Advanced thermoplastic materials, such as polyether-ether-ketone (PEEK) and highly cross-linked polyethylene (HXLPE), have been increasingly used as orthopaedic implant materials. Similar to other implants, PEEK-on-HXLPE prostheses produce debris from polymer wear that may activate the immune response, which can cause osteolysis, and ultimately implant failure. In this study, we examined whether the anti-inflammatory properties of zinc oxide nanoparticles (ZnO NPs) could attenuate polymer wear particle-induced inflammation. RAW264.7 ​cells were cultured with PEEK or PE particles and gradient concentrations of ZnO NPs. Intracellular mRNA expression and protein levels of pro-inflammatory factors TNF-α, IL-1β, and IL-6 were detected. An air pouch mouse model was constructed to examine the inflammatory response and expression of pro-inflammatory factors in vivo. Furthermore, an osteolysis rat model was used to evaluate the activation of osteoclasts and destruction of bone tissue induced by polymer particles with or without ZnO NPs. Protein expression of the MEK-ERK-COX-2 pathway was also examined by western blotting to elucidate the mechanism underlying particle-induced anti-inflammatory effects. ZnO NPs (≤50 ​nm, 5 ​μg/mL) showed no obvious cytotoxicity and attenuated PEEK or PE particle-induced inflammation and inflammatory osteolysis by reducing MEK and ERK phosphorylation and decreasing COX-2 expression. ZnO NPs (≤50 ​nm, 5 ​μg/mL) attenuated polymer wear particle-induced inflammation via regulation of the MEK-ERK-COX-2 axis. Further, ZnO NPs reduced bone tissue damage caused by particle-induced inflammatory osteolysis. Polymer wear particles can induce inflammation and osteolysis in the body after arthroplasty. ZnO NPs attenuated polymer particle-induced inflammation and inflammatory osteolysis. Topical use of ZnO NPs and blended ZnO NP/polymer composites may provide promising approaches for inhibiting polymer wear particle-induced inflammatory osteolysis, thus expanding the range of polymers used in joint prostheses.

Objective Coronavirus disease 2019 (COVID-19) has caused a global pandemic in the last three years. The lack of reliable evidence on the risk of miscarriage due to COVID-19 has become a concern for patients and obstetricians. We sought to identify rigorous evidence using two-sample Mendelian randomization (MR) analysis. Methods Seven single-nucleotide polymorphisms (SNPs) associated with COVID-19 were used as instrumental variables to explore causality by two-sample MR. The summary data of genetic variants were obtained from the Genome Wide Association Study (GWAS) among European populations in the UK Biobank and EBI database. Inverse variance weighting (IVW) method was taken as the gold standard for MR results, and other methods were taken as auxiliary. We also performed sensitivity analysis to evaluate the robustness of MR. Results The MR analysis showed there was no clear causal association between COVID-19 and miscarriage in the genetic prediction [OR 0.9981 (95% CI, 0.9872–1.0091), p = 0.7336]. Sensitivity analysis suggested that the MR results were robust [horizontal pleiotropy (MR-Egger, intercept = 0.0001592; se = 0.0023; p = 0.9480)]. Conclusions The evidence from MR does not support COVID-19 as a causal risk factor for miscarriage in European populations. The small probability of direct placental infection, as well as the inability to stratify the data may explain the results of MR. These findings can be informative for obstetricians when managing women in labor.

Acne vulgaris is a chronic inflammatory disease of the skin resulting from androgen‐induced increased sebum production and altered keratinization. Nicotinamide (NAM), an amide form of vitamin B3 with a well‐established safety profile, has shown good therapeutic potential in treating acne and its complications. NAM has anti‐inflammatory effects and reduces sebum but its function in androgen biosynthesis remains unknown. In this study, we used a widely used cell model, starved human adrenal NCI‐H295R cells, to examine the effects of NAM in androgen production and its mediated network changes. By treating NCI‐H295R cells with 1‐25 mmol/L of NAM, we found that cell viability was only slightly inhibited at the highest dose (25 mmol/L). NAM reduced testosterone production in a dose‐dependent manner. Transcriptomic analysis demonstrated that key enzymes of androgen biosynthesis were significantly decreased under NAM treatment. In addition, gene set enrichment analysis (GSEA) showed that gene sets of cell cycle, steroid biosynthesis, TGFβ signalling, and targets of IGF1 or IGF2 were enriched in NAM‐treated cells. Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway and Gene ontology (GO) analysis of the differentially expressed genes also suggested that steroidogenesis and SMAD signalling were affected by NAM. Overall, these crucial genes and pathways might form a complex network in NAM‐treated NCI‐H295R cells and result in androgen reduction. These findings help explain the potential molecular actions of NAM in acne vulgaris, and position NAM as a candidate for the treatment of other hyperandrogenic disorders.

Objective: Aseptic loosening, the most frequent complication after total joint replacement, is probably caused by an inflammatory response to the shedding of wear debris from the implant. The only effective treatment is surgical revision. Using a mouse model, we investigated whether enalapril inhibits wear debris-induced inflammatory osteolysis. Methods: Titanium (Ti) alloy particles were introduced, and calvarial bone from syngeneic mice was implanted into air pouches established in BALB/c mice. Histological and molecular analyses were performed with inflammatory tissue samples obtained from mice treated with and without enalapril. Results: Enalapril inhibited tissue inflammation and inflammatory osteolysis induced by Ti particles, reducing pouch membrane thickness and decreasing inflammatory cell infiltration. In addition, enalapril inhibited the expression of the inflammatory cytokines vascular endothelial growth factor and tumor necrosis factor-α. Conclusions: Our study provides evidence that enalapril inhibits Ti particle-induced inflammatory osteolysis, and it may be a potentially useful treatment for aseptic loosening.

Introduction Wear particles induced inflammatory osteolysis is the most important initiating factors in the mechanism of aseptic loosening. However, the molecular network changes in this process remain largely elusive. Methods Here, we performed whole transcriptome analysis using Ti particles induced RAW264.7 cell model to identify specific genes and pathways. Results Sequencing results totally identified 159 mRNAs, 96 lncRNAs, 31 circRNAs, and 12 miRNAs were significantly differently expressed. Of these, we selected two of each RNA for qRT-PCR validation and the results were highly consistent with the RNA-seq data. GSEA analysis shows that upregulated gene sets were related to the three classical inflammation pathway, cytokine–cytokine receptor interaction, TNF, and NF-kappa B signaling pathway. The enriched genes included not only IL-1β and TNF-α, which were independently verified before sequencing, but also other inflammatory osteolysis-related genes such as Mmp9, Fas, and Ccl2. Co-differentially expressed RNAs were employed to construct the ceRNA co-regulatory network. Conclusion: The results revealed that 4 lncRNAs and 2 circRNAs formed a regulatory network to simultaneously regulate miR-3065-3p targeting Myo18a. The present study helps to comprehensively understand the molecular mechanisms and regulatory interaction networks during early inflammatory response.