Mesenchymal stem cell (MSC)-derived exosomes (Exos) enhanced new bone formation, coupled with positive effects on osteogenesis and angiogenesis. This study aims to define the role of microRNA (miR)-21-5p delivered by human umbilical MSC-derived Exos (hucMSC-Exos) in the osteonecrosis of the femoral head (ONFH). We first validated that miR-21-5p expression was downregulated in the cartilage tissues of ONFH patients. Besides, hucMSCs delivered miR-21-5p to hFOB1.19 cells and human umbilical vein endothelial cells (HUVECs) through the secreted Exos. Loss- and gain-of-function approaches were performed to clarify the effects of Exo-miR-21-5p, SOX5, and EZH2 on HUVEC angiogenesis and hFOB1.19 cell osteogenesis. It was established that Exo-miR-21-5p augments HUVEC angiogenesis and hFOB1.19 cell osteogenesis in vitro, as reflected by elevated alkaline phosphatase (ALP) activity and calcium deposition, and increased the expression of osteogenesis-related markers OCN, Runx2 and Collagen I. Mechanistically, miR-21-5p targeted SOX5 and negatively regulated its expression, while SOX5 subsequently promoted the transcription of EZH2. Ectopically expressed SOX5 or EZH2 could counterweigh the effect of Exo-miR-21-5p. Further, hucMSC-Exos containing miR-21-5p repressed the expression of SOX5 and EZH2 and augmented angiogenesis and osteogenesis in vivo. Altogether, our study uncovered the role of miR-21-5p shuttled by hucMSC-Exos, in promoting angiogenesis and osteogenesis, which may be a potential therapeutic target for ONFH.

We transplanted RADA16-PRG self-assembled nanopeptide scaffolds (SAPNSs), bone mesenchymal stem cells (BMSCs), and a brain-derived neurotrophic factor (BDNF)-expressing adeno-associated virus (AAV) into rats subjected to acute spinal cord injury (SCI) to investigate the effects of these transplantations on acute SCI repair and explore their mechanisms. Forty-eight SCI rats were randomly divided into four groups: BBR, BR, B, and NC groups. Seven and 28 days after SCI, evoked potentials (EPs) and BBB scores were assessed to evaluate the recovery of rats’ motor behavior and sensory function after injury. HE and toluidine blue staining were performed to investigate the histological structure of the spinal cord tissue of rats from each group, and immunofluorescence staining was used to observe the red fluorescent protein (RFP) intensity of BMSCs and glial fibrillary acidic protein (GFAP) and neurofilament (NF) in the damaged area in each group. RT–PCR was utilized to detect the expression levels of the BDNF, GFAP, and neuron-specific enolase (NSE) genes in the injured area in each group. The results showed that cotransplantation of RADA16-PRG-SAPNs, BMSCs, and BDNF-AVV promoted the spinal cord’s motor and sensory function of SCI rats; increased levels of BMSCs, inhabited glial cells proliferation, and promoted neurons proliferations in the injured area; and increased NF, BDNF, and NSE levels and decreased its GFAP in the injured area. Thus, cotransplantation of RADA16-PRG-SAPNS, BMSCs, and BDNF-AAV can prolong the survival time of BMSCs in rats, reduce the postoperative scarring caused by glial proliferation, and promote the migration and proliferation of neurons in the injured area, resulting in the promotion of functional repair after acute SCI.

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BACKGROUND Although the chemical components of basal, reflex, and emotional tears are different, the presence of distinctions in the tears of different emotions is still unknown. The present study aimed to address the biochemical basis behind emotional tears through non-targeted metabolomics analysis between positive and negative emotional tears of humans. METHODS Samples of reflex (C), negative (S), and positive (M) emotional tears were collected from healthy college participants. Untargeted metabolomics was performed to identify the metabolites in the different types of tears. The differentially altered metabolites were screened and assessed using univariate and multivariate analyses. RESULTS The global metabolomics signatures classified the C, S, and M emotional tears. A total of 133 significantly differential metabolites of ESI- mode were identified between negative and positive emotional tears. The top 50 differential metabolites between S and M were highly correlated. The significantly altered pathways included porphyrin & chlorophyll metabolism, bile secretion, biotin metabolism, arginine & proline metabolism and among others. CONCLUSION The metabolic profiles between reflex, positive, and negative emotional tears of humans are distinct. Secretion of positive and negative emotional tears are distinctive biological activities. Therefore, the present study provides a chemical method to detect human emotions which may become a powerful tool for diagnosis of mental disease and identification of fake tears.

Background Basal, reflex, and emotional tears differ in chemical components. It is not yet known whether chemical differences exist in tears of different emotions. We investigated the biochemical basis of emotional tears by performing non-targeted metabolomics analyses of positive and negative emotional tears of humans. Methods Samples of reflex, negative, and positive emotional tears were obtained from 12 healthy college participants (11 females and one male). Untargeted metabolomics was performed to identify metabolites in different types of tears. The differentially altered metabolites were screened and assessed using univariate and multivariate analyses. Results The orthogonal partial least squares discriminant analysis model showed that reflex, negative, and positive emotional tears were clearly separated. A total of 133 significantly differentially expressed metabolites of electrospray ionization source (ESI-) mode were identified between negative and positive emotional tears. The top 50 differentially expressed metabolites between negative and positive emotional tears were highly correlated. Pathway analysis revealed that secretion of negative emotional tears was associated with some synapses in the brain, regulation of a series of endocrine hormones, including the estrogen signaling pathway, and inflammation activities, while secretion of positive emotional tears was correlated with biotin and caffeine metabolism. Conclusions It is indicated that metabolic profiles of reflex, positive, and negative emotional tears of humans are distinct, and secretion of the tears involves distinct biological activities. Therefore, we present a chemical method for detecting human emotions, which may become a powerful tool for the diagnosis of mental diseases and the identification of fake tears.