{"title":"MiR-22-3p facilitates bone marrow mesenchymal stem cell osteogenesis and fracture healing through the SOSTDC1-PI3K/AKT pathway","authors":"Chunqiu Wang, Xinguo Wang, Hui Cheng, Jiahu Fang","doi":"10.1111/iep.12500","DOIUrl":"10.1111/iep.12500","url":null,"abstract":"<p>Bone fractures are the most common form of musculoskeletal trauma worldwide. Numerous microRNAs (miRNAs) have been suggested to be participants in regulating bone-related diseases. Recent studies revealed the regulatory role of miR-22-3p in osteogenic differentiation, but its role in fracture healing has not been investigated previously. Here, a rat femoral fracture model was established, Bone marrow mesenchymal stem cells (BMSCs) were isolated to detect the specific function and underlying mechanisms of miR-22-3p. MiR-22-3p and sclerostin domain-containing 1 (SOSTDC1) expression was determined by RT-qPCR and immunohistochemistry staining. The levels of proteins associated with osteogenic differentiation were assessed by western blotting. Flow cytometry was conducted to identify the isolated rat BMSCs. Alizarin red staining, alkaline phosphatase staining and Oil Red O staining were used to evaluate the osteogenic and adipogenic differentiation of rat BMSCs. The interaction between miR-22-3p and SOSTDC1 was verified using a luciferase reporter assay. Haematoxylin and Eosin (H&E) staining of the bone tissues was performed to analyse the effect of miR-22-3p on histopathological changes in vivo. MiR-22-3p was downregulated in the callus tissues of rat femoral fracture, while the expression of SOSTDC1 was upregulated. The isolated rat BMSCs had the capacity for both osteogenic and adipogenic differentiation. The differentiation capacity of BMSCs into osteoblasts was increased by miR-22-3p overexpression. MiR-22-3p activated the PI3K/AKT pathway by targeting SOSTDC1. SOSTDC1 overexpression and PI3K/AKT signalling inhibitor LY294002 abolished the enhancing effect of miR-22-3p overexpression on the osteogenesis of BMSCs. Thus MiR-22-3p facilitated the femoral fracture healing in rats. MiR-22-3p overexpression promoted fracture healing via the activation of PI3K/AKT pathway by targeting SOSTDC1.</p>","PeriodicalId":14157,"journal":{"name":"International Journal of Experimental Pathology","volume":"105 2","pages":"52-63"},"PeriodicalIF":3.0,"publicationDate":"2023-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139048647","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}
U Baylan, A Baidoshvili, S Simsek, CG Schalkwijk, HWM Niessen, PAJ Krijnen
{"title":"Increased accumulation of the advanced glycation endproduct Ne(carboxymethyl) lysine in the intramyocardial vasculature in patients with epicarditis","authors":"U Baylan, A Baidoshvili, S Simsek, CG Schalkwijk, HWM Niessen, PAJ Krijnen","doi":"10.1111/iep.12499","DOIUrl":"10.1111/iep.12499","url":null,"abstract":"<p>Advanced glycation end-products (AGEs) are implicated in the pathogenesis of vascular disease. In previous studies we have found increased deposition of N(e)-(carboxymethyl)lysine (CML) in intramyocardial vasculature in the heart in acute myocardial infarction and myocarditis. It is known that the process of inflammation plays a role in the formation of AGEs. In this study we have explored the presence of CML (a major AGE) in the heart of patients with epicarditis using a monoclonal anti-CML antibody. Nine patients with epicarditis (<i>n</i> = 9) died and their hearts were used for this study, control were hearts from patients who died from conditions unrelated to heart disease and without signs of myocarditis or epicarditis CML deposition and complement were significantly increased in patients with epicarditis compared to control hearts. Thus epicarditis increases CML depositions in the intramyocardial vasculature.</p>","PeriodicalId":14157,"journal":{"name":"International Journal of Experimental Pathology","volume":"105 2","pages":"48-51"},"PeriodicalIF":3.0,"publicationDate":"2023-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/iep.12499","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138561843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Circular RNA circVAPA modulates macrophage pyroptosis in sepsis-induced acute lung injury through targeting miR-212-3p/Sirt1/Nrf2/NLRP3 axis","authors":"Yanjing Huang, Jinquan Lin, Zhiwei Wu, Yiming Li","doi":"10.1111/iep.12497","DOIUrl":"10.1111/iep.12497","url":null,"abstract":"<p>Sepsis-induced acute lung injury (ALI) is an inflammatory condition involving the pyroptosis of macrophages. This study investigated the role of circular RNA hsa_circ_0006990 (circVAPA) in regulating macrophage pyroptosis in ALI and the underlying mechanisms. The expression pattern of circVAPA was examined in the mouse model of ALI and in the LPS-treated RAW264.7 macrophage cell line. Lung tissue damage was evaluated by haematoxylin and eosin staining, immunohistochemistry and a myeloperoxidase activity assay. The molecular mechanisms were investigated by luciferase reporter assay, western blot, RT-qPCR and ELISA. circVAPA was down-regulated in the lung tissues of ALI mice and LPS-induced RAW264.7 cells. circVAPA over-expression alleviated lung tissue injury and dampened LPS-induced pyroptosis and Th17-associated inflammatory responses. miR-212-3p was identified as a target of circVAPA, and miR-212-3p negatively regulated the expression of Sirt1. Sirt1 knockdown largely abolished the effect of circVAPA over-expression on pyroptosis. CircVAPA/miR-212-3p/Sirt1 axis also regulates Nrf2 and NLRP3 expression upon LPS challenge. By targeting miR-212-3p, circVAPA over-expression negatively regulates the expression of Sirt1 and pyroptosis-related factors (Nrf2 and NLRP3), which alleviates the inflammatory damages in sepsis-induced ALI.</p>","PeriodicalId":14157,"journal":{"name":"International Journal of Experimental Pathology","volume":"105 1","pages":"21-32"},"PeriodicalIF":3.0,"publicationDate":"2023-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138487467","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}
Beatriz Lima Adjafre, Iásly Costa Lima, Ana Paula Negreiros Nunes Alves, Rafael Aires Lessa, Arcelina Pacheco Cunha, Maria Gonçalves Pereira, Ana Maria Sampaio Assreuy, Mário Rogério Lima Mota
{"title":"Anti-inflammatory and healing effect of the polysaccharidic extract of Opuntia ficus-indica cladodes in cutaneous excisional wounds in rats","authors":"Beatriz Lima Adjafre, Iásly Costa Lima, Ana Paula Negreiros Nunes Alves, Rafael Aires Lessa, Arcelina Pacheco Cunha, Maria Gonçalves Pereira, Ana Maria Sampaio Assreuy, Mário Rogério Lima Mota","doi":"10.1111/iep.12498","DOIUrl":"10.1111/iep.12498","url":null,"abstract":"<p>This study aimed to investigate the anti-inflammatory and wound healing effects of the polysaccharide extract from <i>Opuntia ficus-indica</i> cladodes (TPL-Ofi) using a rat cutaneous wound model. After anaesthesia, four 7-mm-diameter dorsal wounds per animal (<i>n</i> = 6/group for each experimental day of evaluation) were created in female Wistar rats using a surgical punch. The animals were treated topically twice daily with TPL-Ofi (0.01–1%; treated group) or sterile saline (control group) for a period of 21 days. Ulcerated tissue was collected for analysis of histological parameters (inflammation score, number of polymorphonuclear, mononuclear, fibroblast/myofibroblasts and blood vessels), immunohistochemical (fibroblast growth factor 2 [FGF-2]) and oxidative stress markers (myeloperoxidase [MPO] and glutathione [GSH]). After 21 days of treatment, body weight, net organ weight and plasma biochemical levels were measured. TPL-Ofi, containing a total carbohydrate content of 65.5% and uronic acid at 2.8%, reduced oedema on the second day and increased the nociceptive threshold on the second and third days. TPL-Ofi reduced mononuclear infiltrate on the second and MPO activity on the fifth day. TPL-Ofi increased GSH levels on the second day, as well as fibroblast/myofibroblasts counts, neoangiogenesis and FGF-2 levels on the fifth and seventh days. No changes were observed in body weight, net organ weight or toxicology assessment. Topical application of TPL-Ofi exhibited anti-inflammatory and antinociceptive effects, ultimately improving wound healing in cutaneous wounds.</p>","PeriodicalId":14157,"journal":{"name":"International Journal of Experimental Pathology","volume":"105 1","pages":"33-44"},"PeriodicalIF":3.0,"publicationDate":"2023-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138290947","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}
Parmis Khoshnoudi, Soroush Sabiza, Mohammad Khosravi, Babak Mohamadian
{"title":"Exploring effect of M2 macrophages on experimental full-thickness wound healing in streptozotocin-induced diabetic rats","authors":"Parmis Khoshnoudi, Soroush Sabiza, Mohammad Khosravi, Babak Mohamadian","doi":"10.1111/iep.12496","DOIUrl":"10.1111/iep.12496","url":null,"abstract":"<p>Diabetes mellitus is one of the most prevalent medical conditions, in both humans and animals. People with diabetes mellitus often experience slower than normal wound healing, making it a serious health concern. This study investigates the effect of M2 differentiated macrophages on full-thickness wound healing in white Westar rats exposed to streptozocin 70 mg/kg. A full-thickness skin defect with dimensions of 2 × 2 cm was created on the back of all the animals, and their blood sugar was simultaneously assessed. The monocytes were isolated from blood samples using the plastic adherence method and were exposed to dexamethasone (5–10 <i>μ</i>) for 24 h. Subsequently, they were washed with PBS and incubated in fresh cell culture medium for 5 days. The differentiated M2 cells were injected into four points of the experimental ulcers of the treatment group. Macroscopic and microscopic changes were evaluated and compared over a period of two weeks between the test and control groups. The infusion of these cells a few days after wounding enhances wound healing parameters significantly, as evidenced by an increase in germinating tissue formation, wound contraction, inflammation reduction, and collagen increase in the treated group.</p>","PeriodicalId":14157,"journal":{"name":"International Journal of Experimental Pathology","volume":"105 1","pages":"13-20"},"PeriodicalIF":3.0,"publicationDate":"2023-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134648932","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":"Notoginsenoside R1 promotes osteogenic differentiation of human bone marrow mesenchymal stem cells via ERα/GSK-3β/β-catenin signalling pathway","authors":"Wei Lu, Yuanxin Shi, Minglei Qian","doi":"10.1111/iep.12494","DOIUrl":"10.1111/iep.12494","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>Human bone marrow mesenchymal stem cells (hBMSCs) are attractive therapeutic agents for bone tissue regeneration owing to their osteogenic differentiation potential. Notoginsenoside R1 (NGR1) is a novel phytoestrogen with diverse pharmacological activities. Here, we probed whether NGR1 has an effect on the osteogenic differentiation of hBMSCs. EdU, CCK-8 and Transwell assays were used to measure proliferation and migration of hBMSCs after treatment with different doses of NGR1. hBMSCs were treated with osteogenic differentiation induction medium for osteogenesis. Alizarin red S (ARS) and alkaline phosphatase (ALP) staining were used to measure mineralized nodule formation and ALP activity in hBMSCs, respectively. ICI 182780, an antagonist of oestrogen receptor alpha (ERα) was used to inhibit ERα expression. The results showed that NGR1 enhanced hBMSC proliferation and migration. NGR1 increased ALP activity and mineralized nodule formation as well as promoting <i>ALP</i>, <i>RUNX2</i> and <i>OCN</i> expression in hBMSCs. NGR1 enhanced ERα expression and promoted GSK-3β/β-catenin signal transduction in hBMSCs. ICI 182780 reversed NGR1-mediated activation of the GSK-3β/β-catenin signalling and promoted an effect on hBMSC behaviour. Thus NGR1 promotes proliferation, migration and osteogenic differentiation of hBMSCs via the ERα/GSK-3β/β-catenin signalling pathway.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14157,"journal":{"name":"International Journal of Experimental Pathology","volume":"105 1","pages":"4-12"},"PeriodicalIF":3.0,"publicationDate":"2023-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71412173","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}
Weiwei Zhu, Xiaojing Liu, Liqing Luo, Xiao Huang, Xiaozhi Wang
{"title":"Interaction between mitochondrial homeostasis and barrier function in lipopolysaccharide-induced endothelial cell injury","authors":"Weiwei Zhu, Xiaojing Liu, Liqing Luo, Xiao Huang, Xiaozhi Wang","doi":"10.1111/iep.12495","DOIUrl":"10.1111/iep.12495","url":null,"abstract":"<p>This study aimed to investigate the effects of mitochondrial homeostasis on lipopolysaccharide (LPS)-induced endothelial cell barrier function and the mechanisms that underlie these effects. Cells were treated with LPS or oligomycin (mitochondrial adenosine triphosphate synthase inhibitor) and the mitochondrial morphology, mitochondrial reactive oxygen species (mtROS), and mitochondrial membrane potential (ΔΨm) were evaluated. Moreover, the shedding of glycocalyx-heparan sulphate (HS), the levels of HS-specific degrading enzyme heparanase (HPA), and the expression of occludin and zonula occludens (ZO-1) of Tight Junctions (TJ)s, which are mediated by myosin light chain phosphorylation (p-MLC), were assessed. Examining the changes in mitochondrial homeostasis showed that adding heparinase III, which is an exogenous HPA, can destroy the integrity of glycocalyx. LPS simultaneously increased mitochondrial swelling, mtROS, and ΔΨm. Without oligomycin effects, HS, HPA levels, and p-MLC were found to be elevated, and the destruction of occludin and ZO-1 increased. Heparinase III not only damaged the glycocalyx by increasing HS shedding but also increased mitochondrial swelling and mtROS and decreased ΔΨm. Mitochondrial homeostasis is involved in LPS-induced endothelial cell barrier dysfunction by aggravating HPA and p-MLC levels. In turn, the integrated glycocalyx protects mitochondrial homeostasis.</p>","PeriodicalId":14157,"journal":{"name":"International Journal of Experimental Pathology","volume":"104 6","pages":"272-282"},"PeriodicalIF":3.0,"publicationDate":"2023-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/iep.12495","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41201020","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Floyd D. Wilson, Tahir M. Mir, Mohammad K. Ashfaq, Jin Zhang, Nirmal D. Pugh, Ikhlas A. Khan, Lanny W. Pace, Frederic J. Hoerr
{"title":"Histomorphometric lung density evaluation of Immulina treatment using a murine influenza pneumonia model","authors":"Floyd D. Wilson, Tahir M. Mir, Mohammad K. Ashfaq, Jin Zhang, Nirmal D. Pugh, Ikhlas A. Khan, Lanny W. Pace, Frederic J. Hoerr","doi":"10.1111/iep.12493","DOIUrl":"10.1111/iep.12493","url":null,"abstract":"<p>Histomorphometric lung density measurements were used to evaluate the effects of Immulina on mouse pneumonia. Mice were intra-nasally exposed to H1N1 influenza virus at a dose of 5 × 10<sup>4</sup> PFU/50 μL/mouse. Lung density was measured using the NIH ImageJ software program. Density values were compared to semiquantitative pneumonia severity scores. Lung photomicrographs were evaluated at 25-×, 40-× and 400-× magnification. The study included viral inoculated controls (IC) and non-inoculated controls (NC) and mice either treated or not treated with Immulina. Three doses of Immulina were included (25, 50 or 100 mg/kg) and administered using 3 protocols: prophylactic treatment (P), prodromal treatment (PD) and therapeutic treatment (TH) (note that in most of the evaluations of the data for the three treatment protocols were combined). Groups of mice were evaluated on days 3, 5, 7, 10 and 15 following exposure. The occurrence of “digital pneumonia” (DP) was defined as a density measurement above the 95% confidence limit of the corresponding NC values. A significant reduction in the occurrence of DP with Immulina treatment at the higher doses compared to IC was seen as early as day 3 and persisted up to day 15. There were also statistically significant dose-variable reductions in lung density in response to Immulina. The study suggests early administration of Immulina (P or PD protocols) may enhance resistance against influenza-induced viral pneumonia. A moderate correlation between pneumonia severity scores and lung density was observed for the 25-× and 40-× images (<i>R</i> = 0.56 and 0.53 respectively), and a strong correlation (<i>R</i> = 0.68) for 400-× images.</p>","PeriodicalId":14157,"journal":{"name":"International Journal of Experimental Pathology","volume":"104 6","pages":"283-291"},"PeriodicalIF":3.0,"publicationDate":"2023-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/iep.12493","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41123718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"British Society for Matrix Biology Spring Meeting 2023: Vascular Inflammation and the Extracellular Matrix","authors":"","doi":"10.1111/iep.12486","DOIUrl":"10.1111/iep.12486","url":null,"abstract":"","PeriodicalId":14157,"journal":{"name":"International Journal of Experimental Pathology","volume":"104 5","pages":"A1-A10"},"PeriodicalIF":3.0,"publicationDate":"2023-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10264051","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bin Zhou, Yan Xu, Li Xu, Yi Kong, Kang Li, Bolin Chen, Jia Li
{"title":"Inhibition of inflammation and infiltration of M2 macrophages in NSCLC through the ATF3/CSF1 axis: Role of miR-27a-3p","authors":"Bin Zhou, Yan Xu, Li Xu, Yi Kong, Kang Li, Bolin Chen, Jia Li","doi":"10.1111/iep.12490","DOIUrl":"10.1111/iep.12490","url":null,"abstract":"<p>Non-small cell lung cancer (NSCLC) imposes a significant economic burden on patients and society due to its low overall cure and survival rates. Tumour-associated macrophages (TAM) affect tumour development and may be a novel therapeutic target for cancer. We collected NSCLC and tumour-adjacent tissue samples. Compared with the tumour-adjacent tissues, the Activation Transcription Factor 3 (ATF3) and Colony Stimulating Factor 1 (CSF-1) were increased in NSCLC tissues. Levels of ATF3 and CSF-1 were identified in different cell lines (HBE, A549, SPC-A-1, NCI-H1299 and NCI-H1795). Overexpression of ATF3 in A549 cells increased the expression of CD68, CD206 and CSF-1. Moreover, levels of CD206, CD163, IL-10 and TGF-β increased when A549 cells were co-cultured with M0 macrophages under the stimulation of CSF-1. Using the starbase online software prediction and dual-luciferase assays, we identified the targeting between miR-27a-3p and ATF3. Levels of ATF3, CSF-1, CD206, CD163, IL-10 and TGF-β decreased in the miR-27a mimics, and the tumour growth was slowed in the miR-27a mimics compared with the mimics NC group. Overall, the study suggested that miR-27a-3p might inhibit the ATF3/CFS1 axis, regulate the M2 polarization of macrophages and ultimately hinder the progress of NSCLC. This research might provide a new therapeutic strategy for NSCLC.</p>","PeriodicalId":14157,"journal":{"name":"International Journal of Experimental Pathology","volume":"104 6","pages":"292-303"},"PeriodicalIF":3.0,"publicationDate":"2023-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10139769","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}