Kamran Abbasi, Parveen Ali, Virginia Barbour, Thomas Benfield, Kirsten Bibbins-Domingo, Gregory E Erhabor, Stephen Hancocks, Richard Horton, Laurie Laybourn-Langton, Robert Mash, Peush Sahni, Wadeia Mohammad Sharief, Paul Yonga, Chris Zielinski
{"title":"Time to treat the climate and nature crisis as one indivisible global health emergency.","authors":"Kamran Abbasi, Parveen Ali, Virginia Barbour, Thomas Benfield, Kirsten Bibbins-Domingo, Gregory E Erhabor, Stephen Hancocks, Richard Horton, Laurie Laybourn-Langton, Robert Mash, Peush Sahni, Wadeia Mohammad Sharief, Paul Yonga, Chris Zielinski","doi":"10.1080/08923973.2023.2276510","DOIUrl":"10.1080/08923973.2023.2276510","url":null,"abstract":"","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54228842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mingming Li, Kuo Gu, Qingling Kong, Guonian Wang, Jing Gu
{"title":"Sufentanil inhibits the metastasis and immune response of breast cancer via mediating the NF-κB pathway.","authors":"Mingming Li, Kuo Gu, Qingling Kong, Guonian Wang, Jing Gu","doi":"10.1080/08923973.2023.2228476","DOIUrl":"10.1080/08923973.2023.2228476","url":null,"abstract":"<p><strong>Objective: </strong>Breast cancer (BC) causes cancer-related death in women. Sufentanil is used for cancer pain and postoperative analgesia. This study aimed to explore the role of sufentanil in BC.</p><p><strong>Methods: </strong>BC cells were treated with sufentanil, and cell viability was evaluated using the cell counting kit-8 (CCK-8) assay. Biological behaviors were analyzed using EDU assay, flow cytometry, transwell assay, western blotting, and ELISA. The levels of NF-κB pathway-related factors were examined using western blotting. A xenograft tumor model was established to assess the effects of sufentanil on tumor growth <i>in vivo</i>.</p><p><strong>Results: </strong>Sufentanil at the concentration of 20, 40, 80, and 160 nM suppressed cell viability (IC50 = 39.84 in MDA-MB-231 cells, and IC50 = 47.46 in BT549 cells). Sufentanil inhibited the proliferation, invasion, epithelial-mesenchymal transition (EMT), and inflammation, but induced apoptosis of BC cells. Mechanically, sufentanil suppressed the activation of the NF-κB pathway. Rescue experiments showed that RANKL (NF-κB receptor agonist) abrogated the effects induced by sufentanil. Moreover, sufentanil inhibited tumor growth, inflammatory response, but promoted apoptosis <i>via</i> the NF-κB pathway <i>in vivo</i>.</p><p><strong>Conclusions: </strong>Sufentanil decelerated the progression of BC by regulating the NF-κB pathway, suggesting sufentanil may be used in BC therapy.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10113366","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Targeting the cGAS-STING pathway as an inflammatory crossroad in coronavirus disease 2019 (COVID-19).","authors":"Reza Elahi, Salar Hozhabri, Amirhosein Moradi, Amir Siahmansouri, Armin Jahani Maleki, Abdolreza Esmaeilzadeh","doi":"10.1080/08923973.2023.2215405","DOIUrl":"10.1080/08923973.2023.2215405","url":null,"abstract":"<p><strong>Context and objective: </strong>The emerging pandemic of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has imposed significant mortality and morbidity on the world. An appropriate immune response is necessary to inhibit SARS-CoV-2 spread throughout the body.</p><p><strong>Results: </strong>During the early stages of infection, the pathway of stimulators of interferon genes (STING), known as the cGAS-STING pathway, has a significant role in the induction of the antiviral immune response by regulating nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and Interferon regulatory factor 3 (IRF3), two key pathways responsible for proinflammatory cytokines and type I IFN secretion, respectively.</p><p><strong>Discussion: </strong>During the late stages of COVID-19, the uncontrolled inflammatory responses, also known as cytokine storm, lead to the progression of the disease and poor prognosis. Hyperactivity of STING, leading to elevated titers of proinflammatory cytokines, including Interleukin-I (IL-1), IL-4, IL-6, IL-18, and tissue necrosis factor-α (TNF-α), is considered one of the primary mechanisms contributing to the cytokine storm in COVID-19.</p><p><strong>Conclusion: </strong>Exploring the underlying molecular processes involved in dysregulated inflammation can bring up novel anti-COVID-19 therapeutic options. In this article, we aim to discuss the role and current studies targeting the cGAS/STING signaling pathway in both early and late stages of COVID-19 and COVID-19-related complications and the therapeutic potential of STING agonists/antagonists. Furthermore, STING agonists have been discussed as a vaccine adjuvant to induce a potent and persistent immune response.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9667343","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Baoshan Hu, Lianxin Wang, Naikun Sun, Gang Rui, Shengrong Lin
{"title":"Leukoreduced PRP enhanced proliferation and ECM production yet inhibited senescence, inflammation, and multi-differentiation potential of AFSCs by downregulating HMGB1.","authors":"Baoshan Hu, Lianxin Wang, Naikun Sun, Gang Rui, Shengrong Lin","doi":"10.1080/08923973.2023.2232106","DOIUrl":"10.1080/08923973.2023.2232106","url":null,"abstract":"<p><strong>Background: </strong>This study assessed the role and potential mechanism of platelet-rich plasma (PRP) in the progression of intervertebral disk degeneration (IVDD).</p><p><strong>Methods: </strong>Annulus fibrosus (AF)-derived stem cells (AFSCs) from New Zealand white rabbits received the transfection with high mobility group box 1 (HMGB1) plasmids and the subsequent treatment with bleomycin, 10% leukoreduced PRP or leukoconcentrated PRP. Dying cells were indicated by immunocytochemistry analysis for senescence-associated β-galactosidase (SA-β-gal) staining. The proliferation of these cells was evaluated based on the population doubling time (PDT). The expressions of HMGB1, pro-aging and anti-aging molecules, extracellular matrix (ECM)-related catabolic/anabolic factors, and inflammatory genes at the molecular or transcriptional levels were quantified <i>via</i> Western blot or reverse transcription-quantitative PCR (RT-qPCR). Besides, the adipocytes, osteocytes, and chondrocytes were separately dyed by Oil Red O, Alizarin Red S, and Safranin O staining.</p><p><strong>Results: </strong>Bleomycin enhanced the senescent morphological changes and increased the PDT and the expressions of SA-β-gal, pro-aging molecules, ECM-related catabolic factors, inflammatory genes, and HMGB1 while suppressing the expressions of anti-aging and anabolic molecules. Leukoreduced PRP reversed the effects of bleomycin and inhibited the differentiation of AFSCs into adipocytes, osteocytes, and chondrocytes. Besides, HMGB1 overexpression offset the roles of leukoreduced PRP in AFSCs.</p><p><strong>Conclusion: </strong>Leukoreduced PRP promotes cell proliferation and ECM production of AFSCs, while inhibiting their senescence, inflammation, and multi-differentiation potentials <i>via</i> downregulating HMGB1 expression.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9773691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"mTORC1 inhibition may improve T lymphocytes affected by aging.","authors":"F Asghari, M H Karimi, A A Pourfathollah","doi":"10.1080/08923973.2023.2232101","DOIUrl":"10.1080/08923973.2023.2232101","url":null,"abstract":"<p><strong>Background: </strong>Due to the increase of the elderly's population and related social and economic problems, it is very important to provide strategies on health. In this regard, induction of T lymphocytes responses, the most important cells of the immune system, may be a good approach. Among different agents considered as antiaging factors, mTORC1 pathway inhibitors are significant. So, the purpose of this study was to evaluate the effect of two mTORC1 inhibitors, Everolimus and Metformin, on age-related features of activated T cells.</p><p><strong>Materials and methods: </strong>Optimum doses of drugs was determined with evaluating the effect of treatments on IL-2 gene expression. T cells isolated from old and young mice were treated with drugs and PHA. IL-2 production was evaluated by ELISA. Also, the expression of CD28, PD-1, and KLRG-1, proliferation, and intracellular oxidative stress were assessed by flow cytometry-based assays, phenotyping, CFSE, and DCF-DA assay respectively.</p><p><strong>Results: </strong>Both drugs increased IL-2 production in the T cells of old mice. Also, using drugs especially Metformin could improve age-related phenotypical markers and increase the proliferation of T cells of old mice significantly. In addition, Metformin and Everolimus reduced intracellular oxidative stress in aged cells. However, the effect of both drugs on the T cells of young mice wasn't significant or was in opposite to the results of old mice T cells.</p><p><strong>Discussion: </strong>In line with studies noting mTOR inhibitors as antiaging drugs, Metformin and Everolimus may improve T cells affected from aging <i>in vitro</i>, and a decrease in intracellular oxidative stress may be one of their mechanism of function.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10000311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Marwa Monier Mahmoud Refaie, Manar Fouli Gaber Ibrahim, Michael Atef Fawzy, Elshymaa A Abdel-Hakeem, Eman Shaaban Mahmoud Abd El Rahman, Nagwa M Zenhom, Sayed Shehata
{"title":"Molecular mechanisms mediate roflumilast protective effect against isoprenaline-induced myocardial injury.","authors":"Marwa Monier Mahmoud Refaie, Manar Fouli Gaber Ibrahim, Michael Atef Fawzy, Elshymaa A Abdel-Hakeem, Eman Shaaban Mahmoud Abd El Rahman, Nagwa M Zenhom, Sayed Shehata","doi":"10.1080/08923973.2023.2222228","DOIUrl":"10.1080/08923973.2023.2222228","url":null,"abstract":"<p><strong>Background: </strong>Myocardial necrosis is one of the most common cardiac and pathological diseases. Unfortunately, using the available medical treatment is not sufficient to rescue the myocardium. So that, we aimed in our model to study the possible cardioprotective effect of roflumilast (ROF) in an experimental model of induced myocardial injury using a toxic dose of isoprenaline (ISO) and detecting the role of vascular endothelial growth factor/endothelial nitric oxide synthase (VEGF/eNOS) and cyclic guanosine monophosphate/cyclic adenosine monophosphate/ sirtuin1 (cGMP/cAMP/SIRT1) signaling cascade.</p><p><strong>Materials and methods: </strong>Animals were divided into five groups; control, ISO given group (150 mg/kg) i.p. on the 4th and 5th day, 3 ROF co-administered groups in different doses (0.25, 0.5, 1 mg/kg/day) for 5 days.</p><p><strong>Results: </strong>Our data revealed that ISO could induce cardiac toxicity as manifested by significant increases in troponin I, creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH), malondialdehyde (MDA), tumor necrosis factor alpha (TNFα), and cleaved caspase-3 with toxic histopathological changes. Meanwhile, there were significant decreases in reduced glutathione (GSH), total antioxidant capacity (TAC), VEGF, eNOS, cGMP, cAMP and SIRT1. However, co-administration of ROF showed significant improvement and normalization of ISO induced cardiac damage.</p><p><strong>Conclusion: </strong>We concluded that ROF successfully reduced ISO induced myocardial injury and this could be attributed to modulation of PDE4, VEGF/eNOS and cGMP/cAMP/SIRT1 signaling pathways with antioxidant, anti-inflammatory, and anti-apoptotic properties.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9661544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Imperatorin inhibits LPS-induced bone marrow-derived macrophages activation by decreased NF-κB p65 phosphorylation.","authors":"Yuan Jiang, Hui Fang, Siqi Lin, Yunyun Chen, Yuanzheng Fu, Yifan Tu, Qiang Li, Zhaoyuan Hui","doi":"10.1080/08923973.2023.2196603","DOIUrl":"10.1080/08923973.2023.2196603","url":null,"abstract":"<p><strong>Background: </strong>Imperatorin (IMP) is a secondary metabolite of plants and is the most abundant in Angelica dahurica. Previous studies showed that IMP exhibited anti-inflammatory activity in RAW264.7 cell line. Here, we aim to investigate the roles and mechanisms of IMP in bone marrow-derived macrophages (BMDMs), in view of the difference between primary macrophages and cell lines.</p><p><strong>Methods: </strong>BMDMs were stimulated with LPS for the inflammation model. Flow cytometry was performed with BMDMs treated with different doses of IMP (0-20mg/L) within staining Annexin V-APC for 5 min. The cytokines and inflammatory mediators were detected by RT-PCR or ELISA. RNA-seq was performed in IMP-treated BMDMs or control, stimulated with LPS for 6h. Western blotting is carried out to determine the phosphorylation of p65, ERK1/2, JNK1, p38, and Akt.</p><p><strong>Results: </strong>Our results showed that IMP inhibited IL-12p40, IL-6, TNF-α and IL-1β in LPS-stimulated BMDMs. RNA-seq analysis suggested that IMP inhibits Toll-like receptor signaling pathway (KEGG), TNF signaling pathway (KEGG), NF-κB signaling pathway (KEGG), Inflammatory Response (GO). In addition, IMP inhibited <i>myd88</i>, <i>tpl2</i>, <i>cxcl1</i>, <i>ptgs2</i>(COX-2) expression in mRNA level. Finally, we found decreased phosphorylation of NF-κB p65 in IMP-treated BMDMs, after stimulated with LPS.</p><p><strong>Conclusion: </strong>IMP inhibits IL-12p40, IL-6, TNF-α, and IL-1β expression in LPS-stimulated BMDMs. IMP inhibits macrophage activation, which maybe resulted in decreased phosphorylation of NF-κB p65. Furthermore, IMP may protect against the progress of inflammatory-related diseases.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9624395","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Folake Olubukola Asejeje, Khalid Damilare Akinola, Michael Abayomi Abiola
{"title":"Sodium benzoate exacerbates hepatic oxidative stress and inflammation in lipopolysaccharide-induced liver injury in rats.","authors":"Folake Olubukola Asejeje, Khalid Damilare Akinola, Michael Abayomi Abiola","doi":"10.1080/08923973.2023.2191818","DOIUrl":"10.1080/08923973.2023.2191818","url":null,"abstract":"<p><strong>Background: </strong>Liver damage is a global health concern associated with a high mortality rate. Sodium benzoate (SB) is a widely used preservative in the food industry with a wide range of applications. However, there's a lack of scientific reports on its effect on lipopolysaccharide-induced hepatic dysfunction.</p><p><strong>Objective: </strong>The present study investigated the influence of SB on lipopolysaccharide (LPS)-induced liver injury.</p><p><strong>Materials and methods: </strong>Twenty-eight rats were randomly allocated into four groups: control (received distilled water), SB (received 600 mg/kg), LPS (received 0.25 mg/kg), and LPS + SB (received LPS, 0.25 mg/kg, and SB, 600 mg/kg). SB was administered orally for 14 days while LPS was administered intraperitoneally for 7 days.</p><p><strong>Results: </strong>Administration of SB to rats with hepatocyte injury exacerbated liver damage with a significant increase in the activities of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP). We also observed that SB aggravated LPS-mediated hepatic oxidative stress occasioned by a marked decrease in antioxidant status with a concomitant increase in lipid peroxidation. Furthermore, LPS - mediated increase in inflammatory biomarkers as well as histological deterioration in the liver was exacerbated following the administration of SB to rats.</p><p><strong>Conclusion: </strong>Taken together, the study provides experimental evidence that SB exacerbates hepatic oxidative stress and inflammation in LPS-mediated liver injury.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9160775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mina Djalali, Sepide Talebi, Ehsan Djalali, Mina Abdolahi, Nikolaj Travica, Mahmoud Djalali
{"title":"The effect of omega-3 fatty acids supplementation on inflammatory biomarkers in subjects with migraine: a randomized, double-blind, placebo-controlled trial.","authors":"Mina Djalali, Sepide Talebi, Ehsan Djalali, Mina Abdolahi, Nikolaj Travica, Mahmoud Djalali","doi":"10.1080/08923973.2023.2196600","DOIUrl":"10.1080/08923973.2023.2196600","url":null,"abstract":"<p><strong>Objective: </strong>Imbalances in immune regulation are important features of migraine pathophysiology. In line with this, the current study investigated the efficacy of omega-3 fatty acids supplementation on inflammatory and anti-inflammatory markers in patients with migraines.</p><p><strong>Materials and methods: </strong>This randomized, double-blind, placebo-controlled trial consisted of 40 patients that were prone to experiencing episodic migraines. For two months, participants were randomized into one group that received omega-3 supplementation (n= 20), 600 mg of EPA and 300 mg of DHA, twice daily) or another group that received a placebo (n= 20). Transforming growth factor β (TGF-β), interleukin (IL)-4, interferon-gamma (IFN-γ), and interleukin (IL)-17 serum levels were assessed using enzyme-linked immunosorbent assay methods at baseline and following the intervention. The current study was registered on ClinicalTrials.gov with the registration number NCT02532023.</p><p><strong>Results: </strong>After two months of intervention, the administration of omega-3 fatty acids resulted in a significant rise in the concentrations of anti-inflammatory cytokine IL-4 (p=0.010) as well as a significant reduction in concentrations of pro-inflammatory cytokine IFN-γ (p=0.001) compared with the placebo. However, no significant changes were observed in serum TGF-β and IL-17 levels.</p><p><strong>Discussion: </strong>Our findings indicated consumption of omega-3 fatty acids may have a potentially beneficial response on the inflammatory immune response in patients with migraines. Larger trials are needed to corroborate these findings.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9387632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Human umbilical-cord-derived mesenchymal stem cells in combination with rapamycin reduce cartilage degradation via inhibition of the <i>AKT/mTOR</i> signaling pathway.","authors":"Yanan Bie, Qianqing Chen, Jiahuan Xu, Baofang Ou, Boyu Chen, Yajin Guan, Shuilin Xie","doi":"10.1080/08923973.2023.2189062","DOIUrl":"10.1080/08923973.2023.2189062","url":null,"abstract":"<p><strong>Background and aims: </strong>Mesenchymal stem cell (MSC) therapy is a promising strategy for treating osteoarthritis (OA). However, the inflammatory microenvironment, apoptosis of transplanted cells, and shear forces during direct injection limit the therapeutic efficacy. This study aimed to explore the role of rapamycin combined with human umbilical-cord-derived mesenchymal stem cells (hUMSCs) in OA rabbits <i>in vivo</i>.</p><p><strong>Methods: </strong>OA rabbits received an intra-articular injection of a collagenase solution. Gross observations, X-ray examinations, and histological examinations were performed to detect cartilage degradation levels. The fluorescent membrane dye DiR was used to label hUMSCs. In the combination therapy group, rapamycin was injected into the rabbit knee joint one day post the intra-articular injection of hUMSCs. Bioinformatics and transcriptome profiling of the knee meniscus were used to evaluate the potential molecular mechanisms of the combination therapy.</p><p><strong>Results: </strong>Our study shows that rapamycin combined with hUMSCs significantly ameliorated OA severity <i>in vivo</i>, enhancing matrix synthesis and promoting cartilage repair. The combination therapy was more efficient than rapamycin or hUMSC treatment alone. Moreover, bioinformatics and transcriptomic analyses revealed that combination therapy might enhance autophagy in chondrocytes, partially by inhibiting the mTOR pathway.</p><p><strong>Conclusions: </strong>Our study indicates that the combination therapy of rapamycin and hUMSCs may promote cartilage repair in OA rabbits through the mTOR pathway and offers a novel approach for OA therapy.</p><p><strong>The translational potential of this article: </strong>Our study provides new evidence to support the use of hUMSCs in combination with rapamycin as a potential candidate for OA treatment.</p>","PeriodicalId":13420,"journal":{"name":"Immunopharmacology and Immunotoxicology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9201583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}