Cerebral palsy (CP) is a condition resulting from perinatal brain injury and can lead to physical disabilities. Exosomes derived from human amniotic mesenchymal stromal cells (hAMSC-Exos) hold promise as potential therapeutic options. This study aimed to investigate the impact of hAMSC-Exos on neuronal cells and their role in regulating apoptosis both in vitro and in vivo. hAMSC-Exos were isolated via ultracentrifugation and characterized via transmission electron microscopy, particle size analysis, and flow cytometry. In vitro, neuronal damage was induced by lipopolysaccharide (LPS). CP rat models were established via left common carotid artery ligation. Apoptosis levels in cells and CP rats were assessed using flow cytometry, quantitative reverse transcription polymerase chain reaction (RT-qPCR), Western blotting, and TUNEL analysis. The results demonstrated successful isolation of hAMSC-Exos via ultracentrifugation, as the isolated cells were positive for CD9 (79.7%) and CD63 (80.2%). Treatment with hAMSC-Exos significantly mitigated the reduction in cell viability induced by LPS. Flow cytometry revealed that LPS-induced damage promoted apoptosis, but this effect was attenuated by treatment with hAMSC-Exos. Additionally, the expression of caspase-3 and caspase-9 and the Bcl-2/Bax ratio indicated that excessive apoptosis could be attenuated by treatment with hAMSC-Exos. Furthermore, tail vein injection of hAMSC-Exos improved the neurobehavioral function of CP rats. Histological analysis via HE and TUNEL staining showed that apoptosis-related damage was attenuated following hAMSC-Exo treatment. In conclusion, hAMSC-Exos effectively promote neuronal cell survival by regulating apoptosis, indicating their potential as a promising therapeutic option for CP that merits further investigation.

Cerebral palsy (CP) is a prevalent cause of physical disability in children, often resulting from hypoxic-ischemic encephalopathy, with current therapies often failing to address the underlying pathophysiology. This study aimed to investigate the potential synergistic effects of human amnion-derived mesenchymal stem cells (hAMSCs) combined with scalp acupuncture in a rat model of CP. Twenty male Sprague-Dawley rats were randomly divided into four groups: Sham, CP, hAMSCs, and hAMSCs+scalp acupuncture (hAMSCs+AP). The CP model was induced via left common carotid artery ligation. hAMSCs were administered through tail vein injection, followed by scalp acupuncture at Baihui (GV20) and Qubin (GB7) points. Neurobehavioral function was assessed using the Bederson score, and brain tissues were analyzed using hematoxylin and eosin (H&E) staining, TUNEL staining, and RT-qPCR for apoptosis-related genes. The CP group exhibited significant neurobehavioral deficits and increased apoptosis. Both hAMSCs and hAMSCs+AP treatments improved neurobehavioral function and reduced apoptosis. The combination therapy further decreased apoptosis levels, normalized mRNA expression of Bax, Caspase 9, and Caspase 3, and alleviated histological damage. The combination of hAMSCs and scalp acupuncture provides a promising treatment for CP, potentially alleviating brain damage through apoptosis regulation. Further studies are required to elucidate the detailed mechanisms and assess clinical feasibility and safety.

Background: Neuroblastoma (NB) is the most common childhood cancer, but doctors are unable to predict its overall survival (OS) rate before surgery. We aimed to predict the OS of NB children with some clinical features obtained from biopsy before surgery. Methods: Clinical features of NB children were retrospectively collected from the Therapeutically Applicable Research to Generate Effective Treatments database. The C-index, area under the receiver operating characteristic curve (AUC), calibration curves, and decision curves analysis were used to estimate nomogram models. Results: A total of 488 NB children were evaluated, and the Boruta algorithm was used to detect risk factors. The results showed that artificial neural networks with selected features were able to predict more than 90% of NB children. Five risk factors were used in the construction of the nomogram, including age at diagnosis, MYCN status, ploidy value, histology, and mitosis-karyorrhexis index (MKI). The C-index of the nomogram in training cohort and validation cohort was 0.716 and 0.731. AUC values for 1-, 3-, and 5-years OS predictions were 0.706, 0.755, and 0.762, respectively, and showed good calibrations. Decision curve analysis indicated a better predictability with the nomogram model based on Cox regression compared with one that included all variables and histology only. Also, the Kaplan–Meier curves showed a significantly higher survival probability in the low-risk group (total score <118.34) versus the high-risk group (total score ≥ 118.34) ( p < 0.05) using the nomogram model. Conclusions: A web application based on the nomogram model in the present study can be accessed at https://mdzhou.shinyapps.io/DynNomapp/ , which could help doctors make accurate clinical decisions about NB children.

The exact pathogenesis of autism spectrum disorder (ASD) is still unclear, yet some potential mechanisms may not have been evaluated before. Cuproptosis is a novel form of regulated cell death reported this year, and no study has reported the relationship between ASD and cuproptosis. This study aimed to identify ASD in suspected patients early using machine learning models based on biomarkers of the cuproptosis pathway. We collected gene expression profiles from brain samples from ASD model mice and blood samples from humans with ASD, selected crucial genes in the cuproptosis signaling pathway, and then analysed these genes with different machine learning models. The accuracy, sensitivity, specificity, and areas under the receiver operating characteristic curves of the machine learning models were estimated in the training, internal validation, and external validation cohorts. Differences between models were determined with Bonferroni’s test. The results of screening with the Boruta algorithm showed that FDX1, DLAT, LIAS, and ATP7B were crucial genes in the cuproptosis signaling pathway for ASD. All selected genes and corresponding proteins were also expressed in the human brain. The k-nearest neighbor, support vector machine and random forest models could identify approximately 72% of patients with ASD. The artificial neural network (ANN) model was the most suitable for the present data because the accuracy, sensitivity, and specificity were 0.90, 1.00, and 0.80, respectively, in the external validation cohort. Thus, we first report the prediction of ASD in suspected patients with machine learning methods based on crucial biomarkers in the cuproptosis signaling pathway, and these findings may contribute to investigations of the potential pathogenesis and early identification of ASD.

This study aimed to investigate changes in the blood metabolic profiles of newborns with varying intrauterine growth conditions. Specifically, we analyzed the levels of amino acids, carnitine, and succinylacetone among full-term newborns, including small for gestational age (SGA), appropriate for gestational age (AGA), and large for gestational age (LGA). We aim to identify differential metabolites and metabolic pathways that may offer insights into clinical interventions. A total of 5106 full-term newborns were included in the study. Blood samples were obtained from all newborns between 3 and 5 days after birth and analyzed using tandem mass spectrometry to detect blood metabolites. Subsequently, we screened for different metabolites and metabolic pathways among the groups using the MetaboAnalystR package (Version 1.0.1) in R software (R-3.6.0). The levels of blood amino acids and carnitine metabolism differed significantly among newborns with varying intrauterine growth conditions. Full-term SGA newborns exhibited a decrease in multiple amino acids and an increase in multiple carnitines, while full-term LGA newborns showed an increase in multiple amino acids and acylcarnitines. Continuous monitoring of the short-term and long-term growth and metabolic status of full-term SGA and LGA newborns is warranted with individualized dietary and nutritional adjustments to promote healthy growth in a timely manner. The findings of this research contribute to the broader understanding of SGA/LGA and shall inform future research on metabolomics, interventions, and long-term outcomes.

Background: Cerebral palsy (CP) from perinatal hypoxic-ischaemic brain injury lacks effective therapies. Human amniotic mesenchymal stem cell-derived exosomes (hAMSC-exos) show neuroprotective potential, but their mechanisms remain unclear. This study investigated the effects and molecular pathways of hAMSC-exos in a neonatal rat CP model and an oxygen-glucose deprivation/reoxygenation (OGD/R) neuronal model. Methods: hAMSC-exos were isolated and characterised. Severe CP was induced in postnatal day 21 rats by carotid ligation and hypoxia; hAMSC-exos or vehicle were given via tail vein 24 h later. Brain histology, ultrastructure, TSC1/mTOR/ULK1 pathway proteins, and apoptosis were assessed. In vitro , cortical neurons underwent OGD/R with or without exosomes; mitochondrial function (ATP, ROS, membrane potential), morphology, dynamics proteins (DRP1, FIS1, MFN1, MFN2), and PINK1/Parkin-mediated mitophagy were evaluated. Results: hAMSC-exos significantly ameliorated cortical neuronal degeneration, Nissl loss, and mitochondrial ultrastructural damage, and reduced autophagosome accumulation. They reversed CP-induced TSC1 upregulation, restored mTOR phosphorylation, and decreased ULK1 phosphorylation, correlating with fewer apoptotic neurons. In vitro , exosomes restored ATP content, reduced mitochondrial ROS, and normalised membrane potential. OGD/R caused excessive mitochondrial elongation via MFN1 upregulation; exosomes selectively downregulated MFN1 without affecting fission proteins (DRP1, FIS1). Moreover, exosomes restored impaired PINK1/Parkin-mediated mitophagy, increasing co-localisation of phospho-PINK1, phospho-Parkin, and LAMP1 with mitochondria, and rescued their phosphorylated protein levels. Conclusion: hAMSC-exos protect against hypoxic-ischaemic injury through coordinated regulation of mitochondrial quality control, involving suppression of excessive TSC1/mTOR/ULK1-mediated autophagy ( in vivo ) and restoration of PINK1/Parkin-mediated mitophagy ( in vitro ), collectively preserving mitochondrial integrity and reducing neuronal apoptosis. These findings support hAMSC-exos as a promising cell-free therapeutic strategy for CP.