The purpose of this study was to explore the relationship between and among the caregiver's personal factors, the care recipient's functional status, the caregiver's perceived self-efficacy, social support, reactions to caregiving, and health promotion behaviors in family caregivers of community-dwelling stroke patients in Taiwan. A structured home-interview survey methodology was used to collect data from 134 primary caregivers responsible for care of stroke patients in Taipei, Taiwan. The study results indicated that, in general, caregivers were female spousal caregivers (mean age 52 years, average caregiving period 24 months). Regression analyses revealed that the caregiver's health status was the strongest positive predictor of caregiver self-efficacy. Spousal caregivers with a better-perceived health status were more satisfied with their resources of social supports. Spousal caregivers with poor perceived health status had a higher level of caregiving strain. Results for the overall model indicated caregiver's social support and the care recipient's functional status made significant contributions in explaining the caregiver's health promotion behaviors. Implications for further practice suggest establishing community training programs and support groups for family caregivers.

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Background Low differentiation rates of mesenchymal stem cells (MSCs) limit their therapeutic effects on patients in clinical studies. Our previous study demonstrated that overexpressing p130 or E2F4 affected the multipotential differentiation of MSCs, and the underlying mechanism was attributed to the regulation of the G1 phase. Improving the efficiency of MSC differentiation into epithelial cells is considered to be a new method. Therefore, this study was conducted to evaluate the effects of overexpressing p130 or E2F4 in MSCs on improving re-epithelization in lipopolysaccharide (LPS)-induced ARDS animals. Methods Mouse MSCs (mMSCs) stably transfected with p130 and E2F4 were transplanted intratracheally into LPS-induced ARDS mice. After 7 and 14 days, the mice were sacrificed, and the histopathology of the lungs was assessed by haematoxylin-eosin staining and lung injury scoring. Homing and differentiation of mMSCs were analysed by labelling and tracking mMSCs with NIR815 dye and immunofluorescent staining. Surfactant proteins A and C and occludin in the lungs were assessed by western blot. Permeability was evaluated by analysing the protein concentration of BALF using ELISA. Alveolar fluid clearance was assessed by absorbance measurements of BALF. Lung fibrosis was assessed by Masson’s trichrome staining and Ashcroft scoring. Results The engraftment of mMSCs overexpressing p130 or E2F4 led to attenuated histopathological impairment of the lung tissue, and the lung injury scores of the LPS+mBM-MSC-p130 and LPS+mBM-MSC-E2F4 groups were also decreased ( p < 0.05). Overexpression of p130 or E2F4 also increased the retention of mMSCs in the lung ( p < 0.05), increased differentiation into type II alveolar epithelial cells ( p < 0.05), and improved alveolar epithelial permeability ( p < 0.05). Additionally, mMSCs overexpressing p130 or E2F4 inhibited lung fibrosis according to the deposition of collagen and the fibrosis score in the lungs ( p < 0.05). Conclusion Overexpressing p130 or E2F4 in mMSCs could further improve the injured structure and function of epithelial cells in the lungs of ARDS mice as a result of improved differentiation of mMSCs into epithelial cells. Electronic supplementary material The online version of this article (10.1186/s13287-019-1169-1) contains supplementary material, which is available to authorized users.

Hyperglycemia is one of the most important pathogenesis of diabetic osteopathy. Several lines of studies indicate Runx2 plays a critical role in the process of osteogenic differentiation. However, little studies have analyzed the effect of Runx2 on osteoblast differentiation of rat bone mesenchymal stem cells (rBMSCs) in high-glucose condition. In this study, the effect of Runx2 on osteoblast differentiation in high-glucose condition was evaluated by the expression of osteogenesis-related maker including Runx2, ALP, OC, and OPN, as well as ALP staining, ALP activity, and Alizarin red S staining. Western blot analysis was performed to detect the protein expression levels of p-AKT, AKT, p-GSK3β, GSK3β, and β-catenin. Immunofluorescence staining analysis was performed to detect subcellular localization of β-catenin. Our results revealed that high glucose significantly inhibited osteogenic differentiation, hyperosmolarity did not cause a suppression. In addition, Runx2 could upregulate the expression of osteogenic-related genes and increase matrix mineralization, while applying 10 µM PI3K/AKT inhibitor LY294002 abolished the beneficial effect. Collectively, these results indicate that Runx2 alleviates high glucose-induced inhibition of osteoblast differentiation by modulating PI3K/AKT/GSK3β/β-catenin pathway.

Emerging evidence has indicated that colony-stimulating factor-1 (CSF1) modulates neuroinflammation in the central nervous system and the development of neuropathic pain, while the underlying mechanism remains unknown. Here, we identified the increased expression of CSF1 derived from activated astrocytes in the ipsilateral dorsal horn in rats with spinal nerve ligation (SNL). Suppression of CSF1 expression alleviated neuroinflammation, neuronal hyperexcitability, and glutamatergic receptor subunit upregulation in the dorsal horn and improved SNL-induced pain behavior. We also found reduced miR-214-3p expression in the ipsilateral dorsal horn following an SNL procedure; miR-214-3p directly bound to the 3′-UTR of CSF1 mRNA and negatively regulated CSF1 expression. Intrathecal delivery of miR-214-3p mimic reversed the enhanced expression of CSF1 and astrocyte overactivity and alleviated the IL-6 upregulation and pain behavior induced by SNL. Moreover, suppression of spinal miR-214-3p increased astrocyte reactivity, promoted CSF1 and IL-6 production, and induced pain hypersensitivity in naive animals. Furthermore, SNL induced the expression of DNA methyltransferase 3a (DNMT3a) that was associated with the hypermethylation of the miR-214-3p promoter, leading to reduced miR-214-3p expression in the model rodents. Treatment with the DNMT inhibitor zebularine significantly reduced cytosine methylation in the miR-214-3p promoter; this reduced methylation consequently increased the expression of miR-214-3p and decreased the content of CSF1 in the ipsilateral dorsal horn and, further, attenuated IL-6 production and pain behavior in rats with SNL. Together, our data indicate that the DNMT3a-mediated epigenetic suppression of miR-214-3p enhanced CSF1 production in astrocytes, which subsequently induced neuroinflammation and pain behavior in SNL model rats.

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Certain microRNAs (miRs) have important roles in the maintenance of bone development and metabolism, and a variety of miRs are known to be deregulated in diabetes. The present study investigated the role of miR-203-3p in the regulation of bone loss by assessing jaw bones of a rat model of type 2 diabetes. The results indicated that miR-203-3p inhibited osteogenesis in the jaws of diabetic rats and in rat bone marrow mesenchymal stem cells cultured in high-glucose medium. A luciferase re porter assay was used to verify the bioinformatics prediction that miR-203-3p targets the 3′-untranslated region of Smad1, which is an important mediator of the bone morphogenetic protein (BMP)/Smad pathway. Overexpression of Smad1 attenuated the miR-203-3p-mediated suppres sion of osteogenic differentiation. It was therefore indicated that the BMP/Smad pathway is attenuated and the transforming growth factor-β/activin pathway is promoted by Smad1 reduction. Taken together, it was indicated that miR-203-3p inhibits osteogenesis in jaw bones of diabetic rats by targeting Smad1 to inhibit the BMP/Smad pathway.

Complex regional pain syndrome type 1 (CRPS-I) remains one of the most clinically challenging neuropathic pain syndromes and its mechanism has not been fully characterized. Cannabinoid receptor 2 (CB2) has emerged as a promising target for treating different neuropathic pain syndromes. In neuropathic pain models, activated microglia expressing CB2 receptors are seen in the spinal cord. Chemokine fractalkine receptor (CX3CR1) plays a substantial role in microglial activation and neuroinflammation. We hypothesized that a CB2 agonist could modulate neuroinflammation and neuropathic pain in an ischemia model of CRPS by regulating CB2 and CX3CR1 signaling. We used chronic post-ischemia pain (CPIP) as a model of CRPS-I. Rats in the CPIP group exhibited significant hyperemia and edema of the ischemic hindpaw and spontaneous pain behaviors (hindpaw shaking and licking). Intraperitoneal administration of MDA7 (a selective CB2 agonist) attenuated mechanical allodynia induced by CPIP. MDA7 treatment was found to interfere with early events in the CRPS-I neuroinflammatory response by suppressing peripheral edema, spinal microglial activation and expression of CX3CR1 and CB2 receptors on the microglia in the spinal cord. MDA7 also mitigated the loss of intraepidermal nerve fibers induced by CPIP. Neuroprotective effects of MDA7 were blocked by a CB2 antagonist, AM630. Our findings suggest that MDA7, a novel CB2 agonist, may offer an innovative therapeutic approach for treating neuropathic symptoms and neuroinflammatory responses induced by CRPS-I in the setting of ischemia and reperfusion injury.