Acta histochemicaPub Date : 2025-06-23DOI: 10.1016/j.acthis.2025.152274
Lei Yang , Yue Zhang , Jiansong Wu , Lei Wang , Shan Liu , Li Zhou , Jigang Zhang , Chengxin Li
{"title":"Calcipotriol inhibits the proliferation of psoriasis HaCaT cells by activating the ferroptosis pathway","authors":"Lei Yang , Yue Zhang , Jiansong Wu , Lei Wang , Shan Liu , Li Zhou , Jigang Zhang , Chengxin Li","doi":"10.1016/j.acthis.2025.152274","DOIUrl":"10.1016/j.acthis.2025.152274","url":null,"abstract":"<div><div>Calcipotriol is a well-established treatment for psoriasis and other dermatological conditions. This study aimed to investigate whether calcipotriol exerts its therapeutic effects through ferroptosis and to elucidate its underlying molecular mechanisms using bioinformatics and cellular experiments. Differentially expressed genes (DEGs) and their functional enrichment were analyzed in psoriatic skin lesions using bioinformatics. A lipopolysaccharide (LPS)-induced HaCaT cell model was established to simulate psoriatic inflammation. The effects of calcipotriol at various concentrations and time points on HaCaT cell proliferation, apoptosis, and expression of key markers were assessed. Additionally, ferrostatin-1 (a ferroptosis inhibitor) and RSL3 (a ferroptosis inducer) were used to evaluate ferroptosis-related changes, including cell proliferation, apoptosis, reactive oxygen species (ROS) levels, glutathione (GSH) content (via ELISA), and protein expression of GPX4 and Ki-67 (via Western blot). Bioinformatics analysis revealed significant differential expression of ferroptosis-related genes, such as GPX4 and SLC7A11, in psoriatic lesions. Calcipotriol treatment inhibited HaCaT cell proliferation in a dose- and time-dependent manner, elevated ROS levels, and reduced GSH, GPX4, and Ki-67 expression. These effects were reversed by ferrostatin-1, which restored antioxidant defenses and cell viability. Conversely, RSL3 increased ROS levels and partially negated the protective effects of ferrostatin-1. These findings suggest that calcipotriol regulates ferroptosis-related gene expression and inhibits keratinocyte proliferation through induction of oxidative stress and ferroptosis, offering new insights into its mechanism of action in psoriasis treatment.</div></div>","PeriodicalId":6961,"journal":{"name":"Acta histochemica","volume":"127 3","pages":"Article 152274"},"PeriodicalIF":2.3,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144338776","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}
Acta histochemicaPub Date : 2025-06-11DOI: 10.1016/j.acthis.2025.152273
Feige Nian , Linfeng Guo , Zhangli Fei , Mingfeng Yang , Lihong Chen , Ye Zhang , Bin Zhang , Yezhou Qian , Zhufeng Zhang
{"title":"AARS1-mediated Osterix lactylation promotes its transcriptional activity during osteoblast differentiation","authors":"Feige Nian , Linfeng Guo , Zhangli Fei , Mingfeng Yang , Lihong Chen , Ye Zhang , Bin Zhang , Yezhou Qian , Zhufeng Zhang","doi":"10.1016/j.acthis.2025.152273","DOIUrl":"10.1016/j.acthis.2025.152273","url":null,"abstract":"<div><div>AARS1 is a newly reported lactyl-transferase that plays vital roles in tumorigenesis and innate immune response. However, the function of AARS1-mediated lactylation in osteoblast differentiation is still unclear. Here, we found that silencing of AARS1 impaired the ALP activity and formation of mineralized nodules during osteoblast differentiation. Additionally, our findings demonstrated that AARS1 catalyzed lactylation of Osterix (Osx), a crucial transcription factor involved in the differentiation process of osteoblast cells. Lactylation of Osx increased its binding to target genes and promoted the interaction between Osx and WDR5, facilitating H3K4 tri-methylation on downstream target genes. This in turn enhanced the expression of Osx target genes and osteoblast differentiation. In summary, our study revealed a novel role of AARS1-mediated Osx lactylation during osteoblast differentiation.</div></div>","PeriodicalId":6961,"journal":{"name":"Acta histochemica","volume":"127 3","pages":"Article 152273"},"PeriodicalIF":2.3,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144253587","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}
Acta histochemicaPub Date : 2025-06-06DOI: 10.1016/j.acthis.2025.152272
Anthea Miller , Giorgia Pia Lombardo , Laura Spiccia , Valentina Natale , Alba Migliorato , Marek Bednarski , Małgorzata Iciek , Anna Bilska-Wilkosz , Mateusz Sablik , Eugenia Rita Lauriano , Magdalena Kotańska , Simona Pergolizzi
{"title":"Characterization of immune cells in the rat intestinal mucosa and liver involved in inflammation caused by LPS and evaluation of the effects of N-acetylcysteine and disulfiram (well-known sulfur drugs) for this inflammation","authors":"Anthea Miller , Giorgia Pia Lombardo , Laura Spiccia , Valentina Natale , Alba Migliorato , Marek Bednarski , Małgorzata Iciek , Anna Bilska-Wilkosz , Mateusz Sablik , Eugenia Rita Lauriano , Magdalena Kotańska , Simona Pergolizzi","doi":"10.1016/j.acthis.2025.152272","DOIUrl":"10.1016/j.acthis.2025.152272","url":null,"abstract":"<div><div>Lipopolysaccharide (LPS)-induced inflammation is an experimental rat model often used as a tool for testing new drugs as candidates for treating various diseases associated with inflammation. New methods now allow for precise imaging of tissues and changes induced by various factors. To increase knowledge about LPS-induced inflammation and promote strategies for investigating new therapies, this study aims to characterize immune cells involved in inflammation in the rat intestinal mucosa and liver and to evaluate the therapeutic effect of two well-known sulfur drugs N-acetylcysteine (NAC) and disulfiram (DSF) on this model LPS was administered intraperitoneally to rats once a day, for 10 days. NAC and DSF were administered 5 h after LPS. At the end of experiment, animals were euthanized, and the intestine and liver were collected. The immune cells of the intestinal mucosa and liver were characterized with the following antibodies: Toll-like receptors (TLR2 and TLR4), smooth muscle alpha-actin (α-SMA), major histocompatibility complex II (MHC-II), and serotonin (5-HT). In samples obtained from inflamed rat intestinal mucosa, it was possible to detect TLR2-positive and TLR4-positive cells, and numerous α-SMA-positive cells, indicating an inflammatory state. Furthermore, an increase in serotonin positive neuroendocrine cells compared to normal was demonstrated, which could be associated with intestinal inflammation. The number of these positive cells was much smaller in the samples derived from animals treated with NAC or DSF, suggesting anti-inflammatory action of these drugs. In the inflamed rat liver, several immune cells positive for these antibodies were observed and NAC or DSF decreased the amount of these positive cells. In conclusion, this study shows that bacterial LPS can activate various innate immune system cell populations, such as dendritic cells, neutrophils, Kupffer cells, myofibroblasts and enterocytes. Moreover, this study demonstrates the beneficial effects on NAC and DSF in alleviating inflammation and relieving tissue fibrosis in the LPS-induced inflammation in the rat intestinal mucosa and liver.</div></div>","PeriodicalId":6961,"journal":{"name":"Acta histochemica","volume":"127 3","pages":"Article 152272"},"PeriodicalIF":2.3,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144223494","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}
Acta histochemicaPub Date : 2025-05-24DOI: 10.1016/j.acthis.2025.152270
Wanting Zhang , Quanjiang Li , Rui Tian , Zhujie Deng , Ronghui Sun , Xiubin Kuang , Jun Peng , Bin Xie , Chen Huang , Zhengqiang Yuan
{"title":"Exosomal delivery of AZD5582 to overcome TRAIL resistance as an optimal therapy against triple-negative breast cancer","authors":"Wanting Zhang , Quanjiang Li , Rui Tian , Zhujie Deng , Ronghui Sun , Xiubin Kuang , Jun Peng , Bin Xie , Chen Huang , Zhengqiang Yuan","doi":"10.1016/j.acthis.2025.152270","DOIUrl":"10.1016/j.acthis.2025.152270","url":null,"abstract":"<div><div>Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer that lacks effective targeted therapies mainly due to drug resistance. Therefore, there is an urgent need to develop highly effective therapeutic strategies for TNBC. Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) selectively induces apoptosis in transformed and cancerous cells, indicating its potential for anti-cancer therapy. Unfortunately, the clinical trials of recombinant TRAIL (rTRAIL) had actually failed due to the very common TRAIL resistance in cancers. Exosomal delivery of TRAIL (EV-T) has been shown to greatly improve the cytotoxicity of TRAIL. Moreover, the TRAIL resistance was closely correlated with the upregulation of inhibitors of apoptosis proteins (IAPs) in cancer cells. As a potent antagonist of IAPs, AZD5582 (AZD) was previously shown to drastically sensitize TRAIL response. Herein, we hypothesize that AZD may be loaded into EV-T for co-delivery of AZD and TRAIL to make a synergistic combination anticancer therapy against TNBC. First, TRAIL-expressing mesenchymal stem cells (MSCs) were used to prepare EV-Ts. Then, AZD was loaded into EV-T by ultrasound to prepare the composite nanodrug AZD@EV-T. EV encapsulation significantly improved AZD stability and cellular delivery efficiency, leading to the synergistically augmented cytotoxicity and apoptosis induction in both breast and kidney cancer cell lines, whilst sparing the normal MSCs. The potential mechanisms underlying the synergism appeared to be associated with the concomitant upregulation of death receptor 5 (DR5) and expressional suppression of various anti-apoptotic factors. Importantly, the AZD@EV-T therapy triggered strikingly enhanced growth inhibition and apoptosis in the subcutaneously established BT549 xenograft tumors, consequently leading to the complete tumor regression. It also demonstrated significant potential for treating kidney cancer in A498 kidney tumor organoids. Together, AZD@EV-T effectively overcomes TRAIL resistance and may represent a highly effective and innovative anticancer therapy for both TNBC and kidney cancers.</div></div>","PeriodicalId":6961,"journal":{"name":"Acta histochemica","volume":"127 3","pages":"Article 152270"},"PeriodicalIF":2.3,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144131386","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":"Lysophosphatidic acid (LPA) receptor signaling enhances malignant potential in highly migratory lung cancer cells under hypoxic conditions","authors":"Moemi Tamura, Miwa Takai, Mao Yamamoto, Narumi Yashiro, Anri Taniguchi, Yuka Kusumoto, Shion Nagano, Nanami Shimomura, Toshifumi Tsujiuchi","doi":"10.1016/j.acthis.2025.152268","DOIUrl":"10.1016/j.acthis.2025.152268","url":null,"abstract":"<div><div>Hypoxia contributes to tumor progression, promoting cancer cell motility, invasion and metastasis. Lysophosphatidic acid (LPA) receptors are implicated in the pathogenesis of cancer. In this study, we investigated the role of LPA receptor signaling in modulating malignant behavior under hypoxic conditions (1 % O<sub>2</sub>) in lung cancer cells. We generated highly migratory A549-R12 cells from the parental lung cancer A549 cells for this purpose. <em>LPAR1</em> and <em>LPAR2</em> expression levels were lower in both A549 and A549-R12 cells cultured at 1 % O<sub>2</sub> compared to those cultured at 21 % O<sub>2</sub>, while <em>LPAR3</em> expression remained unchanged between the two cell lines. Cell motility increased in both A549 and A549-R12 cells cultured at 1 % O<sub>2</sub>. Notably, A549-R12 cells exhibited greater motility under 1 % O<sub>2</sub> conditions than A549 cells. Treatment with AM966 (an LPA<sub>1</sub> antagonist) and (2S)-OMPT (an LPA<sub>3</sub> agonist) further increased the motility of A549-R12 cells, while GRI-977143 (an LPA<sub>2</sub> agonist) decreased their motility. Moreover, the invasion activity of A549-R12 cells was higher than that of A549 cells, with 1 % O<sub>2</sub> conditions significantly enhancing A549-R12 cell invasion. AM966 and (2S)-OMPT stimulated, whereas GRI-977143 inhibited, the invasion of A549-R12 cells. In the presence of LPA, cell viability to cisplatin (CDDP) was higher in A549-R12 cells cultured at both 21 % and 1 % O<sub>2</sub> compared to A549 cells. These results suggest that LPA receptor signaling plays a key role in regulating malignant progression in highly migratory lung cancer cells under hypoxic conditions.</div></div>","PeriodicalId":6961,"journal":{"name":"Acta histochemica","volume":"127 3","pages":"Article 152268"},"PeriodicalIF":2.3,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144123613","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}
Acta histochemicaPub Date : 2025-05-19DOI: 10.1016/j.acthis.2025.152269
Kairan Yang , Ting Xu , Chengkang Lin , Zuisu Yang , Haiyan Lyu , Falei Yuan
{"title":"Non-specific background in immunoglobulin G staining can be effectively eliminated using heating or a catalase inhibitor","authors":"Kairan Yang , Ting Xu , Chengkang Lin , Zuisu Yang , Haiyan Lyu , Falei Yuan","doi":"10.1016/j.acthis.2025.152269","DOIUrl":"10.1016/j.acthis.2025.152269","url":null,"abstract":"<div><div>Immunoglobulin G (IgG) staining is a widely used method for assessing blood-brain barrier (BBB) integrity. However, significant non-specific binding is often observed in many studies, which can interfere with the accurate interpretation of results. In this study, the horseradish peroxidase (HRP)-based polymer method and the streptavidin-biotin complex (SABC) method were used to perform IgG staining. The effects of hydrogen peroxide, heating, and a catalase inhibitor on reducing background staining were evaluated in brain sections from untreated mice and those subjected to middle cerebral artery occlusion (MCAO). The results showed that immunohistochemistry without hydrogen peroxide pretreatment still produced minimal background in paraffin-embedded sections. However, IgG staining with hydrogen peroxide pretreatment led to substantial background in vibratome sections. Compared to the SABC method, a mixture of the catalase inhibitor 3-amino-1,2,4-triazole and hydrogen peroxide reduced background staining by 35.4 % ± 5.7 % in the cortex of untreated mouse brains and by 36.9 % ± 1.8 % in the contralateral cortex of MCAO mice when using the polymer method. Additionally, heating at 75°C was sufficient to eliminate non-specific binding in brain sections from both untreated and MCAO mice. Hydrogen peroxide pretreatment alone was ineffective in removing background staining in brain sections from either untreated or MCAO mice. In summary, this study demonstrates that hydrogen peroxide pretreatment is effective in reducing background only when combined with a catalase inhibitor but is unnecessary when the tissue is heated. Heating is a simple and effective method for removing the IgG staining background when detecting BBB leakage.</div></div>","PeriodicalId":6961,"journal":{"name":"Acta histochemica","volume":"127 3","pages":"Article 152269"},"PeriodicalIF":2.3,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144084107","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}
Acta histochemicaPub Date : 2025-05-10DOI: 10.1016/j.acthis.2025.152260
Crystal Brown , Emily Stidham , Elly Beck , Ali Eickhoff , Brianna Hill , Kalyani Nair , Craig Cady
{"title":"Quantifying mechanical, proliferation, and migrational properties of bulk ovarian cancer cells and ovarian cancer stem cells","authors":"Crystal Brown , Emily Stidham , Elly Beck , Ali Eickhoff , Brianna Hill , Kalyani Nair , Craig Cady","doi":"10.1016/j.acthis.2025.152260","DOIUrl":"10.1016/j.acthis.2025.152260","url":null,"abstract":"<div><div>There are a limited number of studies analyzing ovarian cancer stem cell properties. The goal of this study was to analyze the mechanical and migrational properties of ovarian cancer stem cells with the well-researched bulk ovarian cancer cells. Through the use of atomic force microscopy (AFM), the mechanical properties of both cell types were gathered. In preparation for AFM analysis, an optimal fixation method was developed and performed on the cells. AFM analysis provided mechanical properties for both cell types, including cellular stiffness, maximum adhesion force, surface area, and mean surface roughness. Cell proliferation and transwell migration assays were assessed to determine the aggressiveness of both cancer cell types. A clear trend between both cell types was expected for the mechanical and potential aggression properties. The data from both analyses were used to create a baseline for migration, proliferation, and mechanical properties of ovarian cancer stem cells and bulk ovarian cancer cells. Further studies will assess if these properties are impacted by chemotherapy exposure.</div></div>","PeriodicalId":6961,"journal":{"name":"Acta histochemica","volume":"127 2","pages":"Article 152260"},"PeriodicalIF":2.3,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143931803","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}