Alzheimer's disease-associated inflammatory pathways might contribute to osteoporosis through the interaction between PROK2 and CSF3.

This study aimed to explore the potential molecular pathways and targets of Alzheimer's disease leading to osteoporosis using bioinformatics tools. The Alzheimer's and osteoporosis microarray gene expression data were retrieved from the Gene Expression Omnibus, and differentially expressed genes in the blood microenvironment related to Alzheimer's disease and osteoporosis were identified. The intersection of the three datasets (GSE97760, GSE168813, and GSE62402) was used to obtain 21 co-expressed targets in the peripheral blood samples in patients with Alzheimer's disease and osteoporosis. Based on the degree algorithm, the top 10 potential core target genes related to these diseases were identified, which included CLEC4D, PROK2, SIGLEC7, PDGFB, PTCRA, ECH1, etc. Two differentially expressed mRNAs, Prokineticin 2 (PROK2) and three colony-stimulating factor 3 (CSF3), were screened in the GSE62402 dataset associated with osteoporosis. Protein-protein rigid docking with ZDOCK revealed that PROK2 and CSF3 could form a stable protein docking model. The interaction of PROK2 and CSF3, core genes related to osteoporosis inflammation, plays an important role in the mechanism of osteoporosis in patients with Alzheimer's. Therefore, abnormalities or alterations in the inflammatory pathways in the peripheral blood samples of Alzheimer's patients may affect the course of osteoporosis.

Ursolic acid inhibits Th17 cell differentiation via STAT3/RORγt pathway and suppresses Schwann cell-mediated Th17 cell migration by reducing CXCL9/10 expression.

Th17 cells represent important immune cells. Ursolic acid (UA) can regulate immune cell activities. This study was aimed to explore the effects of UA on Th17 cell differentiation and Schwann cell(SCs)-mediated migration and the potential mechanism. Naïve CD4+ T cells were isolated from rat peripheral blood, induced for Th17 cell differentiation, and treated with UA. The proportion of Th17 cells was detected by flow cytometry assay. SCs were co-cultured with Th17 cells. Th17 cell migration was detected by Transwell assay. The molecule expression was determined by Western blot and qRT-PCR. UA inhibited the Th17 cell differentiation and suppressed the STAT3/RORγt pathway. STAT3 overexpression up-regulated p-STAT3 and RORγt expression and promoted Th17 cell differentiation under the UA treatment. In LPS- and IFN-γ-stimulated-SCs, UA suppressed the expression of chemokines CXCL9/10, but had no significant effect of CCL20 expression. The expression CXCL9/10 receptor CXCR3 was higher in Th17 cells than that in Treg cells, while the expression CCL20 receptor CCR6 was lower in Th17 cells than that in Treg cells. UA, anti-CXCR3, and anti-CCR6 treatment inhibited SCs-mediated Th17 cell migration, and anti-CXCR3 exerted stronger inhibitory effect than Anti-CCR6. UA inhibited Th17 cell differentiation through STAT3/RORγt pathway and suppressed Th17 cell migration through down-regulating CXCL9/10 expression in SCs.

Elevated Substance P Is a Risk Factor for Postoperative Delirium in Patients with Hip Fracture.

Objective: Hip fractures are quite common worldwide, especially among the elderly, and are associated with a high incidence of postoperative delirium, which worsens functional results and increases death. The causes of postoperative delirium in patients with hip fractures are unknown, and a separate pathobiology has been hypothesized. Substance P is a neuropeptide that has been linked to a number of immune-inflammatory and neurological conditions. The purpose of this study was to see if serum substance P levels could predict postoperative delirium in a group of hip fracture patients. Methods: A total of 148 hip fracture patients were enrolled in the study, all of whom had no substantial pre-existing medical or cognitive issues. Demographic and regular laboratory data were gathered as a starting point. ELISA was used to examine substance P levels before and after surgery (after 1 day). Patients were then divided into two groups: "postoperative delirium" and "no postoperative delirium." Intergroup comparisons, study of delirium prevalence rates in postoperative serum substance P quartile categories, and binary logistic regression for postoperative delirium category as outcome were all done. Results: Except for serum low-density lipoprotein (LDL) levels, there were no statistically significant variations in preoperative substance P levels or other baseline characteristics between the two groups. The "postoperative delirium" group had significantly higher postoperative substance P levels than the "no postoperative delirium" group (46.36.1 versus 31.94.7 pg/ml). There was a significant difference in postoperative delirium rates between the quartile categories of postoperative substance P, with the fourth quartile having the highest rate. Regression analysis revealed that postoperative substance P levels were related with a significantly increased OR (1.265, CI: 1.172-1.283) of postoperative delirium. Conclusion: In the current sample of hip fracture patients, a higher postoperative serum substance P level was linked to a higher risk of postoperative delirium. Further research into the utility of early postoperative serum substance P as a delirium indicator in hip fracture patients is needed.

MEG3 promotes proliferation and inhibits apoptosis in osteoarthritis chondrocytes by miR-361-5p/FOXO1 axis.

BACKGROUND: This study aimed to investigate the role of long non-coding RNA (lncRNA) maternally expressed 3 (MEG3) and related molecular mechanisms, in osteoarthritis (OA). METHODS: Cartilage tissues of OA patients and healthy volunteers were isolated and cultured. After transfection with the appropriate constructs, chondrocytes were classified into Blank, pcDNA3.1-NC, pcDNA3.1-MEG3, si-NC, si-MEG3, pcDNA3.1-NC + mimics NC, pcDNA3.1-MEG3 + mimics NC, pcDNA3.1-NC + miR-361-5p mimics and pcDNA3.1-MEG3 + miR-361-5p mimics groups. qRT-PCR was used to detect the expression of MEG3, miR-361-5p and FOXO1. Western blot, luciferase reporter assay, RIP, CCK-8, and flow cytometry analysis were performed to reveal the morphology, proliferation, and apoptotic status of cartilage cells. Histological analysis and immunostaining were conducted in the OA rat model. RESULTS: Expression of MEG3 and FOXO1 was significantly decreased in OA compared with the normal group, while the expression of miR-361-5p was increased. MEG3 might serve as a ceRNA of miR-361-5p in OA chondrocytes. Moreover, using western blot analyses and the CCK-8 assay, MEG3 was shown to target miR-361-5p/FOXO1, elevate cell proliferation, and impair cell apoptosis. Functional analysis in vivo showed that MEG3 suppressed degradation of the cartilage matrix. CONCLUSION: MEG3 can contribute to cell proliferation and inhibit cell apoptosis and degradation of extracellular matrix (ECM) via the miR-361-5p/FOXO1 axis in OA chondrocytes.