This retrospective study aimed to assess the safety of patients with severe cerebral palsy (CP), who received allogeneic umbilical cord blood stem cells (UCBSCs) treatment from August 2009 to December 2012 in Guangdong Provincial Hospital of Chinese Medicine. A total of 47 patients with average age of years were evaluated in this study. There was no significant association with allogeneic UCBSCs treatments found in the data of the laboratory index . No casualties occurred. Some adverse events during treatments were found in 26 (55.3%) patients, including fever (42.6%) and vomiting (21.2%). Intrathecal infusion and the ages at the initiation of treatment (10 years old) were risk factors for the occurrence of adverse events by logistic regression analysis. However, all adverse events disappeared after symptomatic treatment. No treatment related serious adverse events were found in follow-up visits within 6 months. In conclusion, allogeneic UCBSCs treatment was relatively safe for severe CP patients. This retrospective study aimed to assess the safety of patients with severe cerebral palsy (CP), who received allogeneic umbilical cord blood stem cells (UCBSCs) treatment from August 2009 to December 2012 in Guangdong Provincial Hospital of Chinese Medicine. A total of 47 patients with average age of years were evaluated in this study. There was no significant association with allogeneic UCBSCs treatments found in the data of the laboratory index . No casualties occurred. Some adverse events during treatments were found in 26 (55.3%) patients, including fever (42.6%) and vomiting (21.2%). Intrathecal infusion and the ages at the initiation of treatment (10 years old) were risk factors for the occurrence of adverse events by logistic regression analysis. However, all adverse events disappeared after symptomatic treatment. No treatment related serious adverse events were found in follow-up visits within 6 months. In conclusion, allogeneic UCBSCs treatment was relatively safe for severe CP patients.

Body fat distribution is a heritable risk factor for cardiovascular and metabolic disease. In humans, rare Inhibin beta E ( INHBE , activin E) loss-of-function variants are associated with a lower waist-to-hip ratio and protection from type 2 diabetes. Hepatic fatty acid sensing promotes INHBE expression during fasting and in obese individuals, yet it is unclear how the hepatokine activin E governs body shape and energy metabolism. Here, we uncover activin E as a regulator of adipose energy storage. By suppressing β-agonist-induced lipolysis, activin E promotes fat accumulation and adipocyte hypertrophy and contributes to adipose dysfunction in mice. Mechanistically, we demonstrate that activin E elicits its effect on adipose tissue through ACVR1C, activating SMAD2/3 signaling and suppressing PPARG target genes. Conversely, loss of activin E or ACVR1C in mice increases fat utilization, lowers adiposity, and drives PPARG-regulated gene signatures indicative of healthy adipose function. Our studies identify activin E–ACVR1C as a metabolic rheostat promoting liver–adipose cross talk to restrain excessive fat breakdown and preserve fat mass during prolonged fasting, a mechanism that is maladaptive in obese individuals.

Experimental autoimmune encephalomyelitis (EAE) is characterized by demyelination of the central nervous system. Emodin is an anthraquinone derivative with comprehensive anti-inflammatory, anti-cancer, and immunomodulatory effects and is widely used in the treatment of inflammatory, tumor, and immune system diseases. However, none of the clinical or experimental studies have explored the therapeutic efficacy of emodin in EAE/multiple sclerosis (MS). Thus, we evaluated the protective effect of emodin on EAE mediated via inhibition of microglia activation and inflammation. Wild-type mice were randomly divided into the normal control, EAE, low-dose emodin, and high-dose emodin groups. Clinical scores and pathological changes were assessed 21 days after immunization. The network pharmacology approach was used to elucidate the underlying mechanisms by using an online database. Molecular docking, polymerase-chain reaction tests, western blotting, and immunofluorescence were performed to verify the network pharmacology results. An in vivo experiment showed that high-dose emodin ameliorated clinical symptoms, inflammatory cell infiltration, and myelination. Pharmacological network analysis showed AKT1 was the main target and that emodin played a key role in MS treatment mainly via the PI3K–Akt pathway. Molecular docking showed that emodin bound well with PI3K, AKT1, and NFKB1. Emodin decreased the expression of phosphorylated(p)-PI3K, p-Akt, NF-κB, and myeloid differentiation factor 88 and the levels of markers (CD86 and CD206) in M1- and M2-phenotype microglia in EAE. Thus, the emodin inhibited microglial activation and exhibited anti-inflammatory and neuroprotective effects against EAE via the Myd88/PI3K/Akt/NF-κB signalling pathway. In conclusion, emodin has a promising role in EAE/MS treatment, warranting further detailed studies.

Modern pharmacological studies have shown that emodin, the main effective component of rhubarb, has good anti-inflammatory and antioxidant effects, but its pharmacodynamic mechanism remains unclear yet. This study aims to elucidate the multitarget action mechanism of emodin in ischemic stroke through network pharmacology and in vivo experiments. Sprague-Dawley rats were randomly divided into control (normal saline), sham (normal saline), model (normal saline), and emodin groups (n = 9 per group). Emodin was administered at 40 mg/kg/d for 3 consecutive days. The rats were subjected to middle cerebral artery occlusion for 2 h, followed by reperfusion for 24 h to establish the cerebral ischemia-reperfusion injury. To search for relevant studies in databases, emodin, ischemic stroke, and stroke were used as keywords. Subsequently, protein-protein interaction networks and complex disease target networks were established, and an enrichment analysis and molecular docking of core targets were performed. Gene expression was detected through western blotting and reverse-transcription polymerase chain reaction. Localization and expression of proteins were detected through immunohistochemistry. Furthermore, the neurological function, 2,3,5-triphenyltetrazolium chloride staining, levels of brain tissue inflammatory factors, the role of the blood-brain barrier (BBB), and relevant signaling pathways were assessed in vivo. The molecular docking of core targets revealed that the docking between vascular endothelial growth factor A (VEGF-A) and emodin was the most efficient. Emodin pretreatment decreased the neurological score from 2.875 to 1.125. Moreover, emodin inhibited the degradation of occludin and claudin-5 caused by matrix metalloprotein kinase (MMP)-2/MMP-9, thereby protecting the BBB. Additionally, related proteins such as hypoxia-inducible factor-1α/VEGF-A and nuclear factor kappa B were down-regulated. Thus, emodin may play a protective role during cerebral ischemia reperfusion through mediation of the Hif-1α/VEGF-A signaling pathway to inhibit the expression of inflammatory factors.

Objectives. This study aims to study the material basis and effective mechanism of musk for ischemic stroke (IS) based on the network pharmacology approach. Methods. We collected the chemical components and target gene of musk from the BATMAN‐TCM analytical platform and identified ischemic stroke‐related targets from the following databases: DisGeNET, NCBI‐Gene, HPO, OMIM, DrugBank, and TTD. The targets of musk and IS were uploaded to the String database to construct the protein‐protein interaction (PPI) network, and then, the key targets were analyzed by topological methods. At last, the function biological process and signaling pathways of key targets were carried out by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and cluster analysis by using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) server and Metascape platform. Results. A total of 29 active compounds involving 1081 predicted targets were identified in musk and there were 1104 IS‐related targets. And 88 key targets of musk for IS were obtained including AKT1, MAPK1/3, TP53, TNF, SRC, FOS, CASP3, JUN, NOS3, and IL1B. The GO and KEGG enrichment analysis suggested that these key targets are mainly involved in multiple pathways which participated in TNF signaling pathway, estrogen signaling pathway, prolactin signaling pathway, neurotrophin signaling pathway, T‐cell receptor signaling pathway, cAMP signaling pathway, FoxO signaling pathway, and HIF1 signaling pathway. Conclusion. This study revealed that the effective mechanisms of musk against IS would be associated with the regulation of apoptosis, inflammatory response, and gene transcription.

Background: Neuropathic pain is a common complication in neuromyelitis optica spectrum disorder (NMOSD), which seriously affects the quality of life of NMOSD patients, with no satisfactory treatment. And risk factors of neuropathic pain are still uncertain. Objective: To investigate the risk factors of neuropathic pain in a NMOSD cohort. Materials and methods: Our study was a retrospective case-cohort study, the patients diagnosed with NMOSD in the Department of Neurology from the Second Affiliated Hospital of Guangzhou University of Chinese Medicine from January 2011 to October 2021 were screened. Inclusion criteria were: (1) patients diagnosed as NMOSD according to the International Panel for NMO Diagnosis (IPND) criteria, (2) the aquaporin-4 immunoglobulin G antibodies (AQP4-IgG) test was performed. Patients without AQP4-IgG antibody were excluded. Clinical data, including sex, age of the first onset, symptoms of the first episode including neuropathic pain and attack types, localization of lesions of the first episode on Magnetic Resonance Imaging (MRI), Extended disability status Scale (EDSS) of the first onset, treatment of immunosuppression in the first acute phase, disease modifying therapy (DMT), treatment of neuropathic pain and APQ4-IgG status were collected from the hospital system database. Neuropathic pain was defined according to the International Association for the Study of Pain criteria and was described as “pain arising as a direct consequence of a lesion or disease affecting the somatosensory system”. Results: One hundred nineteen patients were screened and finally 86 patients fulfilling the inclusion and exclusion criteria were enrolled in our study. The prevalence of neuropathic pain in patients with NMOSD was 43.0%. Univariate analysis showed that the factors associated with neuropathic pain were the age at the onset, the attack type of optic neuritis, the attack type of myelitis, length of spinal cord involvement, localization of thoracic lesion, optic lesion, upper thoracic lesions, lower thoracic lesions, extended spinal cord lesions (≥ 3 spinal lesions), extended thoracic lesions (≥ 4 thoracic lesions), intravenous immunoglobulin and mycophenolate mofetil. Multivariate regression analysis showed that extended thoracic lesions (OR 20.21 [1.18–346.05], P = 0.038) and age (OR 1.35 (1–1.81) P = 0.050) were independently associated with neuropathic pain among NMOSD patients and that gender (OR 12.11 (0.97–151.64) P = 0.053) might be associated with neuropathic pain among NMOSD patients. Conclusion: Extended thoracic lesions (≥ 4 thoracic lesions), age and gender might be independent risk factors of neuropathic pain among patients with NMOSD. However, with a small sample size and predominantly female, caution must be applied and these results need validating in further cohorts.