia). Se observaron mayores niveles de cortisol en los partos vaginales acelerados; las cesáreas tuvieron menores niveles de cortisol y hormona estimulante de la tiroides. Las intervenciones clínicas, con altos o bajos niveles hormonales, están en directa relación con el tipo de parto. Conclusiones: El cortisol y la hormona estimulante de la tiroides medidos en plasma de cordón umbilical variaron según el tipo de parto. Esto es una primera cuantificación de hormonas en plasma de cordón umbilical y su posible regulación placentaria a propósito del tipo de parto.

Introduction: The placenta synthesizes and secretes several hormones allowing the regulation of pregnancy, labor and maternal-fetal metabolic adaptation. Their behavior associated with the type of delivery, may provide relevant information on epigenetic effects. Objective: To describe the type of delivery with the levels of oxytocin, cortisol and thyroid hormones in umbilical cord plasma at birth. Method: Neurohormonal levels from umbilical cord plasma obtained immediately post expulsion, were quantified in 50 women with mainly normal pregnancies. Results incorporated into the clinical database of each participant, statistically analyzed in Stata v.14.0. Protocol approved by ethics committee. Results: 33 were vaginal deliveries (12 spontaneous, 13 accelerated, 8 induced) and 17 cesarean sections (7 elective and 10 emergency). Higher cortisol levels were observed in accelerated vaginal deliveries, cesarean sections had lower cortisol and thyroid stimulating hormone levels. While clinical interventions, with high or low hormone levels, were related to the type of delivery. Conclusions: Cortisol and thyroid stimulating hormone measured in umbilical cord plasma varied according to the type of delivery. This is a first quantification of hormones in umbilical cord plasma and their possible placental regulation in relation to the type of delivery.

Drug testing in biological samples vs. maternal surveys for the detection of substance use during whole pregnancy.

BACKGROUND: Early diagnosis of nicotine, ethanol and drug use during pregnancy is critical in order to provide adequate care. Current screening procedures show limitations in terms of reliability and short windows of detection. OBJECTIVES: To investigate the prevalence and identify biomarkers of substance use and changes in substance use during pregnancy. To compare drug testing results in different types of biological samples (maternal hair, meconium, placenta, umbilical-cord) with self-reported data. PARTICIPANTS AND SETTING: Prospective cohort study using data from pregnant women and their newborns. METHODS: Biological matrices were collected at birth and analyzed by liquid chromatography tandem mass spectrometry. A paper survey was provided to determine substance use habits. RESULTS: 867 mother-newborn pairs were included. According to the analysis of biological samples, 29.1% cases were positive for one or more substances (13.6% nicotine, 8.4% ethanol, 8.3% cocaine, 6.4% cannabis, 5.7% opioids). The profile of the substance-using mother was a single woman, <28 years-old, with no higher education and unemployed. Segmental maternal hair analysis showed a decrease in tobacco, cannabis and cocaine use throughout pregnancy (p < 0.001). The level of concordance between results from interviews and from biological analyses was weak for opioids, cocaine, and cannabis (kappa coefficient < 0.40). Maternal hair detected the highest number of cases, followed by meconium and by placenta and/or umbilical-cord. CONCLUSIONS: Maternal survey was not a reliable screening technique. Analysis of maternal hair detected the highest number of cases with the broadest detection window (whole pregnancy).

Rare earth elements in umbilical cord and risk for orofacial clefts.

Questions remain about the effects of rare earth elements (REEs) on reproductive health, and no study has explored in utero exposure to REEs and risk of orofacial clefts (OFCs). We recruited subjects from a case-control study conducted in Shanxi Province, China. Concentrations of fifteen REEs were quantified in umbilical cord samples by means of Inductively Coupled Plasma Mass Spectrometry measurements. We employed logistic regression and weighted quantile sum (WQS) regression models to estimate the association between REEs exposures and OFCs. Of 226 subjects included in our study, 34 were cleft lip only, 44 were cleft lip with cleft palate and 6 were cleft palate only. In the logistic regression model, concentrations above the median of all subjects were associated with an increased OFCs risk of 2.35-fold (95% CI: 1.22, 4.53) for Lanthanum and 2.12-fold for Neodymium (95% CI: 1.10, 4.10) adjusting for maternal age, BMI, gestational weeks, sex of infants and passive smoking. In WQS model, a quartile increase in the index resulting in an increase of 3.10 (95% CI: 1.38, 6.96) in the odds of OFC. Lanthanum and Neodymium were suggested to be important factors. The results were largely consistent for OFC subtypes. In conclusion, in utero exposure to mixtures of REEs increased the risk of OFCs. Lanthanum and Neodymium were likely to be important factors in the development of OFCs.

Human umbilical cord mesenchymal stem cells-derived exosomal microRNA-451a represses epithelial-mesenchymal transition of hepatocellular carcinoma cells by inhibiting ADAM10.

Exosomes derived from human umbilical cord mesenchymal stem cells (hucMSCs) expressing microRNAs (miRNAs) have been highlighted in human cancers. However, the detailed molecular mechanism of hucMSCs-derived exosomal miR-451a on hepatocellular carcinoma (HCC) remains further investigation. Our study aims to explore the impact of exosomal miR-451a on the progression of HCC. Expression of miR-451a and a disintegrin and metalloprotease 10 (ADAM10) in HCC tissues and adjacent normal tissues were determined. The exosomes were extracted from hucMSCs and co-cultured with Hep3B and SMMC-7721 cell lines. After the treatment of relative exosomes or exosome inhibitor GW4869 in Hep3B and SMMC-7721 cells, the paclitaxel resistance and malignant phenotypes of HCC cells were measured. Moreover, the effect of hucMSCs-derived exosomes on the expression of miR-451a and ADAM10 in HCC cells was assessed. The targeting relationship between miR-451a and ADAM10 was verified to detect the impact of ADAM10-wild type and ADAM10-mutant type (MUT) on HCC cell processes. Low expression of miR-451a and high expression of ADAM10 indicated a poor prognosis of HCC patients. MiR-451a was up-regulated while ADAM10 was down-regulated in HCC cells after co-culture with HucMSC-derived exosomes. The exosomes elevated miR-451a and inhibited ADAM10 to suppress the paclitaxel resistance, cell cycle transition, proliferation, migration and invasion, and promote apoptosis of HCC cells. ADAM10 was verified to be a target gene of miR-451a. ADAM10-MUT promoted HCC process independent of miR-451a mimic. HucMSC-derived exosomal miR-451a could restrict the epithelial-mesenchymal transition of HCC cells by targeting ADAM10, which might provide new targets for HCC treatment.

Umbilical cord N-terminal procollagen of type l collagen (P1NP) and beta C-terminal telopeptide (ßCTX) levels in term pregnancies with vitamin D deficiency.

AIMS: The aim of the present study was to evaluate umbilical cord N-terminal procollagen of type l collagen (P1NP) and beta C-terminal telopeptide (ßCTX) levels in term pregnancies with vitamin D deficiency. MATERIALS AND METHODS: Ninety-two pregnant women between 19 and 35-years-old who delivered at term gestational age were included in the study and divided into deficient (n = 32), insufficient (n = 30), and normal (control) vitamin D levels (n = 30). RESULTS: Maternal demographic characteristics and biochemical parameters were similar among groups. The mean umbilical cord P1NP level was 221.4 (211.7-231.0, 95%CI) pg/mL in the vitamin D deficiency group, 282.5 (271.2-293.8, 95%CI) pg/mL in the vitamin D insufficiency group, and 280.9 (270.9-290.8, 95%CI) pg/mL in the control group and significantly lower in vitamin D deficiency group than others (p < .001). Umbilical cord P1NP level was similar in the vitamin D insufficiency group and control group (p = .971). The mean umbilical cord ßCTX level was 5530, 9 (5511.5-5550.3, 95%CI) pg/mL in the vitamin D deficiency group, 5516.3 (5498.4-5534.2, 95%CI) pg/mL in the vitamin D insufficiency group, and 5510 (5491.4-5528.5, 95%CI) pg/mL in the control group, which was statistically similar among the groups (p = .251). CONCLUSION: Our results indicated that vitamin D deficiency during pregnancy affects fetal bone osteoblast activity.

Effects of passage through the digestive tract on incretin secretion: Before and after birth.

AIMS/INTRODUCTION: It was reported that fetuses secrete endogenous incretin; however, the stimulants of fetal incretin secretion are not fully understood. To investigate the association between the passage of amniotic fluid through the intestinal tract and fetal secretion of incretin, we analyzed umbilical cord incretin levels of infants with duodenum atresia. MATERIALS AND METHODS: Infants born from July 2017 to July 2019 (infants with duodenum atresia and normal term or preterm infants) were enrolled. We measured and compared the concentrations of glucagon-like peptide-1 (GLP-1) and gastric inhibitory peptide/glucose-dependent insulinotropic polypeptide (GIP) in the umbilical vein and preprandial blood samples after birth. RESULTS: A total of 98 infants (47 term, 46 preterm and 5 with duodenum atresia) were included. In patients with duodenum atresia, umbilical vein GLP-1 and GIP levels were the same as those in normal infants. In postnatal samples, there were positive correlations between the amount of enteral feeding and preprandial serum concentrations of GLP-1 (r = 0.47) or GIP (r = 0.49). CONCLUSIONS: Our results show that enteral feeding is important for secretion of GLP-1 and GIP in postnatal infants, whereas the passage of amniotic fluid is not important for fetal secretion of GLP-1 and GIP. The effect of ingested material passing through the digestive tract on incretin secretion might change before and after birth. Other factors might stimulate secretion of GLP-1 and GIP during the fetal period.

Physicochemical characterization and self-assembly of human amniotic membrane and umbilical cord collagen: A comparative study.

The diverse application of collagen has created a need to discover renewable and economical sources with prevailing/improved physico-chemical properties. To address this scenario, the present study has extracted collagen from Human Amniotic Membrane (AM) and Umbilical cord, which are treated as medical waste and compared its physico-chemical properties. Collagen was extracted by pepsin solubilization using various salt concentrations (1 M, 2 M and 4 M). Umbilical Cord Collagen (UC) yield was 10% higher than Amniotic Membrane Collagen (AC). UC reported 58% higher sulphated glycosaminoglycan content than AC. Electrophoretic pattern of AC and UC in both disulphide bond reducing and non-reducing conditions showed bands corresponding to collagen type I, III, IV, V and XV. Collagen morphology was examined using SEM and the amino acid content was quantified by HPLC and LC-MS/MS. Triple helicity was confirmed by CD and FTIR spectra. Thermal transition temperature of AC and UC was found equivalent to animal collagen. Self-assembly, fibril morphology and spatial alignment was studied using AFM and DLS. Biocompatibility was analyzed using 3T3 fibroblast cells. In conclusion, UC with higher yield, presented with better physico-chemical, structural and biological properties than AC could serve as an efficient alternative to the existing animal collagen for diverse applications.

Human Umbilical Cord Tissue-Derived Multipotent Mesenchymal Stromal Cells Exhibit Maximum Secretory Activity in the Presence of Umbilical Cord Blood Serum.

Using multiplex analysis, we performed a comparative study of cytokine and growth factor production by human umbilical cord tissue-derived multipotent mesenchymal stromal cells (UC-MSC) cultured under standard conditions and in the presence of human umbilical cord blood serum (UCBS). It was found that the secretion of most studied molecules, including well-known inductors of regeneration HGF, G-CSF, GM-CSF, and VEGF by UCMSC considerably increased in the presence of 5% UCBS. The use of UCBS allows not only obtaining xenogenic-free cellular and cell-free therapeutic products, but also increasing the secretion of most biologically active molecules capable of stimulating repair processes.

Essential trace elements in umbilical cord tissue and risk for neural tube defects.

Deficient or excessive quantities of essential trace elements (ETEs)1 in the fetal environment can compromise developmental processes. We investigated whether concentrations of zinc (Zn), manganese (Mn), selenium (Se), cobalt (Co), molybdenum (Mo), and nickel (Ni) in umbilical cord tissue are associated with risk for neural tube defects (NTDs). Umbilical cord tissues from 166 cases of NTD cases and 166 matched controls were collected and element concentrations were measured using inductively coupled plasma-mass spectrometry. Associations between ETE concentrations and the risk for NTDs were estimated using multivariate logistic regression while adjusting for potential confounders. Bayesian kernel machine regression (BKMR) was used to examine the joint effects of these ETEs. We found that median concentrations of Ni were higher but those of Mo and Co were lower in the NTD group than in the control group. Co was the only element that was associated with NTD risk after adjusting for confounders (OR 0.31, 95 % CI 0.12-0.79 for the second and OR 0.37, 95 % CI 0.15-0.91 for the top tertile relative to the lowest tertile). The association between Co and NTD risk was confirmed with the BKMR model. In addition, a joint effect of the six ETE mixture on NTD risk was observed: the risk decreased with the levels of the mixture from 25th percentile through 75th percentile. In conclusion, higher levels of Co were associated with lower risk for NTDs, and NTD risk decreased with the levels of the six ETEs as a co-exposure mixture, suggesting a protective effect.

Exosomes from human umbilical cord Mesenchymal stem cells attenuates stress-induced hippocampal dysfunctions.

Human Mesenchymal Stem Cells (MSCs) especially human umbilical cord MSCs is the novel regenerative cell resource for regenerative therapy. However, the biological underpinning of MSCs in neuroprotections requires deep understanding. Exosomes is an important biological factor due to its multiple types of contents with various biological function. In current study, we collected the exosome from umbilical cord mesenchymal stem cells (hUC-MSCs) and tested the neuroprotective effects to brain stress. Proteomic analysis indicates significant enriched protein components display the functions in metabolic regulation. We then injected the exosome (MSC-Ex) to adult mice by i.v injection. On physiological level, treatment of MSC-Ex increased the adiponectin level in peripheral central nervous system (CNS). Moreover, MSC-Ex significantly accelerated the differentiation of adult neural stem cells but did not benefit the related cognitive behavior. We then created acute brain disorder model with STZ intra-hippocampal injection. Compared with STZ group, treatment of MSC-Ex improved cognitive function. Moreover, MSC-Ex promotes hippocampal neurogenesis that was suppressed by STZ injection. In conclusion, hUC-MSCs derived exosome would exert the neural regenerative effects associating with its metabolism regulatory capacity.

Effects of human umbilical cord mesenchymal stem cells derived from exosomes on migration ability of endometrial glandular epithelial cells.

The present study aimed to investigate the effects of human umbilical cord mesenchymal stem cells (Huc­MSCs)­derived exosomes on the migratory abilities of endometrial glandular epithelial cells, and to evaluate the underlying mechanism from the perspective of epithelial­mesenchymal transition (EMT). Huc­MSCs were prepared from human umbilical cord, and eutopic endometrial glandular epithelial cells were isolated from patients with endometriosis. The exosomes derived from Huc­MSCs (Huc­MSCs­exo) were prepared using an exosome extraction kit. The endometrial glandular epithelial cells were randomly divided into two groups: Huc­MSCs­exo and control. Cell migratory ability was assessed and western blotting was used to detect the expression levels of EMT. The results of the present study demonstrated that Huc­MSCs­exo treatment significantly enhanced the migration of endometrial glandular epithelial cells from patients with endometriosis (P<0.05). The present study also demonstrated that treatment with Huc­MSCs­exo inhibited the expression levels of E­cadherin and promoted the expression levels of Vimentin and N­cadherin at both the mRNA and protein level. The results of the current study indicate that Huc­MSCs­exo enhance the migratory ability of endometrial glandular epithelial cells via promotion of EMT.

Effects of Recombinant AavLEA1 Protein on Human Umbilical Cord Matrix Mesenchymal Stem Cells Survival During Cryopreservation.

Recently, many studies have found that late embryogenesis abundant (LEA) proteins could protect cells from drought, high salinity, and other stress conditions. Because LEA proteins maintain the integrity and stability of cell membranes, LEA proteins increase the cell's tolerance to dehydration stress, and reduce the osmotic and freezing damage during freezing. Whether LEA proteins could reduce cryopreservation damage and improve cell viability remains to be confirmed. In this study, we purified the recombinant AavLEA1 proteins, examined their thermal solubility and the effect of AavLEA1 proteins on the osmotic stress of cells, and studied the effects of the AavLEA1 protein on cryopreservation of human umbilical cord matrix mesenchymal stem cells (hUCM-MSCs). We utilized three concentrations of AavLEA1 protein (0.1, 0.5, and 2 mg/mL) to cryopreserve hUCM-MSCs and analyzed cell viability and apoptosis of MSCs after slow-cooling cryopreservation. We also examined the cryopreservation effect of AavLEA1 protein on hUCM-MSCs survival with 0%, 2%, 5%, and 10% (v/v) dimethyl sulfoxide (DMSO). We found that the survival rate of hUCM-MSCs supplemented with AavLEA1 protein was significantly higher than that of MSCs cryopreserved with low concentration of DMSO solution, and the apoptosis and necrosis rates were correspondingly reduced. In conclusion, recombinant AavLEA1 protein can improve the efficiency of MSC cryopreservation, increase the hUCM-MSCs viability, and partly replace DMSO during cryopreservation.

Umbilical cord-derived Wharton's jelly for regenerative medicine applications.

BACKGROUND: The last decade has seen an explosion in the interest in using biologics for regenerative medicine applications, including umbilical cord-derived Wharton's Jelly. There is insufficient literature assessing the amount of growth factors, cytokines, hyaluronic acid, and extracellular vesicles including exosomes in these products. The present study reports the development of a novel Wharton's jelly formulation and evaluates the presence of growth factors, cytokines, hyaluronic acid, and extracellular vesicles including exosomes. METHODS: Human umbilical cords were obtained from consenting caesarian section donors. The Wharton's jelly was then isolated from the procured umbilical cord and formulated into an injectable form. Randomly selected samples from different batches were analyzed for sterility testing and to quantify the presence of growth factors, cytokines, hyaluronic acid, and extracellular vesicles. RESULTS: All samples passed the sterility test. Growth factors including IGFBP 1, 2, 3, 4, and 6, TGF-α, and PDGF-AA were detected. Several immunomodulatory cytokines, such as RANTES, IL-6R, and IL-16, were also detected. Pro-inflammatory cytokines MCSFR, MIP-1a; anti-inflammatory cytokines TNF-RI, TNF-RII, and IL-1RA; and homeostatic cytokines TIMP-1 and TIMP-2 were observed. Cytokines associated with wound healing, ICAM-1, G-CSF, GDF-15, and regenerative properties, GH, were also expressed. High concentrations of hyaluronic acid were observed. Particles in the extracellular vesicle size range were also detected and were enclosed by the membrane, indicative of true extracellular vesicles. CONCLUSION: There are numerous growth factors, cytokines, hyaluronic acid, and extracellular vesicles present in the Wharton's jelly formulation analyzed. The amount of these factors in Wharton's jelly is higher compared with other biologics and may play a role in reducing inflammation and pain and augment healing of musculoskeletal injuries.

Human Umbilical Cord Wharton's Jelly-Derived Mesenchymal Stem Cells Labeled with Mn2+ and Gd3+ Co-Doped CuInS2-ZnS Nanocrystals for Multimodality Imaging in a Tumor Mice Model.

Mesenchymal stem cell (MSCs) therapy has recently received profound interest as a targeting platform in cancer theranostics because of inherent tumor-homing abilities. However, the terminal tracking of MSCs engraftment by fluorescent in situ hybridization, immuno-histochemistry, and flow-cytometry techniques to translate into clinics is still challenging because of a dearth of inherent MSCs-specific markers and FDA approval for genetic modifications of MSCs. To address this challenge, a cost-effective noninvasive imaging technology based on multifunctional nanocrystals (NCs) with enhanced detection sensitivity, spatial-temporal resolution, and deep-tissue diagnosis is needed to be developed to track the transplanted stem cells. A hassle-free labeling of human umbilical cord Wharton's Jelly (WJ)-derived MSCs with Mn2+ and Gd3+ co-doped CuInS2-ZnS (CIS-ZMGS) NCs has been demonstrated in 2 h without requiring an electroporation process or transfection agents. It has been found that WJ-MSCs labeling did not affect their multilineage differentiation (adipocyte, osteocyte, chondrocyte), immuno-phenotypes (CD44+, CD105+, CD90+), protein (ß-actin, vimentin, CD73, α-SMCA), and gene expressions. Interestingly, CIS-ZMGS-NCs-labeled WJ-MSCs exhibit near-infrared (NIR) fluorescence with a quantum yield of 84%, radiant intensity of ∼3.999 × 1011 (p/s/cm2/sr)/(µW/cm2), magnetic relaxivity (longitudinal r1 = 2.26 mM-1 s-1, transverse r2 = 16.47 mM-1 s-1), and X-ray attenuation (78 HU) potential for early noninvasive multimodality imaging of a subcutaneous melanoma in B16F10-tumor-bearing C57BL/6 mice in 6 h. The ex vivo imaging and inductively coupled plasma mass-spectroscopy analyses of excised organs along with confocal microscopy and immunofluorescence of tumor results also significantly confirmed the positive tropism of CIS-ZMGS-NCs-labeled WJ-MSCs in the tumor environment. Hence, we propose the magnetofluorescent CIS-ZMGS-NCs-labeled WJ-MSCs as a next-generation nanobioprobe of three commonly used imaging modalities for stem cell-assisted anticancer therapy and tracking tissue/organ regenerations.

hUC-MSCs secreted exosomes inhibit the glioma cell progression through PTENP1/miR-10a-5p/PTEN pathway.

OBJECTIVE: The mesenchymal stem cells (MSCs) have been widely studied for their anti-tumor property, due to the characteristic of homing towards tumor sites and immunosuppression. Nevertheless, the underlying molecular mechanisms that link MSCs to the targeted tumor cells, such as glioma, are not clear. MATERIALS AND METHODS: Here, we examined the inhibitory properties and new molecular mechanisms of the human umbilical cord (hUC-MSCs) derived exosomes on the human glioma U87 cells using a co-culture system in vitro. The cell counting kit-8 (CCK-8) assay was performed to measure the anti-tumor activity of hUC-MSCs derived exosomes. The cell apoptosis was assessed by flow cytometry and the immunoblotting assay was applied in order to assess the associated proteins level. The data revealed that hUC-MSCs derived exosomes could repress cell proliferation and induce cell apoptosis. RESULTS: Mechanistically, we identified that lncRNA PTENP1 could be packaged into exosome from hUC-MSCs, transferred to U87 cells, and then stabilized PTEN by binding miR-10a-5p competitively. CONCLUSIONS: Therefore, our data suggested that the exosomes from hUC-MSCs possess a higher anti-tumor capacity, at least partially, via regulating miR-10a-5p/PTEN signaling, which thereby may represent a possible target for early diagnosis and treatment of glioma clinically.

Dysregulation of inflammatory cytokines and inhibition of VEGFA in the human umbilical cord are associated with negative pregnancy outcomes.

INTRODUCTION: Cytokines and vascular endothelial growth factors (VEGF) are involved in all aspects of pregnancy: from placentation, through fetal development, parturition and neonatal well-being. Umbilical cord inflammatory cytokines and/or VEGF have not been well studied with respect to dysregulation associated with disorders of pregnancy or maternal/neonatal outcomes. METHODS: Here we have used multiplex ELISA to screen umbilical cord lysates (comprising cord blood, endothelia and Wharton's jelly, n = 380), for levels of IFN-γ, IL1-ß, IL-6, IL-8, IL-10, TNF-α and VEGFs A, C and D and associations with 46 ICD9/10 codes encompassing obstetric, maternal and neonatal variables. RESULTS: No significant differences were observed for IFNγ, VEGFC or VEGFD with any clinical outcomes. The cytokines IL1-ß, IL-6, IL-8, IL-10, and TNF-α showed varying levels of induction and suppression with primarily fetal-placental and neonatal complications. The largest number of significant differences between umbilical cytokines and clinical outcomes were observed for chorioamnionitis (IL1-ß, IL-6, IL-8, TNF-α), and meconium passage during birth (IL1-ß, IL-6, IL-8) where significant pro-inflammatory responses occurred and sex differences in IL-8 expression were noted. In contrast, gonococcal infection showed suppressed immune response significantly lowering IL1-ß, IL-6, IL-8, IL-10 and TNF-α. For 12/46 negative pregnancy outcomes, strong suppression of VEGFA occurred. DISCUSSION: Angiogenic and inflammatory changes in the umbilical cord could be detrimental by increasing vascular permeability in the umbilical artery or vein and/or altering vascular tone, either of which would alter blood flow affecting delivery and removal of compounds. Further elucidation of inflammatory responses in the umbilical cord may provide mechanistic understanding of adverse pregnancy outcomes.

Investigation of the relationship between umbilical cord pH and intraventricular hemorrhage of infants delivered preterm

SUMMARY OBJECTIVE: We measured the level of pH gases in premature infants at birth, and examined the relationship between brain ultrasonography on the third and seventh day after birth. A case-control study conducted at the Neonatal Intensive Care Unit (NICU) of Shahid Akbar Abadi Hospital, Iran, during the years 2016-2017. METHODS: All premature infants who were admitted to NICU were enrolled in the current study. At birth, a blood gas sample was taken from the umbilical cord of the infants. On the third and seventh day after birth, an ultrasound of the brain of each neonate was performed by a radiologist. The umbilical cord was evaluated for blood gases in 72 neonates (mostly boys). RESULTS: Sixty-six newborns had normal sonography, and 16.7% (12 cases) had anomalies. A total of 75% of the 8 infants with intravenous bleeding were girls, which were significantly different from those in the non-hemodynamic group (62.5% male) (P 0.049). However, the type of delivery, mean weight, height, head circumference, the circumference of the chest, and Apgar score did not differ between the two groups. Mean pH, HCO3- and PCO2 in umbilical cord blood gas samples were not significantly different between the two groups with or without intraventricular hemorrhage (IVH). Although it was not related to gender and type of delivery in newborns CONCLUSION: Blood gases do not help in determining the occurrence of IVH in infants. Nevertheless, it is associated with immaturity and fetal age.

RESUMO OBJETIVOS: Medimos o nível de gases de pH em bebês prematuros, no nascimento dos neonatos, e examinamos a relação entre a ecografia cerebral no terceiro e no sétimo dia após o nascimento. Um estudo de casos e controles realizados na Unidade de Cuidados Intensivos Neonatais (UCIN) do Hospital Shahid Akbar Abadi durante os anos de 2016-2017, Irã. MÉTODOS: Todos os recém-nascidos prematuros que deram entrada na UCIN foram inscritos no estudo atual. Ao nascer, foi retirada uma amostra de gás em sangue, do sangue do cordão umbilical dos bebês. No terceiro e sétimo dia após o nascimento, um radiologista realizou uma ecografia do cérebro de cada neonato. O cordão umbilical foi avaliado para detectar gases no sangue em 72 neonatos (em sua maioria do sexo masculino). RESULTADOS: Sessenta e seis recém-nascidos tinham ecografia normal e 16.7% (12 casos) tinham anomalias. 75% das 8 crianças com hemorragia intravenosa eram meninas, que foram significativamente diferentes das do grupo não hemodinâmico (62.5% homens) (P.0.049). Contudo, o tipo de parto, o peso médio, a altura, o perímetro cefálico, a circunferência do tórax e a pontuação de Apgar não foram diferentes entre os grupos. O pH médio, HCO3 e PCO2 nas amostras de gás no sangue do cordão umbilical não foram significativamente diferentes entre dois grupos com ou sem hemorragia intraventricular (Hiv). Apesar de não estar relacionado com o gênero e o tipo de parto em recém-nascidos. Conclusão: os gases sanguíneos não ajudam a determinar o aparecimento de Hiv nos bebês. Contudo, está associado com a imaturidade e idade fetal.

Two parenteral amino acid solutions and plasma levels of amino acids in the neonate: A randomized trial.

OBJECTIVE: In neonates on total parenteral nutrition (TPN), amino acids may be a risk factor for developing total parenteral nutrition-associated cholestasis (TPNAC). We aimed, first, to compare methionine, cysteine, and taurine plasma levels between neonates on TPN who were receiving an intravenous amino acid solution based on a breast milk aminogram and those on an intravenous solution of pediatric amino acids based on an umbilical cord aminogram, and second, to determine the frequency of TPNAC. METHODS: A double-blind randomized controlled trial was conducted. Ninety-four neonates with a birthweight of 1000g or more and a gestational age of 30 wk or older were admitted and enrolled. Blood samples were obtained at 0, 7, and 14 d of TPN, and plasma amino acid concentrations were determined by ultra-high-resolution liquid chromatography. Continuous variables were compared using the Wilcoxon rank-sum test or Student's t test; categorical variables were compared using the Fisher exact test. RESULTS: Thirty-five neonates completed the study (Primene, n = 14; TrophAmine, n = 21). On day 14, methionine plasma concentrations were significantly lower in the Primene group than in the TrophAmine group (27 µmol/L versus 32.9 µmol/L, P = 0.044); the taurine concentration was significantly higher in the same group (72.4 µmol/L versus 45.3 µmol/L, P < 0.0001). There were no differences in TPNAC incidence. CONCLUSIONS: Administering an intravenous solution of pediatric amino acids based on the umbilical cord aminogram yielded a higher taurine and lower methionine plasma concentration than did administering a similar solution based on the breast milk aminogram.

Discovery of Populusone, a Skeletal Stimulator of Umbilical Cord Mesenchymal Stem Cells from Populus euphratica Exudates.

Populusone (1), a cembrane-type macrocyclic trinorditerpenoid, was isolated from the exudates of Populus euphratica and shown to have an unprecedented carbon skeleton, The structure was identified using spectroscopic methods and X-ray crystallography. A possible pathway for the biosynthesis of 1 was proposed. Populusone (10 µM) was found to promote proliferation and differentiation of umbilical cord derived mesenchymal stem cells into keratinocyte like cells.

Evaluation of dehydrated human umbilical cord biological properties for wound care and soft tissue healing.

Chronic wounds are a significant health care problem with serious implications for quality of life because they do not properly heal and often require therapeutic intervention. Amniotic membrane allografts have been successfully used as a biologic therapy to promote soft tissue healing; however, the umbilical cord, another placental-derived tissue, has also recently garnered interest because of its unique composition but similar placental tissue origin. The aim of this study was to characterize PURION® PLUS Processed dehydrated human umbilical cord (dHUC) and evaluate the biological properties of this tissue that contribute to healing. This was performed through the characterization of the tissue composition, evaluation of in vitro cellular response to dHUC treatment, and in vivo bioresorption and tissue response in a rat model. It was observed that dHUC contains collagen I, hyaluronic acid, laminin, and fibronectin. Additionally, 461 proteins that consist of growth factors and cytokines, inflammatory modulators, chemokines, proteases and inhibitors, adhesion molecules, signaling receptors, membrane-bound proteins, and other soluble regulators were detected. Cell-based assays demonstrated an increase in adipose-derived stem cell and mesenchymal stem cell proliferation, fibroblast migration and endothelial progenitor cell vessel formation in a dose-dependent manner after dHUC treatment. Lastly, rat subcutaneous implantation demonstrated biocompatibility since dHUC allografts were resorbed without fibrous encapsulation. These findings establish that dHUC possesses biological properties that stimulate cellular responses important for soft tissue healing. © 2018 The Authors. Journal Of Biomedical Materials Research Part B: Applied Biomaterials Published By Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 1035-1046, 2019.