Animal models and experimental medicine最新文献

{"title":"Analysis of energy expenditure and behavioral characteristics in different mouse strains under normal and disease conditions","authors":"Jiacheng Zeng,&nbsp;Yuanjun Ji,&nbsp;Yan Zou,&nbsp;Jing Tan,&nbsp;Teng Wu,&nbsp;Conghui Shen,&nbsp;Tongsheng Huang,&nbsp;Shijie Xiong,&nbsp;Mengying Liu,&nbsp;Maoquan Yang,&nbsp;Jingwei Lai,&nbsp;Jiangwei Ma,&nbsp;Junhong Wan,&nbsp;Xinlu Fu,&nbsp;Jiang Qian,&nbsp;Hui Li,&nbsp;Ludong Yuan,&nbsp;Weibin Cai","doi":"10.1002/ame2.70268","DOIUrl":"10.1002/ame2.70268","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Metabolic and behavioral traits in mice exhibit substantial variability across strains, ages, and disease states, which can confound preclinical study outcomes. However, systematic characterization of these parameters (e.g., energy metabolism, activity, and feeding behavior) across diverse experimental conditions remains limited.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Core metabolic and behavioral parameters were assessed via metabolic cages in five 8-week-old mouse strains (ICR, C57BL/6J, BALB/c, BALB/c-nude, NOD-SCID), six C57BL/6J age groups (3 weeks to 18 months), and four mouse disease models (LPS-induced pneumonia, chronic kidney disease, acute myocardial infarction, and type 1 diabetes). Data were stratified by light/dark cycles and statistically compared.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Herein, metabolic and behavioral phenotypes of mice were systematically characterized across different strains, ages, and four disease models (three organ-specific, one systemic). Distinct strain- and age-related differences in basal metabolism, activity, and energy expenditure were observed. Specifically, ICR mice displayed higher basal aerobic metabolism, whereas C57BL/6J mice exhibited greater locomotor activity; metabolism and energy balance also underwent marked shifts during development, pregnancy, and aging. Furthermore, all disease models presented unique metabolic rearrangements: LPS-induced acute pneumonia reduced aerobic metabolism and locomotor activity; CKD caused hypometabolism, polydipsia, and a substrate shift to carbohydrate oxidation; AMI increased respiratory exchange ratio (RER) and water intake; and T1DM induced polyphagia and polydipsia, with normal metabolism but impaired energy utilization.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Mouse metabolic and behavioral phenotypes are highly dependent on strain, age, and disease state. These findings highlight the need to standardize experimental conditions (e.g., age, strain, disease state) and account for baseline variability when designing preclinical studies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":"9 8","pages":"1633-1647"},"PeriodicalIF":3.4,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13412605/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148610818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sappanwood extract modulates hepatic structure–function in hepatomegaly and hepcidin related iron regulatory pathways in a phenylhydrazine induced hemolytic anemia rat model relevant to thalassemia","authors":"Mohammad Indra Pratama,&nbsp;Ratu Safitri,&nbsp;Desak Made Malini,&nbsp;Mas Rizky A. A. Syamsunarno,&nbsp;Mohammad Ghozali,&nbsp;Madihah Madihah","doi":"10.1002/ame2.70264","DOIUrl":"10.1002/ame2.70264","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Hepatomegaly in hemolytic disorders, including in thalassemia, is a common complication, primarily due to hemosiderosis and activation of extramedullary hematopoiesis. Globin chain imbalance leads to chronic hemolysis and ineffective erythropoiesis, which are associated with suppression of hepcidin expression. Reduced hepcidin levels may increase iron absorption and accumulation, contributing to oxidative stress and liver tissue damage. Iron chelation therapy, such as deferipron, is effective but has side effects, so safer alternatives are needed. Sappanwood (<i>Caesalpinia sappan</i> L.) contains the active compound brazilin, which chelates iron and exhibits antioxidant activity, potentially reducing oxidative stress, improving iron metabolism disorders, and reducing hepatomegaly. This study aims to evaluate the potential of sappanwood extract as a natural iron chelator and antioxidant.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This experimental study used male Wistar rats (180–250 g) with a model of iron overload hemolytic anemia, which were divided into normal controls, negative controls (phenylhydrazine 40 mg/kg BW), positive controls (deferiprone 75 mg/kg BW), and sappanwood extract (SWE) treatment (50, 100, 200 mg/kg BW) for 14 days. The parameters measured included iron metabolism, hepatomegaly, liver function, hepcidin-related gene expression, and oxidative stress. Data were analyzed using ANOVA, with <i>p</i> &lt; 0.05 considered significant.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The results showed that administration of 100 mg/kg BW SWE provided optimal improvement (<i>p</i> &lt; 0.05), including reductions in hepatomegaly, SGPT, hemosiderin, lipid peroxidation, bilirubin, extramedullary hematopoiesis, and modulation in iron-related gene expression, including <i>Hamp, Bmp6, Epo</i>, and <i>Ftl</i>.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These findings confirm the potential of sappanwood as a potential therapeutic candidate for the management of iron overload in thalassemia.</p>\u0000 </section>\u0000 </div>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":"9 8","pages":"1674-1689"},"PeriodicalIF":3.4,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13443226/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148681232","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exosome-mediated gut–brain axis signaling in neurodegenerative diseases: Mechanisms, experimental evidence, and therapeutic perspectives—A narrative review","authors":"Waheeb Sami Aggad,&nbsp;Rakesh Ghosh,&nbsp;Hailah M. Almohaimeed,&nbsp;Zuhair M. Mohammedsaleh,&nbsp;Fayez M. Saleh,&nbsp;Amany I. Almars,&nbsp;S. Renuka Jyothi,&nbsp;Rajashree Panigrahi,&nbsp;Ajoy Kumer,&nbsp;Bikram Dhara","doi":"10.1002/ame2.70226","DOIUrl":"10.1002/ame2.70226","url":null,"abstract":"<p>The stomach and the brain are connected by a sophisticated two-way communication mechanism called the gut–brain axis. Extracellular vesicles, particularly exosomes, that move bioactive substances between the stomach and the brain, such as proteins, lipids, metabolites, and microRNAs, may improve the gut–brain axis. In the past years, the role of exosome-mediated communication has been recognized as significant in relation to the etiology, continued progression, and potential treatment of neurodegenerative disorders. The authors of this review article present a summary of the current understanding of the relationship of gut microbiome, exosome biogenesis, and the pathophysiological development of neurodegenerative diseases. Evidence from laboratory studies, animal studies, and newly emerging human studies suggests that microbiome-based metabolites and inflammatory mediators may modulate how exosomes are produced, what they carry, and how they interact with the blood–brain barrier. These exosomal signals may impact neuroinflammation, neuronal signaling, and the spread of pathological proteins of neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease. In addition, they examine some possible ways to target the gut–brain axis from a therapeutic perspective, including manipulating the gut microbiome, providing probiotics and/or prebiotics, performing fecal microbiota transplantation, and/or using engineered extracellular vesicles as vehicles for drug delivery. The authors also outline some of the methodological differences that make it difficult to assess the effects of exosomes.</p>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":"9 8","pages":"1527-1538"},"PeriodicalIF":3.4,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13394756/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148038656","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A modified D-galactose-induced aging rat model with low-dose intraperitoneal ozone: Redox, functional, and skin outcomes","authors":"Isabella Kurnia Liem,&nbsp;Raisa Nauli,&nbsp;Firda Asma’ul Husna,&nbsp;Sasanthy Kusumaningtyas,&nbsp;Deswaty Furqonita,&nbsp;Ferbian Milas Siswanto,&nbsp;Soegianto Ali","doi":"10.1002/ame2.70271","DOIUrl":"10.1002/ame2.70271","url":null,"abstract":"<p>Aging impairs quality of life, making experimental models essential to evaluate interventions that modulate age-related changes. This study aimed to characterize a modified D-galactose-induced aging model and explore the effects of intermittent low-dose ozone exposure on redox balance and functional outcomes. Twenty-seven 12-week-old male Wistar rats were randomly assigned to healthy, aging (D-galactose induction), and ozone-treated (D-galactose + ozone) groups. Plasma and skin MDA levels, SOD activity, and GSH levels were measured colorimetrically. Physical performance was assessed using physical health score, morbidity proportion, body weight, muscle strength (hanging test), hair regrowth, and skin structure (Hematoxylin–Eosin and Masson's trichrome staining). Compared with healthy rats, the aging group showed increased plasma MDA levels (<i>p</i> = 0.007), MDA/SOD ratios (<i>p</i> = 0.005), and MDA/GSH ratios (<i>p</i> = 0.016). In ozone-treated rats, plasma MDA and MDA/SOD tended to decrease compared with aging rats, while GSH tended to increase. In the skin, redox markers were comparable across groups, except for a significantly lower MDA/SOD ratio in the ozone-treated group (<i>p</i> = 0.043) compared with the aging group. D-Galactose induction reduced physical health (<i>p</i> = 0.017), increased morbidity, and tended to reduce body-weight gain and hanging ability. Ozone-treated rats showed improved physical health (<i>p</i> = 0.041), lower morbidity, accelerated hair regrowth, and preserved skin structure, particularly dermal firmness and collagen thickness (<i>p</i> = 0.013). The modified D-galactose model partially induced redox imbalance and functional deterioration, whereas intermittent low-dose ozone exposure tended to restore redox homeostasis, preserve physical health, accelerate hair regrowth, and maintain the skin structure without inducing supraphysiological effects.</p>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":"9 8","pages":"1690-1698"},"PeriodicalIF":3.4,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13420297/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148623140","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regional gas exchange evaluation during ex vivo lung perfusion in a swine model of localized lung dysfunction","authors":"Giulia Maria Ruggeri,&nbsp;Elena Chiodaroli,&nbsp;Matteo Montoli,&nbsp;Sara Pieropan,&nbsp;Alessandro Santini,&nbsp;Gianluca Lopez,&nbsp;Michele Battistin,&nbsp;Luigi Vivona,&nbsp;Sebastiano Maria Colombo,&nbsp;Jacopo Fumagalli,&nbsp;Eleonora Carlesso,&nbsp;Stefano Ferrero,&nbsp;Lorenzo Rosso,&nbsp;Stefano Gatti,&nbsp;Antonio Maria Pesenti,&nbsp;Giacomo Grasselli,&nbsp;Alberto Zanella","doi":"10.1002/ame2.70224","DOIUrl":"10.1002/ame2.70224","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Ex vivo lung perfusion (EVLP) allows the evaluation of lungs that do not meet standard transplantation criteria. Current procedures do not permit the identification of regional functional deficits. We investigated the feasibility of assessing lobar gas exchange during EVLP in a swine model.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In five healthy swine, lungs were procured with beating heart and connected to an open-atrium EVLP circuit. Each pulmonary vein was cannulated for lobar perfusate sampling. After baseline assessment, the left inferior bronchus (LIB) and then the left superior bronchus (LSB) were temporarily clamped to simulate localized injury. At each step, perfusate gas analyses from each vein and the left atrium (LA), lung mechanics, pulmonary hemodynamics, and computed tomography (CT) were obtained.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>At baseline, no differences were observed between LA and lobar samples. Occlusion of LIB and LSB produced up to 95% non- or poorly aerated tissue in the affected lobe, with lobar shunt increasing to 97% [88%–103%] (LIB) and 97% [78%–106%] (LSB). Corresponding lobar PaO₂/FiO₂ fell to 47 [46–54] and 45 [43–67] mmHg, whereas LA-mixed venous blood maintained higher values (299 [188–373] and 349 [347–377] mmHg, respectively). Bronchial occlusions caused overall significant worsening of lung function, including increased pulmonary vascular resistance, and reduction in total air lung volume and normally aerated tissue on CT scan analysis. In Left Inferior Lobe (LIL), histological samples showed significant interstitial congestion and alveolar hemorrhage.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Lobar-specific perfusate gas analysis during EVLP provides accurate functional assessment and enables the localization of lung injury, potentially improving graft evaluation before transplantation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":"9 8","pages":"1517-1526"},"PeriodicalIF":3.4,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13394259/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148260781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Strategies for inducing diabetes in laboratory animals: Advances from chemical, surgical, immunologic, dietary, and genetic approaches","authors":"Milad Faraji,&nbsp;Maedeh Faraji,&nbsp;Nasrin Kazemipour","doi":"10.1002/ame2.70259","DOIUrl":"10.1002/ame2.70259","url":null,"abstract":"<p>Diabetes mellitus is a metabolic disorder characterized by hyperglycemia resulting from defects in insulin secretion, insulin action, or both. It involves complex metabolic, hormonal, and immunological mechanisms that cannot be fully reproduced in vitro, making in vivo animal models essential for mechanistic and translational research. This review provides a comprehensive overview of strategies used to induce diabetes in laboratory animals. The principal approaches are categorized as follows: (i) chemical induction (e.g., streptozotocin, alloxan, dithizone), (ii) dietary and hormonal interventions (e.g., high-fat diets, glucocorticoids), (iii) immune- and virus-mediated models (e.g., Coxsackievirus-triggered diabetes), (iv) surgical models (e.g., partial pancreatectomy), and (v) genetically engineered or spontaneously diabetic strains (e.g., NOD mice, GK rats, db/db mice). For each category, we describe the underlying mechanisms, typical protocols (including doses, duration, and onset of hyperglycemia), and their relevance for modeling type 1 or type 2 diabetes. Although chemical models are widely applied because of their technical simplicity, reproducibility, and relatively low cost, they may not fully replicate autoimmune or progressive metabolic features of human disease. Comparative tables summarize model characteristics, including mechanisms, strengths, limitations, disease onset, and research applications, to facilitate informed model selection. No single animal model fully reproduces the species-specific immune complexity, progressive metabolic deterioration, and long-term complications observed in human diabetes. Nevertheless, these models provide controlled and mechanistically tractable systems for investigating β-cell dysfunction, insulin resistance, inflammatory pathways, and therapeutic interventions. Careful alignment between model characteristics and research objectives—and, when appropriate, the complementary use of multiple models—is therefore essential to enhance translational relevance.</p>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":"9 8","pages":"1548-1566"},"PeriodicalIF":3.4,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13424741/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148633092","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SnRNA-seq reveals cellular heterogeneity and proliferation mechanisms in limb venous malformations","authors":"Junjie Lin,&nbsp;Tingting Liu,&nbsp;Bin Fang,&nbsp;Xiaojuan Feng,&nbsp;Wenting Jiao,&nbsp;Changkuan Chen,&nbsp;Yaqing Ding,&nbsp;Gaozan Zhu,&nbsp;Wenqiu Wang,&nbsp;Wenbo Liu,&nbsp;Yuanqi Li,&nbsp;Shoufu Hou,&nbsp;Jianshe Wei,&nbsp;Junbo Qiao","doi":"10.1002/ame2.70256","DOIUrl":"10.1002/ame2.70256","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Background&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Venous malformations (VMs) are congenital vascular anomalies characterized by abnormal vascular proliferation, with limb VMs often leading to functional impairment and physical discomfort. However, the cellular heterogeneity and underlying molecular mechanisms driving pathological proliferation in limb VMs remain incompletely elucidated.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;In this study, we collected 10 tissue samples including specimens from 5 limb VM patients and 5 normal control tissues and performed single-nucleus RNA sequencing (snRNA-seq) to comprehensively map the cellular landscape of VMs. We first identified distinct cell subpopulations covering vascular endothelial cells, vascular smooth muscle cells, and immune cells, and compared gene expression levels between VM and normal tissues. Afterward, we conducted weighted gene co-expression network analysis (hdWGCNA) and constructed the protein–protein interaction (PPI) network to screen critical proliferation-related genes in VMs. We further analyzed the signaling pathways associated with these candidate genes and carried out subsequent functional validation experiments to explore the biological role of core gene TEK in proliferative vascular endothelial cells (PVECs). Besides, we also analyzed the characteristic pathways of the PVEC subpopulation to clarify its proliferation-related molecular features.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;We found obvious expression differences of genes in various cell subpopulations between VM and normal tissues. Three genes, namely tyrosine protein kinase receptor (TEK), Fms-like tyrosine kinase 1 (FLT1), and EGF-like domain multiple 7 (EGFL7), were identified as key proliferation-related genes with significant upregulation in VM lesions, and these three genes were closely associated with the activation of PI3K/AKT/mTOR, IL6/JAK/STAT3, and TNF-α/NF-κB pathways. Functional experimental results showed that TEK knockdown could significantly inhibit proliferative vascular endothelial cell (PVEC) proliferation and promote cell apoptosis, and reverse the abnormal activation of inflammatory pathways. As a vital pathogenic cell subpopulation, PVECs facilitated abnormal vascular proliferation through activating pathways including the G2/M checkpoint and E2F targets.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Conclusions&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Collectively, our study systematically elucidated the cellular heterogeneity framework and proliferation mechanisms of limb VMs, identifying TEK, FLT1, and EGFL7 as key regulators of pathological","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":"9 8","pages":"1567-1586"},"PeriodicalIF":3.4,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13451655/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148690554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IRF-1 modulates hepatic ferroptosis and aggravates liver ischemia/reperfusion injury via DYRK1α","authors":"Jinping Zhang,&nbsp;Jinming Zhang,&nbsp;Siyuan Song,&nbsp;Mingyang Li,&nbsp;Liying Sun,&nbsp;Zhijun Zhu,&nbsp;Dongdong Lin","doi":"10.1002/ame2.70194","DOIUrl":"10.1002/ame2.70194","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The purpose is to define the contribution of the interferon regulatory factor-1–dual-specificity tyrosine phosphorylation-regulated kinase 1α (IRF-1–DYRK1α) axis to hepatocellular ferroptosis during liver ischemia/reperfusion injury (LIRI).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Ferroptosis was induced in AML12 hepatocytes with erastin. After gain- or loss-of-function manipulation of IRF-1 and DYRK1α, we quantified glutathione peroxidase 4 (GPX4) and acyl-CoA synthetase long-chain family member 4 (ACSL4), reactive oxygen species (ROS), malondialdehyde (MDA), and glutathione (GSH). In vivo, wild-type (WT) mice, IRF-1 knockout (Irf1^−/−) mice, and WT mice treated with the DYRK1α inhibitor harmine underwent a 70% warm LIRI model. Liver and blood were collected for histology, serum transaminases, cytokine ELISA, protein analyses, and flow cytometry.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>IRF-1 knockdown attenuated LIRI, accompanied by suppression of hepatocellular ferroptosis. DYRK1α inhibition reversed IRF-1–mediated decreases in GSH and GPX4 and prevented increases in MDA, ROS, and ACSL4 in AML12 cells, indicating DYRK1α participation in IRF-1–driven ferroptosis. In mice, pharmacologic inhibition of DYRK1α with harmine reduced hepatic ferroptosis and ameliorated LIRI.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>IRF-1 aggravates LIRI, at least in part, by promoting hepatocellular ferroptosis via DYRK1α. Targeting the IRF-1–DYRK1α axis may offer a therapeutic strategy to limit perioperative liver injury.</p>\u0000 </section>\u0000 </div>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":"9 8","pages":"1587-1601"},"PeriodicalIF":3.4,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13394601/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148260816","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"One-step generation of heritable mitochondrial DNA multiplex-engineered rats using DddA-derived cytosine base editor","authors":"Xu Zhang,&nbsp;Keru Li,&nbsp;Lei Tan,&nbsp;Wei Chen,&nbsp;Shan Gao,&nbsp;Chenyang Liu,&nbsp;Shuo Pan,&nbsp;Jiayue He,&nbsp;Ning Liu,&nbsp;Gefan Wan,&nbsp;Wei Dong,&nbsp;Weining Kong,&nbsp;Bin Shen,&nbsp;Xiaolong Qi,&nbsp;Yuanwu Ma","doi":"10.1002/ame2.70154","DOIUrl":"10.1002/ame2.70154","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Mitochondrial DNA (mtDNA) mutations are implicated in a wide range of diseases, underscoring the need to elucidate the relationship between mtDNA mutations and disease pathology. These diseases are often characterized by the presence of multiple mutations; however, research has been hampered by the lack of suitable animal models carrying multiplex mtDNA mutations. Such models cannot be produced through traditional breeding due to matrilineal inheritance of mtDNA.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Based on the TALE-based mitochondrial genome editing tools, we generated rats harboring multiple mtDNA mutations by microinjecting mixed pairs of DdCBE plasmids into one-cell-stage zygotes. The efficiency of mtDNA editing and the potential off-target effects were assessed through deep sequencing and long reads sequencing methodologies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In this study, we established double- and triple-site mutant rats with the editing efficiencies of up to 58.5% and confirmed that these mutations can be stably transmitted through the germline. Moreover, our results demonstrated that DdCBE-mediated mtDNA multi-site editing of mtDNA exhibits minimal off-target effects in both the mitochondrial and nuclear genomes in vivo.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This work represents the first successful generation of heritable multi-site mtDNA mutant rats, providing a valuable model for elucidating the pathophysiological mechanisms of mitochondrial disorders and for developing potential therapeutics.</p>\u0000 </section>\u0000 </div>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":"9 8","pages":"1648-1660"},"PeriodicalIF":3.4,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13393515/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147534769","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multipathway modulation of neuroinflammation and oxidative stress by hesperidin in a rat single prolonged stress model of post-traumatic stress disorder","authors":"Godson Emeka Anyanwu,&nbsp;Ogan Christopher Akanaku,&nbsp;Augustine Oviosun,&nbsp;Precious E. Ekwueme,&nbsp;Paul Anyiom Odey,&nbsp;Chima Paul Okechukwu Ugwu,&nbsp;Chinyere Nkemjika Anyanwu","doi":"10.1002/ame2.70244","DOIUrl":"10.1002/ame2.70244","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Post-traumatic stress disorder (PTSD) is a complicated neuropsychiatric disorder that is marked by long-term neuroinflammation, oxidative stress, and poor neuroplasticity in stress-sensitive brain areas. Hesperidin is a citrus-derived flavanone glycoside that has been reported to have multitarget neuroprotective effects with antioxidant, anti-inflammatory, and neurotrophic regulatory activities. However, its integrated effects across convergent pathological pathways in validated PTSD models remain insufficiently defined.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Male Wistar rats were subjected to the single prolonged stress (SPS) paradigm and treated with hesperidin (50, 100, and 200 mg/kg), fluoxetine (20 mg/kg), or vehicle for 14 days. Biochemical assessments (malondialdehyde [MDA], catalase [CAT], superoxide dismutase [SOD]) and immunohistochemical measurements of neuronal and glial integrity (NeuN, glial fibrillary acidic protein [GFAP], brain-derived neurotrophic factor [BDNF]) in the hippocampus, amygdala, and prefrontal cortex were performed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>SPS exposure induced marked oxidative imbalance, evidenced by increased MDA levels and reduced CAT activity, alongside significant upregulation of tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), and IL-1β, increased astrocytic reactivity (GFAP), and reduced BDNF expression. Hesperidin treatment significantly attenuated lipid peroxidation, partially restored CAT activity, and suppressed pro-inflammatory cytokines, with the most pronounced effect observed for IL-1β. Notably, hesperidin reduced astrocytic activation and preserved neuronal morphology, while enhancing BDNF expression in a dose-dependent manner, with optimal effects at 50–100 mg/kg. Conversely, there was little group variation in the activity of SOD, implying pathway-selective redox regulation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Hesperidin has multipathway, coordinated, modulatory effects on oxidative stress, neuroinflammation, glial activation, and neurotrophic signaling in the SPS model of PTSD. These findings support its utility as a mechanistic probe for interrogating convergent stress-related neuropathological pathways.</p>\u0000 </section>\u0000 </div>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":"9 8","pages":"1661-1673"},"PeriodicalIF":3.4,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13444398/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148681244","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}