Tissue & cell最新文献

{"title":"The Leydig organ of elasmobranchs: Shed light on an active and mysterious defense center with immunological characterization of its cells","authors":"Giampaolo Bosi ,&nbsp;Paolo Merella ,&nbsp;Emanuela Franchella ,&nbsp;Bahram Sayyaf Dezfuli ,&nbsp;Luisa Giari","doi":"10.1016/j.tice.2025.102755","DOIUrl":"10.1016/j.tice.2025.102755","url":null,"abstract":"<div><div>In elasmobranchs, blood cells originate from the thymus, spleen, and two organs associated with the gonads and esophagus: the epigonal and Leydig organs (LO), respectively. In the LO parenchyma, various granulocyte types, thrombocytes, and lymphocytes were observed, with notable species-specific diversity. Cells of the LO in the catshark <em>Galeus melastomus</em> were characterized using immunohistochemistry, immunofluorescence, and electron microscopy. Image analysis of sections treated with the anti-proliferative cell nuclear antigen antibody revealed that approximately 40 % of LO cells were in mitosis and approximately 15 % were myeloid progenitors positive for the anti-c-kit antibody. Additionally, a panel of 12 immunological markers revealed that 18.4 %, 17.8 %, 13.7 %, and 14.1 % of the LO section area was occupied by cells positive for anti-serotonin, interleukin-6, histamine, and immunoglobulin E-like receptor antibodies, respectively. Two main reactive cell types, mast cell and macrophage lineage, were revealed by co-localization image analysis using confocal microscopy. Ultrastructural observation identified granulocytes and macrophages as the main cell types. To our knowledge, this is the first report on the distinct patterns of LO cell populations and their morphological features, confirming granulopoietic role of the elasmobranch LO.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"93 ","pages":"Article 102755"},"PeriodicalIF":2.7,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143075605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The neuroprotective effect of elderberry diet on the tramadol-induced toxicity in the hippocampus of adult male rats","authors":"Keysan Sohrabi ,&nbsp;Ibrahim Mohammadzadeh ,&nbsp;Seyedeh Mah Sa Kiaeipour Siahkal ,&nbsp;Mohammad Javad Ebrahimi ,&nbsp;Maral Moafi ,&nbsp;Negin Adimi ,&nbsp;Sina Dolatshahi ,&nbsp;Amirreza Beirami ,&nbsp;Maral Hasanzadeh ,&nbsp;Alireza joudaki ,&nbsp;Soheil Taherpouran ,&nbsp;Siavash Parvardeh ,&nbsp;Gholam Hossein Meftahi ,&nbsp;Mohammadamin Sabbaghalvani ,&nbsp;Susan Roustaee ,&nbsp;Ghazal khanjari ,&nbsp;Haleh Hemmatparast ,&nbsp;Mojtaba Sani ,&nbsp;Meysam Hassani Moghaddam ,&nbsp;Abbas Aliaghaei","doi":"10.1016/j.tice.2025.102757","DOIUrl":"10.1016/j.tice.2025.102757","url":null,"abstract":"<div><div>Pain relievers such as tramadol are among the most commonly prescribed around the world. However, Long-term tramadol use has been shown to cause neurotoxicity, neuroinflammation, and cognitive impairment, which has limited its clinical use. Elderberry (EB), a plant extract widely recognized for its medicinal properties, is used in this study to investigate the effects of a plant-based diet on tramadol's adverse effects in the hippocampus region. The effects of EB oral diet on the devastating effects of tramadol on the hippocampus structure and function of 36 male albino rats were evaluated using behavioral, electrophysiological, and histological setups. Three groups (Control, Tramadol, and Tramadol+EB) were examined using behavioral, electrophysiological, and histological setups. The behavioral findings showed that the EB diet could improve most of the memory-related indices in Tramadol+EB compared to the Tramadol group. Regarding the fEPSP slope and population spike amplitude, these electrophysiological parameters returned to control levels in the Tramadol+EB group. Additionally, a decrease in caspase-3 expression was observed in hippocampal cells. While there was a reduction in astrogliosis in the Tramadol+EB group compared to the Tramadol group, no significant differences were noted in the morphological variations of astrocytes between the groups. In conclusion, although further studies are necessary to elucidate other aspects of EB's effects on the brain, it may be considered a potential neuroprotective agent in acute to sub-chronic tramadol exposure.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"93 ","pages":"Article 102757"},"PeriodicalIF":2.7,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143075612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular changes of cellular senescence in dental pulp stem cells during in vitro culture: A potential role of PSG4","authors":"Xiaolin Lyu ,&nbsp;Wenan Xu ,&nbsp;Jian Zhou ,&nbsp;Xiaohang Chen ,&nbsp;Wenjing Yi ,&nbsp;Leyi Chen ,&nbsp;Ziting Wang ,&nbsp;Songlin Wang ,&nbsp;Buling Wu","doi":"10.1016/j.tice.2025.102758","DOIUrl":"10.1016/j.tice.2025.102758","url":null,"abstract":"<div><div>Cellular senescence prevents the application of mesenchymal stem cells in tissue engineering and stem cell therapy. Effective regulation of senescence is the key to maintain the functional stability of mesenchymal stem cells and improve their clinical application. This study aims to explore the molecular mechanism changes in human dental pulp stem cells (hDPSCs) during replicative senescence, focusing on the potential role of pregnancy-specific glycoprotein (PSGs) family member PSG4 in modulating cellular senescence. RNA sequencing was performed on hDPSCs at different passages and with PSG4 overexpression to reveal changes in gene expression during the process. Gain- and loss-of-function studies suggested that PSG4 regulated cellular senescence. PSG4 expression levels were significantly elevated during cellular senescence and closely correlated with cell cycle regulation. This study provides new insights into the molecular mechanisms underlying of hDPSCs’ replicative senescence. PSG4 acts as a pivotal regulator of replicative senescence in hDPSCs by impacting cell cycle process.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"93 ","pages":"Article 102758"},"PeriodicalIF":2.7,"publicationDate":"2025-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143081144","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"EZH1-DNMT1 axis inhibits the expression of TFPI2 to promote osteogenic differentiation of periosteum-derived stem cells and accelerate fracture repair","authors":"Yang Liu,&nbsp;Lu Chen,&nbsp;Liang Chang,&nbsp;Shuren Wang","doi":"10.1016/j.tice.2025.102759","DOIUrl":"10.1016/j.tice.2025.102759","url":null,"abstract":"<div><h3>Background</h3><div>The periosteum lies in a dynamic environment with a niche of periosteum-derived stem cells (PDSCs) for their reparative needs. Here, we report that epigenetic repression of tissue factor pathway inhibitor 2 (TFPI2) mediates the osteogenic potential of PDSCs and the ensuing fracture repair.</div></div><div><h3>Methods</h3><div>Significantly overexpressed TFPI2 after fracture was screened using the GSE152677 dataset, and the expression of TFPI2 in bone tissues of post-fracture mice was verified by RT-qPCR and immunohistochemistry. Loss- and gain-of-function assays were conducted using adenoviruses. Primary mouse PDSCs were extracted, and their osteogenic potential was assessed using ALP staining, alizarin red staining, and western blot analysis. The epigenetic modifiers of TFPI2 were verified using ChIP-qPCR, Co-IP, and qMSP.</div></div><div><h3>Results</h3><div>TFPI2 expression was elevated after fracture, whereas enhancer of zeste homolog 1 (EZH1) expression was significantly downregulated. Inhibition of TFPI2 expression promoted fracture repair in mice, which was correlated with enhanced osteogenic differentiation of PDSCs. EZH1 repressed TFPI2 expression by modifying trimethylation of histone H3 at lysine 27 (H3K27me3). EZH1 promoted TFPI2 promoter DNA methylation by recruiting DNA-methyltransferase 1 (DNMT1), leading to transcriptional repression of TFPI2. Overexpression of DNMT1 and EZH1 significantly promoted recovery in fractured mice, which was reversed by inhibition of TFPI2.</div></div><div><h3>Conclusions</h3><div>These results suggest that artificial overexpression EZH1 mediates TFPI2 inhibition by recruiting DNMT1, promoting osteogenic differentiation of PDSCs to accelerate fracture repair.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"93 ","pages":"Article 102759"},"PeriodicalIF":2.7,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143075604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unlocking exosome therapeutics: The critical role of pharmacokinetics in clinical applications","authors":"Krishna Yadav ,&nbsp;Kantrol Kumar Sahu ,&nbsp;Sucheta ,&nbsp;Sunita Minz ,&nbsp;Madhulika Pradhan","doi":"10.1016/j.tice.2025.102749","DOIUrl":"10.1016/j.tice.2025.102749","url":null,"abstract":"<div><div>Exosomes are microscopic vesicles released by cells that transport various biological materials and play a vital role in intercellular communication. When they are engineered, they serve as efficient delivery systems for therapeutic agents, making it possible to precisely deliver active pharmaceutical ingredients to organs, tissues, and cells. Exosomes' pharmacokinetics, or how they are transported and metabolized inside the body, is affected by several factors, including their source of origination and the proteins in their cell membranes. The pharmacokinetics and mobility of both native and modified exosomes are being observed in living organisms using advanced imaging modalities such as in vitro-in vivo simulation, magnetic resonance imaging, and positron emission tomography. Establishing comprehensive criteria for the investigation of exosomal pharmacokinetic is essential, given its increasing significance in both therapy and diagnostics. To obtain a thorough understanding of exosome intake, distribution, metabolism, and excretion, molecular imaging methods are crucial. The development of industrial processes and therapeutic applications depends on the precise measurement of exosome concentration in biological samples. To ensure a seamless incorporation of exosomes into clinical practice, as their role in therapeutics grows, it is imperative to conduct a complete assessment of their pharmacokinetics. This review provides a brief on how exosome-based research is evolving and the need for pharmacokinetic consideration to realize the full potential of these promising new therapeutic approaches.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"93 ","pages":"Article 102749"},"PeriodicalIF":2.7,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143137638","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High expression of SERPINE1 and CTSL in keratinocytes in pressure injury caused by ischemia-reperfusion injury","authors":"Lexuan Bi ,&nbsp;Yaxin Liu ,&nbsp;Lei Zhang ,&nbsp;Xiaoli Zhang ,&nbsp;Dong Wang","doi":"10.1016/j.tice.2025.102746","DOIUrl":"10.1016/j.tice.2025.102746","url":null,"abstract":"<div><h3>Introduction</h3><div>Pressure Injury (PI) is a complex disease process which is influenced by multiple factors, among which ischemia-reperfusion (I/R) injury is closely related to the progression of PI. But its biomarkers are still unclearly. Understanding its physiological mechanisms and related molecular biomarkers is a key to developing effective prevention and therapeutic strategies.</div></div><div><h3>Methods</h3><div>This study through obtained the candidate genes of the differentially expressed genes (DEGs) from the PI rat model by transcriptome sequencing, PI single-cell sequencing database, and genes related to I/R injury from GeneCards database to analyze and screen prognostic related target genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genomes (KEGG) pathway analysis were performed using clusterProfiler package, and a protein-protein interaction (PPI) network was constructed to identify hub genes. The genes related to I/R injury were identified and analyzed using three machine learning algorithms. Then, the hub genes were evaluated using nomogram and receiver operating characteristic (ROC) curves, and validated using immunohistochemistry in the PI rat model.</div></div><div><h3>Results</h3><div>There were finally 7 candidate genes obtained from the intersection of the three datasets. GO and KEGG pathway analysis revealed that the DEGs were enriched in complement and coagulation cascades, and the keratinocyte differentiation is a significant factor. Then, two hub genes Serine protease inhibitor clade E member 1 (SERPINE1) and Cathepsin L (CTSL) were identified through three machine learning algorithms. The two hub genes were indicated had a high prognosis value by nomogram and ROC curves. SERPINE1 and CTSL both play crucial roles in vasculogenesis, coagulation and degradation of the extracellular matrix, which is essential for wound healing. The results of immunohistochemistry demonstrated that SERPINE1 and CTSL are significantly upregulated in skin tissue from PI caused by I/R injury, and their mRNA expression levels significantly correlate with PI outcomes.</div></div><div><h3>Conclusion</h3><div>According to our research we referred that the SERPINE1 and CTSL might be the potential biomarkers of PI.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"93 ","pages":"Article 102746"},"PeriodicalIF":2.7,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143048000","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Resilience in adversity: Exploring adaptive changes in cancer cells under stress","authors":"Taissa dos Santos Uchiya ,&nbsp;Helena Napoli da Cunha ,&nbsp;Matheus Correia Casotti ,&nbsp;Giulia de Souza Cupertino de Castro ,&nbsp;Gabrielle Feu Pereira ,&nbsp;João Augusto Diniz Moura ,&nbsp;André Manhães Machado ,&nbsp;Fabio Victor Vieira Rocha ,&nbsp;Lorena Souza Rittberg Mauricio ,&nbsp;Victor Alves Lopes ,&nbsp;Fellipe Pesente ,&nbsp;Giulia Maria Giacinti ,&nbsp;Francisco Felipe Coelho ,&nbsp;Elizeu Fagundes de Carvalho ,&nbsp;Iúri Drumond Louro ,&nbsp;Débora Dummer Meira","doi":"10.1016/j.tice.2025.102756","DOIUrl":"10.1016/j.tice.2025.102756","url":null,"abstract":"<div><h3>Objective</h3><div>Cancer cells undergo adaptive processes that favor their survival and proliferation when subjected to different types of cellular stress. These changes are linked to oncogenic processes such as genetic instability, tumor proliferation, therapy resistance, and invasion. Therefore, this study aimed to review studies that discuss possible morphological and genetic changes acquired by neoplastic cells under stressful conditions.</div></div><div><h3>Methods</h3><div>The articles used in this integrative review were searched on PubMed, Web of Science, CAPES, BVS and Scopus. Studies that discussed how cells undergo morphogenetic changes as an adaptive response to stress in cancer were included.</div></div><div><h3>Results</h3><div>This article reviewed 82 studies that highlighted multiple types of stress to which cancer can be subjected, such as oxidative, thermal and mechanical stress; glucose and other nutrients deficiency; hypoxia and chemotherapy. Neoplastic cells under stress can undergo adaptive changes that make it possible to overcome this obstacle. In this adaptive process, the acquisition of certain mutations implies cellular morphological changes such as Epithelial-Mesenchymal Transition, polyploidy, mitochondrial and cytoskeletal changes. These adaptive changes occur concomitantly with processes related to oncogenesis such as gene instability, tumor proliferation, resistance to therapy and invasion.</div></div><div><h3>Conclusions</h3><div>This study reveals that adaptations to cellular stress promote morphological and functional changes that accompany or accelerate oncogenesis. It has been revised how epithelial-mesenchymal transition, polyploidy and mitochondrial dysfunctions not only reinforce the survival of tumor cells in adverse environments, but also increase therapeutic resistance and invasive capacity. Also noteworthy are the contributions on genomic instability associated with stress and the potential of senescent cells in tumor heterogeneity, both as factors of tumor resistance and progression. These insights suggest new therapeutic targets and prognostic biomarkers, expanding the possibilities for more effective strategies to combat cancer.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"93 ","pages":"Article 102756"},"PeriodicalIF":2.7,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143047502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of smoking on oral mucosa: A cytological and cellular proliferation study","authors":"Magdi M. Salih ,&nbsp;Thamer A. Tamr ,&nbsp;Abdulhakeem S. Alamri ,&nbsp;Eman H. Khalifa","doi":"10.1016/j.tice.2025.102754","DOIUrl":"10.1016/j.tice.2025.102754","url":null,"abstract":"<div><h3>Background</h3><div>Cigarette smoking is known to induce various cellular changes and proliferative activities within the oral mucosa. This study compares the effects of smoking on cellular proliferation and cytological alterations using the AgNORs and Pap staining methods.</div></div><div><h3>Methods</h3><div>We performed statistical analyses to evaluate the mean AgNORs count in smokers and non- smokers. Additionally, we assessed the presence of reactive cellular changes in smokers using the Pap staining method. Cytological alterations, including inflammatory changes, were documented in both groups, and we focused on the prevalence of such changes in smokers.</div></div><div><h3>Results</h3><div>The mean AgNORs count was found to be 3.68 in smokers, which is consistent with marked reactive cellular changes. Inflammatory changes and reactive cellular changes, observed in 33.3 % and 59.3 % of cases, respectively, were significantly more prevalent in smokers. These findings suggest that smoking induces epithelial alterations, even in the absence of clinical symptoms, due to the physiochemical environment created by the elements in tobacco. This study also supports previous research indicating that cigarette smoking modifies cell growth control processes and increases cell proliferation in the oral mucosa.</div></div><div><h3>Conclusion</h3><div>Cigarette smoking significantly elevates cellular proliferation, as indicated by the increased AgNORs counts in smokers. The combined use of Pap staining and AgNORs counting proved effective at detecting cellular proliferation before clinical symptoms appeared in smokers. Additional research is recommended to assess the impact of factors such as age, sex, and daily cigarette consumption on different oral regions. Comparative studies involving other proliferation indicators, such as Ki-67 or molecular testing, are also advised.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"93 ","pages":"Article 102754"},"PeriodicalIF":2.7,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143048002","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acceleration of bone healing by a growth factor-releasing allo-hybrid graft","authors":"Houman Parsaei ,&nbsp;Enam Alhagh Charkhat Gorgich ,&nbsp;Abdollsamad Eateghadi ,&nbsp;Narjes Tavakoli ,&nbsp;Marcus Ground ,&nbsp;SeyedJamal Hosseini","doi":"10.1016/j.tice.2025.102740","DOIUrl":"10.1016/j.tice.2025.102740","url":null,"abstract":"<div><h3>Introduction</h3><div>Human amniotic membrane (hAM) has a highly biocompatible natural scaffold that is abundant in several extracellular matrix (ECM) components, including but not limited to platelet-derived growth factor (PDGF), transforming growth factor (TGF), and fibroblast growth factor (FGF). In our study, we have focused on a mixture of hAM and demineralized bone matrix (DBM) as an allo-hybrid graft to deliver it into the site of bone defect to decrease bone remodeling time.</div></div><div><h3>Methods</h3><div>Allo-hybrid grafts were prepared by coating the jelly made of decellularized and lyophilized hAM (AMJ) on the surface of DBM and subsequently underwent in vitro studies, such as alkaline phosphatase activity, MTT assay, and SEM analysis. Twenty-four male rats were included in the study, and after creating calvarial defects, rats were divided into four groups: DBM implanted, allo-hybrid implanted, AMJ injection, and a negative control (NC). Bone regeneration was assessed using computed tomography (CT scan) and histological analysis at 1, 2, and 3 months after surgery.</div></div><div><h3>Results</h3><div>CT scan analysis clearly showed improved new bone growth in the allo-hybrid group compared to the NC group. Also, the Hounsfield unit of the allo-hybrid group (774.91 ± 47.8) after 90 days confirms CT scans. Histological staining revealed immature bone in allo-hybrid and DBM groups, along with the creation of a medullary cavity and bone marrow two months after surgery. Three months after surgery, the allo-hybrid group showed signs of new, mature bone, while no sign of healing could be seen in the NC group at any time points. Over a 90-day period, the allo-hybrid group recovered the bone defect area near 90 %. It is relatively twice as much as AMJ group.</div></div><div><h3>Conclusion</h3><div>Histological properties of bone defects and bone regeneration can both be improved by allo-hybrid grafts coated with AMJ.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"93 ","pages":"Article 102740"},"PeriodicalIF":2.7,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143047981","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effects of autophagy-modifying drugs chloroquine and lithium on the skin melanoma microenvironment","authors":"Iuliia Taskaeva ,&nbsp;Anastasia Shatruk ,&nbsp;Igor Ivanov ,&nbsp;Nataliya Bgatova","doi":"10.1016/j.tice.2025.102753","DOIUrl":"10.1016/j.tice.2025.102753","url":null,"abstract":"<div><h3>Background</h3><div>Skin melanoma is a highly metastatic cancer with an increasing global incidence. Despite advancements in immunotherapy, new treatment strategies based on tumor biology are essential for improving outcomes and developing novel therapies. Autophagy plays a critical role in melanoma cell metabolism and affects the tumor microenvironment (TME). This study aims to evaluate the impact of autophagy-modifying drugs on extracellular matrix (ECM) remodeling and changes in the TME cytokine profile.</div></div><div><h3>Methods</h3><div>Immunohistochemical analysis was performed using paraffin-embedded tumor samples of B16-bearing C57BL/6 mice to assess the effects of autophagy-modifying drugs, lithium or chloroquine, on the matrix degradation proteins, their main substrates, lysyl oxidase and collagen fibril formation-associated proteins. The cytokine profile of the tumor was defined to estimate the effect of autophagy-modifying drugs on the TME.</div></div><div><h3>Results</h3><div>Chloroquine and lithium administration caused a decrease in the expression of matrix metalloproteinases, and chloroquine contributed to the accumulation of collagen type I. Moreover, chloroquine dramatically decreased LOX levels. Decorin expression levels were reduced in tumors of mice treated with chloroquine or lithium. Significant changes in the cytokine profile were detected after chloroquine treatment, with increased expression of IL1, IL4, IL6, M-CSF, TGFβ2 and TNF-α genes observed in the tumors.</div></div><div><h3>Conclusion</h3><div>Autophagy-modifying drugs affect the TME, in particular, chloroquine promotes ECM remodeling, accumulation of collagen type I deposits and probably the formation of abnormal collagen fibril structures. In addition, chloroquine-treated mice showed high expression of pro-tumorigenic cytokines and growth factors, such as IL1, IL4, IL6, M-CSF, TGFβ2 and TNF-α in the TME.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"93 ","pages":"Article 102753"},"PeriodicalIF":2.7,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143047525","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}