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Background: Mesenchymal stem cells (MSCs) have shown potential in repairing chemotherapy-induced premature ovarian failure (POF). However, challenges such as stem cell loss and immune phagocytosis post-transplantation hinder their application. Due to easy and safe handling, in vitro ovarian culture is widely available for drug screening, pathophysiological research, and in vitro fertilization. MSCs could exhibit therapeutic capacity for ovarian injury, and avoid stem cell loss and immune phagocytosis in vitro tissue culture system. Therefore, this study utilizes an in vitro ovarian culture system to investigate the reparative potential of human umbilical cord mesenchymal stem cells (hUCMSCs) and their mechanism. Methods: In this study, a chemotherapy-induced POF model was established by introducing cisplatin in vitro ovarian culture system. The reparative effects of hUCMSCs on damaged ovarian tissue were validated through Transwell chambers. Tissue histology examination, immunohistochemical staining, Western blotting, and RT-PCR were employed to evaluate the expression effects of hUCMSCs on ferroptosis and fibrosis-related genes during the process of repairing cisplatin-induced POF. Results: Cisplatin was found to activate ovarian follicles in vitro POF model. Transcriptomic sequencing analysis revealed that cisplatin could activate genes associated with ferroptosis. hUCMSCs alleviated cisplatin-induced POF by suppressing the expression of ferroptosis. Moreover, inhibiting ferroptosis by hUCMSCs also ameliorated ovarian hormone levels and reduced the expression of fibrosis-related factors α-SMA and COL-I in the ovaries. Conclusions: This study confirms that cisplatin-induced ovarian damage via ferroptosis in vitro POF model, and hUCMSCs repair ovarian injury by inhibiting the ferroptosis pathway and suppressing fibrosis. This research contributes to evaluating the effectiveness of hUCMSCs in treating chemotherapy-induced POF by inhibiting ferroptosis in an in vitro ovarian culture system and provides a potential therapeutic strategy for chemotherapy-induced POF. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is a major global concern. Mesenchymal stem cell-derived exosomes (MSC-EXOs) have demonstrated efficacy as a therapeutic approach for colorectal cancer. However, the precise mechanism by which MSC-EXOs treat colorectal cancer remains unclear. Human umbilical cord (hUC)-MSC-EXOs were isolated and identified. Cell Counting Kit-8 (CCK-8), Transwell, and colony formation assays were used to assess the activity of CRC cells. Glucose consumption, lactic acid production, and extracellular acidification rate (ECAR) were measured to assess glycolytic activity. Cell stemness was assessed using a sphere-formation assay. Furthermore, MSC-exosomal microRNAs (miRNAs) in CRC tissues were analyzed using the EVmiRNA database, and aberrantly expressed miRNAs in CRC cells were obtained from the Gene Expression Omnibus (GEO) database. The binding relationship between miR-486-5p and the never in mitosis gene A-related kinase 2 (NEK2) was predicted using the Starbase database and validated through RNA binding protein immunoprecipitation (RIP) and dual luciferase assays. These results showed that hUC-MSC-EXOs inhibited the proliferation and metastasis of CRC cells. Moreover, glycolysis and stemness abilities of CRC cells also decreased after treatment with hUC-MSC-EXOs. miR-486-5p was found to be enriched in hUC-MSC-EXOs and significantly downregulated in CRC cells. miR-486-5p directly bound to NEK2. Overexpression of NEK2 reversed the inhibitory effect of miR-486-5p on CRC cell glycolysis and stemness. Our study highlights that hUC-MSC-EXO miR-486-5p inhibits glycolysis and cell stemness in CRC by targeting NEK2. This finding offers compelling evidence supporting the potential application of hUC-MSC-EXOs in the treatment of CRC. [ABSTRACT FROM AUTHOR]

The 2016 Amsterdam Placental Workshop Group Consensus Statement recommends sampling a block of the placenta close to the umbilical cord insertion site (UCIB) for histopathological evaluation. This piece of placenta at the umbilical cord insertion is presumed to give a better yield of inflammation (if present). We aimed to investigate the utility of the UCIB in the detection of maternal and/or fetal inflammatory responses (MIR and/or FIR), in comparison with the other sections of the placental parenchyma. This is a retrospective cross‐sectional study including all placentas with histologic chorioamnionitis. The histopathological slides of placentas were reviewed as per Amsterdam consensus guidelines. Diagnostic performance of UCIB in identifying MIR and/or FIR, relative to the other placental sections, was assessed. UCIB revealed diagnostic sensitivity, specificity, and diagnostic accuracy of 79.2% (95% CI: 74.2–83.6%), 100.0% (95% CI: 95.6–100.0%), and 83.6% (95% CI: 79.5–87.2%), respectively, in the detection of FIR, while showing a low sensitivity of 52.6% (95% CI: 47.5–57.6%) in detecting MIR. In 59 (24.6%) cases, FIR was not seen in the corresponding placental parenchymal sections but was detected in the UCIBs. This study is the first study to confirm that a section from the UCIB is essential for the detection of FIR, which affirms the Amsterdam consensus sampling recommendations. [ABSTRACT FROM AUTHOR]

Objective Materials and Methods Results Conclusion This retrospective study aimed to compare the outcomes of dinoprostone vaginal insert (PROPESS) and double balloon cook catheter (DBC) in term nulliparous pregnancies.A total of 1682 cases were enrolled, all of which were divided into two groups: PROPESS and DBC. The primary outcomes were rate of vaginal delivery (VD) and cesarean section (CS) and successful VD within 24 h and CS indications; the secondary outcomes were labor duration, oxytocin augmentation, complications during labor, maternal/neonatal outcomes, and predictors of successful VD within 24 h.There was no statistical difference in the rates of VD between the PROPESS group (73.74%) and the DBC group (77.73%) (p = 0.36). The VD rate within 24 h was significantly higher in PROPESS group than in the DBC group (55.45% vs. 38.43%, p < 0.001). The occurrence of nonreassuring fetal heart rate (NRFHR) patterns was higher in the CS indications of the PROPESS group than in the DBC group (56.86% vs. 37.81%, p < 0.001). The oxytocin augmentation was significantly lower in the PROPESS group than in the DBC group (52.79% vs. 94.9%, p < 0.001). The incidence of chorioamnionitis was significantly higher in the DBC group as compared with PROPESS group (4.36% vs. 1.34%, p < 0.001), while neonatal outcomes were comparable between the two groups. PROPESS (p < 0.001, odds ratio [OR] 2.478, 95% confidence interval [CI] 1.718–3.574), oxytocin augmentation (p < 0.001, OR 32.759, 95% CI 20.654–51.958), and amniotomy (p = 0.016, OR 1.897, 95% CI 1.331–2.704) were predictors of VD within 24 h.The effectiveness of delivery was comparable between the two groups. The PROPESS group resulted in a high successful VD rate within 24 h, although accompanied by NRFHR occurrence. Two cases with fetal presentation change (cephalic to breech) and four cases with umbilical cord prolapse were observed in the DBC group. PROPESS, oxytocin augmentation, and amniotomy were associated with VD interval within 24 h. [ABSTRACT FROM AUTHOR]

Background: Understanding how C-peptide levels in the umbilical cord can be used to predict when a diabetic mother's newborn will experience hypoglycemia is urgently needed. This study aimed to assess the role of umbilical cord C-peptide levels in the early prediction of hypoglycemia among neonates of diabetic mothers. Methods: We carried out this cross-sectional study on 52 singleton newborns born to diabetic mothersin the neonatal resuscitation room and obstetric operation room at Zagazig University Hospital. The umbilical cord C-peptide concentration was assessed via an enzyme-linked immunosorbent assay. Complete blood count, blood glucose level, insulin level, and glycated hemoglobin (HbA1C), were performed for neonates and mothers. Neonatal blood glucose was measured hourly three times. Results: A significant association was found between neonatal C-peptide levels and maternal premature rupture of membranes (p=0.013). Compared to normoglycemic neonates, hypoglycemic neonates had significantly higher C peptide levels (p<0.001). The best cut-off value of neonatal C-peptide for the prediction of neonatal hypoglycemia is =0.3685 ng/ml, with an area under the curve of 0.963, a sensitivity of 88.9%, a specificity of 88.4%, a positive predictive value of 61.5%, a negative predictive value of 97.4%, and accuracy of 88.5% (p<0.001). Conclusions: This study underscores the importance of monitoring umbilical cord C-peptide levels as a potential early predictor of neonatal hypoglycemia among infants born to diabetic mothers. [ABSTRACT FROM AUTHOR]

Mesenchymal stem cells have made remarkable progress in recent years. Many studies have reported that human umbilical cord mesenchymal stem cells (hUC-MSCs) have no toxicity, but thromboembolism appeared in patients treated with hUC-MSCs. Therefore, people are still worried about the safety of clinical application. The study aims to determine the safety, potential toxic mechanism and biodistribution of hUC-MSCs. F344RG rats were given 5 or 50 million cells/kg of hUC-MSCs by single administration in compliance with Good Laboratory Practice standards. Standard toxicity was performed. RNA sequencing was then performed to explore the potential toxic mechanisms. In parallel, the biodistribution of hUC-MSCs was examined. The dose of 5 million cells/kg hUC-MSCs had no obvious toxicity on symptom, weight, food intake, hematology, serum biochemistry, urine biochemistry, cytokines, and histopathology. However, blood-tinged secretions in the urethral orifice and 20% mortality occurred at 50 million cells/kg. Disseminated intravascular coagulopathy (DIC) is the leading cause of death. hUC-MSCs significantly upregulated complement and coagulation cascade pathways gene expression, resulting in DIC. Besides, hUC-MSCs upregulated fibrinolytic system suppressor genes A2m, Serping1 and Serpinf2. hUC-MSCs survived in rats for less than 28 days, no hUC-MSC was detected in tissues outside the lungs. There was no toxicity in F344RG rats at 5 million cells/kg, but some toxicities were detected at 50 million cells/kg. hUC-MSCs significantly upregulated complement and coagulation cascade pathways, upregulated the expression of fibrinolytic system suppressor genes A2m, Serping1 and Serpinf2, to inhibit fibrinolytic system, caused DIC, which provided a new insight into the toxic mechanism of hUC-MSCs. [ABSTRACT FROM AUTHOR]

Introduction: Fetal inflammatory response syndrome associated with acidosis during labor is a high‐risk situation for the fetus. This study evaluated hemodynamic, gasometric, and heart rate variability changes during acute fetal inflammatory response syndrome associated with hypoxia, compared with isolated hypoxia. Material and Methods: Acute fetal inflammatory response syndrome was obtained via an intravenously injection of lipopolysaccharide derived from Escherichia coli. Hypoxia was induced by repeated umbilical cord occlusions during three phases: mild, moderate, and severe umbilical cord occlusions. Two groups were created with chronically instrumented near‐term fetal sheep: one group with isolated hypoxia, the other with hypoxia and fetal inflammatory response syndrome. Hemodynamic, gas parameters, and fetal heart rate variability were compared between the groups. Results: The hypoxia and fetal inflammatory response syndrome group had a higher mortality rate (n = 4/9) compared with the hypoxia group (n = 0/9). Gasometric state was altered earlier in case of lipopolysaccharide injection (pH = 7.22 (7.12–7.24) vs 7.28 (7.23–7.34) p = 0.01; lactate = 10.3 mmol/L (9.4–11.0) vs 6.0 mmol/L (4.1–8.2) p < 0.001 after mild occlusions). After mild occlusions, the hypoxia and fetal inflammatory response syndrome group had higher values on seven heart rate variability parameters compared with the hypoxia group. After moderate occlusions, two parameters remained significantly higher. Conclusions: During fetal inflammatory response syndrome, fetal adaptation to hypoxia is impaired. In case of fetal infection, acidosis during labor is likely to become severe more rapidly, requiring closer fetal monitoring during labor. [ABSTRACT FROM AUTHOR]

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 cells (MSCs) are safe and effective in treating myocardial infarction (MI) and have broad application prospects. However, the heterogeneity of MSCs may affect their therapeutic effect on the disease. We recently found that MSCs derived from different segments of the same umbilical cord (UC) showed significant difference in the expression of genes that are related to heart development and injury repair. We therefore hypothesized that those MSCs with high expression of above genes are more effective to treat MI and tested it in this study. Methods: MSCs were isolated from 3 cm-long segments of the maternal, middle and fetal segments of the UC (maternal-MSCs, middle-MSCs and fetal-MSCs, respectively). RNA-seq was used to analyze and compare the transcriptomes. We verified the effects of MSCs on oxygen-glucose deprivation (OGD)-induced cardiomyocyte apoptosis in vitro. In vivo, a rat MI model was established by ligating the left anterior descending coronary artery, and MSCs were injected into the myocardium surrounding the MI site. The therapeutic effects of MSCs derived from different segments of the UC were evaluated by examining cardiac function, histopathology, cardiomyocyte apoptosis, and angiogenesis. Results: Compared to fetal-MSCs and middle-MSCs, maternal-MSCs exhibited significantly higher expression of genes that are associated with heart development, such as GATA-binding protein 4 (GATA4), and myocardin (MYOCD). Coculture with maternal-MSCs reduced OGD-induced cardiomyocyte apoptosis. In rats with MI, maternal-MSCs significantly restored cardiac contractile function and reduced the infarct size. Mechanistic experiments revealed that maternal-MSCs exerted cardioprotective effects by decreasing cardiomyocyte apoptosis, and promoting angiogenesis. Conclusion: Our data demonstrated that maternal segment-derived MSCs were a superior cell source for regenerative repair after MI. Segmental localization of the entire UC when isolating hUCMSCs was necessary to improve the effectiveness of clinical applications. [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]

Optimal dosing in pregnant and lactating women requires an understanding of the pharmacokinetics in the mother, fetus, and breastfed infant. Physiologically‐based pharmacokinetic (PBPK) modeling can be used to simulate untested scenarios and hence supplement clinical data to support dosing decisions. A PBPK model for the antiretroviral dolutegravir (mainly metabolized by UGT1A1) was verified using reported exposures in non‐pregnant healthy volunteers, pregnant women, and the umbilical cord, lactating mothers, and breastfed neonates. The model was then applied to predict the impact of UGT1A1 phenotypes in extensive (EM), poor (PM), and ultra‐rapid metabolizers (UM). The predicted dolutegravir maternal plasma and umbilical cord AUC in UGT1A1 PMs was 1.6‐fold higher than in EMs. The predicted dolutegravir maternal plasma and umbilical cord AUC in UGT1A1 UMs mothers was 1.3‐fold lower than in EMs. The predicted mean systemic and umbilical vein concentrations were in excess of the dolutegravir IC90 at 17, 28, and 40 gestational weeks, regardless of UGT1A1 phenotype, indicating that the standard dose of dolutegravir (50 mg q.d., fed state) is generally appropriate in late pregnancy, across UGT1A1 phenotypes. Applying the model in breastfed infants, a 1.5‐, 1.7‐, and 2.2‐fold higher exposure in 2‐day‐old neonates, 10‐day‐old neonates, and infants who were UGT1A1 PMs, respectively, compared with EMs of the same age. However, it should be noted that the exposure in breastfed infants who were UGT1A1 PMs was still an order of magnitude lower than maternal exposure with a relative infant daily dose of <2%, suggesting safe use of dolutegravir in breastfeeding women. [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]

Background: Radiation-induced lung injury (RILI) is associated with alveolar epithelial cell death and secondary fibrosis in injured lung. Mesenchymal stem cell (MSC)-derived exosomes have regenerative effect against lung injury and the potential to intervene of RILI. However, their intervention efficacy is limited because they lack lung targeting characters and do not carry sufficient specific effectors. SARS-CoV-2 spike glycoprotein (SARS-CoV-2-S-RBD) binds angiotensin-converting enzyme 2 (ACE2) receptor and mediates interaction with host cells. MiR-486-5p is a multifunctional miRNA with angiogenic and antifibrotic potential and acts as an effector in MSC-derived exosomes. Ferroptosis is a form of cell death associated with radiation injury, its roles and mechanisms in RILI remain unclear. In this study, we developed an engineered MSC-derived exosomes with SARS-CoV-2-S-RBD- and miR-486-5p- modification and investigated their intervention effects on RIPF and action mechanisms via suppression of epithelial cell ferroptosis. Results: Adenovirus-mediated gene modification led to miR-486-5p overexpression in human umbilical cord MSC exosomes (p < 0.05), thereby constructing miR-486-5p engineered MSC exosomes (miR-486-MSC-Exo). MiR-486-MSC-Exo promoted the proliferation and migration of irradiated mouse lung epithelial (MLE-12) cells in vitro and inhibited RILI in vivo (all p < 0.05). MiR-486-MSC-Exo suppressed ferroptosis in MLE-12 cells, and an in vitro assay revealed that the expression of fibrosis-related genes is up-regulated following ferroptosis (both p < 0.05). MiR-486-MSC-Exo reversed the up-regulated expression of fibrosis-related genes induced by TGF-β1 in vitro and improved pathological fibrosis in RIPF mice in vivo (all p < 0.05). SARS-CoV-2-S-RBD-modified and miR-486-5p-engineered MSC exosomes (miR-486-RBD-MSC-Exo) were also constructed, and the distribution of DiR dye-labeled miR-486-RBD-MSC-Exo in hACE2CKI/CKI Sftpc-Cre+ mice demonstrated long-term retention in the lung (p < 0.05). MiR-486-RBD-MSC-Exo significantly improved the survival rate and pathological changes in hACE2CKI/CKI Sftpc-Cre+ RIPF mice (all p < 0.05). Furthermore, miR-486-MSC-Exo exerted anti-fibrotic effects via targeted SMAD2 inhibition and Akt phosphorylation activation (p < 0.05). Conclusions: Engineered MSC exosomes with SARS-CoV-2-S-RBD- and miR-486-5p-modification were developed. MiR-486-RBD-MSC-Exo suppressed ferroptosis and fibrosis of MLE-12 cells in vitro, and alleviated RILI and long-term RIPF in ACE2 humanized mice in vivo. MiR-486-MSC-Exo exerted anti-fibrotic effects via SMAD2 inhibition and Akt activation. This study provides a potential approach for RIPF intervention. [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: Significant numbers of neonatal deaths occurring each year are caused by infections that can be directly associated with improper and unhygienic umbilical cord care practices. The objectives of this study were to describe the umbilical cord care practices among mothers whose babies were admitted for suspected sepsis at the Federal Teaching Hospital and Turai Umaru Yar’adua Maternal and Children Hospital Katsina, Nigeria, assess the relationship between umbilical cord care practices and neonatal sepsis, and the influence of home delivery on this relationship. Methodology: This was a hospital-based descriptive observational study of 60 selected neonates with clinical features of sepsis admitted into the special care baby unit (SCBU) of the two hospitals between July and December 2022. The study involved the collection and microbiological analysis of blood samples using the BacT/Alert microbial detection system, and the administration of a structured questionnaire on the mother of each enrollee to collect relevant information about cord care practices. Data were analyzed using SPSS version 22.0. The Chisquare (x 2 ) test and Odds ratio (with 95% confidence interval) were used to determine the association of risk factors with culture-confirmed sepsis, and a p value less than 0.05 was considered statistically significant. Results: Of the 60 neonates blood samples, 31 (51.7%) were culture-positive for neonatal sepsis while 29 (48.3%) were culture-negative. There was no statistically significant association between risk factors such as application of traditional materials for cord care and place of delivery, and culture-confirmed neonatal sepsis (p>0.05). However, neonates whose mothers use traditional materials for cord care were more likely to develop sepsis than those who do not (OR=2.027, 95% CI=0.716-5.736). Concerning place of delivery, which is an important determinant of umbilical cord hygiene, babies delivered at home were almost 3 times more likely to have culture-confirmed sepsis than those delivered in the hospital (OR=2.975, 95% CI=1.040-8.510). A total of 26 out of the 60 (45.3%) mothers of the neonates agreed to have used unhygienic and traditional materials for cord care, with charcoal (39.0%), local herbs (27.0%), cow dung/urine concoction (19.0%), and others (15.0%), such as lubricants, ash, and balm, being the most commonly used materials for cord care. Conclusion: Neonatal infection is common among newborns in Federal Teaching Hospital and Turai Umaru Yar’adua Maternal and Children Hospital (TUYMCH), Katsina, northwest Nigeria, with a prevalence of culture confirmed neonatal sepsis of 51.7%. Although there was no statistically significant association between unhygienic cord practices and neonatal sepsis in this study, babies whose mothers use traditional materials for cord care were more likely to develop sepsis. There is a high rate of use of harmful and unhygienic traditional materials for cord care in our environment. This habit can be discouraged through health education using the mass media and health talks in health facilities. The use of chlorhexidine, the recommended antiseptic for cord care by the World Health Organization and the Nigeria Federal Ministry of Health, should be encouraged. [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]

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]

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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]

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]

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]

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]

Aim: To compare composite adverse perinatal outcomes (CAPO) in women with early- and late-onset intrahepatic cholestasis of pregnancy (ICP). Materials and Methods: This study was designed as a single-center, retrospective study in a tertiary hospital and included a total of 198 patients with ICP, including 36 patients with early-onset ICP (EO-ICP) and 162 patients with late-onset ICP (LO-ICP). ICP that developed before the 28thweek of gestation was defined as EO-ICP, and ICP that occurred after the 28thweek of gestationwas defined as LO-ICP. The existence of at least one of the following criteria was defined as CAPO: umbilical cord arterial pH < 7.20, fifth-minute Apgar score < 5, andneonatal intensivecarestay of>24 hours. Results:The rates of spontaneous preterm birth and neonatal intensive care admission were statistically significantly higher in the EO-ICP group (p<0.001). In the same group, a significantly higher number of neonates were born with meconium (p=0.040). The use of ursodeoxycholic acid was significantly greater in the EO-ICP group (p=0.007). The two groups did not show any significant differences in terms of neonatal umbilical cord arterial pH or base excess (p>0.05), however, the CAPO rate was significantly higher in the EOICP group(p=0.028). Receiver operator characteristic analysis revealed an optimal cut-off value of 33.5 μmol/L for the serum bile acid level, at which this parameter had 74% sensitivity and 68% specificity (area under the curve=0.759; p<0.001) in the prediction of CAPO. Conclusion: We consider that the high CAPO rates in the fetuses of patients with EO-ICP are due to the effect of high serum bile acid levels on the fetus for a longer time than in the LO-ICP group. The differentiation of cases of EO-ICP and LO-ICP will serve as a guide for clinicians in predicting possible complications. [ABSTRACT FROM AUTHOR]

Stem cells transplantation (SCT) is known as a newfound strategy for multiple sclerosis (MS) treatment. Human umbilical cord mesenchymal stem cells (hUCMSCs) contain various regenerative features. Experimental autoimmune encephalomyelitis (EAE) is a laboratory model of MS. This meta-analysis study was conducted to assess the overall therapeutic effects of hUCMSCs on reduction of clinical score (CS) and restoration of active movement in EAE-induced animals. For comprehensive searching (in various English and Persian databases until May 1, 2024), the main keywords of "Experimental Autoimmune Encephalomyelitis", "Multiple Sclerosis", "Human", "Umbilical Cord", "Mesenchymal", and "Stem Cell" were hired. Collected data were transferred to the citation manager software (EndNote x8) and duplicate papers were merged. Primary and secondary screenings were applied (according to the inclusion and exclusion criteria) and eligible studies were prepared for data collection. CS of two phases of peak and recovery of EAE were extracted as the difference in means and various analyses including heterogeneity, publication bias, funnel plot, and sensitivity index were reported. Metaanalysis was applied by CMA software (v.2), P<0.05 was considered a significant level, and the confidence interval (CI) was determined 95% (95% CI). Six eligible high-quality (approved by ARRIVE checklist) papers were gathered. The difference in means of peak and recovery phases were -0.775 (-1.325 to -0.225; P=0.006; I²=90.417%) and -1.230 (-1.759 to -0.700; P<0.001; I²=93.402%), respectively. The overall therapeutic effects of SCT of hUCMSCs on the EAE cases was -1.011 (95% CI=-1.392 to -0.629; P=0.001). hUCMSCs transplantation through the intravenous route to the animal MS model (EAE) seems a considerably effective procedure for the alleviation of motor defects in both phases of peak and recovery. [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]