The glutamine synthetase (GS), an astrocyte-specific enzyme, is involved in lipopolysaccharide (LPS)-induced inflammation which activates the mitogen-activated protein kinase (MAPK) signaling. Endocannabinoid 2-arachidonyl glycerol (2-AG) has been described to serve as an endogenous mediator of analgesia and neuroprotection. However, whether 2-AG can directly influence astrocytic GS and MAPK expressions remains unknown. In the present study, the effects of 2-AG on astrocytic GS expression, p38 and ERK1/2 expression, cell viability, and apoptosis following LPS exposure were investigated. The results revealed that LPS exposure increased GS expression with p38 activation in the early phase and decreased GS expression with activation of ERK1/2, decrease of cell viability, and increase of apoptosis in the late phase. Inhibition of p38 reversed GS increase in the early phase while inhibition of ERK1/2 reversed GS decrease in the late phase induced by LPS exposure. 2-AG protected astrocytes from increase of apoptosis and decrease of cell viability induced by the late phase of LPS exposure. In the early phase of LPS exposure, 2-AG could suppress the increase of GS expression and activation of p38 signaling. In the late phase of LPS exposure, 2-AG could reverse the decrease of GS expression and activation of ERK1/2 induced by LPS. These findings suggest that 2-AG could maintain the GS expression in astrocytes to a relatively stable level through modulating MAPK signaling and protect astrocytes from LPS exposure.

Objective: Bone marrow mesenchymal stem cells (BMSCs) show significant potential for osteogenic differentiation. However, the underlying mechanisms of osteogenic capability in osteoporosis‐derived BMSCs (OP‐BMSCs) remain unclear. This study aims to explore the impact of YTHDF3 (YTH N6‐methyladenosine RNA binding protein 3) on the osteogenic traits of OP‐BMSCs and identify potential therapeutic targets to boost their bone formation ability.Methods: We examined microarray datasets (GSE35956 and GSE35958) from the Gene Expression Omnibus (GEO) to identify potential m⁶A regulators in osteoporosis (OP). Employing differential, protein interaction, and machine learning analyses, we pinpointed critical hub genes linked to OP. We further probed the relationship between these genes and OP using single‐cell analysis, immune infiltration assessment, and Mendelian randomization. Our in vivo and in vitro experiments validated the expression and functionality of the key hub gene.Results: Differential analysis revealed seven key hub genes related to OP, with YTHDF3 as a central player, supported by protein interaction analysis and machine learning methodologies. Subsequent single‐cell, immune infiltration, and Mendelian randomization studies consistently validated YTHDF3's significant link to osteoporosis. YTHDF3 levels are significantly reduced in femoral head tissue from postmenopausal osteoporosis (PMOP) patients and femoral bone tissue from PMOP mice. Additionally, silencing YTHDF3 in OP‐BMSCs substantially impedes their proliferation and differentiation.Conclusion: YTHDF3 may be implicated in the pathogenesis of OP by regulating the proliferation and osteogenic differentiation of OP‐BMSCs.

Objective. Neuropathic pain (NP) is a type of intractable chronic pain with complicated etiology. The exact molecular mechanism underlying NP remains unclear. In this study, we searched for molecular biomarkers of NP. Methods. Differentially expressed genes (DEGs) were predicted by analyzing three NP-related microarray datasets in Gene Expression Omnibus with robust rank aggregation. A weighted gene coexpression network analysis was conducted to construct a network of differentially expressed genes, followed by the evaluation of correlations between gene sets and the determination of hub genes. The candidate genes from the key module were identified using a gene set enrichment analysis. Results. In total, 353 upregulated and 383 downregulated genes were obtained, among which five hub genes were determined to be related to pain phenotypes. Reverse transcription-quantitative polymerase chain reaction was performed to verify the expression of these hub genes in the dorsal root ganglia of rats with spared nerve injury, which revealed the decreased expression of EMC4. Hence, EMC4 was defined as a biomarker for NP development. Conclusions. The results of this study form a basis for further research into the mechanism of NP development and are expected to aid in the development of novel therapeutic strategies.

Periprosthetic joint infection (PJI) caused by Brucella spp. is an exceedingly rare occurrence, leading to a lack of consensus regarding its diagnosis and treatment. This review mainly aimed to assess the diagnosis and treatment strategy of Brucella-induced PJI. We summarized the data by reporting 4 cases from the Hexi area of China and conducting a systematic review. A comprehensive literature search was performed in PubMed, Web of Science, Embase, and the Chinese Biology Medicine database for relevant publications using predefined search terms. Included studies were case reports or series on human Brucella-induced PJI that described patient outcomes. Data on demographics, diagnosis, treatment, and outcomes were extracted and analyzed. A total of 61 patients of Brucella-related PJI were summarized. Serological antibody tests provided the best diagnostic yield with a 100% positive rate (35/35), compared to lower sensitivities for joint aspiration culture (53.84%, 21/39) and blood culture (41.67%, 5/12). In the presence of radiological implant loosening, 32 patients underwent one- or 2-stage revision with combination antibiotic therapy. For 29 patients without loosening, treatment included antibiotic therapy alone or combined with drainage and debridement or revision. No recurrence was reported at the end of the follow-up. Preoperative serological tests are prioritized for diagnosing Brucella PJI. Loose implants should be managed with revision surgery, while stable implants may be treated initially with antibiotics alone or combined with debridement.