Immunobiology最新文献_第2页

Precolostral antibody reactivity against Histophilus somni conserved proteins and Escherichia coli whole cells in stillborn and live calves

IF 2.5 4区医学 Q3 IMMUNOLOGY

Immunobiology

Pub Date : 2025-01-26 DOI: 10.1016/j.imbio.2025.152874

Rafał Baran, Joanna Bajzert, Tadeusz Stefaniak, Paulina Jawor

Recent studies have demonstrated that neither the uterus nor the fetal gastrointestinal tract is sterile. We hypothesized that antibodies (Ab) that react with bacterial antigens are common in fetuses. Plasma samples from 121 stillborn calves were used as the experimental group and 21 live-born healthy calves were used as the control group. In precolostral plasma samples, IgG₁, IgG₂, and IgM Ab reactivity with Histophilus somni rHsp60 and rOMP40 proteins and Escherichia coli whole cells was tested by ELISA. Selected samples from stillborn and live-born calves were evaluated for antibody reactivity with E. coli antigens separated by SDS-PAGE to verify the recognized protein profile. To investigate whether the antibodies were of maternal origin or self-produced, the sera of the dams were evaluated by immunoblotting.

In calves, positive reactions to all antigens were detected by ELISA. In ELISA, the greatest variation in the results was observed for IgM class reactivity with selected proteins and the E. coli strain. Stillborn calves showed significantly greater reactivity in the IgG₁ subclass with only E. coli. Immunoblotting analysis revealed reactions of IgG₁ and IgM class Ab with E. coli antigens of different molecular weights, both in the control and stillborn groups. The reactivity of the tested calves was not identical to that of their mothers, indicating that the antibodies were self-produced by the calves during pregnancy.

These results suggest that calves are exposed to different Gram-negative bacteria during pregnancy, and that the stillborn group elicited diverse responses.

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引用次数: 0

Predictive value and mechanism of lncRNA MANCR for pediatric severe pneumonia via miR-20a-5p / MAPK1 axis

IF 2.5 4区医学 Q3 IMMUNOLOGY

Immunobiology

Pub Date : 2025-01-22 DOI: 10.1016/j.imbio.2025.152871

Yuting Cai , Jiaxi Xie , Jinkai Yang

Severe community-acquired pneumonia (SCAP) significantly threats the safety of children's lives. Long non-coding RNA (lncRNA) MANCR is overexpressed in lung adenocarcinoma (LUAD) tissue, promote the proliferation, invasion, and migration, decreased cell apoptosis of LUAD cells. This study aimed to detect lncRNA MANCR levels in pediatric SCAP, and explore the diagnostic and prognostic significance of MANCR in pediatric SCAP. The mechanism of MANCR was examined in a lipopolysaccharide (LPS)-induced cell model. Serum MANCR level was detected by RT-PCR in participants. The diagnostic and prognostic value of MANCR was analyzed via ROC and KM curves. LPS constructed the pneumonia cell mode. Cell viability and apoptosis were detected by CCK-8 and flow cytometry respectively. ELISA examined the concentration of inflammatory factors. Serum MANCR level was elevated in SCAP patients. High MANCR could predict SCAP from controls (AUC = 0.852, sensitivity = 0.727, specificity = 0.836). High MANCR level is a predictor for poor prognosis of pediatric SCAP (P < 0.001, HR = 5.810, 95 %CI = 2.450–13.781). LPS inhibited cell viability and promoted apoptosis and inflammation of NCI-H1563 cells. Silence of MANCR could promote cell viability, inhibit the cell apoptosis and secretion of CRP, PCT, IL-6, IL-1β, and TNF-α via miR-20a-5p / MAPK1 axis in LPS-stimulated NCI-H1563 cells (P < 0.05). High MANCR levels in pediatric SCAP patients could predict the occurrence and poor prognosis of SCAP. MANCR knockout could inhibit cell apoptosis and inflammatory factors, and enhance cell viability via miR-20a-5p / MAPK1 axis in LPS-stimulated NCI-H1563 cells.

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引用次数: 0

Toll-like receptor upregulation in liver and peripheral blood mononuclear cells of patients with amoebic liver abscess

IF 2.5 4区医学 Q3 IMMUNOLOGY

Immunobiology

Pub Date : 2025-01-21 DOI: 10.1016/j.imbio.2025.152869

Sandhya Khunger , Abhishek Mewara , Upninder Kaur , Ajay Duseja , Pallab Ray , Naveen Kalra , Navneet Sharma , Rakesh Sehgal

Aim

We aimed to understand the host and microbe interactions at the time of infection and inflammatory response in amoebic liver abscess (ALA) patients based on toll-like receptor (TLR) expression (mRNA), cytokine and IgG subtypes levels.

Methods and results

Liver aspirates from 100 ALA patients and 11 liver autopsy samples were used as negative controls. Blood samples from 100 ALA and 41 healthy individuals were collected. mRNA expression of TLR 1 to 9 genes was measured using reverse transcriptase polymerase chain reaction (RT-PCR). Serum cytokines level was quantified by flow cytometry. In-house ELISA for the analysis of IgG and its subtypes in the serum samples was performed. A total of 7 TLR genes (TLR1, TLR2, TLR4, TLR6, TLR7, TLR8 and TLR9) and 6 TLR genes (TLR1, TLR2, TLR3, TLR4, TLR5 and TLR8) were found to be elevated in liver aspirates and PBMCs respectively. Increased serum cytokine levels were observed in ALA patients vs. healthy controls. Interestingly, a significant increase in IgG and its subtypes (IgG1, IgG3 and IgG4) was found in the serum of ALA patients.

Conclusion

Increased levels of TLR, pro- and anti-inflammatory cytokines, IgG and its subtypes, are possibly linked with early-stage infection in ALA patients.

Impact statement

The role of TLRs in association with ALA might provide insights into new therapeutic strategies.

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引用次数: 0

Effect of perioperative analgesia on immunity in lung cancer

IF 2.5 4区医学 Q3 IMMUNOLOGY

Immunobiology

Pub Date : 2025-01-20 DOI: 10.1016/j.imbio.2025.152867

Xiaomin Fan , Ziqi Huang , Ziying Chen , Liang Yun , Xinjian Zhang

COX inhibitors are frequently used for pain management during the perioperative period and may influence tumor progression and the tumor microenvironment by modulating inflammation and immune responses. This study investigates the effects of COX inhibitors on tumor growth and the immune microenvironment. In vivo experiments demonstrate that COX inhibitors can reduce tumor cell growth, elevate PD-L1 expression on tumor cells, and enhance the proportion of myeloid cells within the tumor immune microenvironment. Furthermore, COX inhibitors are found to improve the efficacy of the immune checkpoint inhibitor anti-PD-L1. These results underscore the influence of perioperative COX inhibitors on tumor immunity and suggest potential new strategies for optimizing tumor immunotherapy.

引用次数: 0

LncRNA FENDRR/ miR-424-5p serves as a diagnostic biomarker for sepsis and its predictive value for clinical outcomes

IF 2.5 4区医学 Q3 IMMUNOLOGY

Immunobiology

Pub Date : 2025-01-18 DOI: 10.1016/j.imbio.2025.152870

Xue Luo , Xin Chen , Ying Gu , Honggang Jia , Xinyu Lin , Ling Wang , Jingyun Feng

Purpose

This study intends to investigate the relationship between FENDRR and miR-424-5p and their clinical significance in sepsis, aiming to provide new diagnostic markers and prognostic markers for sepsis.

Methods

136 patients with sepsis and 132 healthy volunteers were included as study subjects. The expression levels of FENDRR and miR-424-5p were detected by qPCR. ROC was applied to evaluate the diagnostic value of FENDRR and miR-424-5p. COX analyzed the independent risk factors for the occurrence of death in sepsis patients. Dual luciferase reporter assay detected the binding of FENDRR and miR-424-5p. The miR-424-5p target genes were predicted and enriched for GO function and KEGG pathway.

Results

FENDRR was up-regulated and miR-424-5p was down-regulated in patients with sepsis. FENDRR can target and bind to miR-424-5p. Both FENDRR and miR-424-5p showed significant diagnostic potential in sepsis and their combination significantly improved the diagnostic efficiency. FENDRR/miR-424-5p were significantly correlated with WBC, CRP, APACH II, and SOFA of sepsis patients. FENDRR and miR-424-5p were independent risk factors for mortality in sepsis patients. Sepsis patients with high FENDRR levels or low miR-424-5p levels had higher mortality. GO and KEGG enrichment analyses revealed that the targets of miR-424-5p were predominantly associated with cell functions and inflammatory signaling pathways.

Conclusion

Upregulated FENDRR and downregulated miR-424-5p expression can serve as biomarkers of sepsis with predictive value on the onset and prognostic outcome. FENDRR and miR-424-5p were correlated with the severity of sepsis and FENDRR can play a function in the sepsis progression via targeting miR-424-5p.

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引用次数: 0

Clostridium butyricum attenuates LPS-induced myocardial injury in septic mice by modulating CD4 + CD25 + FOXP3 + Treg 丁酸梭菌通过调节CD4 + CD25 + FOXP3 + Treg减轻脓毒症小鼠lps诱导的心肌损伤。

IF 2.5 4区医学 Q3 IMMUNOLOGY

Immunobiology

Pub Date : 2025-01-01 DOI: 10.1016/j.imbio.2024.152857

Jinglin Zhao , Liuli Wu , Rupan Zhang , Mei Yuan , Junchao Huang , Xiongfei Jia , Xiaoqin Mao

Sepsis-induced myocardial injury has become a major threat to patient health and safety. Intestinal microbiota imbalance plays a crucial role in sepsis regulation. Using 16srRNA technology, we explored how intestinal colonization of Clostridium butyricum over 28 days impacted mice with LPS-induced sepsis. Significant changes were noted in the gut microbiota of the mice, highlighting that C. butyricum can positively influence the immune state in septic myocardial injury models. The bacterium's ability to prevent intestinal mucosal damage and alleviate the immunosuppressive state during the later stages of sepsis by regulating CD4 + CD25 + FOXP3 + Treg cells is particularly noteworthy. This suggests a therapeutic role for C. butyricum in sepsis management by protecting against myocardial injury and improving immune regulation.

脓毒症引起的心肌损伤已成为威胁患者健康和安全的主要疾病。肠道菌群失衡在脓毒症的调节中起着至关重要的作用。利用16srRNA技术，我们研究了28天内丁酸梭菌的肠道定植对lps诱导的脓毒症小鼠的影响。小鼠肠道菌群发生显著变化，提示丁酸梭菌对脓毒性心肌损伤模型的免疫状态有积极影响。细菌通过调节CD4 + CD25 + FOXP3 + Treg细胞来预防脓毒症后期肠黏膜损伤和缓解免疫抑制状态的能力尤其值得注意。这表明丁酸梭菌在脓毒症管理中的治疗作用是通过保护心肌损伤和改善免疫调节。

引用次数: 0

NOD-like receptor family pyrin domain containing 3 (rs10754558) gene polymorphism in chronic spontaneous urticaria: A pilot case-control study nod样受体家族pyrin结构域包含3 （rs10754558）基因多态性在慢性自发性荨麻疹中：一项试点病例对照研究

IF 2.5 4区医学 Q3 IMMUNOLOGY

Immunobiology

Pub Date : 2025-01-01 DOI: 10.1016/j.imbio.2025.152868

Aya El Gendy , Fawzia Hassan Abo Ali , Shereen A. Baioumy , Sara I. Taha , Mahy El -Bassiouny , Osama M. Abdel Latif

Background

Chronic spontaneous urticaria (CSU) is a persistent skin condition with no known cause or trigger. The unpredictability of CSU attacks lowers patients' quality of life. NOD-like receptor pyrin domain containing 3 (NLRP3) gene dysregulation can result in numerous immunological and inflammatory diseases.

Objective

This case-control study aimed to determine the association between the NLRP3 inflammasome (rs10754558) single nucleotide polymorphism (SNP) and the occurrence, severity and etiology of CSU.

Methods

Each study group included 62 participants; all were subjected to CSU severity evaluation by the urticaria activity score (UAS), autologous serum skin testing (ASST) and NLRP3 (rs10754558) genotyping.

Results

The NLRP3 (rs10754558) CG genotype was the most predominant in both study groups, followed by the CC genotype (41.9 %) in the CSU group and the GG genotype (25.8 %) in the control group. Most of the CSU group (66.1 %) had the C allele, compared to most controls (53.2 %) with the G allele. The frequency of NLRP3 (rs10754558) genotypes and alleles did not differ significantly according to the severity of CSU by UAS (P > 0.05). The prevalence of the CC genotype was significantly higher among the ASST-positive CSU patients. The C allele elevated the likelihood of positive ASST in CSU patients by 21 times, suggesting the autoimmune theory of CSU. None of the ASST-positive patients had the GG genotype.

Conclusion

The NLRP3 inflammasome (rs10754558) C allele may be associated with CSU risk but not severity by UAS. It may also be associated with ASST positivity which suggests a connection between the C-allele and the autoimmune notion of CSU.

背景：慢性自发性荨麻疹（CSU）是一种没有已知病因或诱因的持续性皮肤疾病。CSU发作的不可预测性降低了患者的生活质量。nod样受体pyrin结构域包含3 （NLRP3）基因的失调可导致多种免疫和炎症性疾病。目的：本病例对照研究旨在确定NLRP3炎性小体（rs10754558）单核苷酸多态性（SNP）与CSU发生、严重程度及病因的关系。方法：每个研究组62例；通过荨麻疹活动性评分（UAS）、自体血清皮肤试验（自体血清皮肤试验）和NLRP3 （rs10754558）基因分型对所有患者进行CSU严重程度评估。结果：两组患者均以NLRP3 (rs10754558) CG基因型居多，CSU组其次为CC基因型（41.9%），对照组为GG基因型（25.8%）。大多数CSU组（66.1%）具有C等位基因，而大多数对照组（53.2%）具有G等位基因。NLRP3 （rs10754558）基因型和等位基因频率在不同UAS CSU严重程度间无显著差异（P < 0.05）。在asst阳性的CSU患者中，CC基因型的患病率明显更高。在CSU患者中，C等位基因升高了21倍的可能性，提示CSU的自身免疫理论。asst阳性患者均无GG基因型。结论：NLRP3炎性小体（rs10754558） C等位基因可能与CSU风险相关，但与UAS的严重程度无关。它也可能与自体皮肤抗原阳性有关，这表明c等位基因与CSU的自身免疫概念之间存在联系。

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引用次数: 0

Nucleotide receptor P2X7/STAT6 pathway regulates macrophage M2 polarization and its application in CAR-T immunotherapy 核苷酸受体P2X7/STAT6通路调控巨噬细胞M2极化及其在CAR-T免疫治疗中的应用

IF 2.5 4区医学 Q3 IMMUNOLOGY

Immunobiology

Pub Date : 2025-01-01 DOI: 10.1016/j.imbio.2024.152863

Qin Si , Lu Yang , Jie Liu , Hui Liu , Ruifang Bu , Na Cui

Background

A key factor underlying the failure of Chimeric Antigen Receptor-T Cell (CAR-T) therapy in ovarian cancer (OC) is the presence of an immunosuppressive tumor microenvironment, which is intricately linked to M2 polarization among tumor-infiltrating macrophages. P2X7 receptor has been previously documented as expressed within these macrophages and its correlation with M2 polarization is evident. This investigation scrutinizes whether silencing of P2X7 receptor within macrophages could lead to augmented anti-tumor potency of CAR-T.

Method

Human peripheral blood mononuclear cells were artificially differentiated into macrophages or M2 macrophage in vitro. After silencing P2X7 receptor and/or overexpressing STAT6 within macrophages, the M1 and M2 markers were evaluated via flow cytometry, ELISA, and qRT-PCR. Additionally, the phosphorylation level of STAT6 was monitored by western blot. We engineered CAR-T cells targeting the non-functional P2X7 (nfP2X7) receptor, and co-cultured them with macrophages silencing P2X7 receptor along with OC cells. The anti-tumor effect of these CAR-T cells was assessed through evaluating OC cell viability, lactate dehydrogenase release, and IFN-γ levels.

Result

P2X7 receptor silencing promotes M1 macrophage marker expression (CD86, TNF-α, IL-6, IL-1β), diminishes M2 macrophage marker expression (CD206 and IL-10) and suppresses STAT6 phosphorylation, whereas STAT6 overexpression reverses these phenomena. Furthermore, M2 macrophage suppresses the toxic effect of CAR-T cells on OC cells, while silencing the P2X7 receptor nullifies the immunosuppressive effect of M2 macrophages on CAR-T cells.

Conclusion

Silencing P2X7 receptor can reverse M2 macrophage polarization by suppressing STAT6 activation, thereby enhancing the anti-tumor efficacy of CAR-T cells targeting nfP2X7 receptor in OC cell lines.

背景：嵌合抗原受体- t细胞（CAR-T）治疗卵巢癌（OC）失败的一个关键因素是免疫抑制肿瘤微环境的存在，这与肿瘤浸润巨噬细胞中的M2极化有着复杂的联系。P2X7受体在这些巨噬细胞中表达，其与M2极化的相关性是明显的。这项研究仔细研究了巨噬细胞内P2X7受体的沉默是否会导致CAR-T抗肿瘤效力的增强。方法：体外人工将人外周血单个核细胞分化为巨噬细胞或M2巨噬细胞。在巨噬细胞内沉默P2X7受体和/或过表达STAT6后，通过流式细胞术、ELISA和qRT-PCR评估M1和M2标记物。western blot检测STAT6的磷酸化水平。我们设计了靶向无功能P2X7 （nfP2X7）受体的CAR-T细胞，并与沉默P2X7受体的巨噬细胞以及OC细胞共培养。通过评估OC细胞活力、乳酸脱氢酶释放和IFN-γ水平来评估这些CAR-T细胞的抗肿瘤作用。结果：P2X7受体沉默可促进M1巨噬细胞标志物（CD86、TNF-α、IL-6、IL-1β）表达，降低M2巨噬细胞标志物（CD206、IL-10）表达，抑制STAT6磷酸化，而STAT6过表达可逆转上述现象。此外，M2巨噬细胞抑制CAR-T细胞对OC细胞的毒性作用，而沉默P2X7受体使M2巨噬细胞对CAR-T细胞的免疫抑制作用无效。结论：沉默P2X7受体可通过抑制STAT6激活逆转M2巨噬细胞极化，从而增强靶向nfP2X7受体的CAR-T细胞在OC细胞中的抗肿瘤作用。

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引用次数: 0

Downregulation of the immunoproteasome subunit PSMB8 attenuates sepsis-associated acute kidney injury through the NF-κB pathway 免疫蛋白酶体亚基PSMB8的下调通过NF-κB途径减轻败血症相关的急性肾损伤。

IF 2.5 4区医学 Q3 IMMUNOLOGY

Immunobiology

Pub Date : 2025-01-01 DOI: 10.1016/j.imbio.2024.152862

Min Li , Wenjia Tong , Chao Dai , Guoping Lu , Danqun Jin , Fang Deng

Sepsis-associated acute kidney injury (S-AKI) is a prevalent and life-threatening complication in hospitalized and critically ill patients. Recent researches indicates that immunoproteasome, especially proteasome 20S subunit beta 8 (PSMB8), is highly associated with various kidney diseases. This study aims to investigate the potential involvement of PSMB8 in S-AKI and its impact on apoptosis and inflammation. The model of S-AKI induced by LPS (10 mg/kg) was assessed by histological examination. ELISA and Real-time PCR were used to detect the levels of inflammatory cytokines in the renal cortex. The role of shPSMB8 in LPS-induced apoptosis was detected by flow cytometry. Finally, western blot was performed to assess the NF-κB signaling pathway related proteins, and the nuclear translocation of NF-kB P65 was detected by immunofluorescence microscopy. PSMB8 knockdown substantially protected against renal injury by reducing blood urea nitrogen and creatinine levels and ameliorating inflammation. PSMB8 knockdown inhibited renal expression of interleukin (IL)-1β, IL-6, tumor necrosis factor-α (TNF-α) and COX-2 to improve inflammatory response. Mechanistic studies demonstrated that downregulation of PSMB8 blocked LPS-induced S-AKI phosphorylation and nuclear translocation of NF-κB P65. Collectively, our results suggest that inhibition of PSMB8 significantly contributes to S-AKI via regulation of NF-κB. These findings reveal the pathogenic role of PSMB8 in AKI and suggest a novel therapeutic target for the condition.

脓毒症相关急性肾损伤（S-AKI）是住院和危重患者普遍存在的危及生命的并发症。近年来的研究表明，免疫蛋白酶体，特别是蛋白酶体20S亚基β 8 （PSMB8）与多种肾脏疾病密切相关。本研究旨在探讨PSMB8在S-AKI中的潜在参与及其对细胞凋亡和炎症的影响。采用组织学检查评价LPS （10 mg/kg）诱导的S-AKI模型。采用ELISA和Real-time PCR检测大鼠肾皮质炎性细胞因子水平。流式细胞术检测shPSMB8在lps诱导的细胞凋亡中的作用。western blot检测NF-κB信号通路相关蛋白，免疫荧光显微镜检测NF- kb P65核易位。PSMB8基因敲低通过降低血尿素氮和肌酐水平以及改善炎症来保护肾脏免受损伤。PSMB8敲低可抑制肾组织中白细胞介素(IL)-1β、IL-6、肿瘤坏死因子-α (TNF-α)和COX-2的表达，改善炎症反应。机制研究表明，PSMB8下调可阻断lps诱导的S-AKI磷酸化和NF-κB P65核易位。总之，我们的研究结果表明PSMB8的抑制通过调节NF-κB显著促进S-AKI。这些发现揭示了PSMB8在AKI中的致病作用，并提出了一种新的治疗靶点。

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引用次数: 0

M2-like macrophage-derived exosomes inhibit osteoclastogenesis via releasing miR-1227-5p m2样巨噬细胞来源的外泌体通过释放miR-1227-5p抑制破骨细胞的发生。

IF 2.5 4区医学 Q3 IMMUNOLOGY

Immunobiology

Pub Date : 2025-01-01 DOI: 10.1016/j.imbio.2024.152861

Shan Chen, Jian Liu, Lilei Zhu

Macrophages play a pivotal role in regulating inflammatory response in periodontitis, a condition characterized by excessive osteoclast differentiation. This study aimed to investigate whether exosomes derived from M2 macrophages regulate osteoclast differentiation and to identify the underlying molecular mechanisms. Exosomes were isolated from M2 macrophages and used to treat osteoclasts. Osteoclastogenesis was assessed using tartrate-resistant acid phosphatase staining and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The molecular mechanism was evaluated using microarray analysis, RT-qPCR, dual-luciferase reporter analysis, and RNA pull-down assay. The results showed that exosomes from M2 macrophages inhibited receptor activator of nuclear factor κ-B ligand (RANKL)-induced osteoclast differentiation. Additionally, miR-1227-5p expression in osteoclasts was increased after treatment with exosomes, and inhibition of miR-1227-5p counteracted the suppressive effects of exosomes on osteoclastogenesis. Moreover, OSCAR is a target of miR-1227-5p. In conclusion, exosomal miR-1227-5p suppresses osteoclast differentiation, potentially via targeting OSCAR. These findings provide new insights into the pathogenesis of periodontitis.

巨噬细胞在调节牙周炎炎症反应中起关键作用，牙周炎是一种以破骨细胞过度分化为特征的疾病。本研究旨在探讨来自M2巨噬细胞的外泌体是否调节破骨细胞的分化，并确定其潜在的分子机制。从M2巨噬细胞中分离外泌体，用于治疗破骨细胞。采用抗酒石酸酸性磷酸酶染色和逆转录定量聚合酶链反应（RT-qPCR）评估破骨细胞的发生。采用微阵列分析、RT-qPCR、双荧光素酶报告基因分析和RNA下拉实验对其分子机制进行了评估。结果表明，M2巨噬细胞外泌体对核因子κ-B配体受体激活因子（RANKL）诱导的破骨细胞分化具有抑制作用。此外，外泌体处理后，miR-1227-5p在破骨细胞中的表达增加，抑制miR-1227-5p抵消了外泌体对破骨细胞发生的抑制作用。此外，OSCAR是miR-1227-5p的靶点。总之，外泌体miR-1227-5p可能通过靶向OSCAR抑制破骨细胞分化。这些发现为牙周炎的发病机制提供了新的见解。

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引用次数: 0