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Alzheimer’s disease (AD) is the most common neurodegenerative disease characterized by excessive accumulation of the amyloid-β peptide (Aβ) in the brain, which has been considered to mediate the neuroinflammation process. Microglial activation is the main component of neuroimmunoregulation. In recent years, exosomes isolated from human umbilical cord mesenchymal stem cells (hucMSC-exosomes) have been demonstrated to mimic the therapeutic effects of hucMSCs in many inflammation-related diseases. In this study, exosomes from the supernatant of hucMSCs were injected into AD mouse models. We observed that hucMSC-exosomes injection could repair cognitive disfunctions and help to clear Aβ deposition in these mice. Moreover, we found that hucMSC-exosomes injection could modulate the activation of microglia in brains of the mice to alleviated neuroinflammation. The levels of pro-inflammatory cytokines in peripheral blood and brains of mice were increased and the levels of anti-inflammatory cytokines were decreased. We also treated BV2 cells with hucMSC-exosomes in culture medium. HucMSC-exosomes also had inflammatory regulating effects to alternatively activate microglia and modulate the levels of inflammatory cytokines in vitro.

AimTo determine how different cord clamping strategies affect cerebral oxygenation in the first 15 min after birth in preterm infants.MethodsA post-hoc secondary outcome analysis of a multicentre prospective randomised clinical trial (COSGOD III) conducted between October 2017 and October 2021 in 11 tertiary neonatal intensive care units in six countries in Europe and in Canada. In the present ancillary study, all included premature neonates (<32 weeks gestation) were retrospectively assigned to three groups according to the timing of cord clamping (G1<30 s, G2 30–60 s, G3>30 s). The aim of this study was to evaluate differences in cerebral regional oxygen saturation (crSO2) and cerebral fractional tissue oxygen extraction (cFTOE) within the first 15 min after birth in preterm neonates based on the timing of cord clamping.Results572 infants (n=339 (G1), n=164 (G2) and n=69 (G3)) were included in the final ancillary analysis. There were no statistically significant differences in crSO2 and cFTOE between the three groups. There were no statistically significant differences between the three groups in neonatal morbidities, particularly importantly in the degree of cerebral injury, as measured by any degree of intraventricular haemorrhage or cystic periventricular leukomalacia.ConclusionsNo significant differences in crSO2 and cFTOE during the first 15 min after birth were observed; however, some effect may have been modified by protocol-guided titration of supplemental oxygen in the intervention arm. Thus, in our study, we did not find a correlation between deferred cord clamping and improved cerebral oxygenation immediately after birth.Trial registration number NCT03166722.

Background Facilitating placental transfusion—the transfer of blood from the placenta to the newborn—via delayed cord clamping (DCC) or umbilical cord milking (UCM) at birth has been shown to improve iron stores in healthy term infants and may positively impact long-term neurodevelopmental outcomes. Infants who are non-vigorous at birth and at risk of developing hypoxic-ischemic encephalopathy (HIE) are particularly likely to benefit from placental transfusion. This process may offer neuroprotection by enhancing cardiopulmonary transition, supporting cardiac preload, improving systemic and cerebral perfusion, delivering stem cells and neurotrophic factors, and preventing iron deficiency. While DCC is not currently recommended for non-vigorous term infants requiring immediate resuscitation, UCM offers a viable alternative, as it can be performed quickly. Methods This study is a multicenter, cluster-randomized, crossover-controlled trial comparing UCM with early cord clamping (ECC) in term and late preterm infants who are non-vigorous at birth. The trial will be conducted across seven centers in India. Before the trial begins, each site will be assigned to an initial study arm using a computer-generated randomization scheme. Once 50% of the enrollment is complete, sites will switch to the alternate study arm after a 2-month washout period. The study is designed with sufficient power to assess the composite outcome of death or moderate-to-severe HIE during birth hospitalization and survival without moderate-to-severe neurodevelopmental impairment at 2 years of age. Secondary outcomes include survival without moderate-to-severe neurodevelopmental impairment at 1 year of age and survival without evidence of brain injury on MRI during the birth hospitalization. Discussion The CORDMILK trial aims to generate critical evidence on whether UCM can improve survival without moderate-to-severe HIE during birth hospitalization and survival without significant neurodevelopmental impairment at 2 years of age in late preterm and term neonates who are non-vigorous at birth. Trial registration Clinical Trial Registry–India CTRI/2021/09/036759. Registered on 22/09/2021. ClinicalTrials.Gov number NCT03657394 and NCT03682042.

IntroductionDelayed cord clamping (DCC) is an evidence-based intervention that reduces mortality, anaemia and disability in infants born <37 weeks’ gestation who do not require immediate resuscitation. However, it is neither reliably recorded nor routinely implemented in Australia. The Wait a Minute or More (WAMM) study aims to reduce this gap between the evidence and practice by integrating timely sharing of cord clamping data with Evidence-based Practice for Improving Quality methods to increase the proportion of preterm infants receiving DCC for 60 s or longer (DCC60).MethodsThe WAMM study is a pragmatic stepped wedge cluster randomised trial (SW-CRT), informed by the Integrated-Promoting Action on Research Implementation in Health Services (i-PARIHS) framework. Up to 20 Australian maternity hospitals will participate in this pragmatic SW-CRT to evaluate if in (Population) infants <37 weeks’ gestation who do not need resuscitation, does (Intervention) the WAMM intervention (sharing of anonymised data on DCC60, together with a locally adapted quality improvement (QI) programme), compared with (Control) sharing of anonymised data on DCC60 alone, increase (primary Outcome) the proportion of infants receiving DCC60? At the end of 72 weeks, all sites will complete an 8-week period without the WAMM intervention to evaluate if implementation of DCC is sustained. Alongside the SW-CRT, an embedded process evaluation will assess the fidelity, acceptability, mechanisms of action and contextual barriers and enablers of the WAMM intervention.DiscussionUsing the stepped wedged design and guided by an explicit implementation framework (i-PARIHS), WAMM will provide information on the effectiveness and transferability of a locally adapted QI method to improve DCC60. If proven effective, ultimately scaling up the WAMM intervention globally will greatly improve childhood anaemia, death, disability and long-term costs.Trial registration numberACTRN12624000035527.

Transplantation of stem cells is a promising, emerging treatment for cardiovascular diseases in the modern era. Mesenchymal stem cells (MSCs) derived from the umbilical cord are one of the most promising cell sources because of their capacity for differentiation into cardiomyocytes, endothelial cells and vascular smooth muscle cells in vitro/in vivo. In addition, umbilical cord‐derived MSCs (UC‐MSCs) secrete many effective molecules regulating apoptosis, fibrosis and neovascularization. Another important and specific characteristic of UC‐MSCs is their low immunogenicity and immunomodulatory properties. However, the application of UC‐MSCs still faces some challenges, such as low survivability and tissue retention in a harmful disease environment. Gene engineering and pharmacological studies have been implemented to overcome these difficulties. In this review, we summarize the differentiation ability, secretion function, immunoregulatory properties and preclinical/clinical studies of UC‐MSCs, highlighting the advantages of UC‐MSCs for the treatment of cardiovascular diseases.

Background COVID-19 is a highly infectious respiratory disease. No therapeutics have yet been proven effective for treating severe COVID-19. Objectives To determine whether human umbilical cord mesenchymal stem cell infusion may be effective and safe for the treatment of severe COVID-19. Methods Patients with severe COVID-19 were randomly divided into 2 groups: the standard treatment group and the standard treatment plus hUC-MSC infusion group. The incidence of progression from severe to critical illness, 28-day mortality, clinical symptom improvement, time to clinical symptom improvement, hematologic indicators including C-reactive protein, lymphocyte number, and interleukin 6, and imaging changes were observed and compared between the two groups. Measurements and main results The incidence of progression from severe to critical illness and the 28-day mortality rate were 0 in the hUC-MSC treatment group, while 4 patients in the control group deteriorated to critical condition and received invasive ventilation; 3 of them died, and the 28-day mortality rate was 10.34%. In the hUC-MSC treatment group, the time to clinical improvement was shorter than that in the control group. Clinical symptoms of weakness and fatigue, shortness of breath, and low oxygen saturation obviously improved beginning on the third day of stem cell infusion and reached a significant difference on day 7. CRP and IL-6 levels were significantly lower from day 3 of infusion, the time for the lymphocyte count to return to the normal range was significantly faster, and lung inflammation absorption was significantly shorter on CT imaging in the hUC-MSC group than in the control group. Conclusions Intravenous transplantation of hUC-MSCs is a safe and effective method that can be considered a salvage and priority treatment option for severe COVID-19. Trial registration Chinese Clinical Trial Registration; ChiCTR2000031494; Registered on 2 April 2020; http:// www.medresman.org

The novel coronavirus disease 2019 (COVID-19) has grown to be a global public health emergency since patients were first detected in Wuhan, China. Thus far, no specific drugs or vaccines are available to cure the patients with COVID-19 infection. The immune system and inflammation are proposed to play a central role in COVID-19 pathogenesis. Mesenchymal stem cells (MSCs) have been shown to possess a comprehensive powerful immunomodulatory function. Intravenous infusion of MSCs has shown promising results in COVID-19 treatment. Here, we report a case of a severe COVID-19 patient treated with human umbilical cord Wharton’s jelly-derived MSCs (hWJCs) from a healthy donor in Liaocheng People’s Hospital, China, from February 24, 2020. The pulmonary function and symptoms of the patient with COVID-19 pneumonia was significantly improved in 2 days after hWJC transplantation, and recovered and discharged in 7 days after treatment. After treatment, the percentage and counts of lymphocyte subsets (CD3 + , CD4 + , and CD8 + T cell) were increased, and the level of IL-6, TNF-α, and C-reactive protein is significantly decreased after hWJC treatment. Thus, the intravenous transplantation of hWJCs was safe and effective for the treatment of patients with COVID-19 pneumonia, especially for the patients in a critically severe condition. This report highlights the potential of hWJC infusions as an effective treatment for COVID-19 pneumonia.

Umbilical cord clamping strategies at preterm birth have the potential to affect important health outcomes. The aim of this study was to compare the effectiveness of deferred cord clamping, umbilical cord milking, and immediate cord clamping in reducing neonatal mortality and morbidity at preterm birth. We conducted a systematic review and individual participant data meta-analysis. We searched medical databases and trial registries (from database inception until Feb 24, 2022; updated June 6, 2023) for randomised controlled trials comparing deferred (also known as delayed) cord clamping, cord milking, and immediate cord clamping for preterm births (<37 weeks' gestation). Quasi-randomised or cluster-randomised trials were excluded. Authors of eligible studies were invited to join the iCOMP collaboration and share individual participant data. All data were checked, harmonised, re-coded, and assessed for risk of bias following prespecified criteria. The primary outcome was death before hospital discharge. We performed intention-to-treat one-stage individual participant data meta-analyses accounting for heterogeneity to examine treatment effects overall and in prespecified subgroup analyses. Certainty of evidence was assessed with Grading of Recommendations Assessment, Development, and Evaluation. This study is registered with PROSPERO, CRD42019136640. We identified 2369 records, of which 48 randomised trials provided individual participant data and were eligible for our primary analysis. We included individual participant data on 6367 infants (3303 [55%] male, 2667 [45%] female, two intersex, and 395 missing data). Deferred cord clamping, compared with immediate cord clamping, reduced death before discharge (odds ratio [OR] 0·68 [95% CI 0·51–0·91], high-certainty evidence, 20 studies, n=3260, 232 deaths). For umbilical cord milking compared with immediate cord clamping, no clear evidence was found of a difference in death before discharge (OR 0·73 [0·44–1·20], low certainty, 18 studies, n=1561, 74 deaths). Similarly, for umbilical cord milking compared with deferred cord clamping, no clear evidence was found of a difference in death before discharge (0·95 [0·59–1·53], low certainty, 12 studies, n=1303, 93 deaths). We found no evidence of subgroup differences for the primary outcome, including by gestational age, type of delivery, multiple birth, study year, and perinatal mortality. This study provides high-certainty evidence that deferred cord clamping, compared with immediate cord clamping, reduces death before discharge in preterm infants. This effect appears to be consistent across several participant-level and trial-level subgroups. These results will inform international treatment recommendations. Australian National Health and Medical Research Council.

The objective of the study was to compare the serum ferritin levels (by chemiluminescence immunoassay) among two groups of newborns with intact umbilical cord milking (UCM) versus delayed cord clamping (DCC) at the 3rd month of life. Randomized controlled trial, unblinded, parallel group was conducted at tertiary care referral unit in South India after obtaining informed consent from eligible mothers in late preterm gestation and beyond, and the newborn babies were randomized into two groups by computer-generated sequence (SNOSE method) with two modes of umbilical cord management UCM and DCC. A total of 190 mothers were enrolled, and they were randomized into two arms: DCC group ( n  = 95) and UCM group ( n  = 95). Of these 190 mothers who were enrolled, the intervention was done for 180 babies, i.e., DCC ( n  = 92) and UCM ( n  = 88). Follow-up with serum ferritin was done for 108 babies. DCC-63 and UCM-45. Ferritin levels measured at 3 months of life showed comparable results, i.e., mean ferritin levels in the DCC group was 258.07 ng/ml and in the UCM group was 248.44 ng/ml, with a mean difference of − 9.63 ( p 0.72). Conclusion : Both UCM and DCC resulted in comparable levels of serum ferritin at 3 months of life, implying that a similar amount of placental transfusion occurs in both the groups. UCM is a feasible alternative to prevent anemia during infancy as compared to DCC when the latter cannot be done due to undue limitation. Trial registration : CTRI registration number: CTRI/2021/05/033448. (07/05/2021). What is Known: • DCC is the standard of care for stable term and preterm babies at birth. However, UCM is a reasonable alternative for cord management at birth . What is New: • UCM prevents anemia as effectively as DCC, as evidenced by comparable serum ferritin levels at 3 months of age, further adding to the hypothesis that UCM is a feasible alternative when DCC is not practical .

Background Oxidative stress is a key contributor to the pathophysiology of intrauterine growth restriction (IUGR). Evidence regarding the influence of umbilical cord clamping timing on neonatal oxidative balance remains limited. This study evaluated the effect of delayed cord clamping (DCC) on oxidative stress biomarkers in IUGR and appropriate-for-gestational-age (AGA) neonates. Methods This single-center, prospective randomized controlled trial included 90 neonates born at ≥ 29 weeks of gestation. Participants were randomized into four subgroups: IUGR-DCC ( n  = 25), IUGR-ECC (early cord clamping)( n  = 32), AGA-DCC ( n  = 17), and AGA-ECC ( n  = 16). DCC was defined as clamping at 120 ± 30 s and ECC within 60 s after birth. Umbilical cord blood was analyzed for total antioxidant status (TAS), total oxidant status (TOS), catalase activity, and oxidative stress index (OSI). Results In IUGR infants, DCC was associated with higher TAS (2.01 ± 0.20 vs. 1.69 ± 0.22 mmol/L, p  < 0.001) and catalase activity (74.5 ± 13.7 vs. 63.8 ± 11.1 kU/L, p  = 0.004), and lower TOS (31.8 ± 6.2 vs. 42.7 ± 7.5 µmol/L, p  < 0.001) and OSI (15.8 ± 3.2 vs. 25.4 ± 4.8, p  < 0.001) compared with ECC. Similar differences were found among AGA infants: TAS (2.12 ± 0.18 vs. 1.87 ± 0.20, p  < 0.001), catalase (78.1 ± 10.6 vs. 69.3 ± 12.6, p  = 0.006), TOS (26.2 ± 5.2 vs. 36.1 ± 6.7, p  < 0.001), and OSI (12.5 ± 2.7 vs. 19.1 ± 3.6, p  < 0.001). Multivariate analysis confirmed DCC as an independent predictor of improved oxidative markers. Conclusions Delayed cord clamping improved oxidative stress profiles in both IUGR and AGA neonates, with greater benefit in growth-restricted infants. These results provide biochemical support for DCC, though larger multicenter trials are required to determine long-term clinical relevance. Trial registration This study was prospectively registered at ClinicalTrials.gov under registration number NCT07031583 on 13 June 2025.