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Abstract Background The channel-forming protein Pannexin1 (Panx1) has been implicated in both human studies and animal models of chronic pain, but the underlying mechanisms remain incompletely understood. Methods Wild-type (WT, n = 24), global Panx1 KO (n = 24), neuron-specific Panx1 KO (n = 20), and glia-specific Panx1 KO (n = 20) mice were used in this study at Albert Einstein College of Medicine. The von Frey test was used to quantify pain sensitivity in these mice following complete Freund’s adjuvant (CFA) injection (7, 14, and 21 d). The qRT-PCR was employed to measure mRNA levels of Panx1, Panx2, Panx3, Cx43, Calhm1, and β-catenin. Laser scanning confocal microscopy imaging, Sholl analysis, and electrophysiology were utilized to evaluate the impact of Panx1 on neuronal excitability and morphology in Neuro2a and dorsal root ganglion neurons (DRGNs) in which Panx1 expression or function was manipulated. Ethidium bromide (EtBr) dye uptake assay and calcium imaging were employed to investigate the role of Panx1 in adenosine triphosphate (ATP) sensitivity. β-galactosidase (β-gal) staining was applied to determine the relative cellular expression levels of Panx1 in trigeminal ganglia (TG) and DRG of transgenic mice. Results Global or neuron-specific Panx1 deletion markedly decreased pain thresholds after CFA stimuli (7, 14, and 21 d; P

Abstract Background Traumatic brain injury (TBI) is a common neurotrauma leading to brain dysfunction and death. Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) hold promise in the treatment of TBI. However, their efficacy is modest due to low survival and differentiation under the harsh microenvironment of the injured brain. MG53, a member of TRIM family protein, plays a vital role in cell and tissue damage repair. The present study aims to test whether MG53 preserves hUC-MSCs against oxidative stress and enhances stem cell survival and efficacy in TBI treatment. Methods In this study, we performed a series of in vitro and in vivo experiments in hUC-MSCs and mice to define the function of MG53 enhancing survival, neurogenesis, and therapeutic efficacy of stem cells in murine traumatic brain injury. Results We found that recombinant human MG53 (rhMG53) protein protected hUC-MSCs against H2O2-induced oxidative damage and stimulated hUC-MSC proliferation and migration. In a mouse model of contusion-induced TBI, intravenous administration of MG53 protein preserved the survival of transplanted hUC-MSCs, mitigated brain edema, reduced neurological deficits, and relieved anxiety and depressive-like behaviors. Co-treatment of MG53 and hUC-MSCs enhanced neurogenesis by reducing apoptosis and improving PI3K/Akt-GSK3β signaling. Conclusion MG53 enhances the efficacy of hUC-MSCs in the recovery of TBI, indicating that such adjunctive therapy may provide a novel strategy to lessen damage and optimize recovery for brain injury.

Background: Depression is a major health condition among the aging population. Previous studies indicated that edentulism was a risk factor for depression. The link between edentulism and depression has not been fully clarified. Objectives: This study aimed to estimate whether chewing difficulties play a mediating role in the association between edentulism and depression among middle‐aged and older populations with national cross‐sectional data. Methods: Data were obtained from the latest fourth wave of the China Health and Retirement Longitudinal Study (CHARLS). The outcome variable was set as depression, which was measured by the Center for Epidemiologic Studies Depression Scale (CES‐D‐10). Independent and mediated variables were separately set as self‐assessed edentulism and chewing difficulties. The nearest neighbour propensity score matching (PSM) method was used to construct a matching group to balance the basic characteristics of individuals with and without edentulism with minimised bias in the estimation. Causal mediation analysis was performed to estimate the degree of contribution of chewing difficulties to the association between edentulism and depression. Several sensitivity analyses were performed to evaluate the robustness of the primary result. Results: A total of 15 853 individuals remained for analysis. After PSM, 809 individuals with edentulism and 2628 without edentulism remained for analysis. Among the matched individuals, the mean age was 66.3 ± 9.2 years, 58.5% were female, 78.8% lived in rural areas, 23.5% had edentulism, 51.1% had depressive symptoms, and 50.1% had chewing difficulties. Logistic regression results showed that a higher incidence of edentulism was associated with a higher rate of depression (OR: 1.39, 95% CI: 1.19–1.63) in the matching group. Causal mediation analysis results indicated that the average mediation effect of chewing difficulties on the association between edentulism and depression was 0.010 (95% CI: 0.005–0.015), and the average direct effect was 0.072 (95% CI: 0.036–0.11). The mediation proportion of chewing difficulties was 11.7% (95% CI: 0.079–0.21). Conclusion: A higher prevalence of edentulism was associated with a higher rate of depression among middle‐aged and elderly populations. Chewing difficulties moderately mediated the association between edentulism and depression. Fundamental oral function should not be neglected to improve mental health among the aging population. [ABSTRACT FROM AUTHOR]

Stem cell transplantation is a promising therapy for traumatic brain injury (TBI), but low efficiency of survival and differentiation of transplanted stem cells limits its clinical application. Histone deacetylase 1 (HDAC1) plays important roles in self-renewal of stem cells as well as the recovery of brain disorders. However, little is known about the effects of HDAC1 on the survival and efficacy of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) in vivo. In this study, our results showed that HDAC1 silence promoted hUC-MSCs engraftment in the hippocampus and increased the neuroprotective effects of hUC-MSCs in TBI mouse model, which was accompanied by improved neurological function, enhanced neurogenesis, decreased neural apoptosis, and reduced oxidative stress in the hippocampus. Further mechanistic studies revealed that the expressions of phosphorylated PTEN (p-PTEN), phosphorylated Akt (p-Akt), and phosphorylated GSK-3β (p-GSK-3β) were upregulated. Intriguingly, the neuroprotective effects of hUC-MSCs with HDAC1 silence on behavioral performance of TBI mice was markedly attenuated by LY294002, an inhibitor of the PI3K/AKT pathway. Taken together, our findings suggest that hUC-MSCs transplantation with HDAC1 silence may provide a potential strategy for treating TBI in the future.