Single Umbilical Artery Umbilical Cord Is Associated With High-Grade Distal Fetal Vascular Malperfusion.

PURPOSE AND CONTEXT: Umbilical cord abnormalities with clinical signs of cord compromise are frequently associated with fetal vascular malperfusion (FVM). Single umbilical artery (SUA) has been reported to be associated with high-grade FVM in fetal growth restriction but not in an unselected population; our study aimed to address this issue. METHODS: Clinical and placental phenotypes of 55 consecutive placentas with SUA (Group 1) were compared with those of 655 placentas with 3-vessel umbilical cord (Group 2) from patients who were in the second half of their pregnancy. The placentas were histologically examined using hematoxylin and eosin (H&E) staining and CD 34 immunostaining. KEY RESULTS: Several umbilical cord phenotypes and high-grade distal FVM, based on H&E staining and endothelial fragmentation by CD34 were significantly more common in Group 1, whereas decidual clusters of multinucleate trophoblasts were more common in Group 2. Notably, H&E staining or CD34 immunostaining evaluated separately showed that high-grade distal FVM was more common in Group 1 than in Group 2, but the difference was not statistically significant. CONCLUSIONS: SUA predisposes to remote, advanced, and recent high-grade distal villous FVM, with a pathogenesis partly different from that of stasis-induced FVM, likely related to fetal anomalies associated with SUA.

Distribution of cord inflammation in cases with clinical suspicion of chorioamnionitis.

INTRODUCTION: Identification of acute funisitis, a sign of foetal inflammatory response (FIR), is crucial as their presence is associated with ominous neonatal outcomes. Recommendation on which part of umbilical cord should be sampled to facilitate optimal identification of acute funisitis is limited. METHODS: This is a retrospective cross-sectional study over a seven-month duration recruiting all patients with clinical suspicion of chorioamnionitis and/or maternal intrapartum pyrexia. The distribution and the degree of cord inflammation were assessed. The cases were also evaluated for maternal inflammatory response (MIR) and chorionic vasculitis (CV). RESULTS: Of the 191 placentas, 88 (46.1%) had some degree of cord inflammation. Forty-nine (55.7%) had a differential in cord inflammation, with distal cord section (n = 38) demonstrating significant greater inflammation than that of proximal cord section (n = 11) (p<0.001). There were 20 cases with phlebitis only and 8 cases demonstrated arteritis only in either proximal or distal cord sections. Increasing magnitude of cord inflammation was significantly associated with increasing severity of MIR and the rate of CV (p<0.001). CV was observed in 25 (24.3%) cases showing absence of cord inflammation, while 12 (13.6%) cases with cord FIR demonstrated no CV. DISCUSSION: Inflammatory reaction can occur variably throughout the length of the umbilical cord and chorionic plate vessels, with greater inflammation seen in the distal cord section. We affirm the current Amsterdam recommendation of submitting at least two cross sections of the cord representing proximal and distal sites and two sections from placental parenchyma to facilitate the identification of FIR.

Peripheral cord insertion is associated with adverse pregnancy outcome only when accompanied by clinically significant placental pathology.

OBJECTIVE: To examine the relationship between umbilical cord insertion site, placental pathology and adverse pregnancy outcome in a cohort of normal and complicated pregnancies. METHODS: Sonographic measurement of the cord insertion and detailed placental pathology were performed in 309 participants. Associations between cord insertion site, placental pathology and adverse pregnancy outcome (pre-eclampsia, preterm birth, small-for-gestational age) were examined. RESULTS: A total of 93 (30%) participants were identified by pathological examination to have a peripheral cord insertion site. Only 41 of the 93 (44%) peripheral cords were detected by prenatal ultrasound. Peripherally inserted cords were associated significantly (P < 0.0001) with diagnostic placental pathology (most commonly with maternal vascular malperfusion (MVM)); of which 85% had an adverse pregnancy outcome. In cases of isolated peripheral cords, without placental pathology, the incidence of adverse outcome was not statistically different when compared to those with central cord insertion and no placental pathology (31% vs 18%; P = 0.3). A peripheral cord with an abnormal umbilical artery (UA) pulsatility index (PI) corresponded to an adverse outcome in 96% of cases compared to 29% when the UA-PI was normal. CONCLUSIONS: This study demonstrates that peripheral cord insertion is often part of the spectrum of findings of MVM disease and is associated with adverse pregnancy outcome. However, adverse outcome was uncommon when there was an isolated peripheral cord insertion and no placental pathology. Therefore, additional sonographic and biochemical features of MVM should be sought when a peripheral cord is observed. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

The Effects of Umbilical Cord Mesenchymal Stem Cells on Traumatic Pancreatitis in Rats.

OBJECTIVE: This study explored the therapeutic and protective effects of umbilical cord mesenchymal stem cells (ucMSCs) on traumatic pancreatitis (TP) to provide a theoretical basis for TP treatment with MCSs by establishing a TP rat model. METHODS: We used 60 healthy adult male Sprague Dawley (SD) rats to create four experimental groups: sham, ucMSC control, TP, and ucMSC treatment. We observed ucMSC homing in the rats by fluorescence microscopy and assessed the degree of pancreatic tissue injury by hematoxylin and eosin (HE) staining on days 1, 3, and 7 after transplantation. Furthermore, we used an in vivo imaging system to evaluate the localization of cell membrane-stained ucMSCs in rats with TP. Finally, we measured the serum levels of amylase, lipase, pro-and anti-inflammatory factors, and oxidative stress factors by enzyme-linked immunosorbent assay (ELISA). RESULTS: The pancreatic histopathological score and the serum amylase and lipase levels were lower in the ucMSC treatment group than in the TP group (P < 0.05). Interleukin (IL)-6, tumor necrosis factor-α (TNF-α), and oxidase malondialdehyde (MOD) levels were significantly higher in the ucMSC treatment group than in the TP group. However, IL-10, transforming growth factor-ß, and superoxide dismutase (an antioxidant enzyme, SOD) levels were significantly higher in the ucMSC treatment group than in the TP group (P < 0.05). CONCLUSION: ucMSCs can migrate and implant in injured areas of the pancreas in rats. Furthermore, they participate in pancreatic tissue repair and regulate immunity by inhibiting the systemic inflammatory response and oxidative stress.

Umbilical Cord Wharton's Jelly-Derived Mesenchymal Stem Cells Inhibit the TGF-ß1 Pathway in Hepatic Fibrosis Rats Through a Paracrine Regulation Process.

BACKGROUND: The aim is to verify the therapeutic effect and possible mechanism of human umbilical cord Wharton's jelly-derived transplantation of mesenchymal stem cells (UMSCs) on CCl4-induced hepatic fibrosis rats through in vivo studies and to explore the regulatory mechanism of UMSCs on fibrosis of hepatic stellate cells (HSCs) through in vitro experiments. METHODS: In vivo experiment: Rats were randomly divided into blank control group and hepatic fibrosis group. During the entire trial, the blank control group received subcutaneous injection of normal saline, while in the hepatic fibrosis group received injections of 50% CCl4-olive oil subcutaneously for 10 weeks to establish the rat model of liver fibrosis. Hepatic fibrosis rats were then randomly and evenly divided into umbilical cord mesenchymal stem cell (UMSC) group, bone marrow mesenchymal stem cell (BMSC) group, UMSC-culture medium (CM) group, and control group. Rats in each group were infused with the following substances through the caudal vein as follows: 1 mL UMSCs (2 × 106/mL) in UMSC group, 1 mL BMSCs (2 × 106/mL) in BMSC group, 1 mL UMSCs-CM in CM group, and 1 mL saline in control group. Rats of each group were closely observed (weight, hair condition, activity, appetite, diarrhea, etc.), venous blood samples were collected, the number of white blood cells and lymphocytes were measured, and liver function indicators (ALT, AST, TBIL, ALB) were determined. Three weeks later, rat liver specimens were taken, HE stained, pathological changes were examined and quantified. In vitro experiments: HSCs were seeded in 6-well plates at 1.0 × 105/mL, with a serum-free medium for 24 hours. Then, 2 mL of UMSCs-CM was added in the study group, while an equal amount of complete medium was added to the control group. RT-PCR was used to detect TGF-ß1, Collagen-I, TIMP-2 mRNA expression in HSCs, and western blot was used to detect TGF-ß1 protein expression in HSCs. RESULTS: In vivo experiment: Compared with the control group, after the transplantation, the activity status (weight, spirit, appetite, movement, hair, diarrhea, etc.) of rats in the UMSC group, BMSC group, and CM group were improved. The liver function indexes of these groups, such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBIL) were significantly decreased (p < 0.05), while albumin (ALB) levels were mildly but not significantly increased (p > 0.05). The Knodell score (reflecting the degree of liver inflammation) and Chevallier score (reflecting the degree of liver fibrosis) of liver specimens in pathological examination were also significantly reduced, and the difference in the quantitative scores of those indexes was statistically significant (p < 0.05). There was no statistically significant difference in the number of venous white blood cells and lymphocytes, liver function indexes (ALT, AST, TBIL, ALB), Knodell score, and Chevallier score of liver samples among the UMSC group, BMSC group, and CM group. In vitro experiments: After treatment with UMSCs-CM, the expression of TGF-ß1, Collagen-I, and TIMP-2 mRNA in HSCs was significantly down-regulated compared with that of the control group (treated with complete medium), and it gradually decreased with the extension of the treatment time. Compared with the control group, the expression of TGF-ß1 protein in the HSCs of the experimental group was down-regulated, and this effect was time-dependent, specifically, the control group (2.49 ± 0.43) > the experimental group at 48 hours (1.98 ± 0.26) > the experimental group at 72 hours (1.62 ± 0.20) (F = 7.796, p < 0.05). CONCLUSIONS: In rats with liver fibrosis, transplantation of UMSCs can improve liver function and reduce the inflammatory activity and fibrosis of the liver, possibly through the paracrine mechanism. UMSCs inhibit HSCs fibrosis through a paracrine mechanism, which is time-dependent, possibly by targeting TGF-ß1 and its downstream gene products.

Exosomal microRNA-140-3p from human umbilical cord mesenchymal stem cells attenuates joint injury of rats with rheumatoid arthritis by silencing SGK1.

OBJECTIVE: Over the years, microRNAs (miRNAs) have been involved in the pathogenesis of rheumatoid arthritis (RA). We aim to investigate the role of human umbilical cord mesenchymal stem cells (HUCMSCs)-derived exosomal miR-140-3p in RA development. METHODS: Exosomes(exo) were isolated from human umbilical cord-derived mesenchymal stem cells (HUCMSCs), and this isolation was followed by the transfer of miR-140-3p. RA rat models were constructed by collagen II adjuvant and respectively treated with HUCMSCs-exo or HUCMSCs-exo carrying miR-140-3p mimic/inhibitor, and expression of miR-140-3p and serum- and glucocorticoid-inducible kinase 1 (SGK1) was assessed. Then, RA score and inflammation scoring, fibrosis degree and apoptosis, serum inflammatory response and oxidative stress in joint tissues were determined. The RA synovial fibroblasts (RASFs) were extracted from rats and identified. Conducted with relative treatment, the migration, proliferation and apoptosis in RASFs were determined. RESULTS: MiR-140-3p was decreased while SGK1 was increased in RA rats. HUCMSCs-exo or upregulated exosomal miR-140-3p improved pathological changes and suppressed inflammation, oxidative stress and fibrosis in RA rats, and also constrained and RASF growth. Overexpression of SGK1 reversed the inhibition of RASF growth caused by overexpression of miR-140-3p. CONCLUSION: Upregulated exosomal miR-140-3p attenuated joint injury of RA rats by silencing SGK1. This research provided further understanding of the role of exosomal miR-140-3p in RA development.

The role of human umbilical cord mesenchymal stem cells-derived exosomal microRNA-431-5p in survival and prognosis of colorectal cancer patients.

We aim to discuss the role of miR-431-5p in colorectal cancer (CRC) progression via regulating peroxiredoxin 1 (PRDX1). miR-431-5p and PRDX1 expression were detected in CRC tissues and cells, and the relationship between miR-431-5p expression and prognosis of CRC patients was analyzed. Exosomes were extracted from human umbilical cord mesenchymal stem cells (hUCMSCs) and co-cultured with LoVo cells. MTT assay, flow cytometry and Transwell assay were implemented to test cell viability, apoptosis and invasion and migration ability, respectively. The tumor growth was determined as well, and the binding relation between miR-431-5p and PRDX1 was confirmed. miR-431-5p was downregulated and PRDX1 was upregulated in CRC, and miR-431-5p downregulation was associated with poor prognosis. hUCMSC-Exos suppressed the malignant behaviors of LoVo cells, and overexpression of miR-431-5p further aggravated the inhibitory effect of hUCMSC-Exos on LoVo cells. hUCMSC-Exos inhibited PRDX1 expression via miR-431-5p. PRDX1 was targeted by miR-431-5p. miR-431-5p serves as a prognostic biomarker in CRC, and hUCMSC-Exos transfer of miR-431-5p decelerates CRC cell growth by inhibiting PRDX1.

Third trimester intrauterine fetal death: proposal for the assessment of the chronology of umbilical cord and placental thrombosis.

The timing of umbilical cord and placental thrombosis in the third trimester intrauterine fetal death (TT-IUFD) may be fundamental for medico-legal purposes, when it undergoes medical litigation due to the absence of risk factors. Authors apply to human TT-IUFD cases a protocol, which includes histochemistry and immunohistochemistry (IHC) for the assessment of thrombi's chronology. A total of 35 thrombi of umbilical cord and/or placenta were assessed: 2 in umbilical artery, 6 in umbilical vein, 15 in insertion, 10 in chorionic vessels, 1 in fetal renal vein, 1 in fetal brachiocephalic vein. Thrombi's features were evaluated with hematoxylin-eosin, Picro-Mallory, Von Kossa, Perls, and immunohistochemistry for CD15, CD68, CD31, CD61, and Smooth Muscle Actin. The estimation of the age of the thrombi was established by applying neutrophils/macrophages ratio taking into consideration, according to literature, the presence of hemosiderophagi, calcium deposition, and angiogenesis. To estimate an approximate age of fresh thrombi (< 1 day), a non-linear regression model was tested. Results were compared to maternal risk factors, fetal time of death estimated at autopsy, mechanism, and cause of death. Our study confirms that the maternal risk factors for fetal intrauterine death and the pathologies of the cord, followed by those of the placental parenchyma, are the conditions that are most frequently associated with the presence of thrombi. Results obtained with histological stainings document that the neutrophile/macrophage ratio is a useful tool for determining placental thrombi's age. Age estimation of thrombi on the first day is very challenging; therefore, the study presented suggests the N/M ratio as a parameter to be used, together with others, i.e., hemosiderophagi, calcium deposition, and angiogenesis, for thrombi's age determination, and hypothesizes that its usefulness regards particularly the first days when all other parameters are negative.

In vitro Immunomodulatory Effects of Human Umbilical Cord-Derived Mesenchymal Stem Cells on Peripheral Blood Cells from Warm Autoimmune Hemolytic Anemia Patients.

INTRODUCTION: Autoimmune hemolytic anemia is a potentially lethal disease characterized by autoimmune hemolysis. Although human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) have been reported as a promising therapy, there is limited evidence regarding warm autoimmune hemolytic anemia (wAIHA) patients. This study aimed to investigate the potential therapeutic effects of hUC-MSCs via immune regulation in wAIHA patients. METHODS: Peripheral blood mononuclear cells (PBMCs) from 10 wAIHA patients and 8 healthy controls were isolated from peripheral blood and cultured for 3 days with or without the presence of hUC-MSCs; PBMCs were co-cultured with hUC-MSCs using Transwell assays. The supernatant cytokine levels were measured after culture through AimPlex Multiple Immunoassays for Flow, including IL-2, IL-4, IL-10, IFN-γ, TNF-α, and IL-17A. The percentages of regulatory T cells, regulatory B cells, and Th1/Th2 in PBMCs were also assessed before and after culturing. RESULTS: In the wAIHA group, hUC-MSCs could upregulate the Treg and Breg proportions after culturing for 3 days, and the Treg and Breg percentages increased after co-culturing with hUC-MSCs in the wAIHA group compared with PBMC cultured alone for 3 days (8.29 ± 8.59 vs. 6.82 ± 1.32, 3.82 ± 1.87 vs. 1.75 ± 1.20, respectively). Compared with the PBMC wAIHA group, the levels of TNF-α (2.13 ± 2.07 vs. 16.20 ± 21.13 pg/mL, p = 0.019) and IL-10 (10.51 ± 18.42 vs. 37.78 ± 44.20 pg/mL, p = 0.012) were significantly elevated in the PBMC + hUC-MSCs wAIHA group. CONCLUSION: The hUC-MSCs contributed to the increasing proportion of regulatory cell populations in PBMCs of wAIHA patients, thereby potentially regulating autoimmune response; thus, hUC-MSCs may be a promising approach for wAIHA treatment.

Changing Course of an Umbilical Cord Mass - Chasing the Diagnosis of Angiomyxoma.

Angiomyxoma of the umbilical cord is a rare benign vascular malformation with potential for fetal morbidity and mortality. Gross and histologic features of this lesion are identical to those described as "hemangioma," however "angiomyxoma" is a preferable term as current practice restricts the term "hemangioma" to infantile capillary proliferations that express glucose transporter 1. Here we describe the case of an umbilical cord angiomyxoma with associated pseudocysts diagnosed after delivery at 33 weeks. It presented as a heterogeneous-appearing mass near the fetal cord insertion and mimicked serious fetal anomalies throughout gestation. We found fetal MRI helpful for monitoring this lesion, narrowing the differential, and informing management. Proximity to the fetal end of the cord and uncertainty about diagnosis also required surgical resection of the mass after delivery with umbilicoplasty.

Fractional laser-assisted administration of human umbilical cord mesenchymal stem cells to reduce hypertrophic scars in rabbit ears.

BACKGROUND: The formation of hypertrophic scar is due to the abnormal accumulation and remodeling of the extracellular matrix, especially collagen tissue. Our research was designed to investigate the treatment effect of different administrations of human umbilical cord-derived stem cells and to hypertrophic scars on rabbit ears. METHODS: Thirty New Zealand female white rabbits were treated as hypertrophic scar models. PBS was injected into the scars on the right ear of each group as control, while human umbilical cord-derived stem cells or condition medium of human umbilical cord-derived stem cells were administrated into the left ear through subcutaneous injection or fractional laser-assisted administration. Gross examination, scar elevation index (SEI) calculation and sampling were executed 5 weeks after administration. Then H&E and Masson staining analysis and the expression levels detections of α-SMA, Collagen I, TGF-ß1, IL-1ß, and IL-6 were performed. RESULTS: Our results demonstrated that the severity of hyperplasia was lower than the model group after stem cells and conditioned medium treatment. H&E and Masson staining results showed that the inflammation in scars was greatly alleviated and the degree of fibrosis was reduced after treatment. There was no significant difference in the therapeutic effect between subcutaneous injection or fractional laser-assisted administration. Both stem cells and conditioned medium can down-regulate SEI and factors expression levels in all groups. However, compared with the stem cells, the therapeutic effects of the conditioned medium were lower. CONCLUSIONS: The results confirmed that stem cells had an available treatment effect on hypertrophic scars of rabbit ears. In addition to the paracrine pathway, stem cells may have other ways to treat hypertrophic scars. Fractional laser-assisted administration may become a potential administration of stem cell clinical application in the future.

Development of a multivariable prediction model to identify dairy calves too young to be transported to auction markets in Canada using simple physical examination and body weight.

Calves born on Eastern Canadian dairy farms that are not kept in the herds are traditionally sold through auction markets and are raised for meat purposes such as veal calves. Since February 2020, a new Canadian federal regulation has forbidden calves <9 d old to be sold through auction markets. However, in the absence of a real-time birth registry consultation system, it would be of interest to look for predictors that could be associated with age to allow identification of calves too young to be transported. In the current retrospective cross-sectional study, 1,178 calves with a declared birth date (411 calves aged <9 d old; 34.9%) were assessed in 2 large Québec auction sites. Easy-to-record covariates [body weight (BW), breed phenotype, and presence of an umbilical cord remnant] as well as other clinical signs (umbilical swelling, enlargement, umbilical pain, wet umbilicus, skin tent, sunken eyes, ocular and nasal secretion, and hide cleanliness) were assessed. Two logistic regression models using age as a dichotomous dependent variable (<9 d old vs ≥9 d old) were built. The first model (model 1) considered all covariates, which were selected after univariable analyses and a backward stepwise selection process, whereas a more pragmatic model (model 2) only included the 3 easy-to-record variables (i.e., BW, breed, umbilical cord). Both models had similar accuracy to detect calves <9 d old (sensitivity of 38.4 and 37.5%, and specificity of 85.7 and 84.6% for model 1 and 2, respectively). Model 2 was subsequently more specifically studied as it employs a faster and easier assessment. Decision thresholds were tested for their robustness based on misclassification cost term (MCT) analysis with various prevalence of calves <9 d old and various costs of false-negative:false-positive ratio. Despite statistical significance, model accuracy, even if refined with MCT analysis, was limited at the individual level, showing the limits of using physical signs and BW or their combination as a reliable proxy of age. The sensitivity of these models to find calves <9 d old was not to be used for monitoring compliance with the Canadian federal regulation. The relatively high model specificity may help to use this model as a rule-in test (i.e., targeting positive calves for further investigation) rather than a rule-out test (due to its low sensitivity).

Umbilical Cord Biometry and Fetal Abdominal Skinfold Assessment as Potential Biomarkers for Fetal Macrosomia in a Gestational Diabetes Romanian Cohort.

Backgroundand Objectives: Gestational diabetes mellitus (GDM) is a pregnancy-associated pathology commonly resulting in macrosomic fetuses, a known culprit of obstetric complications. We aimed to evaluate the potential of umbilical cord biometry and fetal abdominal skinfold assessment as screening tools for fetal macrosomia in gestational diabetes mellitus pregnant women. Materials and methods: This was a prospective case−control study conducted on pregnant patients presenting at 24−28 weeks of gestation in a tertiary-level maternity hospital in Northern Romania. Fetal biometry, fetal weight estimation, umbilical cord area and circumference, areas of the umbilical vein and arteries, Wharton jelly (WJ) area and abdominal fold thickness measurements were performed. Results: A total of 51 patients were enrolled in the study, 26 patients in the GDM group and 25 patients in the non-GDM group. There was no evidence in favor of umbilical cord area and WJ amount assessments as predictors of fetal macrosomia (p > 0.05). However, there was a statistically significant difference in the abdominal skinfold measurement during the second trimester between macrosomic and normal-weight newborns in the GDM patient group (p = 0.016). The second-trimester abdominal circumference was statistically significantly correlated with fetal macrosomia at term in the GDM patient group with a p value of 0.003, as well as when considering the global prevalence of macrosomia in the studied populations, 0.001, when considering both populations. Conclusions: The measurements of cord and WJ could not be established as predictors of fetal macrosomia in our study populations, nor differentiate between pregnancies with and without GDM. Abdominal skinfold measurement and abdominal circumference measured during the second trimester may be important markers of fetal metabolic status in pregnancies complicated by GDM.

[MicroRNA-204 Carried by Exosomes of Human Umbilical Cord-derived Mesenchymal Stem Cells Regulates the Polarization of Macrophages in a Mouse Model of Myocardial Ischemia-reperfusion Injury].

Objective To explore the role and mechanism of microRNA-204(miR-204) carried by the exosomes of human umbilical cord-derived mesenchymal stem cells(hUC-MSC) in regulating the polarization of macrophages in a mouse model of myocardial ischemia-reperfusion(I/R) injury. Methods After the hUC-MSCs were isolated,cultured,and identified,their adipogenic and osteogenic differentiation capabilities were determined.The exosomes of hUC-MSCs were separated by ultracentrifugation,and the expression of CD81,CD63,tumor susceptibility gene 101(Tsg101),and calnexin in the exosomes was determined by Nanoparticle Tracking Analysis software,transmission electron microscopy,and Western blotting.Three groups(hUC-MSC,miR-204 mimic,and negative control) were designed for the determination of the expression of miR-204 in the cells and their exosomes by qRT-PCR.The C57BL/6J mice were randomly assigned into a sham operation group,an I/R group,a hUC-MSC exosomes group,a negative control group,and a miR-204 mimic group.Except the sham operation group,the I/R model was established by ligating the left anterior descending artery.The echocardiography system was employed to detect the heart function of mice.HE staining was employed to observe the pathological changes of mouse myocardium.ELISA was employed to determine the levels of interleukin-1ß(IL-1ß),tumor necrosis factor-α(TNF-α),arginase 1(Arg-1),and IL-10 in the myocardial tissue.After the macrophages of mouse myocardial tissue were isolated,flow cytometry was employed to determine the expression of CD11c and CD206,and ELISA to measure the levels of IL-1ß,TNF-α,Arg-1,and IL-10 in the macrophages. Results hUC-MSCs had adipogenic and osteogenic differentiation capabilities,and the exosomes were successfully identified.Compared with the negative control group,the miR-204 mimic group showed up-regulated expression of miR-204 in hUC-MSCs and their exosomes(P<0.001,P<0.001).Compared with the sham operation group,the modeling of I/R increased the left ventricular end-diastolic diameter(LVEDD)(P<0.001),left ventricular end-systolic diameter(LVESD)(P<0.001),myocardial injury score(P<0.001),and the levels of IL-1ß(P<0.001),TNF-α(P<0.001),and CD11c(P<0.001).Meanwhile,it lowered the left ventricular ejection fraction(LVEF)(P<0.001),left ventricular fractional shortening(LVFS)(P<0.001),Arg-1(P<0.001),IL-10(P<0.001),and CD206(P<0.001).Compared with those in the I/R group,the LVEDD(P<0.001),LVESD(P<0.001),myocardial injury score(P<0.001),and the levels of IL-1ß(P<0.001),TNF-α(P=0.010),and CD11c(P<0.001) reduced,while LVEF(P<0.001),LVFS(P<0.001),and the levels of Arg-1(P<0.001),IL-10(P=0.028),and CD206(P=0.022) increased in the hUC-MSC exosomes group.Compared with those in the negative control group,the LVEDD(P<0.001),LVESD(P<0.001),myocardial injury score(P=0.001),and the levels of IL-1ß(P=0.048),TNF-α(P<0.001),and CD11c(P=0.007) reduced,while the LVEF(P<0.001),LVFS(P<0.001),and the levels of Arg-1(P<0.001),IL-10(P=0.001),and CD206(P=0.001) increased in the miR-204 mimic group. Conclusion The hUC-MSC exosomes overexpressing miR-204 can inhibit the polarization of macrophages in the I/R mouse model to M1-type and promote the polarization to M2-type.

Extracellular vesicle-derived microRNA-18b ameliorates preeclampsia by enhancing trophoblast proliferation and migration via Notch2/TIM3/mTORC1 axis.

Preeclampsia (PE), a common disorder of pregnancy, is characterized by insufficient trophoblast migration and inadequate vascular remodelling, such that promotion of trophoblast proliferation might ameliorate PE. In the current study, we sought to study the underlying mechanism of extracellular vesicle (EV)-derived microRNA-18 (miR-18b) in PE. Human umbilical cord mesenchymal stem cells (HUCMSCs) isolated from placental tissues were verified through osteogenic, adipogenic and chondrogenic differentiation assays. Bioinformatics analyses and dual-luciferase reporter gene assay were adopted to confirm the targeting relationship between miR-18b and Notch2. The functional roles of EV-derived miR-18b and Notch2 in trophoblasts were determined using loss- and gain-of-function experiments, and trophoblast proliferation and migration were assayed using CCK-8 and Transwell tests. In vivo experiments were conducted to determine the effect of EV-derived miR-18b, Notch2 and TIM3/mTORC1 in a rat model of PE, with monitoring of blood pressure and urine proteinuria. TUNEL staining was conducted to observe the cell apoptosis of placental tissues of PE rats. We found down-regulated miR-18b expression, and elevated Notch2, TIM3 and mTORC1 levels in the placental tissues of PE patients compared with normal placenta. miR-18b was delivered to trophoblasts and targeted Notch2 and negatively its expression, whereas Notch2 positively mediated the expression of TIM3/mTORC1. EV-derived miR-18b or Notch2 down-regulation enhanced trophoblast proliferation and migration in vitro and decreased blood pressure and 24 hours urinary protein in PE rats by deactivating the TIM3/mTORC1 axis in vivo. In summary, EV-derived miR-18b promoted trophoblast proliferation and migration via down-regulation of Notch2-dependent TIM3/mTORC1.

Biphasic Postnatal Umbilical Cord Shortening.

INTRODUCTION: Variations in postnatal length of refrigerated, unfixed umbilical cords were studied over time to elucidate natural changes and times of stability. METHODS: Length was measured in 132 cords following severance, repeated at varying timed intervals and studied by analysis of variance and regression analysis. RESULTS: Data show immediate rapid initial phase shortening (mean 4.2+/-3.9 cm SD); an interval of lengthening; stable length at hours 3-4 following severance, a slower second phase shortening (mean 1.5+/-0.7 cm SD) beginning at 5 hours and peaking at 12 hours; and gradual lengthening to stable length after 23 hours. Overall, there was a significant net mean decrease of 3.49+/-2.29 cm SD. Shortening was greatest for intact long cord segments (p=0.0001), as much as 11 cm. Two highly significant models for predicting umbilical cord length at delivery (OL) were determined using the post-delivery lengths (Length) measured at different times following delivery (Hours), as follows:At ≤ 3 hours following delivery: OL=1.02xLength cm+1.11xHoursAt >3 hours following delivery: OL=1.07xLength+0.44xHours-0.01x(Hours)2. CONCLUSION: Cord lengths stabilized between hours 3-4 and after 23 hours following severance. Phase one shortening resembles vasoconstriction; phase two resembles rigor mortis. The models allow prediction of the original umbilical cord length at delivery, regardless of the time of measurement.

Heterotopic Liver Nodule Compressing a Two-Vessel Umbilical Cord: An Unusual Cause of Intrauterine Fetal Demise.

Heterotopic liver tissue in the umbilical cord is rare, and the outcome is quite unpredictable based on the few reported cases. We present a case of heterotopic liver nodule in the umbilical cord of a midtrimester fetus who died in utero. Although such association has only been reported once, heterotopic nodular tissue in the umbilical cord must be regarded as a potential cause of fetal demise by a mechanism analogous to the more common umbilical cord abnormalities resulting in umbilical vessel compromise.

Fetal Vascular Malperfusion Due To Long and Hypercoiled Umbilical Cords Resulting in Recurrent Second Trimester Pregnancy Loss: A Case Series and Literature Review.

BACKGROUND: Intrauterine fetal demise due to fetal vascular malperfusion in mid-gestation is a rare occurrence. Abnormally long and hypercoiled umbilical cords are associated with an increased risk of umbilical cord blood flow restriction, which in turn can result in adverse perinatal and maternal outcomes. The factors that regulate umbilical cord development, specifically umbilical cord length and coiling, are poorly understood. METHODS: Maternal history, along with fetal and placental findings (post-mortem, pathological, and molecular), were reviewed for a series of 3 consecutive pregnancies that ended in second trimester intrauterine fetal demise. RESULTS: All 3 umbilical cords were exceptionally long and hypercoiled, and all placentas showed evidence of high-grade fetal vascular malperfusion. At fetopsy, all 3 fetuses were developmentally normal for gestational age and lacked congenital anomalies. Maternal medical history and antenatal testing (including an extensive work-up for maternal hypercoagulability syndromes) were normal and/or noncontributory. CONCLUSION: Although excessively long and hypercoiled cords are generally thought of as sporadic, nongenetic events, rare examples of recurrent intrauterine fetal demise secondary to such exist have been reported. This intrafamilial clustering of a rare event is suggestive that at least a subset of hypercoiled, long umbilical cords may have an underlying genetic etiology.

Bradycardia-to-delivery interval and fetal outcomes in umbilical cord prolapse.

INTRODUCTION: Umbilical cord prolapse is a major obstetric emergency associated with significant perinatal complications. However, there is no consensus on the optimal decision-to-delivery interval, as many previous studies have shown poor correlation between the interval and umbilical cord arterial blood gas or perinatal outcomes. We aim to investigate whether bradycardia-to-delivery or decision-to-delivery interval was related to poor cord arterial pH or adverse perinatal outcome in umbilical cord prolapse. MATERIAL AND METHODS: This was a retrospective study conducted at a university tertiary obstetric unit in Hong Kong. All women with singleton pregnancy complicated by cord prolapse during labor between 1995 and 2018 were included. Women were categorized into three groups. Group 1: persistent bradycardia; Group 2: any type of decelerations without bradycardia; and Group 3: normal fetal heart rate. The main outcome was cord arterial blood gas results of the newborns in different groups. Maternal demographic data and perinatal outcomes were reviewed. Correlation analysis between cord arterial blood gas result and time intervals including bradycardia-to-delivery, deceleration-to-delivery, and decision-to-delivery were performed for the different groups with Spearman test. RESULTS: There were 34, 30, and 50 women in Groups 1, 2, and 3, respectively. Cord arterial pH and base excess did not correlate with decision-to-delivery interval in any of the groups, but they were inversely correlated with bradycardia-to-delivery interval in Group 1 (Spearman's ρ = -.349; P = .043 and Spearman's ρ = -.558; P = .001, respectively). The cord arterial pH drops at 0.009 per minute with bradycardia-to-delivery interval in Group 1 (95% CI 0.0180-0.0003). The risk of significant acidosis (pH < 7) was 80% when bradycardia-to-delivery interval was >20 minutes, and 17.2% when the interval was <20 minutes. CONCLUSIONS: There is significant correlation between bradycardia-to-delivery interval and cord arterial pH in umbilical cord prolapse with fetal bradycardia but not in cases with decelerations or normal heart rate. The drop of cord arterial pH is rapid and urgent delivery is essential in such situations.

Labor dystocia and risk of histological chorioamnionitis and funisitis: a study from a single tertiary referral center.

BACKGROUND: Intrauterine inflammation affects short- and long-term neonatal outcomes. Histological chorioamnionitis and funisitis are acute inflammatory responses in the fetal membranes and umbilical cord, respectively. Although labor dystocia includes a potential risk of intrauterine inflammation, the risk of histological chorioamnionitis and funisitis of labor dystocia has not been evaluated yet. This study aimed to examine the association between labor dystocia and risk of histological chorioamnionitis and funisitis. METHODS: In this retrospective cohort study, the cases who underwent histopathological examinations of the placenta and umbilical cord at Fukushima Medical University Hospital, Japan, between 2015 and 2020, were included. From the dataset, the pathological findings of the patients with labor dystocia and spontaneous preterm birth were reviewed. Based on the location of leukocytes, the inflammation in the placenta (histological chorioamnionitis) and umbilical cord (funisitis) was staged as 0-3. Multiple logistic regression analysis was performed to evaluate the risk of histological chorioamnionitis, histological chorioamnionitis stage ≥2, funisitis, and funisitis stage ≥2. RESULT: Of 317 women who met the study criteria, 83 and 144 women had labor dystocia and spontaneous preterm birth, respectively, and 90 women were included as controls. Labor dystocia was a risk factor for histological chorioamnionitis (adjusted odds ratio, 6.3; 95% confidential interval, 1.9-20.5), histological chorioamnionitis stage ≥2 (adjusted odds ratio, 6.0; 95% confidence interval, 1.7-21.8), funisitis (adjusted odds ratio, 15.4; 95% confidence interval, 2.3-101.3), and funisitis stage ≥2 (adjusted odds ratio, 18.5; 95% confidence interval, 2.5-134.0). Spontaneous preterm birth was also a risk factor for histological chorioamnionitis (adjusted odds ratio, 3.7; 95% confidence interval, 1.7-7.8), histological chorioamnionitis stage ≥2 (adjusted odds ratio, 3.0; 95% confidence interval, 1.2-7.9), and funisitis (adjusted odds ratio, 6.6; 95% confidence interval, 1.4-30.6). However, the adjusted odds ratio was smaller in spontaneous preterm births than in labor dystocia. CONCLUSION: Labor dystocia is a risk factor for severe histological chorioamnionitis and funisitis. Further studies are required to evaluate the effects of histological chorioamnionitis and funisitis on long-term neonatal outcomes.