Causal associations between human gut microbiota and osteomyelitis: a Mendelian randomization study.

Background: Recent studies have emphasized the role of gut microbiota in the onset and progression of osteomyelitis. However, the exact types of gut microbiota and their mechanisms of action remain unclear. Additionally, there is a lack of theoretical support for treatments that improve osteomyelitis by altering the gut microbiota. Methods: In our study, we utilized the largest genome-wide association study (GWAS) meta-analysis to date from the MiBioGen consortium, involving 13,400 participants. The GWAS data for osteomyelitis were sourced from the UK Biobank, which included 4,836 osteomyelitis cases and 486,484 controls. We employed a two-sample Mendelian randomization framework for a detailed investigation into the causal relationship between gut microbiota and osteomyelitis. Our methods included inverse variance weighting, MR-Egger, weighted median, and weighted mode approaches. Additionally, we applied Cochran's Q statistic to assess the heterogeneity of the instrumental variable. Results: At the class level, Bacilli and Bacteroidia were positively correlated with the risk of osteomyelitis. At the order level, only Bacteroidales showed a positive association with osteomyelitis. At the genus level, an increased abundance of Butyricimonas, Coprococcus3, and Tyzzerella3 was positively associated with the risk of osteomyelitis, whereas Lachnospira was negatively associated. Sensitivity analyses showed no evidence of heterogeneity or pleiotropy. Conclusion: This study reveals that classes Bacilli and Bacteroidia, order Bacteroidales, and genera Butyricimonas, Coprococcus3, and Tyzzerella3 are implicated in increasing the risk of osteomyelitis, while the genus Lachnospira is associated with a reduced risk. Future investigations are warranted to elucidate the precise mechanisms through which these specific bacterial groups influence the pathophysiology of osteomyelitis.

Systemic lupus erythematosus Association between Osteomyelitis: A two-sample Mendelian randomization study in European population.

Background: Systemic lupus erythematosus (SLE) has been correlated with osteomyelitis (OM), yet the underlying causal relationship remains poorly understood. This study aims to investigate the causal association between SLE and OM using Mendelian randomization (MR) analysis. Methods: Genetic instrumental variables (IVs) correlated with SLE were extracted from a comprehensive genome-wide association study (GWAS) summary database (5201 cases and 9066 controls). OM was considered a SLE phenotype, and summary data from the fast GWA data portal were utilized for the analysis. Eligible IVs were extracted following rigorous quality control measures (P < 5 × 10-8, LD r2>0.001, distance 1 Mb, and F > 10). MR analysis was conducted using the Inverse Variance Weighted (IVW), MR-Egger, and Weighted Median (WM) methods after excluding potential confounders. Cochran's Q was applied for heterogeneity test. Pleiotropy was evaluated through MR-Egger intercept, MR-Pleiotropy Residual Sum and Outlier (MR-PRESSO) method, and Leave-one-SNP-out analysis. Result: A total of 40 eligible IVs were included for MR analysis. IVW results demonstrated a positive causal association between SLE and OM (P = 0.049, OR = 1.167). Heterogeneity analysis reveal no significant heterogeneity in the IVW analysis (P = 0.5503). Pleiotropy tests, including MR-PRESSO global test and MR-Egger intercept, indicated no evidence of pleiotropy in our findings (P > 0.05). Additionally, the Leave-one-SNP-out analysis showed no substantial deviations when removing individual SNPs, thus supporting the robustness of our results. Conclusion: This study establishes a genetic causal relationship between SLE and OM, indicating an increased risk of developing OM in individuals with SLE. Therefore, proactive management of SLE is advised to mitigate the risk of developing OM.

Fixators dynamization for delayed union and non-union of femur and tibial fractures: a review of techniques, timing and influence factors.

The optimal balance between mechanical environment and biological factors is crucial for successful bone healing, as they synergistically affect bone development. Any imbalance between these factors can lead to impaired bone healing, resulting in delayed union or non-union. To address this bone healing disorder, clinicians have adopted a technique known as "dynamization" which involves modifying the stiffness properties of the fixator. This technique facilitates the establishment of a favorable mechanical and biological environment by changing a rigid fixator to a more flexible one that promotes bone healing. However, the dynamization of fixators is selective for certain types of non-union and can result in complications or failure to heal if applied to inappropriate non-unions. This review aims to summarize the indications for dynamization, as well as introduce a novel dynamic locking plate and various techniques for dynamization of fixators (intramedullary nails, steel plates, external fixators) in femur and tibial fractures. Additionally, Factors associated with the effectiveness of dynamization are explored in response to the variation in dynamization success rates seen in clinical studies.

Use of network pharmacology and molecular docking to explore the mechanism of action of curcuma in the treatment of osteosarcoma.

Curcuma has been used as an adjuvant treatment for osteosarcoma (OS) due to its anticancer compounds. However, the underlying mechanism remains unclear. Therefore, this study aimed to explore the mechanism of action of curcuma in the treatment of OS using network pharmacology and molecular docking. In this study, anticancer compounds were obtained from relevant literature, and curcuma-related targets and OS treatment targets were obtained from public databases. Protein‒protein interaction networks were constructed to screen out the hub genes using the STRING database and Cytoscape software. Cluster analysis of the protein modules was then performed using the Cytoscape MCODE plugin. Furthermore, Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed for common targets among curcuma targets and OS-related targets using the DAVID database. Finally, molecular docking was performed, and the results were verified by Auto dock Tool and PyMOL software. Our research identified 11 potential active compounds, 141 potential therapeutic targets and 14 hub genes for curcuma. AKT1, TNF, STAT3, EGFR, and HSP90AA1 were the key targets closely related to the PI3K/Akt signaling pathways, HIF-1 signaling pathways, ErbB signaling pathways, and FOXO signaling pathways, which are involved in angiogenesis, cancer cell proliferation, metastasis, invasion, and chemotherapy resistance in the microenvironment of OS. Molecular docking suggested that the core compound had a strong affinity for key targets, with a binding energy of less than - 5 kJ/mol. The study showed that curcuma-mediated treatment of OS was a complex process involving multiple compounds, targets, and pathways. This study will enhance the understanding of how curcuma affects the proliferation and invasion of OS cells and reveal the potential molecular mechanism underlying the effect of curcuma on OS lung metastasis and chemotherapy resistance.

The Improvement of Immune Effect of Recombinant Human Beta-Defensin 2 on Hepatitis B Vaccine in Mice.

Immunization with hepatitis B vaccine is an effective measure for prevention and control of hepatitis B Virus (HBV) infection. Although lots of efforts to improve the effect of hepatitis B vaccine have been made, the function of human beta defensin 2 (hBD2) on hepatitis B vaccine keeps unclear. In this article, we report that hBD2 not only promoted the activation and maturation of immature dendritic cells (iDCs) by increasing MHC II and CD86 expression, but it also significantly upregulated the mRNA level of IL-6 and IL-12B in mouse bone marrow-derived dendritic cells. The serum concentrations of IFN-γ in mice stimulated with 300 ng hBD2 increased from 25.21 to 42.04 pg/mL, with a time extension from 4 to 12 h post-injection. During the process of three times immunization (1, 14, 28 days) with 3 µg hepatitis B vaccine combined with or without 300 ng hBD2 with a 2 week interval in BALB/c mice, the antibody against HBsAg (HBsAb) concentration in serum at every time point of observation in the combined group was statistically higher than the hepatitis B vaccine group. The serum concentration of IgG2a subclass HBsAb on the 14th day post last injection in the combined group was significantly higher than the hepatitis B vaccine group. Further, the splenic cells from the mice treated with both hBD2 and hepatitis B vaccine possessed a greater ability to produce a surface antigen of hepatitis B virus (HBsAg) specific IFN-γ than those treated with hepatitis B vaccine alone. The percentages of CD3+/CD4+ T cells and CD3+/CD8+ T lymphocytes in spleens from the mice treated with 300 ng hBD2 were statistically higher than the phosphate buffered saline group. These data suggest that hBD2 improves iDC maturation and the immune efficiency of hepatitis B vaccine in BALB/c mice.

Identifying hub genes of papillary thyroid carcinoma in the TCGA and GEO database using bioinformatics analysis.

BACKGROUND: Thyroid carcinoma (THCA) is a common endocrine malignant tumor. Papillary carcinoma with low degree of malignancy and good prognosis is the most common. It can occur at any age, but it is more common in young adults. Although the mortality rate is decreased due to early diagnosis, the survival rate varies depending on the type of tumor. Therefore, the purpose of this study is to identify hub biomarkers and novel therapeutic targets for THCA. METHODS: The GSE3467, GSE3678, GSE33630 and GSE53157 were obtained from the GEO database, including 100 thyroid tumors and 64 normal tissues to obtain the intersection of differentially expressed genes, and a protein-protein interaction network was constructed to obtain the HUB gene. The corresponding overall survival information from The Cancer Genome Atlas Project-THCA was then included in this research. The signature mechanism was studied by analyzing the gene ontology and the Kyoto Encyclopedia of Genes and Genome database. RESULTS: In this research, we identified eight candidate genes (FN1, CCND1, CDH2, CXCL12, MET, IRS1, DCN and FMOD) from the network. Also, expression verification and survival analysis of these candidate genes based on the TCGA database indicate the robustness of the above results. Finally, our hospital samples validated the expression levels of these genes. CONCLUSION: The research identified eight mRNA (four up-regulated and four down-regulated) which serve as signatures and could be a potential prognostic marker of THCA.