Globulin, the albumin-to-globulin ratio, and fibrinogen perform well in the diagnosis of Periprosthetic joint infection.

BACKGROUND: Although periprosthetic joint infection (PJI) is a severe complication of total joint arthroplasty (TJA), the diagnosis of PJI remains challenging. Albumin (ALB), globulin (GLB), the albumin-to-globulin ratio (AGR), and fibrinogen could be indicators of the body's inflammatory state. This study aimed to compare the diagnostic accuracy of these biomarkers with that of other inflammatory biomarkers in PJI patients. METHODS: We conducted a retrospective cohort study that included a consecutive series of patients undergoing debridement antibiotic irrigation and implant retention (DAIR), one-stage or the first stage of a two-stage revision total knee arthroplasty (TKA) or total hip arthroplasty (THA) for acute (n = 31) or chronic (n = 51) PJI, or revision TKA or THA for aseptic failures (n = 139) between January 2017 and December 2019 in our hospital. The 2013 criteria of the Musculoskeletal Infection Society (2013 MSIS) were used as the reference standard for the diagnosis of PJI. The preoperative ALB, GLB, AGR, fibrinogen, D-dimer, platelet count, fibrin degradation product (FDP), platelet-to-lymphocyte (PLR), platelet count to mean platelet volume ratio (PVR), neutrophil-to-lymphocyte ratio (NLR), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels were assessed. The receiver operating characteristic curve (ROC), sensitivity, and specificity were utilized to compare different biomarkers. RESULTS: Compared with the aseptic patients, the GLB, D-dimer, fibrinogen, FDP, platelet count, PVR, PLR, NLR, ESR, and CRP levels of PJI patients were significantly higher (P < 0.01); however, the ALB and AGR levels were significantly lower (P < 0.01). The area under the curve (AUC), sensitivity and specificity were 0.774, 67.50, 77.54% for ALB; 0.820, 57.50, 89.86% for GLB; 0.845, 66.25, 93.48% for AGR; 0.832, 78.48, 78.95% for fibrinogen; 0.877, 81.48, 85.07% for ESR; 0.909, 83.95, 88.89% for CRP; 0.683, 55.22, 75.83% for D-dimer; 0.664, 38.81, 88.33% for FDP; 0.678, 52.44, 79.86% for platelet count; 0.707, 48.78, 86.33% for PVR; 0.700, 51.22, 80.58% for PLR; and 0.678, 52.44, 81.30% for NLR, respectively. In the clinic, GLB, AGR and fibrinogen could be used for diagnosis of patients suspected of having PJI. CONCLUSION: Our study demonstrated that GLB, AGR, and fibrinogen were promising biomarkers in the diagnosis of PJI.

Microbial Metabolite Sodium Butyrate Attenuates Cartilage Degradation by Restoring Impaired Autophagy and Autophagic Flux in Osteoarthritis Development.

Osteoarthritis (OA) is a degenerative joint disease with multiple etiologies that affects individuals worldwide. No effective interventions are currently available to reverse the pathological process of OA. Sodium butyrate (NaB), a component of short-chain fatty acids (SCFAs), has multiple biological activities, including the attenuation of inflammation and anti-tumor activities in various diseases. However, whether the protective effects of NaB in OA are associated with the promotion of autophagy had not been investigated. Here, we explored the chondroprotective properties of NaB in an interleukin (IL)-1ß-induced inflammatory chondrocyte model and an anterior cruciate ligament transection (ACLT) mouse model. Hematoxylin and eosin (HE), Safranin O, and immunohistochemical staining were performed to evaluate the effects of NaB treatment on articular cartilage. An optimal NaB dose for chondrocyte treatment was determined via cell counting kit-8 assays. Immunofluorescence and transmission electron microscopy were used to detect autophagy in chondrocytes. Flow cytometry was utilized to detect reactive oxygen species (ROS), cell cycle activity, and apoptosis in chondrocytes. Western blot and immunostaining were performed to evaluate the protein expression levels of relevant indicators. We found that the administration of NaB by oral gavage could attenuate cartilage degradation. In parallel, NaB treatment could enhance the activation of autophagy, increase autophagic flux, decrease extracellular matrix degradation, and reduce apoptosis by restraining inflammation, ROS production, and cell cycle arrest in IL-1ß-treated chondrocytes. The protective effects of NaB could be partially abolished by the autophagy inhibitor 3-methyladenine (3-MA), which indicated that the protective effects of NaB against OA were partially governed by the enhancement of autophagy to restrain the formation of inflammatory mediators and ROS and regulate cell cycle progression and apoptosis in chondrocytes. In conclusion, NaB could attenuate OA progression by restoring impaired autophagy and autophagic flux via the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway, both in vitro and in vivo, implying that NaB could represent a novel therapeutic approach for OA.

Filamin B extensively regulates transcription and alternative splicing, and is associated with apoptosis in HeLa cells.

Post­transcriptional mechanisms are an important approach in the treatment of cancer, and may also be hijacked by tumor cells to help adapt to the local microenvironment. Filamin B (FLNB), an actin­binding protein that provides crucial scaffolds for cell motility and signaling, has also been identified as an RNA­binding protein. Recent studies demonstrated that FLNB might play an important role, not only in skeletal development, but also in regulating tumorigenesis; however, the effects of dysregulated expression of FLNB at the molecular level are not clear. In the present study, RNA­sequencing was performed to analyze changes in overall transcriptional and alternative splicing between the knocked­down FLNB and the control in HeLa cells. Decreased FLNB levels resulted in significantly lower apoptosis compared with control cells. FLNB knockdown extensively regulated the expression of genes in cell apoptosis, tumorigenesis, metastases, transmembrane transport and cartilage development. Moreover, FLNB regulated alternative splicing of a large number of genes involved in 'cell death' and the 'apoptotic process'. Some genes and alternative splicing related to skeletal development were enriched and regulated by FLNB. Reverse transcription­quantitative­PCR identified FLNB­regulated transcription and alternative splicing of genes, such as NLR family apoptosis inhibitory protein, interleukin 23 subunit α, metastasis associated lung adenocarcinoma transcript 1, phosphofurin acidic cluster sorting protein 2, bone morphogenetic protein 7, matrix metallopeptidase 13, collagen type II α 1 chain, fibroblast growth factor receptor 2 and vitamin D receptor. The present study is the first study, to the best of the authors' knowledge, to provide transcriptome­wide analysis of differential gene expression and alternative splicing upon FLNB silencing. The present results suggested that FLNB may play an important regulatory role in cervical cancer cell apoptosis via regulation of transcription and alternative splicing, which provide insight for the current understanding of the mechanisms of FLNB­mediated gene regulation.

Identification of the molecular mechanisms of Salvia miltiorrhiza relevant to the treatment of osteoarthritis based on network pharmacology.

Traditional Chinese medicine Salvia miltiorrhiza (SM) is a novel application and has shown significant clinical efficacy in treating osteoarthritis (OA). However, the molecular mechanisms of its action have not been systematically evaluated. This study explores the mechanisms of SM in the treatment of osteoarthritis using a network pharmacology approach. In this study, the active ingredients and related targets of SM were obtained following an ADME (absorption, distribution, metabolism, excretion) approach and utilizing the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. OA-related targets were obtained through GeneCard, PharmGkb, TTD, OMIM, and DRUGBANK databases. The common targets were obtained using the jvenn online tool. The ingredient-target network and the crucial active ingredients were obtained by Cytoscape. The protein-protein interaction (PPI) network and the key targets of SM in the treatment of OA were obtained by the STRING database and Cytoscape. The GO function and KEGG pathway enrichment cluster of the common targets were obtained by Metascape. Molecular docking was obtained by SwissDock to verify the correlation between the crucial active ingredients and key targets. We identified 59 active ingredients including luteolin, tanshinone IIA, dihydrotanshinquinone, and danshenxinkun D with important biological effects in the treatment of OA. We screened 72 common targets of SM-OA, among which IL-6, AKT1, VEGFA, TNF, TP53, FOS, MAPK1, and CASP3 are the key targets. The GO function and KEGG pathway enrichment cluster of the common targets revealed that SM acts on OA mainly through the PI3K-AKT, IL-17, HIF-1, and TNF signaling pathways and that its function is mainly to regulate metabolism, apoptosis, inflammation, and cell proliferation. Moreover, the molecular docking analysis indicated that the crucial ingredients were tightly bound to the key targets. Overall, our study has preliminarily revealed the molecular mechanisms of SM in the treatment of OA through multi-component, multi-target, and multi-channel network pharmacology approaches.