ObjectiveTo systematically review the prevalence of cognitive impairment in patients with sarcopenia. MethodsThe PubMed, EMbase, Web of Science, Cochrane Library, CBM, CNKI, VIP and WanFang Data databases were electronically searched to collect studies related to the objectives from inception to December 10, 2022. Two reviewers independently screened literature, extracted data and assessed the risk of bias of the included studies. Meta-analysis was then performed by using Stata 14.0 software. ResultsA total of 27 studies were included. The overall prevalence rate of cognitive impairment in sarcopenia was 36.1% (95%CI 29.4% to 42.8%). Subgroup analysis showed that the prevalence in Europe was higher than that in other areas. The prevalence of nursing home residents was highest. ConclusionCurrent evidence shows that the prevalence of cognitive impairment in patients with sarcopenia is high. Due to the limited quality and quantity of the included studies, more high quality studies are needed to verify the above conclusion.
Objective To investigate the mechanism of the mechanosensitive ion channel Piezo1 in microglial ferroptosis following spinal cord injury (SCI), and to assess the effects of Piezo1 inhibition on ameliorating the injury microenvironment and promoting neurological functional recovery. Methods Primary microglia cells were extracted from neonatal 1-2 days C57BL/6 mice and divided into control group, Yoda1 (Piezo1 agonist) group, and Yoda1+GsMTx4 (Piezo1 inhibitor) group. Live/dead cell staining, reactive oxygen species (ROS) fluorescence staining, 5, 5’, 6, 6’-tetrachloro-1, 1’, 3, 3’-tetraethylbenzimidazolylcarbocyanine iodide (JC-1) mitochondrial membrane potential detection, and transmission electron microscopy were utilized to assess microglial ferroptosis and mitochondrial functional characteristics. SPF female C57BL/6 mice aged 6 to 8 weeks were used to detect the expression of Piezo1 at different time points after SCI by Western blot, and the two time points with no significant change and the most significant change in Piezo1 expression after SCI were selected for subsequent experiments. T8, T9 SCI models were established by modified Allen’s method, and were divided into sham operation group, injury group, and injury+shPiezo1 group (Piezo1-targeted interfering virus AAV-shPiezo1 was injected in situ to knock down the expression of Piezo1 14 days before modeling). Colocalization of Piezo1 with microglial markers purinergic receptor P2Y12 (P2ry12), and the expressions of glutathione peroxidase 4 (GPX4) and acyl coenzyme A synthetase long chain member 4 (ACSL4) were observed by immunofluorescence staining. Basso Mouse Scale (BMS) score was used to assess hindlimb motor function in mice. The level of ROS was detected by dihydroethidium (DHE) staining; the content of malondialdehyde (MDA) was detected by MDA kit; the levels of tumor necrosis factor α (TNF-α) and interleukin 10 (IL-10) were detected by ELISA assay; the pathological morphology of spinal cord was observed by HE staining. Results In vitro experiments showed that compared with the control group, the Yoda1 group had typical ultrastructural changes of ferroptosis, such as increased microglial cell death, enhanced ROS fluorescence, mitochondrial membrane potential depolarization, mitochondrial shrinkage and mitochondrial cristae breakage (all P<0.05), while the GsMTx4 group could partially reverse the above effects (P<0.05). In vivo experiments demonstrated that the expression of Piezo1 in spinal cord tissue was up-regulated sequentially after SCI, and reached the peak on the 7th day after SCI (P<0.05), and it was mainly localized in P2ry12-positive microglia. Compared with the injury group, in the injury+shPiezo1 group, the expression of ferroptosis core protein GPX4 in microglia was increased, the expression of ACSL4 was decreased, the levels of ROS and MDA in spinal cord tissue were decreased (P<0.05), the level of pro-inflammatory factor TNF-α was decreased, and the level of anti-inflammatory factor IL-10 was increased (P<0.05). In addition, the BMS score was significantly higher than that of the injury group (P<0.05) from the 14th day after operation, and the spinal cord tissue structure was relatively well preserved, and the cavity area was reduced. Conclusion SCI activates the Piezo1 channel in microglia, triggering mitochondrial dysfunction and mediating cellular ferroptosis, thereby aggravating secondary neuroinflammation. Targeted inhibition of Piezo1 effectively blocks the ferroptosis process, ameliorates the immune microenvironment, and promotes tissue repair and locomotor functional recovery after SCI.
Objective To explore the mechanism by which ω-3 polyunsaturated fatty acids (hereinafter referred to as “ω-3”) exert antioxidant stress protection and promote osteogenic differentiation in MC3T3-E1 cells, and to reveal the relationship between ω-3 and the key antioxidant stress pathway involving nuclear factor E2-related factor 2 (Nrf2) and NAD (P) H quinone oxidoreductase 1 (NQO1) in MC3T3-E1 cells. Methods The optimal concentration of H2O2 (used to establish the oxidative stress model of MC3T3-E1 cells in vitro) and the optimal intervention concentrations of ω-3 were screened by cell counting kit 8. MC3T3-E1 cells were divided into blank control group, oxidative stress group (H2O2), low-dose ω-3 group (H2O2+low-dose ω-3), and high-dose ω-3 group (H2O2+high-dose ω-3). After osteoblastic differentiation for 7 or 14 days, the intracellular reactive oxygen species (ROS) level was measured by fluorescence staining and flow cytometry, and the mitochondrial morphological changes were observed by biological transmission electron microscope; the expression levels of Nrf2, NQO1, heme oxygenase 1 (HO-1), Mitofusin 1 (Mfn1), and Mfn2 were detected by Western blot to evaluate the cells’ antioxidant stress capacity; the expression levels of Runt-related transcription factor 2 (RUNX2) and osteocalcin (OCN) were detected by immunofluorescence staining and Western blot; osteogenic potential of MC3T3-E1 cells was evaluated by alkaline phosphatase (ALP) staining and alizarin red staining. Results Compared with the oxidative stress group, the content of ROS in the low and high dose ω-3 groups significantly decreased, and the protein expressions of Nrf2, NQO1, and HO-1 significantly increased (P<0.05). At the same time, the mitochondrial morphology of MC3T3-E1 cells improved, and the expressions of mitochondrial morphology-related proteins Mfn1 and Mfn2 significantly increased (P<0.05). ALP staining and alizarin red staining showed that the low-dose and high-dose ω-3 groups showed stronger osteogenic ability, and the expressions of osteogenesis-related proteins RUNX2 and OCN significantly increased (P<0.05). And the above results showed a dose-dependence in the two ω-3 treatment groups (P<0.05). Conclusion ω-3 can enhance the antioxidant capacity of MC3T3-E1 cells under oxidative stress conditions and upregulate their osteogenic activity, possibly through the Nrf2/NQO1 signaling pathway.