Search

We describe two cases of umbilical cord (UC) angiomyxoma diagnosed prenatally by sonography in the second trimester of pregnancy. In both cases, a complex mass was detected at the placental insertion site, characterized by an echoic nodule surrounding the umbilical vessels and distal edematous Wharton's jelly. Follow‐up scans showed that the mass grew mainly at the expense of its edematous component, with normal uteroplacental Dopplers throughout the remaining of the pregnancy. However, late‐onset fetal growth restriction complicated the progress of pregnancy, requiring delivery by Cesarean section at 37 weeks' gestation in both cases. Neonatal courses were unremarkable. An extensive review of the English literature was also performed, collecting 45 similar cases including ours. Our experience as well as the review of the literature confirms that UC angiomyxoma is an uncommon, sporadic condition that is usually detected incidentally during prenatal sonography and presents as an isolated finding. Nevertheless, it represents a high‐risk condition for pregnancy complications including prematurity, fetal growth restriction, and fetal demise. [ABSTRACT FROM AUTHOR]

The placenta links feto‐maternal circulation for exchanges of nutrients, gases, and metabolic wastes between the fetus and mother, being essential for pregnancy process and maintenance. The allantois and mesodermal components of amnion, chorion, and yolk sac are derived from extraembryonic mesoderm (Ex‐Mes), however, the mechanisms contributing to distinct components of the placenta and regulation the interactions between allantois and epithelium during chorioallantoic fusion and labyrinth formation remains unclear. Isl1 is expressed in progenitors of the Ex‐Mes and allantois the Isl1 mut mouse line is analyzed to investigate contribution of Isl1+ Ex‐Mes / allantoic progenitors to cells of the allantois and placenta. This study shows that Isl1 identifies the Ex‐Mes progenitors for endothelial and vascular smooth muscle cells, and most of the mesenchymal cells of the placenta and umbilical cord. Deletion of Isl1 causes defects in allantois growth, chorioallantoic fusion, and placenta vessel morphogenesis. RNA‐seq and CUT&Tag analyses revealed that Isl1 promotes allantoic endothelial, inhibits mesenchymal cell differentiation, and allantoic signals regulated by Isl1 mediating the inductive interactions between the allantois and chorion critical for chorionic epithelium differentiation, villous formation, and labyrinth angiogenesis. This study above reveals that Isl1 plays roles in regulating multiple genetic and epigenetic pathways of vascular morphogenesis, provides the insight into the mechanisms for placental formation, highlighting the necessity of Isl1 for placenta formation/pregnant maintenance. [ABSTRACT FROM AUTHOR]

Tissue engineering has demonstrated its efficacy in promoting tissue regeneration, and extensive research has explored its application in rotator cuff (RC) tears. However, there remains a paucity of research translating from bench to clinic. A key challenge in RC repair is the healing of tendon–bone interface (TBI), for which bioactive materials suitable for interface repair are still lacking. The umbilical cord (UC), which serves as a vital repository of bioactive components in nature, is emerging as an important source of tissue engineering materials. A minimally manipulated approach is used to fabricate UC scaffolds that retain a wealth of bioactive components and cytokines. The scaffold demonstrates the ability to modulate the TBI healing microenvironment by facilitating cell proliferation, migration, suppressing inflammation, and inducing chondrogenic differentiation. This foundation sets the stage for in vivo validation and clinical translation. Following implantation of UC scaffolds in the canine model, comprehensive assessments, including MRI and histological analysis confirm their efficacy in inducing TBI reconstruction. Encouraging short‐term clinical results further suggest the ability of UC scaffolds to effectively enhance RC repair. This investigation explores the mechanisms underlying the promotion of TBI repair by UC scaffolds, providing key insights for clinical application and translational research. [ABSTRACT FROM AUTHOR]

Knot(s) of the umbilical cord have received emphasis because the clinical assessments and sonographic literature show a crucial role in fetal outcomes. The true umbilical cord knot could be a knot in a singleton pregnancy or an entanglement of two umbilical cords in monoamniotic twins. Clinical manifestations are almost silent, which can raise clinical challenges. They worsen outcomes, and the pathology can be easily missed during prenatal visits because ultrasonographers do not pay attention to the cord during an obstetric ultrasound scan. However, most medical centers now have ultrasound machines that improve fetal assessment. The umbilical cord should be routinely evaluated during a fetal assessment, and suspicion of an umbilical cord knot can be more frequently diagnosed and is detected only incidentally. Clinical outcome is usually good but depends on the knot's characteristics and if it is tight or loose. In this review, we discuss pathophysiology, the theories on formation, the main risk factors, ultrasound signs and findings, different opinions in the management, and features of pregnancy outcomes feature. Synopsis: Umbilical knots impact fetal outcomes. [ABSTRACT FROM AUTHOR]

Introduction: To explore the mechanisms of labor by investigating the autophagy of placental and fetal membranes tissue in normal pregnant women. Methods: Placenta and fetal membranes were collected from women with singleton pregnancies without any medical complications and from women who delivered vaginally (labor‐initiated group; L group) or by caesarean section (labor‐noninitiated group; NL group). Autophagosomes were observed by transmission electron microscopy (TEM). Immunofluorescence and western blotting (WB) were used to detect protein levels of the autophagy markers LC3A and LC3B. TEM, immunohistochemistry (IHC), and WB were used to compare autophagy in different parts of the placenta and fetal membranes in the L and NL groups. The expression of LC3B/LC3A, ROCK1, and ROCK2 in the placenta of nonpregnant and pregnant rats was detected by WB and IHC. Results: TEM and IHC results showed an increase in the number of autophagosomes and autophagic lysosomes in the L group, and WB results indicated an increase in the LC3B/A ratio between the placenta and fetal membranes in the L group. Autophagy was significantly increased on the maternal side of the placenta in the L group, and the level of autophagy became higher near rupture in the fetal membranes and near the point where the umbilical cord joins the placenta in the L group. The LC3B/A ratio increased and ROCK1 and ROCK2 levels decreased in postnatal rats. Discussion: Autophagy can occur in the placenta and fetal membranes and its activity is higher at the onset of labor, suggesting a role in labor. [ABSTRACT FROM AUTHOR]

Small extracellular vesicles (sEVs) secreted by human umbilical cord have therapeutic effects on various degenerative diseases. However, the characteristics and potential functions of human umbilical cord mesenchymal stem cells (huMSCs)‐derived sEVs, especially the role of premature ovarian failure (POF), are poorly understood. Here, we isolated and characterized huMSCs and their sEVs. huMSCs highly expressed CD73, CD90, and CD105. huMSC‐sEVs showed typical exosomal features, highly expressing CD9, TSG101, and CD63. It was shown that huMSC‐sEVs could be taken up by granulosa cells (GCs) and damaged ovarian tissue, which increased the levels of hormone secretion and reduced GCs apoptosis. We further confirmed that the levels of follicle‐stimulating hormone in rat serum decreased dramatically, while the levels of estrogen (E2）and anti‐mullerian hormone (AMH) increased significantly with the treatment of huMSC‐sEVs. Meanwhile, huMSC‐sEVs treatment greatly reduced cell apoptosis and autophagy, while increased the phosphorylation levels of p‐PI3K and p‐Akt. Therefore, treatment with huMSC‐sEVs significantly inhibited GCs apoptosis, improved ovarian morphology, promoted follicular development, inhibited follicular over‐atresia, and improved ovarian reserve capacity in POF rats. Our study verified that activation of PI3K/Akt signaling pathway and regulation of cellular autophagy, thus reducing GCs death, are the mechanisms by which huMSC‐sEVs restore ovarian tissue function. [ABSTRACT FROM AUTHOR]

Oral mucositis (OM) is a severe side effect of anti‐cancer therapy, with limited available treatments. Mesenchymal stem cells (MSCs) and their secreted extracellular vesicles (EVs) have demonstrated effective protection against OM. However, the underlying mechanism remains elusive. In the current study, we purified EVs secreted by human umbilical cord MSCs (hUC‐MSC‐EVs) and investigated their role in lipopolysaccharide (LPS)‐induced human oral keratinocytes (HOKs). We observed that treatment with hUC‐MSC‐EVs significantly reduced the inflammatory response of HOKs to LPS induction. Through small RNA‐seq using miRNAs extracted from hUC‐MSC‐EVs, we identified hsa‐let‐7e‐5p as one of the most highly expressed miRNAs. Bioinformatic analysis data indicated that hsa‐let‐7e‐5p may inhibit the NF‐κB signalling pathway by targeting TAB2. Overexpression of the hsa‐let‐7e‐5p inhibitor significantly attenuated the anti‐inflammatory effect of hUC‐MSC‐EVs in LPS‐induced HOKs, which could be reversed by the knockdown of TAB2. In addition, we administered hUC‐MSC‐EVs in a hamster model for OM and observed that these EVs alleviated OM phenotypes. Taken together, our observations suggest that hsa‐let‐7e‐5p in hUC‐MSC‐EVs could protect the oral mucosa from OM by repressing TAB2 expression. [ABSTRACT FROM AUTHOR]

Objective Methods Results Conclusion To compare the levels of oxidative stress markers in the umbilical cord blood between pregnant women diagnosed with iron deficiency anemia (IDA) and low‐risk controls.The sample consisted of 131 patients, including 55 pregnant women with IDA and 76 controls with similar demographic characteristics. Participants were selected from patients delivered at ≥37 weeks. We compared the two groups in terms of the native thiol, total thiol, disulfide, and ischemia‐modified albumin (IMA) levels measured in pregnant women's umbilical cord venous blood.The native thiol and total thiol values were statistically significantly lower in the anemia group, and the disulfide and IMA values were statistically significantly higher in the IDA group (P < 0.001). Perinatal outcomes were similar between the groups.In the present study, pregnant women with IDA had lower native and total thiol values and higher disulfide and IMA values in umbilical cord blood. Iron deficiency anemia in pregnancy may be a potential cause of increased oxidative stress. [ABSTRACT FROM AUTHOR]

A 35‐year‐old woman (gravida 1, para 0) was admitted to our hospital at 28 weeks' gestation with vaginal bleeding from placenta previa. Severe fetal bradycardia was observed during fetal heart rate monitoring. Ultrasonography showed widely dilated veins on the fetal surface of the placenta and an extraordinarily low umbilical artery peak systolic velocity in the Doppler study. Umbilical cord torsion was suspected. On the subsequent day, we performed a cesarean section due to worsening fetal heart rate patterns. Umbilical artery blood gas analysis indicated severe acidemia (pH 7.063), and umbilical cord torsion was confirmed at the placental cord insertion site. Diagnosing UCT prenatally is challenging; however, it can be suspected by scanning for the widely dilated veins on the fetal placental surface, termed as the “Sunset Sign,” an abnormally low umbilical artery peak systolic velocity, and other fetal Doppler abnormalities. [ABSTRACT FROM AUTHOR]

The cells presented in this work are not classified as cells that make up the immune system. They, however, present functions and molecules, which are characteristic of immune cells. These characteristic functions are, for example, sensing threat, performing phagocytosis, presentation of foreign antigens, cytokine release or enhancing immune memory. The enlisted immune response mechanisms are carried out by the possession of molecules such as Toll‐like receptors, receptors for the Fc fragment of IgG, major histocompatibility complex class II molecules, costimulatory CD80/CD86 proteins and molecules needed for NLRP3 (NOD‐like family pyrin domain containing 3) inflammasome activation. Thanks to these properties, the described nonimmune cells play an important role in the local immune response and support of the entire body in the fight against pathogens. They constitute the first line of defense of tissues and organs against pathogens and molecules recognized as harmful. The cells described in this article are particularly important in immunologically privileged places (e.g. the Bowman's capsule in the kidney), where "typical" immune cells normally do not have access. In this paper, we present immune‐like functions and molecule suites of resident kidney cells (podocytes and mesangial cells), cochlear resident cells, fibrocytes and fibroblasts, as well as some stem cells (mesenchymal stem cells and umbilical cord Wharton's jelly–derived cells). [ABSTRACT FROM AUTHOR]

A 27‐year‐old multiparous woman conceived her fetus naturally. Early second‐trimester ultrasound showed short extremities with systemic subcutaneous edema. The pregnancy was artificially terminated at 19 weeks of gestation because of the abnormalities based on the parents' wishes. The parents desired whole‐exome sequencing to detect a causative gene using the umbilical cord and the parents' saliva. Compound heterozygous variants (NC_000003.11(NM_052989.3):c.230 T > G/NC_000003.11(NM_052985.4):c.1178A > T) were identified. We described a fetus with a novel compound heterozygous variant in IFT122. The phenotype of this case was severer than of other types of cranioectodermal dysplasia. [ABSTRACT FROM AUTHOR]

Platycodi radix is a widely used herbal medicine that contains numerous phytochemicals beneficial to health. The health and biological benefits of P. radix have been found across various diseases. The utilization of umbilical cord stromal stem cells, derived from Wharton's jelly of the human umbilical cord, has emerged as a promising approach for treating degenerative diseases. Nevertheless, growing evidence indicates that the function of stem cells declines with age, thereby limiting their regenerative capacity. The primary objective in this study is to investigate the beneficial effects of P. radix in senescent stem cells. We conducted experiments to showcase that diminished levels of Lamin B1 and Sox‐2, along with an elevation in p21, which serve as indicative markers for the senescent stem cells. Our findings revealed the loss of Lamin B1 and Sox‐2, coupled with an increase in p21, in umbilical cord stromal stem cells subjected to a low‐dose (0.1 μM) doxorubicin (Dox) stimulation. However, P. radix restored the Dox‐damage in the umbilical cord stromal stem cells. P. radix reversed the senescent conditions when the umbilical cord stromal stem cells exposed to Dox‐induced reactive oxygen species (ROS) and mitochondrial membrane potential are significantly changed. In Dox‐challenged aged umbilical cord stromal stem cells, P. radix reduced senescence, increased longevity, prevented mitochondrial dysfunction and ROS and protected against senescence‐associated apoptosis. This study suggests that P. radix might be as a therapeutic and rescue agent for the aging effect in stem cells. Inhibition of cell death, mitochondrial dysfunction and aging‐associated ROS with P. radix provides additional insights into the underlying molecular mechanisms. [ABSTRACT FROM AUTHOR]

Traditional decellularized bioscaffolds possessing intact vascular networks and unique architecture have been extensively studied as conduits for repairing nerve damage. However, they are limited by the absence of electrical conductivity, which is crucial for proper functioning of nervous tissue. This study focuses on investigating decellularized umbilical cord arteries by applying coatings of graphene oxide (GO) and reduced graphene oxide (RGO) to their inner surfaces. This resulted in a homogeneous GO coating that fully covered the internal lumen of the arteries. The results of electrical measurements demonstrated that the conductivity of the scaffolds could be significantly enhanced by incorporating RGO and GO conductive sheets. At a low frequency of 0.1 Hz, the electrical resistance level of the coated scaffolds decreased by 99.8% with RGO and 98.21% with GO, compared with uncoated scaffolds. Additionally, the mechanical properties of the arteries improved by 24.69% with GO and 32.9% with RGO after the decellularization process. The GO and RGO coatings did not compromise the adhesion of endothelial cells and promoted cell growth. The cytotoxicity tests revealed that cell survival rate increased over time with RGO, while it decreased with GO, indicating the time‐dependent effect on the cytotoxicity of GO and RGO. Blood compatibility evaluations showed that graphene nanomaterials did not induce hemolysis but exhibited some tendency toward blood coagulation. [ABSTRACT FROM AUTHOR]

Liver ischemia‐reperfusion injury (IRI) is an important factor affecting the prognosis of liver transplantation, and extended criteria donors (e.g., steatosis donor livers) are considered to be more sensitive to ischemia‐reperfusion injury in liver transplantation. Currently, the application of human umbilical cord mesenchymal stem cells (hMSCs) has great promise in the treatment of various injuries in the liver. This study aimed to investigate the therapeutic role and mechanism of hMSCs in fatty liver IRI. After more than 8 weeks of high‐fat chow feeding, we constructed a fatty liver mouse model and established ischemic injury of about 70% of the liver. Six hours after IRI, liver injury was significantly alleviated in hMSCs‐treated mice, and the expression levels of liver enzyme, inflammatory factor TNF‐α, and apoptotic proteins were significantly lower than those of the control group, which were also significant in pathological sections. Transcriptomics analysis showed that IFNγ was significantly upregulated in the hMSCs group. Mechanistically, IFNγ, which activates the MAPK pathway, is a potent agonist that promotes the occurrence of autophagy in hepatocytes to exert a protective function, which was confirmed by in vitro experiments. In summary, hMSCs treatment could slow down IRI in fatty liver by activating autophagy through upregulation of IFNγ, and this effect was partly direct. Significance statement: This study demonstrated the important therapeutic role of human umbilical cord mesenchymal stem cells (hMSCs) in fatty liver ischemia‐reperfusion injury (IRI) and elaborated the mechanism of IFNγ in activating autophagy and thus playing a protective role, which is of positive significance for the study of functional protection and enhancement of transplanted donor liver. [ABSTRACT FROM AUTHOR]

Background/Objectives: Most studies about Papillon–Lefèvre syndrome (PLS) are limited to case reports and patients of the same nationality. This study aimed to determine the self‐reported prevalence of signs, symptoms and treatment effectiveness in PLS patients from five Latin American countries. Methods: An online survey was conducted among adult and paediatric patients from Mexico, Argentina, Colombia and Brazil. Data were collected using multiple‐choice, open‐ended and image‐chooser questions on demographics, signs and symptoms, perceived treatment effectiveness and quality of life. Results: Seventeen patients (10 males and 7 females) aged 4–47 years were surveyed. All had palmoplantar hyperkeratosis. Other affected sites were the feet and hand dorsum (82.35%), Achilles tendon (88.24%), forearms (58.82%), legs (29.41%) and glutes (23.53%). They frequently presented hyperhidrosis and nail pitting. Four had a history of delayed umbilical cord separation. All used topical treatments, with moderate effectiveness; half used oral retinoids, perceived as highly effective. Most reported decreased quality of life and walking difficulties. Conclusions: The study's results align with prior research on PLS, but reveal new insights, including the impact on patients' quality of life and a history of delayed umbilical cord separation. These findings warrant consideration in future research and patient care. [ABSTRACT FROM AUTHOR]

Aims: The aim of this study is to measure staff compliance with the local umbilical cord lactate (UCL) sampling guideline and investigate the quality of paired UCG samples at a tertiary maternity unit. Methods: We performed a retrospective consecutive sampling of 100 babies delivered via emergency caesarean section and 50 babies with each of all other guideline‐based indications for UCL sampling born on and before 31 December 2021. Data were extracted from physical and electronic records. Compliance with guideline‐based indications for UCL at birth was measured. The proportion of valid UCG samples was calculated. Samples were considered invalid under the following cases: (i) inadvertently collecting from the same vessel, (ii) switching arterial and venous samples, (iii) collecting from only one vessel or (iv) committing errors during sample collection and handling. Results: Of the samples collected at birth from 321 babies, 280 (87%) had UCL. Small for gestational age and concerns about fetal well‐being in labour were indications associated with poorer compliance, 66% and 78%, respectively. About 99 (44%) babies of 226 babies with UCG performed had valid UCG samples. The most common reasons for invalid samples were collection and handling errors (22%) and inadvertent collection from the same vessel (15%). Conclusions: Generally, compliance with the guidelines is good. However, invalid UCG samples were more frequent than expected. [ABSTRACT FROM AUTHOR]

To investigate the role and mechanism of FBLN1 in the osteogenic differentiation and bone regeneration by using umbilical cord mesenchymal stem cells (WJCMSCs). We found that FBLN1 promoted osteogenic differentiation of WJCMSCs and WJCMSC‐mediated bone regeneration. It was showed that there was an m6A methylation site in 3′UTR of FBLN1 mRNA, and the mutation of the m6A site enhanced the stability of FBLN1 mRNA, subsequently fostering the FBLN1 enhanced osteogenic differentiation of WJCMSCs. YTHDF2 was identified as capable of recognizing and binding to the m6A site, consequently inducing FBLN1 instability and repressed the osteogenic differentiation of WJCMSCs. Meanwhile, miR‐615‐3p negatively regulated FBLN1 by binding FBLN1 3′UTR and inhibited the osteogenic differentiation of WJCMSCs and WJCMSC‐mediated bone regeneration. Then, we discovered miR‐615‐3p was found to regulate the functions of FBLN1 facilitated by YTHDF2 through an m6A‐miRNA regulation mechanism. We demonstrated that FBLN1 is critical for regulating the osteogenic differentiation potentials of WJCMSCs and have identified that miR615‐3p mediated the decay of FBLN1 mRNA which facilitated by m6A reading protein YTHDF2. This provided a novel m6A‐miRNA epigenetic regulatory pattern for MSC regulation and bone regeneration. [ABSTRACT FROM AUTHOR]

Objective: To consider the classical use of "pH < 7.0 and/or a base deficiency ≥12 mmol/L" as markers of the risk of neonatal hypoxic–ischemic encephalopathy (HIE), recalling various criticisms of the use of these markers in favor of that of neonatal eucapnic pH, which appears to be a better marker of this risk. Methods: Fifty‐five cases of acidemia with pH < 7.00 were collected from a cohort from the Nice University Hospital with eight cases of HIE. We compared the receiver operating characteristics curves established from the positive likelihood ratio (+LR) for each case of: umbilical cord artery pH (pHa), neonatal eucapnic pH (pH euc‐n) in isolation (not matched to pHa), and matched pHa to its own pH euc‐n. Results: The areas under the curve (AUC) are identical for pHa and pH euc‐n, but AUC for the matched pair pHa–pH euc‐n appears superior but non‐significant because of the small number in our cohort. However, using the bootstrap method, the partial AUC for a sensitivity greater than 75% indicates the significant superiority (P < 0.01) of the matched pair pHa–pH euc‐n approach. Conclusion: The originality of this study lies in the use of two methodologic approaches: (1) standardized partial analysis of the AUCs of the pHa curve and that of pHa matched to its own pH euc‐n, and (2) bootstrap statistical technique, that allowed us to conclude (P < 0.01) that the combined use of pH measured at the cord coupled with its eucapnic correction is better for diagnosing metabolic acidosis and best predicting the risk of HIE. Synopsis: Neonatal eucapnic pH to predict neonatal hypoxic–ischemic encephalopathy appears to be a better marker of this risk. [ABSTRACT FROM AUTHOR]

Aim: This study evaluated the connection of periodontal status with the leukocyte profiles of maternal peripheral blood (MPB) and umbilical cord blood (UCB). Materials and Methods: Ninety‐nine pregnant females were recruited, and their data were collected via questionnaire and from medical records, including demographics, systemic conditions, complete blood count (CBC) and C‐reaction protein (CRP) level in MPB. Full‐mouth periodontal assessment was performed. CBC and CRP levels in UCB were measured after parturition. Results: All subjects and their neonates were generally healthy. 30.3% of the participants presented with periodontal health condition, whereas 69.7% had different severities of periodontal diseases. The counts/percentages of eosinophils and monocytes in UCB from the subjects with periodontal diseases elevated, and the percentage of neutrophils decreased referencing to that from the counterparts (p < 0.05). There were positive correlations for total leukocyte count, neutrophils and lymphocytes counts/percentages in MPB and UCB among the periodontally healthy subjects (r > 0.4, p < 0.05), but such findings did not exist in those with periodontal diseases. Moreover, periodontal diseases independently accounted for the counts/percentages of neutrophils and eosinophils in UCB after controlling confounders in four testing models (ANCOVA, p < 0.05). Conclusion: Maternal periodontal diseases could to some extent disturb the leukocyte profiles of umbilical cord blood. [ABSTRACT FROM AUTHOR]

This study aimed to describe the gestational and morphological aspects of the fetuses and their respective umbilical cords from two pregnant wild boars (Sus scrofa). Morphological descriptions were provided for 23 fetuses and the gestational ages were estimated through fetal characteristics and formula application. The specimens were fixed in 10% formalin for subsequent macroscopic and microscopic examination. Histological characterization was performed using haematoxylin–eosin (H&E), Masson's trichrome (MT) and Verhöeff's staining techniques. The wild boar fetuses exhibited an estimated gestational age of 55 days (in the larger uterus) and 45 days (in the smaller uterus). They displayed well‐developed features consistent with domestic pig fetuses, except for the presence of five pairs of mammae. Additionally, the umbilical cord consisted of two arteries, one vein, an allantoic duct, and a vitelline duct (the latter two identified only microscopically), located in the juxtafetal, intermediate and juxtaplacental portions. The arteries and veins were comprised of endothelium, smooth muscle and collagen fibres, with no elastic fibres observed in the vessel walls. The allantoic duct was lined with simple cuboidal epithelium, while the vitelline duct featured a simple squamous epithelium. In conclusion, the morphological characteristics observed in the examined structures align with the expected patterns for species of the Suidae family. Furthermore, these findings contribute substantially to the morphological characterization of the wild boar, yielding valuable insights into the fetal morphology and the structure of the umbilical cord. [ABSTRACT FROM AUTHOR]

The regeneration of osteochondral lesions by tissue engineering techniques is challenging due to the lack of physicochemical characteristics and dual‐lineage (osteogenesis and chondrogenesis). A scaffold with better mechanical properties and dual lineage capability is required for the regeneration of osteochondral defects. In this study, a hydrogel prepared from decellularized human umbilical cord tissue was developed and evaluated for osteochondral regeneration. Mesenchymal stem cells (MSCs) isolated from the umbilical cord were seeded with hydrogel for 28 days, and cell‐hydrogel composites were cultured in basal and osteogenic media. Alizarin red staining, quantitative polymerase chain reaction, and immunofluorescent staining were used to confirm that the hydrogel was biocompatible and capable of inducing osteogenic differentiation in umbilical cord‐derived MSCs. The findings demonstrate that human MSCs differentiated into an osteogenic lineage following 28 days of cultivation in basal and osteoinductive media. The expression was higher in the cell‐hydrogel composites cultured in osteoinductive media, as evidenced by increased levels of messenger RNA and protein expression of osteogenic markers as compared to basal media cultured cell‐hydrogel composites. Additionally, calcium deposits were also observed, which provide additional evidence of osteogenic differentiation. The findings demonstrate that the hydrogel is biocompatible with MSCs and possesses osteoinductive capability in vitro. It may be potentially useful for osteochondral regeneration. [ABSTRACT FROM AUTHOR]

Objective: The goal of this work was to develop robust techniques for the processing and identification of SUA using artificial intelligence (AI) image classification models. Methods: Ultrasound images obtained retrospectively were analyzed for blinding, text removal, AI training, and image prediction. After developing and testing text removal methods, a small n‐size study (40 images) using fastai/PyTorch to classify umbilical cord images. This data set was expanded to 286 lateral‐CFI images that were used to compare: different neural network performance, diagnostic value, and model predictions. Results: AI‐Optical Character Recognition method was superior in its ability to remove text from images. The small n‐size mixed single umbilical artery determination data set was tested with a pretrained ResNet34 neural network and obtained and error rate average of 0.083 (n = 3). The expanded data set was then tested with several AI models. The majority of the tested networks were able to obtain an average error rate of <0.15 with minimal modifications. The ResNet34‐default performed the best with: an image‐classification error rate of 0.0175, sensitivity of 1.00, specificity of 0.97, and ability to correctly infer classification. Conclusion: This work provides a robust framework for ultrasound image AI classifications. AI could successfully classify umbilical cord types of ultrasound image study with excellent diagnostic value. Together this study provides a reproducible framework to develop AI‐specific ultrasound classification of umbilical cord or other diagnoses to be used in conjunction with physicians for optimal patient care. [ABSTRACT FROM AUTHOR]

Gastroschisis (GS) and omphalocele (OC) are two prevalent congenital abdominal wall defects. This narrative review explores their global prevalence and the potential preventive role of maternal folic acid supplementation. The image includes clinical photographs (A, GS; C, OC) and schematic representations of inferior axial sections (B, GS; D, OC), illustrating key anatomical distinctions. Arrow indicates the abdominal wall membrane; I, intestine; K, kidney; UC, umbilical cord. [ABSTRACT FROM AUTHOR]

Umbilical cord cysts (UCCs)—cysts located in the umbilical cord that are derived from an abnormal embryonic development process—are typically an incidental discovery during prenatal ultrasound. It can be described as either a pseudocyst or a true UCC, which results from focal edema or degeneration of Wharton jelly or the remnants of embryonic development, respectively. Due to the relative rarity of the UCC, the clinical guidance of UCCs is not yet available. Herein, the aim of this paper is to discuss the classification, diagnosis, prognosis, and clinical management of UCCs through a literature review, in order to improve the understanding of UCCs among clinical obstetricians and pediatricians. Synopsis: The classification, diagnosis, prognosis, and clinical management of UCC. [ABSTRACT FROM AUTHOR]

Objective: To characterize obstetric outcomes and the association with umbilical cord (UC) complications among women complaining of reduced fetal movements (RFMs). Methods: This retrospective cohort compared women with a perception of RFMs within 2 weeks prior to delivery with women who reported no changes in fetal movements in terms of maternal characteristics and neonatal outcomes. A primary outcome of UC complications at delivery was defined. Multivariable regression analysis was performed to identify independent associations with RFMs and UC complications. Results: In all, 46 103 women were included, 2591 (5.6%) of whom reported RFMs and 43 512 (94.4%) in the control group. Compared with controls, the RFM group was more likely to be nulliparous (42.6% vs 32.2%, P < 0.001), smokers (6.4% vs 5.4%, P = 0.029), or obese (body mass index >30) (16.4% vs 11.6%, P < 0.001). They were also more likely to have an anterior placenta (56.2% vs 51.8%, P < 0.001) and poly/oligohydramnios (0.7% vs 0.4%, P = 0.015 and 3.6% vs 2.1%, P < 0.001, respectively). Induction of labor was more common in the RFM group (33.9% vs 19.7%, P < 0.001), as well as meconium (16.8% vs 15.0%, P = 0.026) and vacuum extractions (10.1% vs 8.0%, P < 0.001). Higher rates of stillbirth and the severe composite neonatal outcome were observed in the RFM group (1.5% vs 0.2%, P < 0.001 and 0.6% vs 0.3%, P = 0.010, respectively). The RFM group was characterized by higher rates of triple nuchal cord (P = 0.015), UC around body or neck (32.2% vs 29.6%, P = 0.010), and true knot (2.3% vs 1.4%, P = 0.002). Multivariable logistic regression found RFMs to be independently associated with triple nuchal cord and with a true cord knot. A sub‐analysis including only cases of stillbirth (n = 127) revealed even higher rates of UC complications: 7% of all stillbirths presented with a true cord knot (20% true knots were found in stillbirths preceded by RFMs vs 6.1% in stillbirth cases without RFMs). Additionally, 33.8% of all stillbirths presented with nuchal cord (40% preceded by RFMs vs 33.3% without RFMs). Conclusions: RFMs are associated with increased risk of UC complications observed at delivery, as well as increased risk of stillbirth and neonatal adverse outcomes. Synopsis: Reduced fetal movements are associated with umbilical cord complications at delivery such as nuchal cord, triple nuchal cord, or a true knot. [ABSTRACT FROM AUTHOR]

Background: Inflammation and oxidative stress are considered crucial to the pathogenesis of depression. Rat models of depression can be created by combined treatments of chronic unpredictable mild stress (CUMS) and lipopolysaccharide (LPS). Behaviors associated with depression could be improved by treatment with mesenchymal stem cells (MSCs) owing to immunomodulatory functions of the cells. Therapeutic potentials of the MSCs to reverse pro‐inflammatory cytokines, proteins, and metabolites were identified by transcriptomic, proteomic, and metabolomic analysis, respectively. Methods: A depression model was established in male SD rats by 2 weeks of CUMS combined with LPS. The models were verified by behavioral tests, namely SPT, OFT, EPM, and qRT‐PCR for pro‐inflammatory cytokines. Such depressed rats were administered human umbilical cord MSCs (hUC‐MSCs) via the tail vein once a week for 2 and 4 weeks. The homing capacity was confirmed by detection of the fluorescent dye on day 7 after the hUC‐MSCs were labeled with CM‐Dil and administered. The expression of GFAP in astrocytes serves as a biomarker of CNS disorders and IBA1 in microglia serves as a marker of microglia activation were detected by immunohistochemistry at 2 and 4 weeks after final administration of hUC‐MSCs. At the same time, transcriptomics of rat hippocampal tissue, proteomic and metabolomic analysis of the serum from the normal, depressed, and treated rats were also compared. Results: Reliable models of rat depression were successfully induced by treatments of CUMS combined with LPS. Rat depression behaviors, pro‐inflammatory cytokines, and morphological disorders of the hippocampus associated with depression were reversed in 4 weeks by hUC‐MSC treatment. hUC‐MSCs could reach the hippocampus CA1 region through the blood circulation on day 7 after administration owing to the disruption of blood brain barrier (BBB) by microglial activation from depression. Differentiations of whole‐genome expression, protein, and metabolite profiles between the normal and depression‐modeled rats, which were analyzed by transcriptomic, proteomics, and metabolomics, further verified the high association with depression behaviors. Conclusions: Rat depression can be reversed or recovered by treatment with hUC‐MSCs. [ABSTRACT FROM AUTHOR]

Aims: We investigated whether human umbilical cord mesenchymal stem cell (hUC‐MSC)‐derived exosomes bear therapeutic potential against lipopolysaccharide (LPS)‐induced neuroinflammation. Methods: Exosomes were isolated from hUC‐MSC supernatant by ultra‐high‐speed centrifugation and characterized by transmission electron microscopy and western blotting. Inflammatory responses were induced by LPS in BV‐2 cells, primary microglial cultures, and C57BL/6J mice. H2O2 was also used to induce inflammation and oxidative stress in BV‐2 cells. The effects of hUC‐MSC‐derived exosomes on inflammatory cytokine expression, oxidative stress, and microglia polarization were studied by immunofluorescence and western blotting. Results: Treatment with hUC‐MSC‐derived exosomes significantly decreased the LPS‐ or H2O2‐induced oxidative stress and expression of pro‐inflammatory cytokines (IL‐6 and TNF‐α) in vitro, while promoting an anti‐inflammatory (classical M2) phenotype in an LPS‐treated mouse model. Mechanistically, the exosomes increased the NRF2 levels and inhibited the LPS‐induced NF‐κB p65 phosphorylation and NLRP3 inflammasome activation. In contrast, the reactive oxygen species scavenger NAC and NF‐κB inhibitor BAY 11–7082 also inhibited the LPS‐induced NLRP3 inflammasome activation and switched to the classical M2 phenotype. Treatment with the NRF2 inhibitor ML385 abolished the anti‐inflammatory and anti‐oxidative effects of the exosomes. Conclusion: hUC‐MSC‐derived exosomes ameliorated LPS/H2O2‐induced neuroinflammation and oxidative stress by inhibiting the microglial NRF2/NF‐κB/NLRP3 signaling pathway. [ABSTRACT FROM AUTHOR]

Introduction: Umbilical cord prolapse (UCP) is a rare but severe obstetric complication in the presence of a rupture of the membranes. Although it is not possible to prevent a spontaneous rupture of the membranes (SROM), it is possible to prevent an amniotomy, which is a commonly used intervention in labor. This study aimed to explore the incidence and risk factors that are associated with UCP in labor when amniotomy is used vs SROM. Material and methods: A retrospective nationwide register study was conducted of all births in Sweden from January 2014 to June 2020 that were included in the Swedish Pregnancy Register (n = 717 336). The main outcome, UCP, was identified in the data by the International Classification of Diseases (ICD‐10) diagnosis code O69.0. Multiple binary logistic regression analysis was used to identify the risk factors. Results: Amniotomy was performed in 230 699 (43.6%) of all pregnancies. A UCP occurred in 293 (0.13%) of these cases. SROM occurred in 298 192 (56.4%) of all cases, of which 352 (0.12%) were complicated by UCP. Risk factors that increased the odds of UCP for both amniotomy and SROM were: higher parity, non‐cephalic presentation and an induction of labor. Greater gestational age reduced the odds of UCP. Risk factors associated with only amniotomy were previous cesarean section and the presence of polyhydramnios. Identified risk factors for UCP in labor with SROM were a higher maternal age and maternal origin outside of the EU. Conclusions: UCP is a rare complication in Sweden. Beyond confirming the previously recognized risk factors, this study found induction of labor and previous cesarean section to be risk factors in labor when amniotomy is used. [ABSTRACT FROM AUTHOR]

Aims: The current evidence demonstrates that mesenchymal stem cells (MSCs) hold therapeutic potential for ischemic stroke. However, it remains unclear how changes in the secretion of MSC cytokines following the overexpression of heme oxygenase‐1 (HO‐1) impact excessive inflammatory activation in a mouse ischemic stroke model. This study investigated this aspect and provided further insights. Methods: The middle cerebral artery occlusion (MCAO) mouse model was established, and subsequent injections of MSC, MSCHO‐1, or PBS solutions of equal volume were administered via the mice's tail vein. Histopathological analysis was conducted on Days 3 and 28 post‐MCAO to observe morphological changes in brain slices. mRNA expression levels of various factors, including IL‐1β, IL‐6, IL‐17, TNF‐α, IL‐1Ra, IL‐4, IL‐10, TGF‐β, were quantified. The effects of MSCHO‐1 treatment on neurons, microglia, and astrocytes were observed using immunofluorescence after transplantation. The polarization direction of macrophages/microglia was also detected using flow cytometry. Results: The results showed that the expression of anti‐inflammatory factors in the MSCHO‐1 group increased while that of pro‐inflammatory factors decreased. Small animal fluorescence studies and immunofluorescence assays showed that the homing function of MSCsHO‐1 was unaffected, leading to a substantial accumulation of MSCsHO‐1 in the cerebral ischemic region within 24 h. Neurons were less damaged, activation and proliferation of microglia were reduced, and polarization of microglia to the M2 type increased after MSCHO‐1 transplantation. Furthermore, after transplantation of MSCsHO‐1, the mortality of mice decreased, and motor function improved significantly. Conclusion: The findings indicate that MSCs overexpressing HO‐1 exhibited significant therapeutic effects against hyper‐inflammatory injury after stroke in mice, ultimately promoting recovery after ischemic stroke. [ABSTRACT FROM AUTHOR]

Aim: Acute kidney injury is a severe disease that is closely associated with substantial morbidity and mortality. The most common cause of AKI is renal ischemia–reperfusion injury. Mesenchymal stem cells (MSCs) have previously been shown to have renoprotective effects. However, extracellular vesicles secreted by MSCs are thought to be the key for the therapeutic effects of MSCs. This study investigated whether small EVs derived from ACE2‐modified human umbilical cord MSCs could alleviate RIRI and explored their underlying molecular mechanisms Methods: A lentivirus carrying an ACE2 overexpression vector was constructed and used to infect MSCs. The small EVs were isolated from MSC‐conditioned medium by ultracentrifugation. HK‐2 cells were cocultured with MSC‐ACE2‐EVs and subjected to hypoxia/reoxygenation injury. MSCs‐ACE2‐EVs were injected into RIRI mice. Biochemical and morphological characteristics were assessed, and the levels of inflammatory‐related factors, oxidative stress products, and apoptosis in HK‐2 cells and kidney tissues were assessed Results: In vitro, MSC‐ACE2‐EVs had stronger anti‐inflammatory, antioxidative stress, and antiapoptotic effects in HK‐2 cells subjected to H/R than MSC‐NC‐EVs. In vivo, MSC‐ACE2‐EVs could target the injured kidney, reduce blood creatinine and urea nitrogen levels, and protect the kidney from I/R, and this effect may have been related to the activation of the Nrf2/HO‐1 signalling pathway Conclusion: Taken together, our results demonstrated the anti‐inflammatory, antioxidative stress, and antiapoptotic effects of MSC‐ACE2‐EVs, which protected against I/R injury in vitro and vivo. MSC‐ACE2‐EVs may be therapeutic agents for RIRI [ABSTRACT FROM AUTHOR]

Objective: We describe transvaginal color Doppler, HDlive, and HDlive Silhouette features of an umbilical cord cyst (UCC) before 11 weeks of gestation. Methods: In this cohort study, 135 transvaginal dating scans were performed at 7 to 10 + 6 weeks of gestation, and 17 UCCs were identified (12.6%). UCC was evaluated using color Doppler, HDlive, and HDlive Silhouette. The clinical characteristics, pregnancy courses, and outcomes were also investigated. Results: UCC location was on the fetal side in six cases, at the free loop in 10 cases, and on the placental side in one case. There were seven single and 10 multiple cysts. Cyst diameters ranged from 3.3 to 11.3 mm (mean, 5.6; standard deviation, ±2.1). Blood flow inside the cyst was noted in three cases (17.6%). HDlive clearly showed the spatial relationships among UCC, the umbilical cord, midgut herniation, yolk sac, and embryo. Location of UCC could be clearly identified with HDlive. HDlive Silhouette showed central cysts inside UCCs in seven cases (41.2%). HDlive Silhouette also clearly demonstrated the sac of midgut herniation in the umbilical cord in 12 cases (70.6%). All UCCs resolved before 15 weeks (mean, 11.1 weeks; standard deviation, ±1.5). All fetuses with UCCs showed good neonatal outcomes. Conclusion: The incidence of UCC was high compared with that in previous reports. Color Doppler, HDlive, and HDlive Silhouette may provide information on the nature and origin of UCCs before 11 weeks of gestation. UCC before 11 weeks of gestation may be a common, transient, and benign finding. Synopsis: An umbilical cord cyst before 11 weeks of gestation is a common, transient, and benign finding in utero. [ABSTRACT FROM AUTHOR]

Objective: To evaluate perinatal effects of umbilical cord entanglement (UCE) of different body parts. Methods: The database of a tertiary medical center was retrospectively searched for women who gave birth to a liveborn singleton newborn in 2014–2018. Those diagnosed postpartum with UCE were matched 1:10 with women who were not and compared for adverse obstetric and neonatal outcomes, overall and by site of entanglement. Results: A total of 14 299 women were evaluated, of whom 1243 were diagnosed with UCE: 78.7% neck, 26% trunk, 6.7% limb. UCE was associated with lower birth weight percentile and higher rate of small for gestational age, but findings were significant only for neck and trunk UCE. On multivariate regression analysis adjusted for maternal age, parity, gestational age at birth, and history of cesarean delivery, UCE was an independent risk factor for nonreassuring fetal heart rate, labor induction, operative vaginal delivery, cesarean delivery, and meconium‐stained amniotic fluid, but not for lower absolute birth weight/birth weight percentile, small for gestational age, low 1‐min Apgar score, or neonatal asphyxia. Conclusion: While fetuses with UCE might be more compromised during labor, they apparently recover shortly after birth. The impact on perinatal outcomes was similar for UCE of the neck and trunk and lower for UCE of the limb. Synopsis: Umbilical cord entanglement, especially of the neck or trunk relative to the limb, may complicate labor and delivery but does not adversely affect neonatal outcomes. [ABSTRACT FROM AUTHOR]

Background: For the unclear pathogenesis of Sjogren's syndrome (SS), further exploration is necessary. Mesenchymal stem cells (MSCs) and derived exosomes (MSCs‐exo) have exhibited promising results in treating SS. Object: This study aimed to investigate the effect and mechanism of human umbilical cord MSCs (UC‐MSCs) on SS. Methods: Nonobese Diabetic (NOD) mouse splenic T cells were co‐cultured with UC‐MSCs and UC‐MSCs‐exo, and interferon‐gamma (IFN‐γ), interleukin (IL)‐6, IL‐10, prostaglandin E2 (PGE2), and transforming growth factor‐β1 (TGF‐β1) levels in the supernatant were assessed by quantitative real‐time polymerase chain reaction and enzyme‐linked immunosorbent assay. Co‐cultured T cells were injected into NOD mice via the tail vein. The inflammatory cell infiltration in the intestine and the submandibular gland was characterized by hematoxylin‐eosin staining. Treg/Th17 homeostasis within the spleen was determined by flow cytometry. Gut microbiota was detected by 16S rRNA sequencing, and the relationship between differential microbiota and Treg/Th17 cytokines was analyzed by the Pearson correlation coefficient. Results: UC‐MSCs, UC‐MSCs‐exo, and NOD mouse splenic T cells were successfully cultured and identified. After T cells were co‐cultured with UC‐MSCs and UC‐MSCs‐exo, both IFN‐γ and IL‐6 were decreased while IL‐10, PGE2, and TGF‐β1 were increased in transcriptional and translational levels. UC‐MSCs and UC‐MSCs‐exo partially restored salivary secretion function, reduced Ro/SSA antibody and α‐Fodrin immunoglobulin A levels, reduced inflammatory cell infiltration in the intestine and submandibular gland, raised proportion of Treg cells, decreased IFN‐γ, IL‐6, IL‐2, IL‐17, lipopolysaccharide, and tumor necrosis factor‐alpha levels, and raised IL‐10, Foxp3, and TGF‐β1 levels by affecting co‐cultured T cells. The intervention of UC‐MSCs and UC‐MSCs‐exo improved intestinal homeostasis in NOD mice by increasing microbiota diversity and richness. Additionally, differential microbiota was significantly associated with Treg/Th17 cytokine levels. Conclusion: Human UC‐MSCs and UC‐MSCs‐exo improved disease characterization of SS in NOD mice through regulation of gut microbiota and Treg/Th17 cellular immunity. [ABSTRACT FROM AUTHOR]

Strontium (Sr) has important functions in bone remodeling. Incorporating strontium‐doped α‐calcium sulfate hemihydrate (SrCSH) into poly(lactic‐co‐glycolic acid) (PLGA) fibrous scaffolds were expected to increase its bio‐activity and provide a potential material for bone tissue engineering. In the present study, Sr‐containing aligned PLGA/SrCSH fibrous scaffolds similar to the architecture of natural bone were prepared via wet spinning. CCK‐8 assay revealed that Sr‐containing scaffolds possessed better bioactivity and supported favorable cell growth effectively. The aligned PLGA/SrCSH fibers exerted a contact effect on cell attachment, inducing regular cell alignment and influencing a series of cell behaviors. Releasing of high concentration Sr from a‐PLGA/SrCSH scaffolds could induce high expression levels of BMP‐2, increase ALP activity and upregulate RUNX‐2 expression, and further promote the expressions of COL‐I and OCN and the maximum mineralization. This study demonstrated that Sr and ordered structure in a‐PLGA/SrCSH fibrous scaffolds could synergistically enhance the osteogenic differentiation of umbilical cord mesenchymal stem cells (UCMSCs) by regulating cell arrangement and expressions of osteogenic genes. [ABSTRACT FROM AUTHOR]

Exosomes derived from human umbilical cord mesenchymal stem cells (hucMSCs) could alleviate Alzheimer's disease (AD) defects. Additionally, engineered exosomes are more effective in treating diseases. In this study, we established an in vitro model of AD by treating SH‐SY5Y cells with Aβ1‐40. We observed that incubation with hucMSC‐derived exosomes effectively protected SH‐S5Y5 cells from Aβ1‐40‐induced damage. Since NEP plays a central role in suppressing AD development, we screened NEP‐targeting miRNAs that are differentially expressed in control and AD patients. We identified miR‐211‐5p as a potent repressor of NEP expression. Exosomes purified from hucMSCs overexpressing miR‐211‐5p inhibitor exhibited significantly greater efficiency than control exosomes in mitigating the injury caused by Aβ1‐40 treatment. However, this enhanced protective effect was nullified by the knockdown of NEP. These observations demonstrate that inhibition of miR‐211‐5p has the potential to improve the efficacy of hucMSC‐derived exosomes in AD treatment by increasing NEP expression. [ABSTRACT FROM AUTHOR]

New Findings: What is the central question of this study?What are the biggest challenges in performing in vitro studies on isolated human umbilical arteries?What is the main finding and its importance?The protocols presented in this study indicate some potential outcomes important for interpretation of the vascular responsivities of human umbilical arteries and could be useful for planning future in vitro studies with human umbilical arteries. Human umbilical artery (HUA) preparations are of particular importance for in vitro studies on isolated blood vessels because their sampling is not risky for the patient, and they can provide the closest possible impression of changes related to the uteroplacental circulation during pre‐eclampsia. Using organ bath techniques, useful experimental protocols are provided for measuring some pathophysiological phenomena in the vascular responses of HUAs. Several vasoconstrictors (serotonin, prostaglandin F and phenylephrine) and vasodilators (acetylcholine and minoxidil) were seleted for determination of their vasoactivity in HUAs. The role of L‐type voltage‐operated calcium channels and different types of potassium channels (KATP, BKCa and KV) were assessed, as was the impact of homocysteine. Serotonin was confirmed to be the most potent vasoconstrictor, while acetylcholine and phenylephrine caused variability in the relaxation and contraction response of HUA, respectively. The observed increase in serotonin‐induced contraction and a decrease in minoxidil‐induced relaxation in the presence of homocysteine suggested its procontractile effect on HUA preparations. Using selective blockers, it was determined that KATP and KV channels participate in the minoxidil‐induced relaxation, while L‐type voltage‐dependent Ca2+ channels play an important role in the serotonin‐induced contraction. The presented protocols reveal some of the methodological challenges related to HUA preparations and indicate potential outcomes in interpreting the vascular effects of the investigated substances, both in physiological conditions and in the homocysteine‐induced pre‐eclampsia model. [ABSTRACT FROM AUTHOR]

Objectives: To use superb microvascular imaging (SMI) to evaluate longitudinally spiral artery (SA) and uterine artery (UtA) vascular adaptation in normal human pregnancy, and to develop reference ranges for use at various gestational ages throughout pregnancy. Methods: The data for this study were obtained from the National Institutes of Health (NIH)‐funded Human Placenta Project. Women aged 18–35 years, with a body mass index < 30 kg/m2, without comorbidities, with a singleton gestation conceived spontaneously, and gestational age at or less than 13 + 6 weeks were eligible for inclusion. The current analysis was restricted to uncomplicated pregnancies carried to term. Exclusion criteria included maternal or neonatal complications, fetal or umbilical cord anomalies, abnormal placental implantation or delivery < 37 weeks. Women who fulfilled the inclusion criteria formed the reference population of the Human Placenta Project study. Each participant underwent eight ultrasound examinations during pregnancy. The pulsatility index (PI) of both the left and right UtA were obtained twice for each artery and the presence or absence of a notch was noted. Using SMI technology, the total number of SA imaged was recorded in a sagittal placental section at the level of cord insertion. The PI and peak systolic velocity (PSV) were also measured in a total of six SA, including two in the central portion of the placenta, two peripherally towards the uterine fundal portion, and two peripherally towards the lower uterine segment. Results: A total of 90 women fulfilled the study criteria. Maternal UtA‐PI decreased throughout the first half of pregnancy from a mean ± SD of 1.39 ± 0.50 at 12–13 weeks' gestation to 0.88 ± 0.24 at 20–21 weeks' gestation. The mean number of SA visualized in a sagittal plane of the placenta increased from 8.83 ± 2.37 in the first trimester to 16.99 ± 3.31 in the late‐third trimester. The mean SA‐PI was 0.57 ± 0.12 in the first trimester and decreased progressively during the second trimester, reaching a nadir of 0.40 ± 0.10 at 24–25 weeks, and remaining constant until the end of pregnancy. SA‐PSV was highest in early pregnancy with a mean of 57.16 ± 14.84 cm/s at 12–13 weeks' gestation, declined to a mean of 49.38 ± 17.88 cm/s at 20–21 weeks' gestation and continued to trend downward for the remainder of pregnancy, reaching a nadir of 34.50 ± 15.08 cm/s at 36–37 weeks' gestation. A statistically significant correlation was noted between SA‐PI and UtA‐PI (r = 0.5633; P < 0.001). Multilevel regression models with natural cubic splines were used to create reference ranges of SA‐PSV and SA‐PI for given gestational ages. Conclusion: From early gestation, we have demonstrated the ability to image and quantify SA blood flow in normal pregnancy, and have developed reference ranges for use at various gestational ages throughout pregnancy. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Objectives: There is a paucity of literature providing evidence‐based guidelines for the management of large placental chorioangioma (≥ 4 cm in diameter). The objectives of this study were to compare outcomes between patients managed expectantly and those undergoing in‐utero intervention and to describe the different in‐utero techniques used for cessation of blood flow to the tumor and the associated outcome. Methods: This was a retrospective cohort study of 34 patients referred for the management of large placental chorioangioma in a single center between January 2011 and December 2022, who were managed expectantly or underwent in‐utero intervention. In‐utero intervention was performed when the fetus developed any signs of impending compromise, including high combined cardiac output (CCO), worsening polyhydramnios or abnormal fetal Doppler velocimetry findings. Interventions included radiofrequency ablation (RFA), interstitial laser ablation (ILA) and single‐port or two‐port fetoscopic laser photocoagulation (FLP). Treatment selection was dependent on the proximity of the tumor to the umbilical cord insertion (UCI) and placental location. The two‐port technique was performed in patients with a chorioangioma with large feeding vessels (≥ 3 mm) located in the posterior placenta, in which one port was used for occlusion using bipolar forceps and the other port was used for laser photocoagulation of the feeding vessels downstream. The single‐port technique was used for chorioangioma with small feeding vessels (< 3 mm) located in the posterior placenta. ILA or RFA was performed in cases with an anterior placenta. Supportive treatments, including amnioreduction and intrauterine transfusion (IUT), were performed for worsening polyhydramnios and suspected fetal anemia based on middle cerebral artery Doppler flow studies, respectively. Comparative statistical analysis between cases undergoing expectant management vs in‐utero intervention was performed. Descriptive details were provided for patients who underwent in‐utero intervention. Results: Thirty‐four cases of large chorioangioma were evaluated, of which 25 (73.5%) were managed expectantly and nine (26.5%) underwent intervention. The frequency of polyhydramnios was significantly higher in the intervention group compared with the expectant‐management group (66.7% vs 8.0%, P < 0.001). The live‐birth rate among expectantly managed cases with large chorioangioma was significantly higher compared with that in cases that underwent in‐utero intervention (96.0% vs 62.5%, P = 0.01). In the intervention group, preoperative CCO was elevated in all cases with available information and preoperative hydrops was present in 33.3% (3/9) of cases. One patient experienced fetal demise following IUT prior to planned FLP. Among the remaining eight patients, four underwent two‐port FLP, two underwent single‐port FLP, one underwent ILA and one underwent both ILA and RFA. All three cases in which hydrops was present at the time of intervention resulted in fetal demise. Conclusions: In‐utero interventions aimed at cessation of blood flow in the feeding vessels are a therapeutic option for the management of cases with large chorioangioma. The two‐port percutaneous technique appears to improve the efficiency of FLP when a large chorioangioma with large feeding vessels is located in the posterior placenta. We propose that in‐utero interventions for large chorioangioma should be initiated prior to the development of fetal hydrops. © 2023 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

To investigate whether human umbilical cord mesenchymal stem cell‐derived exosomes combined with gelatin methacryloyl (GelMA) hydrogel are beneficial in promoting healing of laser‐injured skin wounds in mice. Supernatants of cultured human umbilical cord mesenchymal stem cells (HUC‐MSCs) were collected to obtain human umbilical cord MSC‐derived exosomes (HUC‐MSCs‐Exos), which were combined with GelMA hydrogel complex to treat a mouse fractional laser injury model. The study was divided into PBS group, EX (HUC‐MSCs‐Exos) group, GEL (GelMA hydrogel) group and EX+GEL (HUC‐MSCs‐Exos combined with GelMA hydrogel) group. The healing of laser‐injured skin in each group was observed by gross view and dermatoscopy, and changes in skin structure, angiogenesis and proliferation‐related indexes were observed during the healing process of laser‐injured skin in each group. The results of the animal experiments showed that the EX and GEL groups alone and the EL+EX group exhibited less inflammatory response compared to the PBS group. The EX and GEL groups showed marked tissue proliferation and favourable angiogenesis, which promoted the wound healing well. The GEL+EX group had the most significant promotion of wound healing compared to the PBS group. qPCR results showed that the expression levels of proliferation‐related factors, including KI67 and VEGF and angiogenesis‐related factor CD31, were significantly higher in the GEL+EX group than in the other groups, with a time‐dependent effect. The combination of HUC‐MSCs‐Exos and GelMA hydrogel is beneficial in reducing the early inflammatory response of laser‐injured skin in mice and promoting its proliferation and angiogenesis, which in turn promotes wound healing. [ABSTRACT FROM AUTHOR]

Study Objective: Umbilical cord abnormalities increase neonatal morbidity and mortality. Considering uncertainties about the best time of an antenatal ultrasonography scan to evaluate the umbilical coiling index (UCI), this systematic review was designed to assess the diagnostic accuracy value of antenatal ultrasound assessments to predict abnormal postpartum UCI. Methods: All observational, cross‐sectional, case–control, cohort, and diagnostic accuracy studies up to March 26, 2022, were searched and assessed according to PRISMA guidelines in Ovid, Cochrane, Scopus, PubMed, Web of Science, Embase, Proquest, Science Direct, and Clinical Key databases, and Google Scholar search engine. Results: The total number of 63 190 documents were retrieved from databases. The duplicates (19 272) were removed, 43 918 articles were screened for relevance, and 56 papers were selected for full‐text evaluation, resulting in 14 qualified pieces subjected to the quality CASP tools for each type of study. Finally, six articles were evaluated, extracted, and confirmed. Overall, we had 16 evaluations (11 normal pregnancies, 4 gestational diabetes mellitus, and 1 group at risk for small gestational age), from which 9 and 7 were respectively performed in the second and third trimesters. Most of the evaluations considered both hypocoiling and hypercoiling. The sensitivity, specificity, and area under curves (AUCs) change range between the evaluations were 0.09–0.97, 0.59–0.96, and 0.262–0.84, respectively. Conclusion: Observing any coiling abnormalities in every trimester, both the second and third, is highly sensitive to predicting abnormal postnatal UCI (pUCI). Conclusively, any detected antenatal abnormality is worth attention. Both trimesters' evaluations are essential, and no superiority is seen for any of them. The systematic review revealed statistical and clinical heterogeneity; a meta‐analysis was impossible. [ABSTRACT FROM AUTHOR]

Mesenchymal Stem Cells (MSCs) are non‐hematopoietic and multipotent stem cells, which have been considered in regenerative medicine. These cells are easily separated from different sources, such as bone marrow (BM), umbilical cord (UC), adipose tissue (AT), and etc. MSCs have the differentiation capability into chondrocytes, osteocytes, and adipocytes; This differentiation potential along with the paracrine properties have made them a key choice for tissue repair. MSCs also have various advantages over other stem cells, which is why they have been extensively studied in recent years. The effectiveness of MSCs‐based therapies depend on several factors, including differentiation status at the time of use, concentration per injection, delivery method, the used vehicle, and the nature and extent of the damage. Although, MSCs have emerged promising sources for regenerative medicine, there are potential risks regarding their safety in their clinical use, including tumorigenesis, lack of availability, aging, and sensitivity to toxic environments. In this study, we aimed to discuss how MSCs may be useful in treating defects and diseases. To this aim, we will review recent advances of MSCs action mechanisms in regenerative medicine, as well as the most recent clinical trials. We will also have a brief overview of MSCs resources, differences between their sources, culture conditions, extraction methods, and clinical application of MSCs in various fields of regenerative medicine. [ABSTRACT FROM AUTHOR]

Key Clinical Message: This case highlights the complex interplay of mental health, stigma, and lack of contraceptive access underlying tragic instances of infanticide. Comprehensive medicolegal investigation paired with cross‐sector efforts to expand reproductive services and transform cultural attitudes is crucial to protect vulnerable women and children. [ABSTRACT FROM AUTHOR]

Background: Umbilical cord blood acid–base sampling is routinely performed at many hospitals. Recent studies have questioned this practice and the association of acidosis with cerebral palsy. Objective: To investigate the associations between the results of umbilical cord blood acid–base analysis at birth and long‐term neurodevelopmental outcomes and mortality in children. Search strategy: We searched six databases using the search strategy: umbilical cord AND outcomes. Selection criteria: Randomised controlled trials, cohorts and case–control studies from high‐income countries that investigated the association between umbilical cord blood analysis and neurodevelopmental outcomes and mortality from 1 year after birth in children born at term. Data collection and analysis: We critically assessed the included studies, extracted data and conducted meta‐analyses comparing adverse outcomes between children with and without acidosis, and the mean proportions of adverse outcomes. The certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluations approach. Main results: We have very low confidence in the following findings: acidosis was associated with higher cognitive development scores compared with non‐acidosis (mean difference 5.18, 95% CI 0.84–9.52; n = two studies). Children with acidosis also showed a tendency towards higher risk of death (relative risk [RR] 5.72, 95% CI 0.90–36.27; n = four studies) and CP (RR 3.40, 95% CI 0.86–13.39; n = four studies), although this was not statistically significant. The proportion of children with CP was 2.39/1000 across the studies, assessed as high certainty evidence. Conclusion: Due to low certainty of evidence, the associations between umbilical cord blood gas analysis at delivery and long‐term neurodevelopmental outcomes in children remains unclear. This article includes Author Insights, a video abstract available at: https://players.brightcove.net/3806881048001/default_default/index.html?videoId=6322480161112. [ABSTRACT FROM AUTHOR]

Background: Photoaging is a degenerative biological process that affects the quality of life. It is caused by environmental factors including ultraviolet radiation (UVR), deep skin burns, smoking, active oxygen, chemical substances, and trauma. Among them, UVR plays a vital role in the aging process. Aim: With the continuous development of modern medicine, clinical researchers have investigated novel approaches to treat aging. In particular, mesenchymal stem cells (MSCs), non‐coding RNAs are involved in various physiological processes have broad clinical application as they have the advantages of convenient samples, abundant sources, and avoidable ethical issues. Methods: This article reviews research progress on five types of stem cell, exosomes, non‐coding RNA in the context of photoaging treatment: adipose‐derived stem cell, human umbilical cord MSCs, epidermal progenitor cells, keratinocyte stem cells, and hair follicle stem cells (HFSCs). It also includes stem cell related exosomes and their non‐coding RNA research. Results: The results have clinical guiding significance for prevention and control of the onset and development of photoaging. It is found that stem cells secrete cytokines, cell growth factors, non‐coding RNA, exosomes and proteins to repair aging skin tissues and achieve skin rejuvenation. In particular, stem cell exosomes and non‐coding RNA are found to have significant research potential, as they possess the benefits of their source cells without the disadvantages which include immune rejection and granuloma formation. [ABSTRACT FROM AUTHOR]

Abortions in horses represent an important health and economic challenge for equine industry. Primary causes of abortion are divided in non‐infectious and infectious. Non‐infectious causes include abnormalities of foetal appendices (umbilical cord and placenta essentially), abnormalities of gestation, maternal and foetal origins. Infectious abortions are caused in almost cases by bacterial infections, followed by viruses, fungi and parasites. New abortive pathogens (as Leptospira, Neospora caninum, Coxiella burnetii, Chlamydophila abortus, and) have been confirmed in equines by comparison already known for their abortive properties in human or in other species. Despite an increasing number of autopsies and continuous improvements in diagnostic tools, in management and surveillance, 20%–40% of the causes of equine abortion remain unknown depending on the country. To increase the likelihood of a definitive diagnosis in cases of abortion and stillbirth in horses, new diagnostic approaches are needed. [ABSTRACT FROM AUTHOR]

Background: The direct application of umbilical cord-derived mesenchymal stem cells (UCMSCs) for promoting skin wound healing and regeneration is challenging due to strict maintenance requirements and unpredictable differentiation results. Methods: We developed dead but functional liquid nitrogen-treated UCMSCs (LNT-MSCs) by rapidly immersing live UCMSCs (live-MSCs) in liquid nitrogen. Results: The LNT-MSCs maintained similar cellular structures and surface markers to those of live-MSCs.We evaluated the therapeutic effects of both live- MSCs and LNT-MSCs on full-thickness skin wound healing in rats. Our results showed that the LNT-MSCs accelerated wound closure by enhancing the proliferation and migration of skin cells, promoting angiogenesis, and inducing a favourable macrophage phenotype shift. The regenerative healing effect of LNTMSCs was comparable to that of live-MSCs, making them a potential alternative strategy for accelerating wound closure that avoids unpredictable differentiation results and creates a ready-to-use cell bank for clinical applications. [ABSTRACT FROM AUTHOR]

Introduction: During pregnancy, the umbilical cord attaches to the placenta in a central, eccentric, marginal or velamentous location. Maternal and fetal complications are associated with marginal and velamentous cord insertions, the most clinically significant being perinatal mortality due to undiagnosed vasa praevia. Current literature describes a wide variation regarding regulation of placental cord insertion (PCI) documentation during antenatal ultrasound examinations. This prospective cross‐sectional study aimed to assess the current practice of antenatal PCI documentation in Australia. Methods: Members of the Australian Sonographer Accreditation Registry were invited to participate in an online survey which was distributed between February and March 2022. Results: Four hundred ninety sonographers met the inclusion criteria for the study of which 330 (67.3%) have more than 10 years' experience as a sonographer and 375 (76.5%) are employed primarily in a public or private setting offering general ultrasound. Most respondents (89.6%) indicated documentation of the PCI site is departmental protocol at the second trimester anatomy scan (17–22 weeks gestation), but PCI documentation is protocol in less than 50% of other obstetric ultrasound examinations listed in the survey. The PCI site is included in the formal ultrasound report at a rate significantly less than inclusion in the departmental protocol and the sonographer's worksheet. Conclusions: Considering the potential maternal and fetal complications associated with abnormal PCI and the ease at which the PCI site is identified in the first and second trimesters, we believe that standard inclusion of the PCI site in departmental protocol and in the formal ultrasound report from 11 weeks gestation, regardless of whether it is normal or abnormal, would prove invaluable. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Aims: Recently, human umbilical cord mesenchymal stem cell (HucMSC)‐derived exosome is a new focus of research in neurological diseases. The present study was aimed to investigate the protective effects of HucMSC‐derived exosome in both in vivo and in vitro TBI models. Methods: We established both mouse and neuron TBI models in our study. After treatment with HucMSC‐derived exosome, the neuroprotection of exosome was investigated by the neurologic severity score (NSS), grip test score, neurological score, brain water content, and cortical lesion volume. Moreover, we determined the biochemical and morphological changes associated with apoptosis, pyroptosis, and ferroptosis after TBI. Results: We revealed that treatment of exosome could improve neurological function, decrease cerebral edema, and attenuate brain lesion after TBI. Furthermore, administration of exosome suppressed TBI‐induced cell death, apoptosis, pyroptosis, and ferroptosis. In addition, exosome‐activated phosphatase and tensin homolog‐induced putative kinase protein 1/Parkinson protein 2 E3 ubiquitin–protein ligase (PINK1/Parkin) pathway‐mediated mitophagy after TBI. However, the neuroprotection of exosome was attenuated when mitophagy was inhibited, and PINK1 was knockdown. Importantly, exosome treatment also decreased neuron cell death, suppressed apoptosis, pyroptosis, and ferroptosis and activated the PINK1/Parkin pathway‐mediated mitophagy after TBI in vitro. Conclusion: Our results provided the first evidence that exosome treatment played a key role in neuroprotection after TBI through the PINK1/Parkin pathway‐mediated mitophagy. [ABSTRACT FROM AUTHOR]

Background: In order to support the comprehensive classification of Leukocyte Adhesion Deficiency‐I (LAD‐I) severity by simultaneous screening of CD11a/CD18, this study assessed clinical, laboratory, and genetic findings along with outcomes of 69 LAD‐I patients during the last 15 years. Methods: Sixty‐nine patients (40 females and 29 males) with a clinical phenotype suspected of LAD‐I were referred to Immunology, Asthma, and Allergy research institute, Tehran, Iran between 2007 and 2022 for further advanced immunological screening and genetic evaluations as well as treatment, were enrolled in this study. Results: The diagnosis median age of the patients was 6 months. Delayed umbilical cord separation was found in 25 patients (36.2%). The median diagnostic delay time was 4 months (min–max: 0–82 months). Forty‐six patients (66.7%) were categorized as severe (CD18 and/or CD11a: below 2%); while 23 children (33.3%) were in moderate category (CD18 and/or CD11a: 2%–30%). During the follow‐ups, 55.1% of children were alive with a mortality rate of 44.9%. Skin ulcers (75.4%), omphalitis (65.2%), and gingivitis (37.7%) were the most frequent complaints. Genetic analysis of the patients revealed 14 previously reported and three novel pathogenic mutations in the ITGB2 gene. The overall survival of patients with and without hematopoietic stem cell transplantation was 79.3% and 55.6%, respectively. Conclusion: Physicians' awareness of LAD‐I considering delayed separation of umbilical cord marked neutrophilic leukocytosis, and variability in CD11 and CD18 expression levels, and genetic analysis leads to early diagnosis and defining disease severity. Moreover, the prenatal diagnosis would benefit families with a history of LAD‐I. [ABSTRACT FROM AUTHOR]