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The biological properties of human mesenchymal stromal cells (hMSCs) have been explored in over a thousand clinical trials in the last decade. Although hMSCs can be isolated from multiple sources, the degree of biological similarity between cell populations from these sources remains to be determined. A comparative study was performed investigating the growth kinetics and functionality of hMSCs isolated from adipose tissue (AT), bone marrow (BM) and umbilical cord tissue (UCT) expanded in monolayer over five passages. Adult hMSCs (AT, BM) had a slower proliferation ability than the UCT-hMSCs, with no apparent differences in their glucose consumption profile. BM-hMSCs produced higher concentrations of endogenous vascular endothelial growth factor (VEGF) compared to AT- and UCT-hMSCs. This study also revealed that UCT-hMSCs were more efficiently transduced by a lentiviral vector carrying a VEGF gene than their adult counterparts. Following cellular immunophenotypic characterization, no differences across the sources were found in the expression levels of the typical markers used to identify hMSCs. This work established a systematic approach for cell source selection depending on the hMSC's intended clinical application. [ABSTRACT FROM AUTHOR]

Objective: Our objective was to determine the feasibility and interobserver reliability of umbilical cord and placental arteriolar flow assessment in low‐risk pregnancies near term. Methods: This was a prospective pilot study in low‐risk pregnancies at 36 weeks with anterior placentas. We excluded any with an indication for antenatal testing or delivery before 39 weeks. Each participant underwent two ultrasounds by different examiners, which included arterial and venous velocimetry at three cord sites (fetal, free loop, and placental) in addition to maternal and fetal placental arterioles. The interobserver reliability was quantified using the Pearson correlation coefficient with that of standard clinical parameters serving as a benchmark for interpretation. Results: Among 53 participants scanned at 356/7–371/7 weeks, the mean examination duration was 20.5 ± 4.2 minutes. Ascertainment success was high for measures at the free loop, placental cord insertion, and fetal placental arterioles (range 90.6%–99.1%) and was lower at the fetal cord insertion and maternal spiral arterioles (range 47.2%–87.7%). Interobserver reliability estimates for free‐loop systolic/diastolic and pulsatility index ranged from 0.38 to 0.44. Interobserver reliability for experimental parameters varied by measurement site, and all were poor at the fetal insertion and in placental arterioles. Parameters had significant variation across cord sites (range 4.3%–21.7%). Conclusion: In our cohort, flow assessments of the free loop, placental insertion, and placental arterioles are feasible, but interrater reliability varies by measurement type and cord site. Future studies are needed to establish feasibility and reliability in nonanterior placentation and to assess clinical relevance. [ABSTRACT FROM AUTHOR]

Background: Mesenchymal stem/stromal cells (MSCs) have attracted interest as a potential therapy given their anti-inflammatory and immunomodulatory properties. However, clinical trials using MSCs for acute respiratory distress syndrome (ARDS) have produced mixed and inconclusive data. In previous work, we performed a "head-to-head" comparison between different sources of MSCs and showed that each source had a unique genomic and proteomic "signature". Method: This study investigated which sources of MSC: bone marrow derived-MSCs (BM-MSCs), adipose tissue derived-MSCs (AD-MSCs) and umbilical cord derived-MSCs (UC-MSCs) would be the optimal candidate to be used as a therapy in an LPS-induced mouse model of ARDS. Immune cells assessment, tissue transcriptomics, animal survival, and endothelial-epithelial barrier assessment were used to evaluate their effects. Results: When comparing the three most commonly used MSC sources, we found that UC-MSCs exhibited greater efficacy compared to other MSCs in improving animal survival, mitigating epithelial/endothelial damage, decreasing lung inflammation via reducing neutrophil infiltration, T cell proliferation, and M1 polarization. Bulk RNA sequencing of lung tissue also showed that UC-MSCs have the capability to downregulate extracellular trap formation, by the downregulation of key genes like Elane and Padi4. Notably, treatment with UC-MSCs demonstrated a significant reduction in Fc-γ R mediated phagocytosis, which has been associated with monocyte pyroptosis and intense inflammation in the context of COVID-19. Conclusion: Our findings suggest that UC-MSCs are an optimal source of MSC to treat acute inflammatory conditions in the lungs, such as ARDS. [ABSTRACT FROM AUTHOR]

Arcuate uterus does not impact the success of infertility treatments, but there is no consensus on whether it influences perinatal outcomes. The objective of the present study was to investigate whether minor congenital uterine anomalies such as an arcuate uterus contribute to perinatal complications. This was a retrospective cohort study at a single institution. The study included 1097 deliveries after 22 weeks of gestation. Transvaginal ultrasound, with three‐dimensional functionality, assessed uterine morphology based on American Society for Reproductive Medicine criteria. We compared maternal backgrounds and perinatal complications between arcuate uterus and normal uterus groups. Statistical analyses, including multivariate analysis, aimed to identify independent risk factors. A total of 69 patients (7.5%) with diagnosed arcuate uterus were included. Maternal background factors showed no significant differences between groups. In perinatal complications, an arcuate uterus was associated with a significantly higher incidence of preterm delivery (13% versus 4.7%, P = 0.01), preterm premature rupture of membranes (7.2% versus 1.6%, P = 0.01), fetal growth restriction (FGR; 16% versus 6.7%, P = 0.01), and abnormal placental cord insertion (33% versus 7.6%, P < 0.01). After multivariate analysis, arcuate uterus emerged as an independent risk factor for preterm delivery (adjusted odds ratio [aOR], 4.0 [95% confidence interval (CI), 1.6–9.9], P < 0.01), FGR (aOR, 2.6 [95% CI, 1.2–5.6], P = 0.02), and abnormal placental cord insertion (aOR, 6.0 [95% CI, 3.4–10.6], P < 0.01). Arcuate uterus stands as an independent risk factor for preterm delivery, FGR, and abnormal placental cord insertion. The findings emphasize the importance of recognizing even minor uterine morphological abnormalities in assessing and managing perinatal complications. [ABSTRACT FROM AUTHOR]

Radiation‐induced lung injury (RILI) is frequently observed in patients undergoing radiotherapy for thoracic malignancies, constituting a significant complication that hampers the effectiveness and utilization of tumor treatments. Ionizing radiation exerts both direct and indirect detrimental effects on cellular macromolecules, including DNA, RNA and proteins, but the impact of oxidized RNA in RILI remains inadequately explored. Mesenchymal stem cells (MSCs) can repair injured tissues, and the reparative potential and molecular mechanism of MSCs in treating RILI remains incompletely understood. This study aimed to investigate the therapeutic effects and mechanisms of action of three distinct sources of MSCs, including human umbilical cord mesenchymal stem cells (UCMSCs), bone marrow mesenchymal stem cells (BMSCs), and adipose‐derived stem cells (ADSCs), in thoracically irradiated mice. Comparative analysis revealed that all three types of MSCs exhibited the ability to mitigate radiation‐induced inflammatory infiltration, alveolar hemorrhage, and alveolar wall thickening in the lung tissue of the mice. MSCs also attenuated RILI by decreasing inflammatory factors, upregulating anti‐inflammatory factor expression, and reducing collagen accumulation. Immunohistochemical results showed that all three MSCs reduced radiation‐induced cell apoptosis and promoted the regeneration of lung tissue cells. The analysis of malondialdehyde (MDA) and 8‐hydroyguanosine (8‐OHG) content indicated that MSCs possess reparative properties against radiation‐induced oxidative damage in lung tissue. The study provides evidence that UCMSCs are a more appropriate therapeutic option for RILI compared to BMSCs and ADSCs. Additionally, MSCs effectively reduce the accumulation of oxidized RNA in RILI, thereby, presenting a unique avenue for investigating the underlying mechanism of MSC‐based treatment for RILI. [ABSTRACT FROM AUTHOR]

Introduction: The umbilical cord (UC) serves as the main pathway for bacteria to reach the neonate's body, potentially causing local and severe infections, sepsis, and even death. Consequently, neonatal mortality remains a significant public health concern, particularly in Ethiopia. The World Health Organization (WHO) recommends that the umbilical cord stump be kept clean and dry, with the exception of applying topical antiseptics. However, various harmful substances are still applied to the umbilical cord of neonates. Data on the geographical distribution and risk factors for harmful umbilical cord stump (UCS) care are scarce. Therefore, this study aims to fill this gap. Methods: A secondary data analysis of the Ethiopian Demographic Health Survey (EDHS 2016) was conducted using a weighted sample of 7,168 live births. ArcGIS version 10.7.1 software was utilized to visualize the spatial distribution of harmful umbilical cord stump (UCS) care practices in Ethiopia. Additionally, a Bernoulli probability model-based spatial scan statistic was applied using Kulldorff's SaTScan version 9.6 software to identify significant clusters of harmful UCS care. A multilevel logistic regression model was used to determine the factors associated with UCS care practices in Ethiopia. Statistical significance was declared at a two-sided P-value of < 0.05. Results: Overall, the prevalence of harmful UCS care in Ethiopia was 15.09% (95% CI: 13.9–16.3), with significant spatial heterogeneity across geographical areas. The hotspot areas of harmful US care were observed in the eastern (Somali) and northern (Tigray and Amhara) parts of Ethiopia. In spatial scan analysis, the most likely primary clusters were observed in South Nation Nationalities and Peoples region (SNNPR), secondary clusters in the Somali, tertiary clusters in Tigray, and the next clusters in the Amhara regions, respectively. In the final multilevel model, maternal age (Adjusted odds ratio/AOR 1.07, 95% CI: 1.02–1.12), institutional delivery (AOR 0.64, 95% CI: 0.42–0.97), female neonates (AOR 1.31, 95% CI: 1.04–1.61), rural residence (AOR 2.18, 95% CI: 1.05–4.52), living in Tigray region (AOR 3.79, 95% CI: 1.38–9.38), living in Somali region (AOR, 2.95% CI: 1.02–8.52), and living in Harari region (AOR 3.51, 95% CI: 1.28–9.60) were identified as a significant factors of harmful US care practice in Ethiopia. Conclusion: In Ethiopia, the distribution of harmful UCS care practices is non-random and highly clustered in the SNNPR, Somalia, Tigray, and Amhara regions. Both individual and community-level factors were significantly associated with the practice. Special emphasis needs to be provided for neonates from those hot-spot areas and to address the identified predictors of harmful umbilical cord stump care practices. [ABSTRACT FROM AUTHOR]

Background: Simulation training provides safe environment for skill acquisition and retention. This study addresses a critical challenge in Africa – umbilical cord and placenta management after childbirth – aiming to bridge theoretical learning with practical experiences through simulation. We realized a new low-cost high-fidelity simulator of placenta and umbilical cord. We conducted a needs-based training course for nursing and midwifery students at St. Luke Hospital of Wolisso, Ethiopia, to validate our new simulator and compare its acceptability and teaching effectiveness with other two simulators (conventional low-fidelity model and human placenta). Methods: We surveyed St. Luke Hospital medical experts to obtain their feedback on the new simulator's face, content, and usability. We carried out a simulation training course for 67 students who received theoretical lectures and simulation courses being divided into three groups according to the simulator used. We assessed the simulators' user acceptability using the Technology Acceptance Model (TAM) and compared the final objective evaluations by tutors between groups. Results: Experts confirmed the new simulator's fidelity, material quality, and usability. Students training on the new simulator demonstrated higher objective scores and perceived it as more useful and user-friendly compared to human placenta, while there was no difference between conventional simulator and human placenta in the TAM items. Conclusion: We validated a new high-fidelity simulator developed by the Sant'Anna School of Advanced Studies in Pisa, Italy, using the TAM scale and robust statistical methods, thanks to a successful collaboration with St. Luke's Hospital in a simulation training course where students achieved higher objective scores and perceived the simulator as more useful and easier to use than a real human placenta, suggesting significant educational benefits and potential for future research. [ABSTRACT FROM AUTHOR]

As Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) are easily accessible, easy to isolate, and ethically acceptable, they represent a promising source of MSCs for use in regenerative medicine. Considering decisions on WJ-MSCs collection requires extensive knowledge of the factors that impact their yield. This study's aim was to evaluate the influence of parameters related to mothers and newborns on the WJ-MSCs yield. The WJ-MSCs were isolated and expanded after being isolated from 79 umbilical cord (UC) samples. Population doubling time and cell proliferation were assessed. By flow cytometry analysis, WJ-MSCs were identified by positivity of CD105, CD90, and CD73 and negativity of CD45 and CD34. There was a statistically significant negative correlation between UC width and P1 doubling time. Maternal age and WJ-MSC yield were shown to be negatively correlated. Birth weight and gestational age showed a significant positive correlation between WJ-MSCs yield and neonatal variables. No significant correlations were detected between the WJ-MSCs and the mother parity, nor the neonatal sex, fetal presentation, or head circumference. The WJ-MSCs yield increases with younger maternal age, higher gestational age, and increased neonatal birth weight. Hence, consideration should be given to these factors when selecting the ideal donors. [ABSTRACT FROM AUTHOR]

Objective Methods Results Conclusion To detect an abnormal intra‐amniotic structure around the internal cervical os using transvaginal sonography at 18–21+6 weeks of gestation.In this cohort study, during a 12‐month period from July 2022 to June 2023, 395 transvaginal scans were performed for second‐trimester cervical‐length screening in singleton pregnancies at 18–21+6 weeks of gestation. Nine abnormal intra‐amniotic structures (AIAS), 87 low‐lying placentas (LLP, second‐trimester placenta previa or placental margin within 2 cm from internal cervical os), and 299 controls (not LLP and no abnormal finding around internal cervical os) were diagnosed. Sonographic features of AIAS and delivery outcomes in the three groups were compared.Sonographic features of nine AIAS cases were: two single bands, one single broad band, one multiple bands, one single tubular, and one multiple tubulars. Blood flow was noted in seven cases. Seven AIAS had disappeared by 26 weeks, one was resolved at 34 weeks, and one (vasa previa and parachute placenta) remained until delivery. Incidences of emergency cesarean section, abnormal placenta and umbilical cord, and abnormal deliveries in AIAS were significantly higher than those in LLP and control groups (P = 0.031). Blood losses during delivery in AIAS and LLP groups were significantly greater than in the control group (P = 0.004), but there was no significant difference in blood loss between AIAS and LLP groups.The incidence of AIAS around the internal cervical os in the second trimester was 2.28% (9/395 fetuses). Mid‐second‐trimester transvaginal sonographic screening for the detection of AIAS around the internal cervical os including vasa previa may be essential to reduce perinatal morbidity. [ABSTRACT FROM AUTHOR]

Ischemia-reperfusion (IR) injury is associated with neurological disorders such as stroke. The therapeutic potential of human umbilical cord mesenchymal stem cells (hUC-MSCs) and their secreted extracellular vesicles (EVs) in alleviating IR injury across various cell types including neuronal cells has been documented. However, the underlying mechanisms through which hUC-MSCs and hUC-MSC-EVs protect neuronal cells from IR-triggered damage are not well understood. In this study, we co-cultured SH-SY5Y neuroblastoma cells with hUC-MSCs or hUC-MSC-EVs and subjected them to oxygen-glucose deprivation/reperfusion (OGD/R) treatment. Our findings indicate that both hUC-MSCs and hUC-MSC-EVs significantly improved viability, reduced apoptosis, promoted autophagy of OGD/R-induced SH-SY5Y cells, and decreased mitochondrial reactive oxygen species levels within them. Furthermore, the neuroprotective effect of hUC-MSCs and hUC-MSC-EVs in OGD/R-induced SH-SY5Y cells was enhanced by overexpressing USP35, a deubiquitinase. Mechanistically, USP35 interacted with and stabilized FUNDC1, a positive regulator of mitochondrial metabolism. Knockdown of FUNDC1 in USP35-overexpressing hUC-MSCs and their secreted EVs eliminated the augmented neuroprotective function induced by excess USP35. In conclusion, these findings underscore the crucial role of USP35 in enhancing the neuroprotective function of hUC-MSCs and their secreted EVs, achieved through the stabilization of FUNDC1 in OGD/R-induced SH-SY5Y cells. Human umbilical cord mesenchymal stem cells and their extracellular vesicles protect neuronal cells from ischemia-reperfusion injury by enhancing cell viability and reducing damage through mechanisms involving the stabilization of FUNDC1 by USP35. [ABSTRACT FROM AUTHOR]

Extraembryonic mesoderm cells (EXMCs) are involved in the development of multiple embryonic lineages and umbilical cord formation, where they subsequently develop into mesenchymal stem cells (MSCs). Although EXMCs can be generated from human naïve embryonic stem cells (ESCs), it is unclear whether human primed ESCs (hpESCs) can differentiate into EXMCs that subsequently produce MSCs. The present report described a three‐dimensional differentiation protocol to induce hpESCs into EXMCs by activating the Wnt pathway using CHIR99021. Single‐cell transcriptome and immunostaining analyses revealed that the EXMC characteristics were similar to those of post‐implantation embryonic EXMCs. Cell sorting was used to purify and expand the EXMCs. Importantly, these EXMCs secreted extracellular matrix proteins, including COL3A1 and differentiated into MSCs. Inconsistent with other MSC types, these MSCs exhibited a strong differentiation potential for chondrogenic and osteogenic cells and lacked adipocyte differentiation. Together, these findings provided a protocol to generate EXMCs and subsequent MSCs from hpESCs. [ABSTRACT FROM AUTHOR]

Background: Routine Doppler study is a common tool for early diagnosis of Fetal Growth Restriction (FGR) and Small for Gestational Age (SGA) patients. It aimed to determine the role of the Foramen Ovale Pulsatility Index (FOPI) study beside routine Doppler study among patients with FGR and SGA fetuses. Methods: This prospective study was conducted on 35 FGR, 32 SGA, and 33 Appropriate for Gestational Age (AGA) fetuses. Demographic data, amniotic fluid index, neonatal outcome, and Doppler velocimetry, including Umbilical Artery Pulsatility Index (UMAPI), Uterine Artery Pulsatility Index (UTAPI), Middle Cerebral Artery Pulsatility Index (MCAPI), Ductus Venosus Pulsatility Index (DVPI), and FOPI were documented. Kolmogorov-Smirnov normality test, one-way ANOVA, Mann-Whitney U, Kruskal-Wallis, non-parametric pairwise comparisons adjusted for Bonferroni correction, Pearson correlation test, Chi square, Fisher's exact test, and Receiver Operating Characteristic Curve (ROC) analysis with Youden's Index (sensitivity+specificity-1) to estimate cut-off point were used to analyze the data at significance level <0.05 for all tests. Results: FOPI cut-off points were 2.24 (sensitivity=77%, specificity=94%) and 1.15 (sensitivity=90%, specificity=20%) to predict FGR and SGA, respectively. FOPI showed a positive correlation with UMAPI and UTAPI (r=0.52 and r=0.30, P<0.001 and P=0.006, respectively), but not with MCAPI and DVPI (r=0.08 and r=0.12, P=0.50 and P=0.30, respectively). Besides, UMAPI, UTAPI, and FOPI were altered among patients with stages I and II FGR. Umbilical cord potential hydrogen (umbilical cord pH), 1- and 5-min Apgar score significantly increased by Birth weight centile; however, UMAPI, FOPI, and UTAPI significantly decreased. Conclusion: UMAPI is recommended to predict short-term neonatal morbidities and demonstrate the early or late onset FGR. Besides, FOPI is suggested as the first-line Doppler study to detect abnormal growth velocity. More studies are warranted, especially considering long-term neonatal morbidities. [ABSTRACT FROM AUTHOR]

Umbilical cord mesenchymal stem cell-derived extracellular vesicles (UC-EVs) are valuable in nanomedicine as natural nanocarriers, carrying information molecules from their parent cells and fusing with targeted cells. miRNA-126, specific to endothelial cells and derived from these vesicles, supports vascular integrity and angiogenesis and has protective effects in kidney diseases. Objective: This study investigates the delivery of miRNA-126 and anti-miRNA-126 via UC-EVs as natural nanocarriers for treating nephrotoxic injury in vitro. Method: The umbilical cord-derived mesenchymal stem cell and UC-EVs were characterized according to specific guidelines. Rat kidney proximal tubular epithelial cells (tubular cells) were exposed to nephrotoxic injury through of gentamicin and simultaneously treated with UC-EVs carrying miRNA-126 or anti-miRNA-126. Specific molecules that manage cell cycle progression, proliferation cell assays, and newly synthesized DNA and DNA damage markers were evaluated. Results: We observed significant increases in the expression of cell cycle markers, including PCNA, p53, and p21, indicating a positive cell cycle regulation with newly synthesized DNA via BrDU. The treatments reduced the expression of DNA damage marker, such as H2Ax, suggesting a lower rate of cellular damage. Conclusions: The UC-EVs, acting as natural nanocarriers of miRNA-126 and anti-miRNA-126, offer nephroprotective effects in vitro. Additionally, other components in UC-EVs, such as proteins, lipids, and various RNAs, might also contribute to these effects. [ABSTRACT FROM AUTHOR]

Maternal obesity has been shown to impair the oxidative status in the placenta and newborns, potentially leading to adverse pregnancy outcomes and long-term effects on the programming of offspring metabolic status. This study aimed to investigate the impact of maternal obesity on maternal and umbilical cord plasma oxidative status, as well as placental oxidative adaptation. Maternal obesity (n = 20), defined as a pre-pregnancy BMI ≥ 25 kg/m2, and maternal leanness (n = 20), defined as a pre-pregnancy BMI < 23 kg/m2, were the group categories used in this study. Both groups were matched according to gestational age at delivery. Maternal blood, umbilical cord blood, and placental tissue were collected to assess nutritional content (cholesterol, triglyceride, and protein), oxidative stress markers (MDA and protein carbonyl), and antioxidant activity (SOD and catalase). Placental protein expression (SOD2, catalase, UCP2, and Nrf2) was evaluated using Western blot analysis. Catalase activity in maternal plasma significantly increased in the maternal obesity group (p = 0.0200), with a trend toward increased MDA and protein carbonyl levels. In umbilical cord plasma, triglyceride, protein carbonyl, and catalase activity were significantly elevated in the maternal obesity group compared with the lean controls (p = 0.0482, 0.0291, and 0.0347, respectively). Placental protein expression analysis revealed significantly decreased SOD2 (p = 0.0011) and catalase (p < 0.0001), along with Nrf2 downregulation (p < 0.0001). An increase in mitochondrial antioxidant UCP2 expression was observed (p = 0.0117). The neonatal protein carbonyl levels positively correlated with placental protein carbonyl (r = 0.7405, p < 0.0001) and negatively correlated with maternal catalase activity (r = −0.4332, p = 0.0052). This study thus provides evidence that maternal obesity is associated with placental and fetal oxidative stress, alongside a concurrent increase in placental antioxidant UCP2 expression. [ABSTRACT FROM AUTHOR]

The combination of cord blood transplant with progenitor cells from partially HLA-matched adult donors (haplo-cord transplant) has been used over the past two decades. In Europe and the US the adult donor graft is CD34 selected and provides early hematopoiesis, but durable engraftment derives from the cord blood graft (CD34 selected haplo-cord). Neutrophil recovery is prompt and rates of acute and chronic GVHD are low. Recent Chinese studies combine cord blood grafts with T-replete haplo-identical grafts (unmodified haplo-cord). The haplo graft usually establishes dominance and UCB chimerism is rarely detected. Comparison studies suggest considerably decreased rates of relapse and improved outcomes, compared with either haplo-identical transplant or CBU transplant, particularly in patients with advanced leukemia. A recent prospective randomized study confirms this. Haplo-cord mitigates the engraftment delay of UCB transplant. The unique biology of UCB grafts results in low GVHD and improved GVL especially beneficial in high-risk disease. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the immunomodulatory effects and potential mechanisms of human nasal mucosa-derived mesenchymal stem cells(hNMSCs) on mouse allergic rhinitis, and to compare them with human umbilical cord-derived mesenchymal stem cells (hUCMSCs). Method: hNMSCs and hUCMSCs were isolated and cultured for identification from human nasal mucosa and umbilical cord tissues. A co-culture system of LPS-stimulated RAW264.7 cells/mouse peritoneal macrophages and MSCs was employed.Changes in inflammatory factors in RAW264.7 cells and the culture medium as well as the expression of NF-κB signaling pathway in RAW264.7 cells were detected. Forty-eight BALB/c mice were randomly divided into control, OVA, hNMSCs, and hUCMSCs groups. An allergic rhinitis (AR) model was established through ovalbumin (OVA) stimulation and treated with hNMSCs and hUCMSCs. Subsequent assessments included related symptoms, biological changes, and the expression of the NF-κB signaling pathway in the nasal mucosa of mice. Results: MSCs can be successfully isolated from human nasal mucosa. Both hNMSCs and hUCMSCs interventions significantly reverseed the inflammation induced by LPS and suppressed the upregulation of the NF-κB signaling pathway in RAW264.7 cells. Treatment with hNMSCs and hUCMSCs alleviated mouse allergic symptoms, reduced levels of total IgE, OVA-specific IgE and IgG1 in mouse serum, TH2-type cytokines and chemokines in mouse nasal mucosa, and TH2-type cytokines in mouse spleen culture medium, while also inhibiting the expression of the NF-κB signaling pathway in the nasal mucosa of mice. moreover, the hNMSCs group showed a more significant reduction in OVA-specific IgG1 in serum and IL-4 expression levels in mouse spleen culture medium compared to the hUCMSCs group. Conclusion: Our findings suggest that hNMSCs can ameliorate allergic rhinitis in mice, with a certain advantage in anti-inflammatory effects compared to hUCMSCs. The NF-κB pathway is likely involved in the anti-inflammatory regulation process by hNMSCs.Therefore, hNMSCs might represent a novel therapeutic approach for allergic rhinitis. [ABSTRACT FROM AUTHOR]

Macroprolactinemia is one of the major causes of hyperprolactinemia. The aim of this study was to clarify the origin of macroprolactin (macro-PRL). We examined macro-PRL in the sera of 826 pregnant women and in those of their babies' umbilical cords at delivery. Macro-PRL was evaluated by precipitation with polyethylene glycol (PEG), gel filtration chromatography (GFC), and absorption with protein G (PG). We detected macro-PRL in 16 out of the 826 pregnant women (1.94 %) and in 14 of their babies, which may indicate the possibility of hereditary origin of macro-PRL. However, the macro-PRL ratios of the babies correlated positively with those of their mothers (r=0.72 for GFC, p<0.001 and r=0.77 for PG, p<0.001), suggesting that the immunoglobulin (Ig)G-type anti-PRL autoantibodies might be actively transferred to babies via the placenta and form macro-PRL by binding to their babies' PRL or PRL-IgG complexes may possibly pass through the placenta. There were two cases in which only mothers had macro-PRL, indicating that the mothers had autoantibodies that did not pass through the placenta, such as IgA, PRL bound to the other proteins or PRL aggregates. No cases were found in which only the babies had macro-PRL and their mothers did not, suggesting that macro-PRL might not arise by non-hereditary congenital causes. Macro-PRL in women of reproductive age might be mostly IgG-type anti-PRL autoantibody-bound PRL. The likely origin of macro-PRL in babies is the transplacental transfer of IgG-type anti-PRL autoantibodies or PRL-IgG complexes from the mothers to their babies. [ABSTRACT FROM AUTHOR]

Background: The advent of tissue engineering and regenerative medicine has introduced innovative approaches to treating degenerative and traumatic injuries, particularly in cartilage, a tissue with limited self-repair capabilities. Among the various stem cell sources, umbilical cord-derived mesenchymal stromal cells (UC-MSCs) have garnered significant interest due to their non-invasive collection, minimal ethical concerns, and robust regenerative potential, particularly in cartilage regeneration. Methods: A comprehensive literature review was conducted using multiple databases, including PubMed, Scopus, Web of Science, and Google Scholar. Search terms focused on "umbilical cordderived mesenchymal stromal cells," "chondrogenesis," "cartilage regeneration," and related topics. Studies published in the past two decades were included, with selection criteria emphasizing methodological rigor and relevance to UC-MSC chondrogenesis. The review synthesizes findings from various sources to provide a thorough analysis of the potential of UC-MSCs in cartilage tissue engineering. Results: UC-MSCs exhibit significant chondrogenic potential, supported by their ability to differentiate into chondrocytes under specific conditions. Recent advancements include the development of biomaterial scaffolds and the application of genetic engineering techniques, such as CRISPR/Cas9, to enhance chondrogenic differentiation. Despite these advancements, challenges remain in standardizing cell isolation techniques, scaling up production for clinical use, and ensuring the long-term functionality of regenerated cartilage. Conclusion: UC-MSCs offer a promising solution for cartilage regeneration in the field of regenerative medicine. Ongoing research is focused on overcoming current challenges through the use of advanced technologies, including bioreactors and gene editing. Collaborative efforts among researchers, clinicians, and bioengineers are essential to translating the potential of UC-MSCs into effective clinical therapies, which could significantly advance tissue regeneration and therapeutic innovation. [ABSTRACT FROM AUTHOR]

Background: Adequate pain relief during childbirth is a very important issue for women and healthcare providers. This study investigates the effects on maternal and neonatal outcomes of two analgesic methods during labor: water immersion and epidural analgesia. Methods: In this retrospective observational cohort study at a first-level hospital, in Spain, from 2009 to 2019, 1134 women, low-risk singleton and at term pregnancy, were selected. Among them, 567 women used water immersion; 567 women used epidural analgesia for pain control. Maternal outcomes included mode of birth and perineum condition. Neonatal outcomes included 5 min Apgar score, umbilical cord arterial pH, and Neonatal Intensive Care Unit admissions. Chi-square tests and Mann–Whitney U tests, together with their effect sizes (Cramer's V, odds ratio, and Cohen's d) were used to test the main hypotheses. Results: Spontaneous vaginal birth was almost 17 times more likely in the water immersion group (OR = 16.866 [6.540, 43.480], p < 0.001), whereas the odds of having a cesarean birth were almost 40 times higher in the epidural group (OR = 39.346 [3.610, 429.120], p < 0.001). The odds of having an intact perineum were more than two times higher for the water immersion group (OR = 2.606 [1.290, 5.250], p = 0.007), whereas having an episiotomy was more than eight times more likely for the epidural group (OR = 8.307 [2.800, 24.610], p < 0.001). Newborns in the water immersion group showed a better 5 min Apgar score and umbilical cord arterial pH and lower rates in admissions at the Neonatal Intensive Care Unit. Conclusions: Women choosing water immersion as an analgesic method were no more likely to experience adverse outcomes and presented better results than women choosing epidural analgesia. [ABSTRACT FROM AUTHOR]

Natural killer (NK) cells are candidates for adoptive cell therapy, and the protocols for their activation and expansion profoundly influence their function and fate. The complexity of NK cell origin and feeder cell cues impacts the heterogeneity of expanded NK (eNK) cells. To explore this, we compared the phenotype and function of peripheral blood‐derived NK (PB‐NK) and umbilical cord blood‐derived NK (UCB‐NK) cells activated by common feeder cell lines, including K562, PLH, and 221.AEH. After first encounter, most PB‐NK cells showed degranulation independently of cytokines production. Meanwhile, most UCB‐NK cells did both. We observed that each feeder cell line uniquely influenced the activation, expansion, and ultimate fate of PB eNK and UCB eNK cells, determining whether they became cytokine producers or killer cells. In addition, they also affected the functional performance of NK cell subsets after expansion, that is, expanded conventional NK (ecNK) and expanded FcRγ– NK (eg‐NK) cells. Hence, the regulation of eNK cell function largely depends on the NK cell source and the chosen expansion system. These results underscore the significance of selecting feeder cells for NK cell expansion from various sources, notably for customized adoptive cell therapies to yield cytokine‐producing or cytotoxic eNK cells. [ABSTRACT FROM AUTHOR]

Introduction: Allergic asthma is prevalent in children, with Dermatophagoides farinae as a common indoor allergen. Current treatments for allergic airway inflammation are limited and carry risks. Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) show promise as a cell-free therapeutic approach. However, the use of engineered MSC-EVs for D. farinae-induced allergic airway epithelial cell inflammation remains unexplored. Methods: We generated miR-146a-5p-engineered EVs from human umbilical cord mesenchymal stem cells (hucMSCs) and established D. farinae-induced mouse and human bronchial epithelial cell allergic models. Levels of IL-1b, IL-18, IL-4, IL-5, IL-6, IL-10, IL-33, TNF-α and IgE were detected using ELISA. The relative TRAF6 and IRAK1 mRNA expression was quantified using qPCR assay and the NLRP3, NF-κB, IRAK1 and TRAF6 protein expression was determined using Western blotting. The regulatory effect of IRAK1 and TRAF6 by miR-146a-5p was examined using a dual luciferase reporter assay, and the nuclear translocation of NF-κB p65 into 16-HBE cells was evaluated using immunofluorescence assay. Results: Treatment with hucMSC-EVs effectively reduced allergic inflammation, while miR-146a-5p engineered hucMSC-EVs showed greater efficacy. The enhanced efficacy in alleviating allergic airway inflammation was attributed to the downregulation of IRAK1 and TRAF6 expression, facilitated by miR-146a-5p. This downregulation subsequently led to a decrease in NF-κB nuclear translocation, which in turn resulted in reduced activation of the NLRP3 inflammasome and diminished production of inflammatory cytokines, including IL-6, TNF-α, IL-1β and IL-18. Conclusion: Our study underscores the potential of miR-146a-5p engineered hucMSC-EVs as a cell-free therapeutic strategy for D. farinae-induced allergic airway inflammation, offering a promising avenue for boosting antiinflammatory responses. [ABSTRACT FROM AUTHOR]

Esophageal fibrosis can develop due to caustic or radiation injuries. Umbilical cord–derived mesenchymal stem cells (UC-MSCs) are known to mitigate fibrosis in various organs. However, the potential effects of UC-MSCs on human esophageal fibrosis remain underexplored. This study investigated the anti-fibrogenic properties and mechanisms of UC-MSC-derived conditioned media (UC-MSC-CM) on human esophageal fibroblasts (HEFs). HEFs were treated with TGF-β1 and then cultured with UC-MSC-CM, and the expression levels of extracellular matrix (ECM) components, RhoA, myocardin related transcription factor A (MRTF-A), serum response factor (SRF), Yes-associated protein (YAP), and transcriptional coactivator with PDZ-binding motif (TAZ) were measured. UC-MSC-CM suppressed TGF-β1-induced fibrogenic activation in HEFs, as evidenced by the downregulation of ECM. UC-MSC-CM diminished the expression of RhoA, MRTF-A, and SRF triggered by TGF-β1. In TGF-β1-stimulated HEFs, UC-MSC-CM decreased the nuclear localization of MRTF-A and YAP. Additionally, UC-MSC-CM diminished the TGF-β1-induced nuclear expressions of YAP and TAZ, while concurrently enhancing the cytoplasmic presence of phosphorylated YAP. Furthermore, UC-MSC-CM reduced TGF-β1-induced phosphorylation of Smad2. These findings suggest that UC-MSC-CM may inhibit TGF-β1-induced fibrogenic activation in HEFs by targeting the Rho-mediated MRTF/SRF and YAP/TAZ pathways, as well as the Smad2 pathway. This indicates its potential as a stem cell therapy for esophageal fibrosis. [ABSTRACT FROM AUTHOR]

The abnormal umbilical cord coiling index (UCI) may be one of the ways to predict adverse pregnancy outcomes. This study attempted to determine the association between abnormal UCI and maternal, fetal, and neonatal outcomes.This longitudinal study was conducted on 400 women referred for delivery from April to August 2021. UCI was calculated by dividing the total number of coils by the total length of the umbilical cord in centimeters. In eligible cases, the length of the umbilical cord and the number of vascular coils along the total umbilical cord were measured after birth. UCI less than the 10th percentile and more than the 90th percentile was considered abnormal, and between the 10th and 90th percentiles was considered normal. Data were analyzed using SPSS version 20. P < 0.05 were considered statistically significant.The mean length of the umbilical cord was 56.12±8.38 cm, the number of umbilical cord rings was 13.70±3.51, and the UCI was 0.24±0.07. In the regression analysis, women with gestational diabetes had a significant association with abnormal UCI (P = 0.044). Thus, the probability of abnormal UCI was about 3.5 times higher in women with gestational diabetes than in normal pregnancies. Also, the history of stillbirth had a significant association with abnormal UCI (P < 0.05).It is recommended to perform a UCI examination after delivery as part of a neonatal examination to find an explanation for maternal, fetal, and neonatal outcomes. [ABSTRACT FROM AUTHOR]

Aim Methods Results Conclusions Prenatal maternal depression is known to affect the neurodevelopment of offspring. This study aimed to investigate the profile of umbilical cord serum in mothers with major depressive disorder (MDD).Liquid chromatography–tandem mass spectrometry (LC–MS) was conducted using umbilical cord serum from mothers with MDD (n = 5) and controls (control, n = 5). The levels of several differentially expressed proteins in umbilical cord serum were compared between the MDD (n = 10) and control groups (n = 10) by enzyme‐linked immunosorbent assay.The proteomic profiles in the umbilical cord serum were different between the MDD and control groups, including the pathways of regulation of plasma lipoprotein particle levels, and synapse organization. Only apolipoprotein A4 (APOA4) was significantly higher in the cord blood of MDD group. APOA4 levels in maternal serum were also significantly higher in the MDD group than those in the control group. The APOA4 levels in the umbilical cord serum were higher than that in the maternal serum.The levels of APOA4, a biomarker of depression, in the umbilical cord serum at birth were elevated in the neonates of MDD mothers. It is, therefore, likely that fetuses of MDD mothers were exposed to higher APOA4 levels in utero and this could have developmental and mental health implications for the offspring. [ABSTRACT FROM AUTHOR]

Purpose Methods Results Conclusion Level of Evidence This systematic review aimed to investigate in animal models the presence of disease‐modifying effects driven by non‐bone marrow‐derived and non‐adipose‐derived products, with a particular focus on umbilical cord and placenta‐derived cell‐based therapies for the intra‐articular injective treatment of osteoarthritis (OA).A systematic review was performed on three electronic databases (PubMed, Web of Science and Embase) according to PRISMA guidelines. The results were synthesised to investigate disease‐modifying effects in preclinical animal studies comparing injectable umbilical cord, placenta, and other sources‐derived products with OA controls. The risk of bias was assessed using the SYRCLE tool.A total of 80 studies were included (2314 animals). Cell therapies were most commonly obtained from the umbilical cord in 33 studies and placenta/amniotic tissue in 18. Cell products were xenogeneic in 61 studies and allogeneic in the remaining 19 studies. Overall, 25/27 (92.6%) of studies on umbilical cord‐derived products documented better results compared to OA controls in at least one of the following outcomes: macroscopic, histological and/or immunohistochemical findings, with 19/22 of studies (83.4%) show positive results at the cartilage level and 4/6 of studies (66.7%) at the synovial level. Placenta‐derived injectable products documented positive results in 13/16 (81.3%) of the studies, 12/15 (80.0%) at the cartilage level, and 2/4 (50.0%) at the synovial level, but 2/16 studies (12.5%) found overall worse results than OA controls. Other sources (embryonic, synovial, peripheral blood, dental pulp, cartilage, meniscus and muscle‐derived products) were investigated in fewer preclinical studies. The risk of bias was low in 42% of items, unclear in 49%, and high in 9% of items.Interest in cell‐based injectable therapies for OA treatment is soaring, particularly for alternatives to bone marrow and adipose tissue. While expanded umbilical cord mesenchymal stem cells reported auspicious disease‐modifying effects in preventing OA progression in animal models, placenta/amniotic tissue also reported deleterious effects on OA joints. Lower evidence has been found for other cellular sources such as embryonic, synovial, peripheral blood, dental‐pulp, cartilage, meniscus, and muscle‐derived products.Level II. [ABSTRACT FROM AUTHOR]

Chronic liver injuries and their complications are leading causes of death, especially in developing countries (Sharma and Nagalli in Sex/Gender-Specific Medicine in the Gastrointestinal Diseases, StatPearls Publishing, 2023). The available and effective treatment plans are limited, implicating the need for innovative treatment approaches (Tsuchiya et al. in Inflamm Regener, 2019;Sharma and Nagalli in Sex/Gender-Specific Medicine in the Gastrointestinal Diseases, StatPearls Publishing, 2023;Younossi et al. in Clin Gastroenterol Hepatol 21:1978–1991, 2023;). This paper aims to summarize the effects and mechanisms of hUC-MSC-exo on liver injuries and its complications; it also suggests future directions for future research. The outcomes of interest are the morphology and histology of the liver, pathology score, liver function enzyme, glucose and lipid metabolism, and the effect hUC-MSC-exo had on gene regulation regarding liver diseases. A comprehensive review of nineteen studies was conducted to assess the effectiveness of the implementation of the hUC-MSC-Exo, instilling confidence in the validity of the findings. Regarding the morphology and histology of the liver and pathology score, hUC-MSC-exo treatment resulted in improved liver morphology post-treatment, as indicated by the reduction in pathology scores. However, these observed improvements in the liver surface are not directly attributed to the hUC-MSC-Exo itself but to the overall healing processes stimulated by the treatment. In physiological outcomes, hUC-MSC-exo also improves glucose and lipid metabolism, especially in diet-induced liver injury and its complications. In gene regulation, one interesting gene in this intervention is the fat mass and obesity-associated (FTO), in which hUC-MSC-exo combined with miRNAs can suppress FTO. HUC-MSC-Exo can improve by utilizing several possible pathways, targeting pinpoints in the pathogenesis of liver disease or glucose and lipid metabolism. This study presents hUC-MSC-exo better in all outcomes of interest compared to the control or sham group. Further specification of indications of the hUC-MSC-exo method may be beneficial and essential to be analyzed in future reviews to better understand the effectiveness of each hUC-MSC-exo dose, duration, and medium. [ABSTRACT FROM AUTHOR]

Different wavelengths emitted from light-emitting diodes (LEDs) are known as an influential factor in proliferation and differentiation of various cell types. Since human umbilical cord matrix-derived mesenchymal cells (hUCMs) are ideal tools for human regenerative medicine clinical trials and stem cell researches, in the present study we investigated the neurogenesis effects of single and intermittent green and red LED irradiation on hUCM cells. Exposure of hUCMs to single and intermittent green (530 nm, 1.59 J/cm2) and red (630 nm, 0.318 J/cm2) lights significantly increased the expression of specific genes including nestin, β-tubulin III and Olig2. Additionally, immunocytochemical analysis confirmed the expression of specific neural-related proteins including nestin, β-tubulin III, Olig2 and GFAP. Also, alternating exposure of hUCM cells to green and red lights increased the expression of some neural markers more than either light alone. Further research are required to develop the application of LED irradiation as a useful tool for therapeutic purposes including neural repair and regeneration. [ABSTRACT FROM AUTHOR]

Human umbilical cord mesenchymal stem cell-derived exosomes (hucMSC-Ex) have emerged as a new treatment strategy for inflammatory bowel disease (IBD) due to their immunoregulatory function. N6-methyladenosine (m6A) plays a crucial role in regulating intestinal immunity, especially in IBD where macrophages play an important role, although its mechanism is not yet fully understood. From this perspective, this research aimed to evaluate the effect of hucMSC-Ex on m6A modification of macrophages in IBD. In the process of alleviating inflammation, hucMSC-Ex promotes macrophage polarization toward the M2 type and regulates intracellular m6A levels by upregulating the expression of m6A "Writer" METTL3 and "Reader" YTHDF1. Solute Carrier Family 37 Member 2 (Slc37a2) was identified by Methylation RNA immunoprecipitation sequencing as the target molecule of the hucMSC-Ex. Mechanically, hucMSC-Ex promoted the binding of METTL3 to the Slc37a2 mRNA complex, and enhanced the binding of Slc37a2 to YTHDF1 to upregulate the intracellular expression of Slc37a2, thereby attenuating the pro-inflammatory function of macrophage. This study confirms the modulatory role of hucMSC-Ex on the m6A modification of macrophages in IBD, providing a new scientific basis for the treatment of IBD with hucMSC-Ex. [ABSTRACT FROM AUTHOR]

Background: Facilitating the healing process of injured anterior cruciate ligament (ACL) tissue is crucial for patients to safely return to sports. Stem cell derived exosomes have shown positive effects on enhancing the regeneration of injured tendons/ligaments. However, clinical application of exosomes in terms of storage and pre-assembly is challenging. We hypothesized that lyophilized exosomes derived from human umbilical cord stem cells (hUSC-EX) could enhance the cell activity of chronically injured ACL cells. Materials and methods: We harvested the 8 weeks injured ACL cells from rabbit under IACUC (No. 110232) approval. The studied exosomes were purified from the culture medium of human umbilical cord stem cells (IRB approval No. A202205014), lyophilized to store, and hydrated for use. We compared exosome treated cells with non-exosome treated cells (control group) from the same rabbits. We examined the cell viability, proliferation, migration capability and gene expression of type I and III collagen, TGFβ, VEGF, and tenogenesis in the 8 weeks injured ACL cells after hUSC-EX treatment. Results: After hydration, the average size of hUSC-EX was 84.5 ± 70.6 nm, and the cells tested positive for the Alix, TSG101, CD9, CD63, and CD81 proteins but negative for the α-Tubulin protein. After 24 h of treatment, hUSC-EX significantly improved the cell viability, proliferation and migration capability of 8 weeks injured ACL cells compared to that of no exosome treatment group. In addition, the expression of collagen synthesis, TGFβ, VEGF, and tenogenesis gene were all significantly increased in the 8 weeks injured ACL cells after 24 h hUSC-EX delivery. Discussion: Lyophilized exosomes are easily stored and readily usable after hydration, thereby preserving their characteristic properties. Treatment with lyophilized hUSC-EX improved the activity and gene expression of 8 weeks injured ACL cells. Conclusion: Lyophilized hUSC-EX preserve the characteristics of exosomes and can improve chronically injured (8 weeks) ACL cells. Lyophilized hUSC-EX could serve as effective and safe biomaterials that are ready to use at room temperature to enhance cell activity in patients with partial ACL tears and after remnant preservation ACL reconstruction. [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 purpose of this research is to explore the biomechanical consequences of maternal injuries on fetal movements. Additionally, the research aims to comprehend the relationship between these injuries and fetal movement within the amniotic sac and to understand the extent to which the amniotic fluid can provide protection during severe injuries. The focus is on the potential impact these injuries could have on surgical procedures and preventative strategies. Using advanced computational simulations, the study investigates how various maternal injuries can influence the behavior of amniotic fluid and the subsequent stress exerted on fetal development. The findings suggest that maternal injuries can induce stress, primarily affecting the posterior regions of the fetus and the umbilical cord, depending on the boundary and initial conditions. This stress is associated with fetal displacement within the amniotic sac. While the amniotic fluid provides a certain level of protection, its limitations become apparent during severe injuries. These insights have implications for the field of surgery, particularly fetal procedures. They underscore the need for improved protective measures and the development of personalized obstetric and neonatal care strategies. Moreover, the study highlights the potential of computational simulations in aiding surgeons. These simulations can provide a more accurate understanding of the critical areas to focus on during surgical procedures, thereby enhancing the precision and safety of these operations. [ABSTRACT FROM AUTHOR]

Commonly known as wild pepper, Piper capense (P. capense) is a culinary herb mainly used as a secret in preparation of "Nkui" and "Nah poh" in Bayangam, West Cameroon. However, it also has many interesting pharmacological properties, which is why the people of sub-Saharan Africa so highly prize it for the treatment of multiple human pathologies. This study aimed to highlight the traditional uses, phytochemical composition, biological activities, and toxicological profile of the P. capense plant, to draw the attention of pharmaceutical companies to its enormous potential for the development of future phyto- or pharmaceutical products. Documentary research was meticulously carried out in the Web of Sciences, Scopus, Pubmed/Medline, and Google Scholar databases according to PRISMA 2020 guidelines. The results show that extracts and compounds isolated from Piper capense have interesting anticancer, antibacterial, antimalarial, hypoglycemic, anti-epileptic, and antidepressant activities. Methanolic extracts and essential oils from P. capense exhibit no harmful effects when directly applied to normal human hepatocytes, umbilical cord cells, intestinal cells, and keratinocyte cell lines. Additionally, methanolic extracts administered acutely or subchronically at low doses (≤250 mg/kg body weight) in Wistar rats also demonstrate no adverse effects. In conclusion, given its interesting activities, P. capense is a viable option for developing new antimalarial, anticancer, antibacterial, hypoglycemic, anti-epileptic, and antidepressant drugs. However, many avenues still need to be explored before translation into drugs. [ABSTRACT FROM AUTHOR]

Handmade cloning (HMC) has a higher yield and is relatively less difficult to operate compared to traditional micromanipulation cloning. Yet, there are few reports on handmade cloning in sheep. Therefore, this study investigates the key nodes such as AC and DC voltage, denucleation method and fusion method in sheep handmade cloning. In addition, it compares the effects of fibroblasts (FC) and umbilical cord mesenchymal stem cells (UC‐MSCs) of different states as donors on the development of HMC embryos. Furthermore, the effect of different freezing solutions on the survival rate of frozen blastocysts without zona pellucida was also investigated. The results indicate that an AC voltage of 150 V/cm and a DC voltage of 1800 V/cm significantly enhanced the fusion and blastocyst rates (p <.01). The blastocyst rate achieved with umbilical cord MSCs as nucleus donors was significantly higher (40.3%) than that achieved with fibroblasts and differentiated umbilical cord MSCs (21.5%, 22.5%) (p <.01). The highest survival rate was achieved using 20% DMSO + 20% EG for freezing without zona pellucida. In conclusion, the most efficient and pregnant ovine HMC cloning method using 150 V/cm AC, 1800 V/cm DC, knife‐cut denucleation, two‐step fusion and the use of UC‐MSCs as nucleus donors resulted in the highest overall efficiency and pregnancy after transplantation. [ABSTRACT FROM AUTHOR]

Vascular endothelial cell dysfunction plays an important role in myocardial ischemia–reperfusion (I/R) injury, and pannexin 1 (Panx1), an ATP-permeable channel, is closely associated with the pathophysiological processes of I/R injury. The purpose of this study was to investigate the protective effects of human umbilical cord mesenchymal stromal cell-derived extracellular vesicles (HuMSC-EVs) and the underlying mechanism in a model of I/R injury. For the cellular model of I/R injury, human umbilical vein endothelial cells (HuVECs) were exposed to hypoxia/reoxygenation (H/R) conditions. The model cells were then treated with HuMSC-EVs, and the effects on cell survival and specific signaling activities were observed. The results showed that after H/R exposure, Panx1 expression and other markers of cellular damage were increased in HuVECs. However, treatment with HuMSC-EVs inhibited the H/R-induced increase in Panx1 expression and improved HuVEC survival. Mechanistically, HuMSC-EVs were found to inhibit the p38 mitogen-activated protein kinase (MAPK)-dependent apoptosis pathway, as evidenced by increased Bcl2 expression and reductions in p38 MAPK phosphorylation, Bax expression, and cleaved-caspase 3 expression. Together our data suggest that HuMSC-EVs alleviate H/R-induced apoptosis among HuVECs by inhibiting activity of the Panx1/p38-MAPK-dependent apoptosis pathway. [ABSTRACT FROM AUTHOR]

Purpose: Chronic wounds that are difficult to heal pose a major challenge for clinicians and researchers. Currently, common treatment methods focus on isolating the wound from the outside world, relying on the tissue at the wound site to grow and heal unaided. Umbilical cord mesenchymal stem cell (MSC) exosomes can promote wound healing by enhancing new blood vessel growth at the wound site. Valproic acid (VPA) reduces the inflammatory response and acts on macrophages to accelerate wound closure. In this study, VPA was loaded into umbilical cord MSC exosomes to form a drug carrier exosome (VPA-EXO) with the aim of investigating the effect of VPA-EXO on wound healing. Methods: This study first isolated and obtained umbilical cord MSC exosomes, then added VPA to the exosomes and explored the ability of VPA-EXO to promote the proliferation and migration of human skin fibroblasts (HSFs) and human umbilical vein endothelial cells (HUVECs), as well as the ability to promote the angiogenesis of HUVECs, by using scratch, Transwell, and angiogenesis assays. An in vitro cell model was established and treated with VPA-EXO, and the expression levels of inflammation and pro-angiogenesis-related proteins and genes were examined using Western blot and qRT-PCR. The therapeutic effect of VPA-EXO on promoting wound healing in a whole skin wound model was investigated using image analysis of the wound site, H&E staining, and immunohistochemical staining experiments in a mouse wound model. Results: The in vitro model showed that VPA-EXO effectively promoted the proliferation and migration of human skin fibroblast cells and human umbilical vein endothelial cells; significantly inhibited the expression of MMP-9, IL-1β, IL-8, TNF-α, and PG-E2; and promoted the expression of vascular endothelial growth factors. In the mouse wound model, VPA-EXO reduced inflammation at the wound site, accelerated wound healing, and significantly increased the collagen content of tissue at the wound site. Conclusions: As a complex with dual efficacy in simultaneously promoting tissue regeneration and inhibiting inflammation, VPA-EXO has potential applications in tissue wound healing and vascular regeneration. In future studies, we will further investigate the mechanism of action and application scenarios of drug-loaded exosome complexes in different types of wound healing and vascular regeneration. [ABSTRACT FROM AUTHOR]

Simple Summary: Our study examined the challenges newborn piglets face, comparing those born with growth restriction, those born with low body weight, and those of normal body weight. We aim to understand if their start in life is related to their physical characteristics and whether this affects their chances of survival. We categorized newborn piglets based on their size and physical characteristics immediately after birth. Over three hours, we assigned vitality scores, measured body temperature, and described behaviors such as seeking sow's milk. We found that piglets with growth restrictions had more difficulty keeping warm and feeding than their counterparts with a low and normal body weight at birth. Consequently, they faced a higher mortality rate within the first 24 h after birth. This suggests they need special care to improve their survival and health. Our research highlights the importance of recognizing and addressing the needs of specifically intra-uterine growth-restricted piglets early on to improve the welfare of these growth-restricted piglets. This observational study explored the early-life challenges of intra-uterine growth restricted (IUGR), low birth body weight (LBW), and normal birth body weight (NBW) piglets. The aim was to understand the impact of birth weight and intra-uterine growth restriction phenotype on neonatal survival and behavior. Based on weight and phenotype, piglets were classified as IUGR (n = 32), LBW (n = 34), and NBW (n = 29) immediately after birth. The piglets were litter- and sex-matched. Vitality scores were assigned based on motor activity and breathing and complemented with an assessment of umbilical cord condition, rectal temperature, crown–rump length (CRL), time to reach the udder, time to suckle, colostrum intake, and weight gain over 24 h. Beyond the lower birth weight, reduced CRL, and higher mortality rate, IUGR piglets faced several other challenges compared with LBW and NBW piglets. Growth-impaired piglets often struggled to engage in early feeding behaviors and displayed consistently lower rectal temperatures at 1, 3 and 24 h after birth. IUGR piglets showed inadequate colostrum intake and weight loss, which were also observed for LBW counterparts. In contrast, no significant differences were observed in vitality scores and umbilical cord conditions across the groups. In conclusion, our findings underscore the impact of intra-uterine growth restriction on neonatal piglets, emphasizing the need for specialized care strategies to improve survival and health outcomes in IUGR. [ABSTRACT FROM AUTHOR]

Background: Mesenchymal stem cells (MSCs) play a key role in regenerative medicine due to their capacity to differentiate into multiple cell lines, regulate the immune system, and exert paracrine effects. The therapeutic impact of MSCs is primarily mediated through their secretome. The secretory and therapeutic potential of MSCs can be improved through preconditioning, which entails the application of hypoxic environments, 3-dimensional cell cultures, and pharmacological agents. Valproic acid (VPA) is a histone deacetylase inhibitor that is employed in medical practice for treating epilepsy and bipolar disorder. Hence, preconditioning MSCs with VPA is expected to induce histone acetylation, enhance gene expression, and beneficially modify the cells' secretomes. Aims: To assess the effectiveness of VPA in enhancing and regulating the therapeutic potential of cells as well as its impact on MSC secretome profiles and ultrastructural morphologies. Study Design: Expiremental study. Methods: Human umbilical cord MSCs were preconditioned with 2 mM VPA for 24 and 48 hours; untreated MSCs served as controls. The secretome secreted by the cells was assessed for its total protein content. Subsequently, interferon-gamma (IFN-γ), interleukin-17 (IL-17), IL-10, vascular endothelial growth factor, nerve growth factor (NGF), glial cell line-derived neurotrophic factor, and brain-derived neurotrophic factor (BDNF) levels in the secretome were analyzed using the ELISA method. The ultrastructural properties of the cells were studied under transmission electron microscopy. Results: Ultrastructural examinations revealed that the chromatin content of VPA-treated cells was reduced. VPA-preconditioned cells exhibited a higher density of rough endoplasmic reticulum, autophagic vesicles, and myelin figures on cytoplasmic structure analysis, which was indicative of increased secretion. Protein secretion was elevated in those cells, with notable increases in NGF and BDNF levels. Furthermore, the cytoskeletal rearrangement and elevated autophagic activity observed in the 48-hour preconditioned cells could indicate the initiation of neuronal differentiation. IL-10, IL-17, and IFN-γ were not detected in the secretome. Conclusion: This study indicate that preconditioning with VPA enhances MSC activity and subsequently modifies the secretome content. [ABSTRACT FROM AUTHOR]

A recent article in Global Medical Genetics discusses the use of mesenchymal stem cells (MSCs) in clinical trials for immune disorders. MSCs have unique properties, including regeneration and immunomodulation, which make them a promising therapeutic approach. The article highlights a phase I trial that used human umbilical cord-derived MSCs (UC-MSCs) to treat refractory immune thrombocytopenia (ITP), a hemorrhagic disease resulting from an immune imbalance. The trial showed that UC-MSCs increased platelet counts and improved bleeding symptoms in patients with refractory ITP. MSCs have the potential to treat various immune-related conditions, and further research is needed to understand their distribution and metabolism in organ tissues. [Extracted from the article]

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]

Human umbilical cord (UC) is an attractive source of mesenchymal stromal/stem cells (MSCs) for tissue engineering and regenerative medicine due to its easy availability, non-invasive procedure of collection, and no ethical concerns. The aim of this study was to isolate MSCs from the Wharton's jelly (WJ) and subamnion (SA) from the same umbilical cord by an optimized explant method, and to compare the morphology, proliferation, and stemness properties of the MSCs from both sources. Cells from the WJ and SA of six umbilical cords were characterized by flow cytometry, differentiation capacity and proliferation assays, immunofluorescence staining, and RT-PCR. The optimized explant method was successfully used to isolate WJ-MSCs and SA-MSCs. The MSCs from both sources showed similar patterns of growth kinetics, adipogenic and osteogenic potential, and the expression of pluripotency markers (OCT4, SOX2, NANOG, and SSEA-4). The current findings support the usage of the optimized explant method to generate a relatively homogenous population of MSCs from Wharton's jelly and subamnion, which can facilitate the reproducibility of the results from experimental and practical applications of the obtained cells. [ABSTRACT FROM AUTHOR]

Background: This study aimed to evaluate the umbilical cord blood chondroitin sulfate proteoglycan 4 (CSPG4) concentrations in pregnancies complicated with fetal growth restriction (FGR) and aimed to investigate the relationship between the CSPG4 levels in these pregnancies and adverse neonatal outcomes. Methods: This prospective case-control study was conducted between August 2023 and January 2024. The study included 80 singleton pregnancies at 35 to 39 weeks of gestation. Among these, 40 were diagnosed with FGR and 40 served as the control group. After the delivery, samples of the cord blood were collected prior to the placental delivery. Results: The CSPG4 levels were significantly higher in the study group (FGR), 1,153 (1,059 - 1,261) pg/mL, than in the control group, 1,107 (873 - 1,197) pg/mL (p = 0.024). When all patients were evaluated, the CSPG4 levels showed a positive correlation with the systolic/diastolic (S/D) ratio of the umbilical arteries (r = 0.276, p = 0.013). A statistically significant negative correlation was observed between the levels of CSPG4 in the umbilical cord blood and the Apgar scores at the 1st (r = -0.256, p = 0.022) and 5th (r = -0.250, p = 0.026) minutes. The discriminatory power of the umbilical cord CSPG4 level in the determination of composite adverse neonatal outcomes was evaluated by ROC analysis and a cutoff point of > 1,091.25 pg/mL, showing a sensitivity of 93.3%, a specificity of 46.2%, and an AUC of 0.661 (95% CI: 0.547 - 0.763, p = 0.019). Conclusions: Elevated levels of CSPG4 have been observed in the umbilical cord blood in pregnancies complicated by FGR; higher levels are associated with adverse neonatal outcomes. [ABSTRACT FROM AUTHOR]

Abstract Background Simulation training provides safe environment for skill acquisition and retention. This study addresses a critical challenge in Africa – umbilical cord and placenta management after childbirth – aiming to bridge theoretical learning with practical experiences through simulation. We realized a new low-cost high-fidelity simulator of placenta and umbilical cord. We conducted a needs-based training course for nursing and midwifery students at St. Luke Hospital of Wolisso, Ethiopia, to validate our new simulator and compare its acceptability and teaching effectiveness with other two simulators (conventional low-fidelity model and human placenta). Methods We surveyed St. Luke Hospital medical experts to obtain their feedback on the new simulator’s face, content, and usability. We carried out a simulation training course for 67 students who received theoretical lectures and simulation courses being divided into three groups according to the simulator used. We assessed the simulators’ user acceptability using the Technology Acceptance Model (TAM) and compared the final objective evaluations by tutors between groups. Results Experts confirmed the new simulator’s fidelity, material quality, and usability. Students training on the new simulator demonstrated higher objective scores and perceived it as more useful and user-friendly compared to human placenta, while there was no difference between conventional simulator and human placenta in the TAM items. Conclusion We validated a new high-fidelity simulator developed by the Sant’Anna School of Advanced Studies in Pisa, Italy, using the TAM scale and robust statistical methods, thanks to a successful collaboration with St. Luke’s Hospital in a simulation training course where students achieved higher objective scores and perceived the simulator as more useful and easier to use than a real human placenta, suggesting significant educational benefits and potential for future research.

Abstract Esophageal fibrosis can develop due to caustic or radiation injuries. Umbilical cord–derived mesenchymal stem cells (UC-MSCs) are known to mitigate fibrosis in various organs. However, the potential effects of UC-MSCs on human esophageal fibrosis remain underexplored. This study investigated the anti-fibrogenic properties and mechanisms of UC-MSC-derived conditioned media (UC-MSC-CM) on human esophageal fibroblasts (HEFs). HEFs were treated with TGF-β1 and then cultured with UC-MSC-CM, and the expression levels of extracellular matrix (ECM) components, RhoA, myocardin related transcription factor A (MRTF-A), serum response factor (SRF), Yes-associated protein (YAP), and transcriptional coactivator with PDZ-binding motif (TAZ) were measured. UC-MSC-CM suppressed TGF-β1-induced fibrogenic activation in HEFs, as evidenced by the downregulation of ECM. UC-MSC-CM diminished the expression of RhoA, MRTF-A, and SRF triggered by TGF-β1. In TGF-β1-stimulated HEFs, UC-MSC-CM decreased the nuclear localization of MRTF-A and YAP. Additionally, UC-MSC-CM diminished the TGF-β1-induced nuclear expressions of YAP and TAZ, while concurrently enhancing the cytoplasmic presence of phosphorylated YAP. Furthermore, UC-MSC-CM reduced TGF-β1-induced phosphorylation of Smad2. These findings suggest that UC-MSC-CM may inhibit TGF-β1-induced fibrogenic activation in HEFs by targeting the Rho-mediated MRTF/SRF and YAP/TAZ pathways, as well as the Smad2 pathway. This indicates its potential as a stem cell therapy for esophageal fibrosis.

Abstract Background Bone defects, especially critical-size bone defects, and their repair pose a treatment challenge. Osteoinductive scaffolds have gained importance given their potential in bone tissue engineering applications. Methods Polycaprolactone (PCL) scaffolds are used for their morphological, physical, cell-compatible and osteoinductive properties. The PCL scaffolds were prepared by electrospinning, and the surface was modified by layer-by-layer deposition using either graphene or graphene oxide. Results Graphene oxide-coated PCL (PCL-GO) scaffolds showed a trend for enhanced physical properties such as fibre diameter, wettability and mechanical properties, yield strength, and tensile strength, compared to graphene-modified PCL scaffolds (PCL-GP). However, the surface roughness of PCL-GP scaffolds showed a higher trend than PCL-GO scaffolds. In vitro studies showed that both scaffolds were cell-compatible. Graphene oxide on PCL scaffold showed a trend for enhanced osteogenic differentiation of human umbilical cord Wharton’s jelly-derived Mesenchymal Stem Cells without any differentiation media than graphene on PCL scaffolds after 21 days. Conclusion Graphene oxide showed a trend for higher mineralisation, but this trend is not statistically significant. Therefore, graphene and graphene oxide have the potential for bone regeneration and tissue engineering applications. Future in vivo studies and clinical trials are warranted to justify their ultimate clinical use. Graphical abstract

background: Poor cord care practices contribute to neonatal morbidity and mortality resulting from neonatal infections including tetanus. Identification of negative practices should ultimately improve care and neonatal outcome. Objective: To evaluate cord care practices among mothers attending the Well Baby/Immunization Clinic of the University of Benin Teaching Hospital (UBTH), Benin City. Subjects and Methods: Four hundred and ninety-seven mothers who brought their babies to Well Baby/Immunization Clinic in UBTH between July and August 2009 were interviewed. A structured, pretested questionnaire was used as test instrument to investigate the care of the umbilical cord of their infants in their last deliveries. Results: Harmful or non-beneficial cord care practices were common (79.5%) among mothers in Benin City. Most delivery units used thread (65.6%) and plastic cord clamp (22.7%) to secure haemostasis at the umbilical stump. Other materials used include suture materials, strips of cloth, bandage, plaster and rubber band. Majority of the mothers practiced hand washing before (86.9%) and after (89.3%) cord care. The traditional practices of cord care in Benin City include the use of hot compress (46.1%), menthol-containing balm, herbs, native chalk, petroleum jelly, palm oil, toothpaste (Close-up ), salt, sand and saliva. The most common single agent for cord treatment was alcohol (methylated spirit). \ Conclusion: The attendant risks associated with harmful cord care practices remain real in our communities. There is need for education of the public, using the mass media and health talks in health facilities, to discourage harmful cord care practices while reinforcing beneficial ones.

Background: The interval between delivery and umbilical cord separation varies worldwide. Some maternal, foetal and perinatal factors including cord care practices are known to affect this interval. Objectives: To establish the mean umbilical cord separation time and the effect of maternal and infant characteristics, perinatal factors and cord care practices on this time among healthy babies in northern Nigeria. Methods: An interviewer questionnaire was administered on mothers of healthy babies at Child Welfare Clinics of a tertiary and secondary level hospital in Kano. In each case, information was obtained about mother's parity, place of antenatal care and delivery, gestational age, birth weight, time of umbilical cord separation after birth and cord treatment practices. Results: Five hundred and seventy seven (96.2 percent) of 600 mothers interviewed, took part in the study, four of these mothers had twin gestation. Responses showed that cord separation time ranged from 2 -14 days (4.20 1.70)Three hundred and forty nine (60.9. p e r c e n t ) mo t h e r s a p p l i e d methylated spirit, 145 (25.3 percent) used hot compress, while 50 (8.7 percent) applied toothpaste on the cord. Twenty (3.5 percent) others applied herbs, while nine (1.6 percent) applied dusting powder to the umbilical stump. Cord separation time wa s significantly shorter among babies whose mothers were of high parity, unbooked, and of low educational status. In addition, the use of razor blade, thread, hot compress or application of herbal preparations or toothpaste significantly shortened the separation time (P

Background: The APGAR scoring system, including conventional, expanded, and combined Apgar scores, has been used to evaluate the condition of the newborn in the first minutes of birth. Umbilical cord arterial blood gas analysis (UCABGA) is another method. We compared the combined Apgar score with UCABGA in predicting short-term outcomes in neonates. Methods: A prospective cohort study was conducted on 363 live births. Neonates with major congenital anomalies, congenital cyanotic heart disease, congenital metabolic disorders, and those who transferred to other hospitals were excluded. Admission, discharge, demographic data, and Apgar scores were recorded in a pre-designed form. After delivery, the umbilical cord was double-clamped, and an arterial blood sample was taken from the clamped part. Statistical analyses were done using SPSS version 22 statistical software, and the receiver operating characteristic (ROC) curve was used to analyze the correlations between variables. Results: Out of 350 Neonates (204 male and 146 female) with a mean gestational age of 33.37±4.12 weeks, 263 (75.1%) neonates were admitted, and 34 neonates (9.7%) died. Retinopathy of prematurity(ROP) and Intraventricular hemorrhage (IVH) were recognized in 42 (12%) and 54 (15.4%) neonates, respectively, and 37 ( 10.6%) neonates ventilated mechanically. ROC curves show higher sensitivity and Specificity of 5th minute Combined Apgar score than PH and base deficit in predicting short-term outcomes except for IVH. Conclusion: The Combined Apgar score at minute 5 is a better predictor than UCABGA in predicting Death, need for admission, retinopathy of prematurity, and need for mechanical ventilation. None are good predictors for IVH.

Introduction: Human umbilical cord-derived mesenchymal stem cells (UC-MSCs) are promising candidates for stem cell therapy. Various methods such as enzymatic treatment, cell scraping, and temperature reduction using temperature-responsive cell culture dishes have been employed to culture and harvest UC-MSCs. However, the effects of different harvesting methods on cell properties and functions in vitro remain unclear. In this study, we investigated the properties and functions of UC-MSC using various cell-harvesting methods. Methods: UC-MSC suspensions were prepared using treatments with various enzymes, cell scraping, and temperature reduction in temperature-responsive cell culture dishes. UC-MSC sheets were prepared in a temperature-responsive cell culture dish. The properties and functions of the UC-MSC suspensions and sheets were assessed according to Annexin V staining, lactate dehydrogenase (LDH) assay, re-adhesion behavior, and cytokine secretion analysis via enzyme-linked immunosorbent assay. Results: Annexin V staining revealed that accutase induced elevated UC-MSC apoptosis. Physical scraping using a cell scraper induced a relatively high LDH release due to damaged cell membranes. Dispase exhibited relatively low adhesion from initial incubation until 3 h. UC-MSC sheets exhibited rapid re-adhesion at 15 min and cell migration at 6 h. UC-MSC sheets expressed higher levels of cytokines such as HGF, TGF-β1, IL-10, and IL-6 than did UC-MSCs in suspension. Conclusions: The choice of enzyme and physical scraping methods for harvesting UC-MSCs significantly influenced their activity and function. Thus, selecting appropriate cell-harvesting methods is important for successful stem cell therapy.

Background: Bone defects, especially critical-size bone defects, and their repair pose a treatment challenge. Osteoinductive scaffolds have gained importance given their potential in bone tissue engineering applications. Methods: Polycaprolactone (PCL) scaffolds are used for their morphological, physical, cell-compatible and osteoinductive properties. The PCL scaffolds were prepared by electrospinning, and the surface was modified by layer-by-layer deposition using either graphene or graphene oxide. Results: Graphene oxide-coated PCL (PCL-GO) scaffolds showed a trend for enhanced physical properties such as fibre diameter, wettability and mechanical properties, yield strength, and tensile strength, compared to graphene-modified PCL scaffolds (PCL-GP). However, the surface roughness of PCL-GP scaffolds showed a higher trend than PCL-GO scaffolds. In vitro studies showed that both scaffolds were cell-compatible. Graphene oxide on PCL scaffold showed a trend for enhanced osteogenic differentiation of human umbilical cord Wharton's jelly-derived Mesenchymal Stem Cells without any differentiation media than graphene on PCL scaffolds after 21 days. Conclusion: Graphene oxide showed a trend for higher mineralisation, but this trend is not statistically significant. Therefore, graphene and graphene oxide have the potential for bone regeneration and tissue engineering applications. Future in vivo studies and clinical trials are warranted to justify their ultimate clinical use. [ABSTRACT FROM AUTHOR]