Biomedicine & Pharmacotherapy最新文献

{"title":"Enhancing lung cancer growth inhibition with calcium ions: Role of mid- and high-frequency electric field pulses","authors":"Nina Rembiałkowska ,&nbsp;Julia Kucharczyk ,&nbsp;Eivina Radzevičiūtė-Valčiukė ,&nbsp;Vitalij Novickij ,&nbsp;Margherita Tonci ,&nbsp;Ata Dündar ,&nbsp;Julita Kulbacka ,&nbsp;Wojciech Szlasa","doi":"10.1016/j.biopha.2024.117691","DOIUrl":"10.1016/j.biopha.2024.117691","url":null,"abstract":"<div><div>Calcium electroporation (CaEP) involves the combination of calcium ions with electroporation, which is induced by pulsed electric fields (PEFs). This study explores the application of high-frequency unipolar nanosecond pulsed electric fields (nsPEFs: 8–14 kV/cm, 200 ns, 10 kHz, 100 kHz, 1 MHz repetition frequency pulse bursts, n = 100) and their potential in inhibiting lung cancer cell growth. As a reference, standard microsecond range parametric protocols were used (100 µs x 8 pulses). Methods included cell permeability quantification through Yo-Pro-1 uptake, cell viability assays, immunofluorescence studies for apoptosis and EMT markers, analysis of cell death types depending on repetition frequency pulse bursts. We determined the susceptibility of human lung cancer to electric pulses, characterized the efficacy of CaEP, and investigated cell death types depending on repetition frequency pulse bursts. We have shown that adding calcium ions to the applied nsPEF protocol increases cytotoxicity. Additionally, the use of these electroporation parameters can modulate key cellular processes, such as the epithelial-mesenchymal transition and apoptosis, as indicated by changes in the expression of markers such as E-cadherin, N-cadherin, BCL-2, and p53. Changes in cell morphology over time were observed using holotomographic microscopy. The study provides insights into the modulation of key cellular processes, indicating that nsPEF technology could improve the outcomes of conventional cancer treatments through enhanced efficacy and potentially mitigating drug resistance mechanisms. The promising results advocate for further research to optimize nsPEF protocols for clinical application, highlighting the potential of electrical fields in advancing cancer therapy.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"181 ","pages":"Article 117691"},"PeriodicalIF":6.9,"publicationDate":"2024-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142663361","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis, characterisation, and anti-tumour activity of nano-immuno-conjugates for enhanced photodynamic therapy of oesophageal cancer stem cells","authors":"Onyisi Christiana Didamson ,&nbsp;Rahul Chandran ,&nbsp;Heidi Abrahamse","doi":"10.1016/j.biopha.2024.117693","DOIUrl":"10.1016/j.biopha.2024.117693","url":null,"abstract":"<div><div>In recent times, oesophageal cancer has been listed as the eleventh most prevalent type of cancer. It is a lethal disease attributed to a high mortality rate, tumour metastasis and poor treatment outcome. A subset of oesophageal cancer referred to as stem cells (CSCs) has been revealed to drive carcinogenesis, metastasis, and treatment failure. Therefore, it is essential to target these CSCs to improve the efficacy of treatment for oesophageal cancer. In this present study, we employed a strategy to target oesophageal CSCs with a nano-immuno-conjugate (NIC) consisting of AlPcS₄Cl, gold nanoparticle (AuNPs) and anti-CD271 antibody synthesised using a chemical reaction. The synthesised NIC was characterised using ultraviolet-visible spectroscopy, transmission electron microscope (TEM), Fourier transform infra-red (FTIR) spectroscopy, dynamic light scattering (DLS), and zeta potential (ZP). The <em>in vitro</em> anti-tumour action of NIC-mediated photodynamic therapy (PDT) was performed on oesophageal CSCs using cell viability/cytotoxicity assays and morphological examination via light microscopy. The characterisation analysis confirmed the successful synthesis of the NIC. The synthesised nano-immuno-conjugates showed significant cytotoxicity and reduction in cell viability in the HKESC-1 oesophageal CSCs. Fluorescence microscopy confirmed the rapid internalisation of the targeted NIC in key cellular organelles of the CSCs, resulting in enhanced effects. Interestingly, NIC exhibited cytocompatibility with non-tumour WS1 cells, thus supporting its clinical application as a safe anti-tumour agent for enhanced PDT. The study demonstrates the improved effects of NIC-mediated PDT as targeted therapeutics against oesophageal CSCs.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"181 ","pages":"Article 117693"},"PeriodicalIF":6.9,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142650033","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The possible role of hypoxia-induced exosomes on the fibroblast metabolism in idiopathic pulmonary fibrosis","authors":"Noé Alvarado-Vasquez ,&nbsp;Claudia Rangel-Escareño ,&nbsp;Javier de Jesús Ramos-Abundis ,&nbsp;Carina Becerril ,&nbsp;María Cristina Negrete-García","doi":"10.1016/j.biopha.2024.117680","DOIUrl":"10.1016/j.biopha.2024.117680","url":null,"abstract":"<div><div>Idiopathic pulmonary fibrosis (IPF) has a high incidence and prevalence among patients over 65 years old. While its exact etiology remains unknown, several risk factors have recently been identified. Hypoxia is associated with IPF due to the abnormal architecture of lung parenchyma and the accumulation of extracellular matrix produced by activated fibroblasts. Exosomes play a crucial role in intercellular communication during both physiological and pathological processes, including hypoxic diseases like IPF. Recent findings suggest that a hypoxic microenvironment influences the content of exosomes in various diseases, thereby altering cellular metabolism. Although the role of exosomes in IPF is an emerging area of research, the significance of hypoxic exosomes as inducers of metabolic reprogramming in fibroblasts is still underexplored. In this study, we analyze and discuss the relationship between hypoxia, exosomal cargo, and the metabolic reprogramming of fibroblasts in the progression of IPF.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"181 ","pages":"Article 117680"},"PeriodicalIF":6.9,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142645323","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Monosaccharides improve symptoms of an animal model for type III galactosemia, through the activation of the insulin pathway","authors":"Patricia Lucas-Rodríguez ,&nbsp;Ana María Brokate-Llanos ,&nbsp;José Manuel Hernandez-Curiel ,&nbsp;Piedad del Socorro Murdoch ,&nbsp;Andrés Garzón ,&nbsp;Angel Carrión ,&nbsp;Manuel J. Muñoz","doi":"10.1016/j.biopha.2024.117677","DOIUrl":"10.1016/j.biopha.2024.117677","url":null,"abstract":"<div><div>Type III galactosemia is characterized by the inability to metabolize galactose due to deficiency of the UDP-galactose-4-epimerase (GALE) gene, which catalyzes the interconversion of UDP-Galactose and UDP-Glucose. Additionally, GALE interconverts UDP-N-Acetylgalactosamine and UDP-N-Acetylglucosamine. These four sugars are needed for glycosylation of biomolecules. GALE deletion is considered lethal, and all described patients carry hypomorphic mutations. Symptoms are diverse and can range from mild to severe, without effective treatment. We have previously generated a <em>Caenorhabditis elegans</em> model for type III galactosemia, which carries a hypomorphic mutation in the GALE gene homologue. In this model, we observed that the symptoms varied depending on the diet. The aim of this work is to identify which dietary metabolites might alleviate the symptoms of type III galactosemia. To identify the molecules responsible, we used a <em>C. elegans</em> model of type III galactosemia and a mouse model to test whether the respond to the treatment is conserved in mammals and thus could be a putative intervention in patients.</div><div>We found that high levels of monosaccharides in the diet is responsible for the beneficial effect in the <em>C. elegans</em> model. This intervention generates an increase of <em>gale-1</em> expression through activation of the insulin pathway which may explain the reduction of the symptoms in animals carrying hypomorphic mutations. The increase of the GALE gene expression after monosaccharides treatment is also conserved in mammals and if maintained in humans, monosaccharide treatment combined with monitorization of GALE expression could be included in the management of patients with type III galactosemia.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"181 ","pages":"Article 117677"},"PeriodicalIF":6.9,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142645311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibition of breast cancer growth with AN-329, a novel Hsp110 inhibitor, by inactivating p-STAT3/c-Myc axis","authors":"Junnan Li ,&nbsp;Ruizhe Gao ,&nbsp;Congke Zhao ,&nbsp;Honglin Xiang ,&nbsp;Xiangyang Le ,&nbsp;Xinyang Zhang ,&nbsp;Qinling Cai ,&nbsp;Lei He ,&nbsp;Qianbin Li ,&nbsp;Liqing Hu ,&nbsp;Hui Zou","doi":"10.1016/j.biopha.2024.117694","DOIUrl":"10.1016/j.biopha.2024.117694","url":null,"abstract":"<div><div>Breast cancer, a leading cause of cancer-related mortality in women, is characterized by its propensity for metastasis. Heat shock protein 110 (Hsp110), a molecular chaperone encoded by the <em>HSPH1</em> gene, has been implicated in cancer progression, including breast cancer, where it is upregulated and associated with worse outcomes. However, the role of Hsp110 in breast cancer pathogenesis and its potential as a therapeutic target have not been thoroughly investigated. This study utilized the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) database to analyze <em>HSPH1</em> gene expression in breast cancer and its correlation with tumor progression and survival. Furthermore, a comprehensive screen of the Specs database led to the identification of AN-329, a novel inhibitor that binds directly to the nucleotide-binding domain of Hsp110, neutralizing its chaperone activity and inhibiting breast cancer cell growth. AN-329 was validated in vitro for its antitumor efficacy and was found to regulate the cell cycle through the p-STAT3/c-Myc axis. This work suggests that AN-329 could be a promising lead for developing innovative therapeutic agents against breast cancer, warranting further research and potential clinical translation.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"181 ","pages":"Article 117694"},"PeriodicalIF":6.9,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142649993","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transplant of gut microbiota ameliorates metabolic and heart disorders in rats fed with a hypercaloric diet by modulating microbial metabolism and diversity","authors":"Betsy Anaid Peña-Ocaña ,&nbsp;Mayel Silva-Flores ,&nbsp;Toya Shotaro ,&nbsp;Leslie García-Gálvez ,&nbsp;Luz Hernández-Esquivel ,&nbsp;Diana Xochiquetzal Robledo-Cadena ,&nbsp;Diana Barrera-Oviedo ,&nbsp;Israel Pérez-Torres ,&nbsp;Oswaldo Tostado-Islas ,&nbsp;Toshinari Maeda ,&nbsp;José S. Rodríguez-Zavala ,&nbsp;Álvaro Marín-Hernández ,&nbsp;Rodolfo García-Contreras ,&nbsp;Ricardo Jasso-Chávez","doi":"10.1016/j.biopha.2024.117667","DOIUrl":"10.1016/j.biopha.2024.117667","url":null,"abstract":"<div><div>Metabolic syndrome (MS) is a cluster of metabolic disorders which have a tight correlation with dysbiosis of gut microbiota (GM) that have to be treated to avoid higher risks for health. In this work, probiotics obtained from healthy cultured GM were provided to rats with metabolic syndrome (MSR) as therapy in treating MS through the correction of dysbiosis. MSR showed obesity, high blood pressure, abnormal blood chemistry parameters and high heart rate respect to control rats (CNTR). Cultivated GM from feces of MSR in media favoring anaerobic species, showed dysbiosis as judged by differences in the 16S rRNA metabarcoding analysis and by affected intermediary metabolism (methane and SCFA production, nutrients consumption and enzyme activities) compared to CNTR. The metabarcoding analysis of cultured healthy GM identified 211 species, which were further transplanted alive in MSR once a week for 9 weeks. Thereafter, in transplanted MSR the excess of <em>Clostridium</em> and <em>Lactobacillus</em> diminished, while <em>Prevotella</em>, <em>Eubacterium</em>, <em>Faecalibacterium</em> and methanogens, among others increased, leading to the recovery of the microbial metabolic capacity. The presence of butyric acid-producing bacteria in the transplanted GM correlated with increased levels of anti-inflammatory cytokines. Therefore, transplanted MSR recovered the normal levels of weight, blood glucose, triglycerides and cholesterol as well as the heart function. Data suggested that the great diversity of species contained in the GM transplanted restored the microbial metabolism, consuming excessive nutrients and secondary metabolites produced by MS. The use of cultivated GM as probiotics may be a safer alternative for the treatment of different diseases.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"181 ","pages":"Article 117667"},"PeriodicalIF":6.9,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142640472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acute effects of L-DOPA/carbidopa/buspirone (Spinalon™) on rhythmic electrical activity of the lumbosacral spinal cord in cats","authors":"Mayra Moreno-Castillo ,&nbsp;Pierre A. Guertin ,&nbsp;Elias Manjarrez","doi":"10.1016/j.biopha.2024.117687","DOIUrl":"10.1016/j.biopha.2024.117687","url":null,"abstract":"<div><div>Discovered by Guertin and colleagues in 2004, Spinalon™ is a fixed-drug combination (L-DOPA, carbidopa, and buspirone) that can acutely induce temporary episodes of rhythmic locomotor-like activity in complete or near-complete spinal cord-injured (SCI) subjects. However, little is known about the mechanisms of action or the direct effects of Spinalon™ on neural elements of the central pattern generators (CPGs). Our study aims at characterizing the effects of Spinalon™ on electrical activity of the spinal cord in segmental areas known to contain key rhythmogenic elements of the CPGs (i.e., lumbosacral) for scratching and locomotion. We recorded spinal cord dorsum signals from decerebrate cats using a multielectrode array placed over the lumbosacral region. We found that a single intravenous injection of 100/25/7.5 mg/kg L-DOPA/carbidopa/buspirone (Spinalon™) specifically reduced the amplitude of electrical sinusoidal waves associated with fictive scratching and promoted the appearance of electrical sinusoidal-like waves occurring at frequencies compatible with fictive locomotion. These observations suggest a profound impact of Spinalon™ on the lumbosacral CPGs.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"181 ","pages":"Article 117687"},"PeriodicalIF":6.9,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142634464","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Magnetoresponsive liposomes applications in nanomedicine: A comprehensive review","authors":"Shayan Shahsavari ,&nbsp;Mohammad Behnam Rad ,&nbsp;Amirhossein Hajiaghajani ,&nbsp;Mohammadreza Rostami ,&nbsp;Fatemeh Hakimian ,&nbsp;Sina Jafarzadeh ,&nbsp;Masoud Hasany ,&nbsp;Joanna F. Collingwood ,&nbsp;Farhang Aliakbari ,&nbsp;Hamideh Fouladiha ,&nbsp;Hassan Bardania ,&nbsp;Daniel E. Otzen ,&nbsp;Dina Morshedi","doi":"10.1016/j.biopha.2024.117665","DOIUrl":"10.1016/j.biopha.2024.117665","url":null,"abstract":"<div><div>Safe and effective cancer therapy requires a suitable nanocarrier that can target particular sites, such as cancer cells, in a selective manner. With the tremendous growth in nanotechnology, liposomes, among various competing nanocarriers, have shown promising advances in cancer therapy. Magnetic nanoparticles and metal ions are wide-reaching candidates for conferring magnetic properties and for incorporation into liposomes. Combining liposomes with magnetic structures enables construction of magnetoresponsive liposomes, allowing stimuli-responsiveness to an alternating magnetic field, magnetic targeting, and tracking by magnetic resonance imaging, which could all occur in parallel. This review presents a comprehensive analysis of the practical advances and novel aspects of design, synthesis and engineering magnetoresponsive liposomes, emphasizing their diverse properties for various applications. Our work explores the innovative uses of these structures, extending beyond drug delivery to include smart contrast agents, cell labeling, biosensing, separation, and filtering. By comparing new findings with earlier studies, we showcase significant improvements in efficiency and uncover new potentials, setting a new benchmark for future research in the field of magnetoresponsive liposomes.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"181 ","pages":"Article 117665"},"PeriodicalIF":6.9,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142632114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacological in vitro profiling of Buddleja officinalis flower extracts in the context of dry eye disease","authors":"Alexander Areesanan ,&nbsp;Andreas Wasilewicz ,&nbsp;Benjamin Kirchweger ,&nbsp;Sven Nicolay ,&nbsp;Amy Zimmermann-Klemd ,&nbsp;Ulrike Grienke ,&nbsp;Judith M. Rollinger ,&nbsp;Carsten Gründemann","doi":"10.1016/j.biopha.2024.117685","DOIUrl":"10.1016/j.biopha.2024.117685","url":null,"abstract":"<div><h3>Background</h3><div>Dry eye disease (DED) is caused by inflammation on the ocular surface and insufficient quality or production of the tear film. Due to various harmful environmental conditions, a gradual increase of DED cases has been reported.</div></div><div><h3>Hypothesis/purpose</h3><div>This study aims for a comprehensive <em>in vitro</em> pharmacological and phytochemical profiling of two different <em>Buddleja officinalis</em> Maxim. extracts to assess their potential for the treatment of DED.</div></div><div><h3>Methods</h3><div>A hydroethanolic (BO-HE) and a lead-like enhanced (BO-LLE) <em>B. officinalis</em> extract were phytochemically characterized by UHPLC-UV-MS and UHPLC-ELSD analyses. Afterwards, the effects of either BO-HE or BO-LLE on <em>in vitro</em> dry eye models, including human corneal epithelial cell-transformed (HCE-T) cells, immortalized human meibomian gland epithelial cells (IHMGECs) and human leukemia monocytic (THP-1) cells, and Jurkat cells, were investigated.</div></div><div><h3>Results</h3><div>Both extracts exhibited strong anti-inflammatory properties with free radical scavenging activities and reduction of intracellular reactive oxygen species (ROS) in UVB-exposed HCE-T cells. Treatment with BO-HE or BO-LLE showed wound healing capacities. Moreover, both extracts differentially modulate mediator secretion in UVB-exposed HCE-T cells. In IHMGECs, the size of secreted lipid droplets was larger in BO-LLE treated cells. As for immune cells, a significant reduction in levels of TNF-α and IL-6 secretion by lipopolysaccharide (LPS)-exposed THP-1 cells was observed. Additionally, BO-LLE effectively inhibited intracellular calcium influx in Jurkat cells even at low concentrations.</div></div><div><h3>Conclusion</h3><div>The results of this study demonstrate pharmacological potential of <em>B. officinalis</em> flowers for the treatment of DED pathology with BO-LLE exerting a slightly more beneficial profile than BO-HE.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"181 ","pages":"Article 117685"},"PeriodicalIF":6.9,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142632709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reparative homing of bone mesenchymal stem cells induced by iMSCs via the SDF-1/CXCR4 axis for articular cartilage defect restoration","authors":"Gang Cheng ,&nbsp;Xulei Wang ,&nbsp;Feng Zhang ,&nbsp;Kang Wang ,&nbsp;Ying Li ,&nbsp;Tingting Guo ,&nbsp;Nuo Xu ,&nbsp;Wei Wei ,&nbsp;Shangxue Yan","doi":"10.1016/j.biopha.2024.117649","DOIUrl":"10.1016/j.biopha.2024.117649","url":null,"abstract":"<div><h3>Background</h3><div>The intrinsic healing ability of articular cartilage is poor after injury or illness, and untreated injury could lead to cartilage degeneration and ultimately osteoarthritis. iMSCs are derived from embryonic induced pluripotent stem cells and have strong therapeutic capabilities in the repair of cartilage defects, while the mechanism of action is unclear. The aim of this study is to clarify the repair mode of iMSCs on cartilage defects in rat knee joints, elucidate the chemotactic effect of iMSCs on autologous BMSCs in rats, and provide a basis for the treatment of cartilage defects and endogenous regeneration with iMSCs.</div></div><div><h3>Methods</h3><div>Based on the establishment of the rat cartilage defect model, the reparative effect of iMSCs on the rat cartilage defect was evaluated. The cartilage repair was evaluated by quantitative score, H&amp;E staining, Masson staining and Safranin-O staining, and the metabolic changes of iMSCs in the joint cavity were detected in vivo. The expression of SOX9, CD29, CD90, ColⅠ, ColⅡ, PCNA, SDF-1, and CXCR4 was detected by immunohistochemistry (IHC), IF, flow cytometry, respectively. After co-culturing iMSCs with BMSCs in vitro, the expression of CXCR4/SDF-1 on the cell membrane surface of BMSCs was detected by western blotting.; The level of p-Akt and p-Erk1/2 in total protein of BMSCs were detected by western blotting.</div></div><div><h3>Significance</h3><div>Our research results provide experimental evidence for the treatment of cartilage defects and endogenous regeneration with iMSCs; This also provides new ideas for the clinical treatment of cartilage defects using iMSCs.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"181 ","pages":"Article 117649"},"PeriodicalIF":6.9,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142633212","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}