Journal of Molecular Histology最新文献

{"title":"Shentong Zhuyu decoction ameliorates postherpetic neuralgia in rats by regulating cAMP/PKA/p-CREB signaling","authors":"Ying Zhu,&nbsp;Jin Tao,&nbsp;Tao Zeng,&nbsp;Changwen Wang","doi":"10.1007/s10735-025-10632-y","DOIUrl":"10.1007/s10735-025-10632-y","url":null,"abstract":"<div><p>Postherpetic neuralgia (PHN) is a debilitating chronic pain condition characterized by allodynia and hyperalgesia. Shengtong Zhuyu decoction (STZYD), a traditional Chinese medicine formula used clinically for pain associated with arthralgia syndromes and blood stasis obstructing the collaterals, was investigated for its potential role and mechanism in alleviating PHN. PHN was induced in male Sprague-Dawley rats via intraperitoneal injection of resiniferatoxin (RTX). STZYD was administered intragastrically to RTX-treated rats for 14 consecutive days. Its chemical components were identified using UHPLC-MS/MS. Analgesic efficacy was assessed by measuring mechanical paw withdrawal threshold and thermal paw withdrawal latency. The expression level of TRPV1 (a nociceptor and heat sensor) was analyzed using western blotting and immunofluorescence staining. ELISA was used to measure the levels of proinflammatory cytokines (IL-6, IL-1β, and TNF-α). Apoptosis was detected via TUNEL staining and western blotting. Underlying molecular mechanisms were evaluated using western blotting and immunohistochemistry. STZYD alleviated increased mechanical withdrawal threshold and thermal withdrawal latency and reducing TRPV1 levels in RTX-induced PHN rats. STZYD downregulated the levels of proinflammatory cytokines and pro-apoptotic proteins, reduced the number of TUNEL-positive cells, and upregulated the levels of anti-apoptotic proteins in RTX-induced PHN rats. Moreover, STZYD downregulated cAMP, PKA, and BNDF protein levels and inhibited CREB phosphorylation in RTX-induced PHN rats. Pharmacological activation of PKA by 8-Br-cAMP counteracted the protective effect of SDZYD in PHN rats. STZYD ameliorates RTX-induced mechanical allodynia and thermal hyperalgesia in rats by suppressing inflammation and DRG cell apoptosis through the inhibition of the cAMP/PKA/p-CREB signaling axis.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 6","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145342646","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":"Melatonin modulates SHH/GLI3 signaling and placental angiogenesis to counter acrylamide embryotoxicity","authors":"Reyhane Vardiyan,&nbsp;Daniyal Ezati,&nbsp;Mehdi jalali,&nbsp;Farzaneh Vafaee,&nbsp;Shabnam Mohammadi","doi":"10.1007/s10735-025-10624-y","DOIUrl":"10.1007/s10735-025-10624-y","url":null,"abstract":"<div><p>Acrylamide (ACR), a prevalent dietary toxicant formed in thermally processed foods via the Maillard reaction, is known to cross the placental barrier. While ACR-induced reproductive and developmental toxicity has been reported, the protective role of melatonin (MTN) via modulation of the <i>SHH/GLI3</i> signaling pathway remains unclear. Pregnant Balb/c mice were divided into three groups (n = 6/group): control (distilled water), ACR (50 mg/kg/d), and ACR (50 mg/kg/d) + MTN (10 mg/kg/d), treated orally from gestational day (GD) 3.5 to GD 13.5. Placentas and embryos were collected for analysis. Oxidative stress (MDA levels), VEGF expression, and <i>SHH/GLI3</i> pathway activity were assessed using immunohistochemistry and qRT-PCR. ACR exposure induced significant embryotoxicity, manifested as a 34% reduction in fetal weight (1.60 ± 0.09 g vs. 1.88 ± 0.14 g in controls, <i>p</i> &lt; 0.001) and a 46.2% reduction in fetal crown-rump length (0.7 ± 0.08 cm vs. 1.1 ± 0.1 cm, <i>p</i> &lt;  0.001). MTN co-treatment significantly ameliorated these growth restrictions. IHC analysis revealed that ACR significantly reduced SHH protein expression in the embryonic intestine and liver (<i>p</i> &lt; 0.01), while it increased GLI3 protein levels (<i>p</i> &lt; 0.01). MTN effectively normalized the expression of both proteins. At the molecular level, ACR downregulated <i>SHH</i> expression (<i>p</i> &lt;  0.001) and upregulated <i>GLI3</i> (<i>p</i> &lt;  0.01), which were reversed by MTN. ACR exposure significantly increased oxidative stress (105% increase in placental MDA, <i>p</i> &lt;  0.001) and reduced placental VEGF expression by 69.3% (<i>p</i> &lt;  0.0001), both of which were significantly mitigated by MTN co-treatment. These integrated findings demonstrate that MTN exerts potent antioxidative and cytoprotective effects by mitigating ACR-induced oxidative stress, restoring <i>SHH/GLI3</i> protein and gene expression, preserving VEGF-mediated placental angiogenesis, and preventing morphological defects. Our results underscore MTN’s therapeutic potential in counteracting ACR-induced teratogenicity and supporting healthy organogenesis.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 6","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145290563","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":"Exosomes from hypoxic pre-treated BMSCs protect against lipopolysaccharide-induced acute lung injury via delivery of circ-LRP6","authors":"Liming Xu,&nbsp;Junping Guo,&nbsp;Yingge Xu,&nbsp;Yueliang Zheng","doi":"10.1007/s10735-025-10626-w","DOIUrl":"10.1007/s10735-025-10626-w","url":null,"abstract":"<div><p>The role of circular RNAs (circRNAs) derived from exosomes of mesenchymal stem cells in acute lung injury (ALI) is poorly understood. This study aimed to determine whether exosomal circRNAs can influence ALI and to uncover the underlying mechanisms. Bone marrow mesenchymal stem cells (BM-MSCs) were pretreated under hypoxic or normoxic conditions, from which exosomes were extracted (normoxic BM-MSC-derived exosomes (Nor Exo) and hypoxic BM-MSC-derived exosomes (Hypo Exo). To assess their in vitro effects on ALI, lipopolysaccharide (LPS)-treated MLE-12 cells were incubated with these exosomes. An ALI mouse model was established through airway perfusion with LPS, and exosomes were administered via the tail vein to evaluate their in vivo effects. The results showed that blocking exosome production could reverse the protective effect of the BM-MSC supernatant on LPS-induced injury in vitro. The exosomes attenuated LPS-induced ALI, with Hypo Exo demonstrating a more pronounced therapeutic effect than Nor Exo, both in vitro and in vivo. Additionally, a higher level of <i>circ-LRP6</i> was detected in Hypo Exo compared with that in Nor Exo. Mechanistically, <i>circ-LRP6</i> was found to regulate Claudin 4 levels in the context of ALI. These findings provide new insights into the potential of exosomal <i>circ-LRP6</i> as a treatment for ALI.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 6","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145284475","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":"A prognostic model for gastric cancer constructed by multiple machine learning algorithms","authors":"Xueli Yang,&nbsp;Xu Huang,&nbsp;Wang Ying,&nbsp;Tao Deng,&nbsp;Jun Zhang,&nbsp;Qianshan Ding","doi":"10.1007/s10735-025-10629-7","DOIUrl":"10.1007/s10735-025-10629-7","url":null,"abstract":"<div><p>Gastric cancer (GC) is a highly heterogeneous disease that requires highly accurate prognostic models. Machine learning is a powerful tool for identifying predictive biomarkers and developing prognostic models. Here, we aim to integrate bioinformatics and machine learning algorithms to construct a risk model to predict prognosis of GC patients. Transcriptome data and clinical information of GC patients were obtained from the Cancer Genome Atlas (TCGA) database. Microarray data (GSE84437 and GSE26253) were obtained from the Gene Expression Omnibus (GEO) database. Univariate Cox regression analysis was used to screen prognostic genes. The risk genes closely related to prognosis were screened by machine learning algorithms and the risk score was calculated. Kaplan-Meier survival curve, time-dependent receiver operating characteristic (ROC) curve, univariate and multivariate Cox regression analysis were used to verify the validity of the risk model. The protein expression of hub genes in GC tissues was evaluated by immunohistochemical staining. 7 hub genes (CGB5, FEM1A, MATN3, ZNF101, MARCKS, BRI3BP and APOD) were identified and correlated with GC prognosis. A high-precision risk model based on random survival forest (RSF) and generalized boosted regression modelling (GBM) was constructed using these 7 hub genes. The risk model has good predictive ability for GC patients’ prognosis, and the risk score could be used as an independent prognostic factor for GC. In addition, the protein expression levels of CGB5, MATN3, MARCKS and APOD in GC tissues were significantly higher than those in normal tissues, and correlated with the pathological characteristics of GC patients. The risk model composed of 7 hub genes can accurately evaluate the prognosis of GC patients, which may contribute to the precise and personalized treatment of GC patients.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 6","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145284477","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":"Oxytocin receptor expression in developing mouse gonads and its modulation by high-dose folic acid","authors":"Hakan Sahin,&nbsp;Fidan Pashayeva,&nbsp;Gozde Erkanli Senturk","doi":"10.1007/s10735-025-10621-1","DOIUrl":"10.1007/s10735-025-10621-1","url":null,"abstract":"<div><p>The oxytocin receptor (OTR) is known to be expressed in various organs, including the adult reproductive system. However, its expression in developing gonads has not yet been reported. This study investigates OTR expression in the ovaries and testes during critical developmental stages, specifically embryonic day 13.5 (E13.5), embryonic day 18.5 (E18.5), and postnatal day 14 (P14). According to our findings, both developing ovaries and testes exhibited OTR expression, including in immature follicle and Sertoli cells. OTR-expressing cells increased in the developing ovary, while a decrease was observed in the postnatal testis. In addition, our results showed that a high dose folic acid (FA) diet affected the number of OTR-expressing cells in developing gonads, particularly during the later stages of embryogenesis. These findings suggest that OTR may play a role in gonadal development and that its expression is influenced by sex. Furthermore, changes in folic acid supplementation may interfere with this developmental process.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 6","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145284479","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":"Fermentation of Panax ginseng C.A. Meyer extract with lactic acid bacteria exerts hepatoprotective effects via activating the NRF2 pathway","authors":"Jia-Jun Liang,&nbsp;Hong-Xia Liu,&nbsp;Jian-Gang Yan,&nbsp;Guo Xie,&nbsp;Wen-Li Liu,&nbsp;Jia-Hui Lin,&nbsp;Xiao-Min Li,&nbsp;Xin-Liang Mao","doi":"10.1007/s10735-025-10586-1","DOIUrl":"10.1007/s10735-025-10586-1","url":null,"abstract":"<div><p>The specific hepatoprotective mechanism of Fermented Panax ginseng C.A. Meyer extract (FGE) has not yet been fully elucidated. In this study, an AAPH-induced liver injury model was established to investigate the hepatoprotective effects of FGE. The hepatoprotective effects of FGE may involve the mediation of the NRF2 pathway by rare ginsenosides such as 20(R)-Rh1, 20(S)-Rg2, Rg5, 20(R)-Rg2, and 20(S)-Rh1. The results showed that FGE effectively improved pathological damage and liver dysfunction, increased SOD and GPx expression in the liver, and inhibited excessive ROS generation both in vivo and in vitro. Mechanistically, FGE regulated the mRNA and protein expression of KEAP1, HO-1, and NQO1, while enhancing NRF2 protein expression and promoting its nuclear translocation. In conclusion, the NRF2 signaling pathway activated by FGE may inhibit AAPH-induced oxidative stress and alleviate the resulting liver injury.</p><h3>Graphical abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 6","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145284476","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":"Pterostilbene (grape flavonoid) mitigates gastric ulcer events in vivo: biochemical and histopathological approaches","authors":"Khaled Abdul-Aziz Ahmed,&nbsp;Khalid M. Alqaisi,&nbsp;Noralhuda Ayad Ibrahim,&nbsp;Najat Jabbar Ahmed,&nbsp;Qosay A. Al-Balas,&nbsp;Ahmed Aj. Jabbar,&nbsp;Muna Horabi,&nbsp;Hanan Ibrahim Althagbi,&nbsp;Goran Noori Saleh,&nbsp;Ahmed Hameed Al-Dabhawi,&nbsp;Rawaz Rizgar Hassan,&nbsp;Talal Salem Al-Qaisi","doi":"10.1007/s10735-025-10634-w","DOIUrl":"10.1007/s10735-025-10634-w","url":null,"abstract":"<div><p>Gastric ulcers are one of the major public health burdens in the modern era, with increased complications that could be a result of alcohol abuse or <i>H. pylori</i> infection. In this study, we investigated the therapeutic potential and acute toxicity effects of Pterostilbene (PSB) in ethanol-mediated gastropathy, as well as its underlying molecular mechanism, in rats. Gastric ulcers are provoked by absolute ethanol (5 mL/kg, i.g.) in male Sprague–Dawley rats after receiving oral treatments: physiological saline (negative, 5 mL/kg), omeprazole (positive control, 20 mg/kg), and PSB (30 and 60 mg/kg). PSB pretreatment significantly alleviated clinical signs, reduced the macroscopic ulcer index, and improved gastric mucosal morphology, including gastric defense barriers (mucus and glycoprotein production). PSB Pretreatment improved ethanol-mediated microscopical alterations, as indicated by reduced submucosal oedema, decreased hemorrhagic/lesion areas, and restoration of mucosal integrity. PSB down-regulated apoptotic actions (reduced P53 and increased Bcl-2 protein expression), lowered inflammatory conditions (decreased TNF-α, IL-6, and increased IL-10), and limited oxidative stress tissue injuries (up-regulated SOD, CAT, and PGE2 while lowering MDA). The PSB gastroprotection may be linked to a strengthened gastric defense and anti-oxidative/anti-inflammatory pathways, ultimately curbing apoptotic actions by modulating death signals, P53, and Bcl-2 proteins. The outcomes present PSB as a viable nutraceutical and biopharmaceutical product for managing stomach disorders, including gastric ulcers.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 6","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145284465","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":"Methyltransferase-like 14 mediated FOXP1 m6A modification alleviates osteoporosis by regulating the Wnt/β-catenin pathway","authors":"Xudong Yao,&nbsp;Tao Peng","doi":"10.1007/s10735-025-10623-z","DOIUrl":"10.1007/s10735-025-10623-z","url":null,"abstract":"<div><p>The impaired osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) contributes significantly to osteoporosis (OP) pathogenesis. While Forkhead box p1 (FOXP1) is known to regulate stem cell differentiation, its specific role in BMSCs osteogenic differentiation during OP remains unclear. Here, BMSCs were cultured in osteogenic medium for 14 d to induce osteogenic differentiation. We found that FOXP1 was upregulated in BMSCs treated with osteogenic medium, and FOXP1 overexpression promoted BMSC osteogenic differentiation, whereas FOXP1 knockdown inhibited BMSCs osteogenic differentiation. Mechanistically, METTL14 mediated m6A methylation of FOXP1 mRNA, which was recognized by YTHDF1/YTHDF3 to enhance its mRNA stability. Notably, METTL14 overexpression promoted osteogenic differentiation of BMSCs, this effect was abolished by FOXP1 knockdown. The stabilized FOXP1 protein activated the Wnt/β-catenin signaling pathway to drive BMSC osteogenesis. In vivo, administration of FOXP1-overexpressing lentivirus in ovariectomized (OVX) mice significantly attenuated osteoporosis progression. Collectively, our findings reveal that METTL14-dependent m6A modification and YTHDF1/YTHDF3-mediated stabilization of FOXP1 alleviate osteoporosis in OVX mice through Wnt/β-catenin activation, positioning FOXP1 as a promising therapeutic target for postmenopausal osteoporosis.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 6","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145284478","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":"Zhuyu pill mitigates NAFLD through activation of IL22/JAK1/STAT3 signaling pathway","authors":"Tong Wang,&nbsp;Xiaobo Zhang,&nbsp;Tao Shen,&nbsp;Zubing Zhou","doi":"10.1007/s10735-025-10622-0","DOIUrl":"10.1007/s10735-025-10622-0","url":null,"abstract":"&lt;div&gt;&lt;p&gt;This study aims to investigate the lipid-lowering, anti-inflammatory, and antioxidant effects of Zhuyu Pill in non-alcoholic fatty liver disease (NAFLD), and to determine whether its therapeutic action is mediated through modulation of the IL-22/JAK1/STAT3 signaling pathway. In animal experiments, C57BL/6 mice were fed a high-fat diet for 17 weeks to induce a NAFLD model. They were randomly divided into a control group, a Zhuyu Pill treatment group, and a positive control group, and the intervention lasted for 6 weeks. Mouse liver tissue and serum were collected for biochemical analysis of blood lipids and liver enzyme activities. Liver sections were processed for HE staining and Oil Red O staining to evaluate histopathological changes and lipid accumulation. ELISA was employed to quantify inflammatory factor levels, while DCFH-DA and MitoSOX staining used to detect reactive oxygen species (ROS) in the liver. In cell experiments, mouse liver cells AML-12 were used as a model, and cells were treated with free fatty acids to simulate the NAFLD microenvironment. ELISA was used to detect changes in the expression of inflammatory factors and detecting the levels of cellular ROS and mitochondrial ROS. In addition, siRNA technology was used to silence IL-22 and activate the JAK/STAT signaling pathway with Colivelin. The changes in lipid deposition and ROS signaling in cells were observed, and the expression changes of IL-22/JAK1/STAT3 signaling pathway related proteins were detected by WB method. In animal experiments, the detection results of serum biochemical indicators in mice showed that Zhuyu Pill can effectively reduce the levels of ALT, AST, TC, TG, LDL-C, and HDL-C. HE and Oil Red O staining revealed that Zhuyu Pill markedly alleviated hepatic lipid accumulation and inflammatory infiltration. The results of inflammatory factors showed that treatment with Zhuyu Pill significantly reduced the levels of pro-inflammatory factors IL-6, TNF-α, IL-1 β, and MCP-1 in mouse serum, while increasing the expression of IL-22. The results of DCFH-DA and MitoSOX staining methods showed that Zhuyu Pill could significantly reduce the level of ROS in the liver tissue of NAFLD mice. In vitro experiments showed that treatment with Zhuyu Pill significantly reduced the levels of pro-inflammatory cytokines IL-6, TNF-α, IL-1 β, and MCP-1 in NAFLD cell models, increased the expression of IL-22, significantly reduced ROS levels, increased the expression of p-JAK1 protein, p-STAT3 protein, BCL-2 protein, and reduced the expression of BAX protein. SiRNA-mediated IL-22 silencing markedly attenuated the therapeutic effects of Zhuyu Pill on reducing lipid deposition and enhancing antioxidant defense, and also diminished its ability to activate the IL-22/JAK1/STAT3 signaling pathway. Meanwhile, STAT3 activator Colivelin was able to partially reverse the effects of IL-22 silencing. Zhuyu Pill can regulate lipid metabolism, inhibit inflammatory response, alleviate oxidati","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 6","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145284490","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":"Sinomenine enhances recovery from corneal alkali burns by attenuating macrophage M1 polarization through modulating the METTL3/IRAKM axis","authors":"Jun-qi Li,&nbsp;Rui-ze Sun","doi":"10.1007/s10735-025-10627-9","DOIUrl":"10.1007/s10735-025-10627-9","url":null,"abstract":"<div><p>Corneal alkali burns trigger the infiltration of inflammation-associated macrophages, which can potentially lead to vision impairment. Although Sinomenine (SIN) is recognized for its anti-inflammatory properties, its role on the polarization of macrophages and its effects on corneal alkali injury remain inadequately understood. In this study, corneal alkali damage was induced using NaOH. HE staining and immunohistochemistry were conducted to assess macrophage infiltration in corneal tissues. Macrophages were isolated via flow cytometry assay. Quantitative real-time PCR (qRT-PCR) was employed to examine the expression of genes associated with macrophage polarization. The results indicated an increase in macrophage infiltration and M1 polarization in mice subjected to corneal alkali injury. Sinomenine treatment effectively inhibited the polarization of M1 macrophages in the cornea. In mice treated with Sinomenine post-injury, there was a reduction in the expression of the m6A methylation writer protein METTL3 in macrophages, which led to an upregulation of IRAKM expression. The elevated IRAKM expression subsequently inhibited the TLR4 inflammatory pathway and reduced corneal inflammatory cell infiltration, ultimately ameliorating corneal alkali burns. Sinomenine attenuates M1 macrophage polarization through upregulating IRAKM by inhibiting the expression of the m6A methylation writer protein METTL3 in macrophages, leading to enhanced outcomes in corneal alkali injuries.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 5","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145256785","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}