Coxsackieviruses possess two proteases that are engaged in cleaving viral polyprotein and hijacking host cell processes such as RNA biosynthesis. Integrator subunit 10 (INTS10), a subunit of the integrator complex, facilitates the processing of small nuclear RNAs (U1 and U2 snRNAs) to regulate cellular transcription. We found that INST10 can be cleaved by Coxsackievirus B (CVB). Hence, we hypothesized that INST10 may play a role in CVB infection. In this study, INTS10 is identified as the substrate of CVB3 protease 3C (3Cpro). The cleavage occurs at the residue Q221 and yields a fragment. Depletion of INTS10 enhanced CVB3 replication and blocked snRNA processing. Overexpression of U1 snRNA inhibited CVB3 infection, whereas its knockdown conversely enhanced it. Similarly, knockdown of U2 snRNA was found to promote CVB3 replication. Taken together, the 3Cpro-mediated cleavage of INTS10 disrupts U snRNA processing, which in turn counteracts the inhibitory effect of snRNA U1 and U2 on virus replication and subverts host defenses.

Periodontitis requires both inflammation suppression and bone regeneration, yet temporal coordination remains challenging. A core-shell nanofibrous membrane (ICA-PCL@ASTA-PLGA) was fabricated by coaxial electrospinning, with an astaxanthin (ASTA)-loaded poly(lactic-co-glycolic acid) (PLGA) shell and an icariin (ICA)-loaded polycaprolactone (PCL) core for sequential drug delivery. Differential degradation enabled rapid initial ASTA release and sustained ICA release over 8 weeks, providing early anti-inflammation followed by osteogenesis. This sequential release drove macrophage polarization from M1 to M2, downregulating proinflammatory and upregulating reparative factors. ASTA inhibited inflammation, while ICA promoted osteogenic gene expression and matrix mineralization, with temporally controlled synergy. These outcomes align with ASTA modulating NF-κB and ICA activating MAPK pathways, as previously reported. In a rabbit periodontitis model, the membrane significantly improved the immune microenvironment and alveolar bone regeneration, outperforming single-drug-loaded scaffolds. This material-guided sequential delivery strategy integrates immunomodulation and osteogenesis, highlighting "material-guided temporal pharmacology" as a paradigm for treating inflammatory tissue defects.

Background:Stroke is a major cause of morbidity and mortality, characterized by neuronal damage and complex cell death pathways. This study aimed to investigate the protective role of spermine oxidase (Smox) in ischemic stroke and its effect on neuronal autophagy.Methods:We employed transient middle cerebral artery occlusion (tMCAO) models and oxygen-glucose deprivation/reoxygenation (OGD/R) experiments in HT22 cells to explore the protective effects of Smox knockdown against ischemic injury and to evaluate changes in autophagy.Results:Smox levels were significantly elevated following stroke, and correlated with increased autophagic activity and neuronal apoptosis. In contrast, knockdown of Smox reduced neuronal death and improved neurological function while decreasing autophagy activation. Mechanistically, Smox may regulate autophagy via the phosphorylation of protein kinase B (AKT), AMP-activated protein kinase (AMPK), and mechanistic target of rapamycin (mTOR); Smox knockdown increased AKT and mTOR phosphorylation, while reducing AMPK phosphorylation, suggesting a potential shift in the regulation of neuronal autophagy.Conclusions:Our findings suggest a dual role for Smox in stroke pathology, indicating that it may influence autophagy via the AKT/AMPK/mTOR signaling, which could be critical for neuronal survival after ischemic injury. Targeting Smox may offer a therapeutic strategy for neuronal protection and recovery in stroke management, suggesting the potential importance of autophagy modulation in ischemic brain injury.

Periodontitis requires both inflammation suppression and bone regeneration, yet temporal coordination remains challenging. A core-shell nanofibrous membrane (ICA-PCL@ASTA-PLGA) was fabricated by coaxial electrospinning, with an astaxanthin (ASTA)-loaded poly(lactic-co-glycolic acid) (PLGA) shell and an icariin (ICA)-loaded polycaprolactone (PCL) core for sequential drug delivery. Differential degradation enabled rapid initial ASTA release and sustained ICA release over 8 weeks, providing early anti-inflammation followed by osteogenesis. This sequential release drove macrophage polarization from M1 to M2, downregulating proinflammatory and upregulating reparative factors. ASTA inhibited inflammation, while ICA promoted osteogenic gene expression and matrix mineralization, with temporally controlled synergy. These outcomes align with ASTA modulating NF-kappa B and ICA activating MAPK pathways, as previously reported. In a rabbit periodontitis model, the membrane significantly improved the immune microenvironment and alveolar bone regeneration, outperforming single-drug-loaded scaffolds. This material-guided sequential delivery strategy integrates immunomodulation and osteogenesis, highlighting "material-guided temporal pharmacology" as a paradigm for treating inflammatory tissue defects.

Myocarditis, the inflammatory disease of the myocardium, is one of the leading causes of dilated cardiomyopathy and sudden cardiac death. Coxsackievirus B (CVB) is one of the common pathogens of myocarditis and cardiomyopathy. In spite of the high prevalence of CVB infection, effective antiviral therapy is lacking, primarily due to that there is no approved antiviral drug available. In the previous study, we demonstrated that the neddylation of 3Dpol, the RNA-dependent RNA polymerase, promotes CVB replication. Therefore, we propose that targeting neddylation might be a therapeutic strategy against CVB infection. Here we studied the antiviral effect of MLN4924, the selective inhibitor of neddylation. We show that MLN4924 exerted potent antiviral effect with negligible cytotoxicity when applied at the early stage of CVB3 infection. MLN4924 treatment significantly inhibited viral replication both in vitro and in the myocardium of CVB3-infected mice. The myocardial damage and inflammatory response induced by CVB3 were significantly alleviated. We show that MLN4924 suppressed the neddylation of 3Dpol, leading to its upregulated degradation. Moreover, MLN4924 upregulated nuclear factor erythroid 2-related factor 2 (NRF2) through inhibiting its ubiquitination and proteasomal degradation, while CVB3 infection clearly enhanced NRF2 ubiquitination. Taken together, we conclude that MLN4924 exerts anti-CVB effect both in vitro and in vivo. In addition to inhibiting the neddylation of viral 3Dpol, upregulated NRF2 also contributes to the antiviral activity of MLN4924. This study demonstrated that targeting neddylation can be a potential antiviral strategy for the treatment of CVB infection.

The pathogenesis of Coxsackievirus B3 (CVB3), the causative pathogen for severe diseases such as myocarditis, pancreatitis, and meningitis, remains largely unknown. Neddylation, the covalent modification of proteins through the conjugation of NEDD8, a ubiquitin-like molecule, plays critical roles in regulating cellular activities. Our previous study demonstrated that 3Dpol, the RNA-dependent RNA polymerase of CVB3, was modified by ubiquitin. Since NEDD8 is highly homologous to ubiquitin in both the sequence and structure, we hypothesized that 3Dpol may also undergo neddylation. Here, we demonstrated that 3Dpol of CVB3 is modified by NEDD8. Proteomics and immunoprecipitation studies identified that NEDD8 expression was upregulated in CVB3-infected cells, and 3Dpol was neddylated. Through the overexpression or knockdown of the subunit of NEDD8-activating enzyme or NEDD8, we show that neddylation promoted CVB3 replication. Furthermore, the overexpression of NEDD8-specific protease 1 completely blocked 3Dpol neddylation and suppressed viral replication. The neddylation sites of 3Dpol, K261, and K457 were identified by mutagenesis studies. We further showed that neddylation enhanced 3Dpol stability. In contrast, when the neddylation sites were mutated (K261R, K457R, or K261/457R), the 3Dpol degradation rate was significantly accelerated. Moreover, the growth kinetics of the recombinant viruses containing the mutated 3Dpol at the neddylation sites was markedly decreased. Through analyzing the 3Dpol interacting proteins with mass spectrometry, we identified that TRIM4 is the E3 ligase, which upregulates 3Dpol neddylation. TRIM4 knockdown markedly suppressed viral replication and almost completely blocked 3Dpol neddylation. In contrast, TRIM4 overexpression promoted CVB3 replication. Taken together, this study demonstrated that 3Dpol neddylation facilitates CVB3 replication.IMPORTANCECVB3 infection is commonly related to the inflammatory disease of the heart, which may develop to dilated cardiomyopathy and heart failure. Neddylation is a process in which the ubiquitin-like molecule NEDD8 is covalently linked to the specific lysine residues of the target proteins. Increasing evidence has shown that the neddylation of either host or viral proteins may alter viral replication. In this study, we demonstrated that 3Dpol, the RNA-dependent RNA polymerase of CVB3, is modified by NEDD8 at its lysine residues 261 and 457, and the neddylation process is mediated by the E3 ligase TRIM4. Neddylation enhances the stability of 3Dpol and facilitates viral replication, while viruses with mutated 3Dpol, which cannot be neddylated, showed decreased replication capacity. Our findings not only add novel insights for understanding the pathogenesis of CVB3 but also identify that targeting neddylation could be a potential antiviral strategy for the treatment of CVB3 infection.

Viral myocarditis, often caused by Coxsackievirus B (CVB), is the leading cause of dilated cardiomyopathy and heart failure. Despite extensive research, the pathogenesis of CVB infection remains incompletely understood. Our previous study found that Anisomycin inhibits CVB replication by promoting the degradation of eukaryotic translation elongation factor 1 alpha 1 (eEF1A1). However, the precise mechanism through which eEF1A1 facilitates the replication of CVB remains to be fully elucidated. Here, we demonstrated that upregulated eEF1A1 is required for CVB3 replication. In vitro transcription and RNA pulldown assay demonstrated that eEF1A1 binds to the 5' cloverleaf region of CVB3 RNA. We observed that eEF1A1 interacts with double-stranded viral RNA, viral precursor protein 3 CD, and poly(A)-binding protein (PABP), which enhances its interaction with 3 CD. We show that CVB3 upregulates eEF1A1 expression by activating NF-κB. Chromosome-immunoprecipitation assay confirmed that NF-κB p65 binds to the EEF1A1 promoter. Luciferase reporter assays validated that NF-κB up-regulates EEF1A1 transcription. We further showed that eEF1A1 promotes CVB3 replication through interacting with viral RNA, 3 CD, and cellular protein PABP. This study highlights that eEF1A1, which is essential for cellular translation, is manipulated by CVB3 to promote viral replication. These findings suggest that targeting eEF1A1 could be a potential antiviral strategy against CVB infection.

The nonstructural 2B protein of coxsackievirus B (CVB) is a transmembrane protein that forms a hydrophilic tetramer viroporin on the cellular membrane structures. 2B plays a key role in the replication of CVB. We hypothesized that blocking the polymerization of 2B may interfere with CVB replication. In this study, a 2B-derived peptide 2B37-50 demonstrated potent anti-CVB3 activity in vitro. A Tat-fused 2B37-50 (Tat-2B37-50) showed significant inhibitory effects on the viral protein expression, RNA synthesis, and replication of CVB3. Tat-2B37-50 treatment elicited a strong in vivo protective efficacy for the myocardial infection caused by CVB3. Tat-2B37-50 was also effective against the infection of enterovirus A71 and coxsackievirus A16. Taken together, Tat-2B37-50 has the potential to be a novel peptide drug for the treatment of CVB infection.

Group B Coxsackieviruses (CVB) are one of the causative pathogens of myocarditis, which may progress to cardiomyopathy. The pathogenesis of CVB is not fully understood, and effective antiviral therapy is not available. N-acetylcysteine (NAC), the classic antioxidant, has been used in clinical practice for several decades to treat various medical conditions. In this study, the anti-CVB effect of NAC was investigated. We show that NAC dramatically suppressed viral replication and alleviated cardiac injury induced by CVB3. To further study the antiviral mechanism of NAC, RNA-sequencing was performed for CVB3-infected cells with NAC treatment. We found that eukaryotic elongation factor 1 alpha 1 (EEF1A1) is one of the most upregulated genes in CVB3-infected cells. However, EEF1A2, the highly homologous isoform of EEF1A1, remains unchanged. EEF1A1 expression was significantly suppressed by NAC treatment in CVB3-infected cells, while EEF1A2 was not affected. eEF1A1 knockdown significantly inhibited CVB3 replication, implicating that eEF1A1 facilitates viral replication. Importantly, we show that eEF1A1, which was not expressed in the myocardia of newborn mice, was significantly upregulated by CVB3 infection. NAC markedly downregulated the expression of eEF1A1 but not eEF1A2 in the myocardia of CVB3-infected mice. Furthermore, NAC accelerated eEF1A1 degradation by promoting autophagy in CVB3-infected cells. We show that p62, one of the critical adaptors of autophagic targets, interacts with eEF1A1 and was downregulated in CVB3-infected cells upon NAC treatment. Taken together, this study demonstrated that NAC shows a potent anti-CVB effect through the downregulation of eEF1A1.

Myocarditis is an inflammatory disease of the cardiac muscle and one of the primary causes of dilated cardiomyopathy. Group B coxsackievirus (CVB) is one of the leading causative pathogens of viral myocarditis, which primarily affects children and young adults. Due to the lack of vaccines, the development of antiviral medicines is crucial to controlling CVB infection and the progression of myocarditis. In this study, we investigated the antiviral effect of baicalein, a flavonoid extracted from Scutellaria baicaleinsis. Our results demonstrated that baicalein treatment significantly reduced cytopathic effect and increased cell viability in CVB3-infected cells. In addition, significant reductions in viral protein 3D, viral RNA, and viral particles were observed in CVB3-infected cells treated with baicalein. We found that baicalein exerted its inhibitory effect in the early stages of CVB3 infection. Baicalein also suppressed viral replication in the myocardium and effectively alleviated myocarditis induced by CVB3 infection. Our study revealed that baicalein exerts its antiviral effect by inhibiting the activity of caspase-1 and viral protease 2A. Taken together, our findings demonstrate that baicalein has antiviral activity against CVB3 infection and may serve as a potential therapeutic option for the myocarditis caused by enterovirus infection.

Coxsackievirus B (CVB) is the major causative pathogen for severe diseases such as viral myocarditis, meningitis, and pancreatitis. There is no effective antiviral therapy currently available for CVB infection primarily due to that the pathogenesis of CVB has not been completely understood. Viruses are obligate intracellular pathogens which subvert cellular processes to ensure viral replication. Dysregulation of ubiquitination has been implicated in CVB infection. However, how ubiquitination is involved in CVB infection remains unclear. Here we found that the 3D protein of CVB3, the RNA-dependent RNA polymerase, was modified at K220 by K48-linked polyubiquitination which promoted its degradation through proteasome. Proteomic analysis showed that the E3 ligase TRIM56 was upregulated in CVB3-infected cells, while the majority of TRIMs remained unchanged. Pull-down and immunoprecipitation analyses showed that TRIM56 interacted with CVB3 3D. Immunofluorescence observation showed that viral 3D protein was colocalized with TRIM56. TRIM56 overexpression resulted in enhanced ubiquitination of CVB3 3D and decreased virus yield. Moreover, TRIM56 was cleaved by viral 3C protease in CVB3-infected cells. Taken together, this study demonstrated that TRIM56 mediates the ubiquitination and proteasomal degradation of the CVB3 3D protein. These findings demonstrate that TRIM56 is an intrinsic cellular restriction factor against CVB infection, and enhancing viral protein degradation could be a potential strategy to control CVB infection.

Once an ischemic stroke occurs, reactive oxygen species (ROS) and oxidative stress degrade the tight connections between cerebral endothelial cells resulting in their damage. The expression of antioxidant genes may be enhanced, and ROS formation may be reduced following Nrf2 activation, which is associated with protection against ischemic stroke. Overexpression of spermine oxidase (Smox) in the neocortex led to increased H2O2 production. However, how Smox impacts the regulation of the blood-brain barrier (BBB) through antioxidants has not been examined yet. We conducted experiments both in the cell level and in the transient middle cerebral artery occlusion (tMCAO) model to evaluate the effect of Smox siRNA lentivirus (si-Smox) knockdown on BBB protection against ischemic stroke. Mice treated with si-Smox showed remarkably decreased BBB breakdown and reduced endothelial inflammation following stroke. The treatment with si-Smox significantly elevated the Bcl-2 to Bax ratio and decreased the production of cleaved caspase-3 in the tMCAO model. Further investigation revealed that the neuroprotective effect was the result of the antioxidant properties of si-Smox, which reduced oxidative stress and enhanced CD31+ cells in the peri-infarct cortical areas. Of significance, si-Smox activated Nrf2 in both bEnd.3 cells and tMCAO animals, and blocking Nrf2 with brusatol diminished the protective effects of si-Smox. The study findings suggest that si-Smox exerts neuroprotective effects and promotes angiogenesis by activating the Nrf2 pathway, thus decreasing oxidative stress and apoptosis caused by tMCAO. As a result, si-Smox may hold potential as a therapeutic candidate for preserving BBB integrity while treating ischemic stroke.

Group B Coxsackieviruses (CVB) are non-enveloped small RNA viruses in the genus Enterovirus, family Picornaviridae. CVB infection causes diverse conditions from common cold to myocarditis, encephalitis, and pancreatitis. No specific antiviral is available for the treatment of CVB infection. Anisomycin, a pyrrolidine-containing antibiotic and translation inhibitor, was reported to inhibit the replication of some picornaviruses. However, it is unknown if anisomycin can act as an antiviral against CVB infection. Here we observed that anisomycin showed potent inhibition on CVB type 3 (CVB3) infection with negligible cytotoxicity when applied at the early stage of virus infection. Mice infected with CVB3 showed markedly alleviated myocarditis with reduced viral replication. We found that CVB3 infection significantly increased the transcription of eukaryotic translation elongation factor 1 alpha 1 (eEF1A1). CVB3 replication was suppressed by EEF1A1 knockdown, while elevated by EEF1A1 overexpression. Similar to the effect of CVB3 infection, EEF1A1 transcription was increased in response to anisomycin treatment. However, eEF1A1 protein level was decreased with anisomycin treatment in a dose-dependent manner in CVB3-infected cells. Moreover, anisomycin promoted eEF1A1 degradation, which was inhibited by the treatment of chloroquine but not MG132. We demonstrated that eEF1A1 interacted with the heat shock cognate protein 70 (HSP70), and eEF1A1 degradation was inhibited by LAMP2A knockdown, implicating that eEF1A1 is degraded through chaperone-mediated autophagy. Taken together, we demonstrated that anisomycin, which inhibits CVB replication through promoting the lysosomal degradation of eEF1A1, could be a potential antiviral candidate for the treatment of CVB infection.

Periodontitis is a chronic inflammatory disease primarily driven by host inflammation and plaque-induced immune responses. Controlling the host inflammatory response and improving the periodontal inflammatory microenvironment are crucial to promoting periodontal tissue regeneration. In this study, the blended nanofiber membranes previously prepared by our research group were improved, and we developed multifunctional chitosan/polyvinyl alcohol/graphene oxide/astaxanthin coaxial nanofiber membranes. Scanning electron microscopy showed that the prepared nanofibers had a smooth surface and a uniform diameter distribution. The mechanical property test results showed that the coaxial nanofiber membranes exhibited higher tensile strength compared to the blended nanofiber membranes, which increased from 4.50 ± 0.32 and 3.70 ± 0.45 MPa to 7.12 ± 0.22 and 5.62 ± 0.79 MPa respectively. Drug release studies indicated that the “shell-core” structure of coaxial nanofibers significantly reduced the initial burst release of astaxanthin (ASTA), with only 13.49 % and 10.71 % release in the first 24 h, and drug release lasted for over a week. Animal experiments confirmed that the coaxial nanofiber membranes loaded with ASTA promoted periodontal bone defect repair while inhibiting periodontal inflammation. In conclusion, the prepared coaxial nanofiber membranes are a promising sustained-release drug system for treating periodontitis.

Enterovirus infections are life-threatening viral infections which occur mainly among children and are possible causes of viral outbreak. Until now, treatment and management of infections caused by members of the genus Enterovirus largely depended on supportive care, and no antiviral medications are currently approved for the treatment of most of these infections. ABSTRACT Enterovirus infections are life-threatening viral infections which occur mainly among children and are possible causes of viral outbreak. Until now, treatment and management of infections caused by members of the genus Enterovirus largely depended on supportive care, and no antiviral medications are currently approved for the treatment of most of these infections. The urgency of discovering new therapeutic options for the treatment of enterovirus infection is increasing. In the present study, we identified that trans-2-hexenoic acid (THA), a natural product from a dietary source, possesses antiviral activity against coxsackievirus B (CVB) and enterovirus A71 (EV-A71) in a dose-dependent manner. We found that THA possesses antiviral activity at 50% effective concentrations (EC50) of 2.9 μM and 3.21 μM against CVB3 and EV-A71 infections, respectively. The time of addition assay revealed that THA inhibits both CVB3 and EV-A71 replication at the entry stage of infection. Additional results from this study further suggest that THA inhibits viral replication by blocking viral entry. Given that THA has received approval as a food additive, treatment of enterovirus infections with THA might be a safe therapeutic option or could pave the way for semisynthetic manufacturing of more antiviral drugs in the future.

Coxsackievirus B (CVB), a member of Enterovirus genus of Picornaviridae, is the leading pathogen of viral myocarditis and dilated cardiomyopathy. The pathogenesis of CVB-induced myocarditis has not been completely elucidated, and no specific antiviral measurement is available presently. Circular RNAs (circRNAs) have been reported to be able to modulate viral replication and infection through bridging over non-coding RNAs (ncRNAs) and coding messenger RNAs (mRNAs). To date, the role of circRNAs in CVB infection is largely unknown. In this study, we found that hsa_circ_0076631 (circ_0076631) significantly promoted CVB type 3 (CVB3) replication. Further study showed that the underneath mechanism was circ_0076631 indirectly interacting with CVB3 through sponging miR-214-3p, which targeted the 3D-coding region of CVB3 genome to suppress viral translation. Knocking down circ-0076631 caused a suppression of CVB3 infection; thus, circ-0076631 may be a potential target for anti-CVB therapy.

生物安全知识是医学生知识体系中的重要环节,通过系统地、科学地学习生物安全知识和技能才能获得生物安全职业素养和感染防控能力,进而为今后从事医学工作奠定了坚实的理论和实践基础.本文阐述了在医学微生物学实验课程中设置生物安全模块的必要性,介绍了该模块的教学设计与实践,评价和总结了生物安全教学模块的教学效果.生物安全教学模块的实施将完善医学生生物安全知识体系,提高医学生生物安全防护意识和实践能力,提升医学生依法解决工作中生物安全相关问题的专业素养和能力.

Coxsackievirus group B (CVB) is a member of the genus Enterovirus in the family Picornaviridae. CVB infection has been implicated as a major etiologic agent of viral myocarditis, dilated cardiomyopathy, meningitis, and pancreatitis among children and young adults. Until date, no antiviral agent has been licensed for the treatment of Coxsackievirus infection. In an effort to identify antiviral agents against diseases caused by the CVB, we found that ethyl 3-hydroxyhexanoate (EHX), a volatile compound present in fruits and food additives, is a potent antiviral compound. In this study, we demonstrated that EHX treatment significantly inhibits CVB replication both in vivo and in vitro. Furthermore, EHX possesses antiviral activity at 50% effective concentration (EC50) of 1.2 μM and 50% cytotoxicity (CC50) of 25.6 μM, yielding a selective index (SI) value as high as 20.8. Insights into the mechanism of antiviral activity of EHX showed that it acts at the step of viral RNA replication. Since EHX has received approval as food additives, treatment of CVB-related infections with EHX might be a safe therapeutic option and may be a promising strategy for the development of semi-synthetic antiviral drugs for viral diseases.

Anti-inflammation and bone regeneration are the two major goals of periodontal therapy. We have demonstrated that chitosan (CS)/polyvinyl alcohol (PVA)/graphene oxide (GO)/astaxanthin (ASTA) nanofibers membranes prepared by electrospinning had favorable micro-morphology, good mechanical properties, and no cytotoxicity. In this study, CS/PVA/GO/ASTA nanofibers membranes were prepared to modulate both inflammatory response and osteogenic induction in vitro study. When the nanofibers membranes were co-cultured with RAW264.7 cells, glycoprotein nonmetastatic melanoma protein in the cells was highly expressed and RAW264.7 cells were polarized to M2 phenotype at the same time. In addition, following stimulation with nanofibers membranes, the messenger RNA (mRNA) and protein levels of Osteocalcin (OCN) and Runx2 in Bone marrow mesenchymal stem cells (BMSCs) were highly expressed. Taken together, these results suggested CS/PVA/GO/ASTA nanofibers membranes may promote the dissipation of inflammation and stimulate the differentiation of BMSCs into osteoblasts.

The phenotypic function of macrophages varies with the local microenvironment. Macrophages play an important role in the development of periodontitis. As one of the sources of GPNMB protein, the phenotype of macrophages is affected by GPNMB expression. In this study, activated macrophages were evaluated by flow cytometry, RT-qPCR and WB, and M2a macrophages had higher GPNMB expression than M0 and M1 macrophages. On this basis, a macrophage model with overexpression of GPNMB was established, and it was observed that GPNMB overexpression promoted the secretion of anti-inflammatory factors by macrophages and inhibited the secretion of pro-inflammatory factors by M1 macrophages.