Animal models and experimental medicine最新文献

{"title":"USB1 deficiency disrupts neutrophil maturation via RNA dysregulation independent of global pre-mRNA splicing","authors":"Hang Li,&nbsp;Guiying Shi,&nbsp;Jiaming Tang,&nbsp;Yiying Huang,&nbsp;Jie Wang,&nbsp;Xuepei Lei,&nbsp;Lin Bai","doi":"10.1002/ame2.70206","DOIUrl":"10.1002/ame2.70206","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>U6 biogenesis 1 (USB1) gene mutations cause poikiloderma with neutropenia (PN), which is clinically characterized by skin hyperpigmentation, nail dysplasia, neutropenia, and an elevated risk of cancer. USB1 functions as an RNA exonuclease involved in RNA maturation and stability regulation, although its precise mechanism of action in the hematopoietic system remains unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We established a myeloid cell-specific USB1 knockout mouse model (USB1fl/fl-Lyz2-cre) using CRISPR/Cas9. Using a combination of research methods, including Western blot, flow cytometry, messenger RNA (mRNA) sequencing, microRNA (miRNA) sequencing, and quantitative polymerase chain reaction (qPCR), we investigated the effects of USB1 deficiency on neutrophil development and differentiation, along with the underlying signaling molecular mechanisms.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Experimental results indicated that USB1 deficiency in mouse myeloid cells not only leads to dysregulation of miRNA expression but also interferes with the developmental, differentiation, and maturation processes of neutrophils by affecting key genes, such as IL1a, Selp, and Kilt. This impact can be traced back to the stages of myeloid progenitor cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>USB1 influences neutrophil maturation and myeloid progenitor cell differentiation by regulating the expression of specific miRNAs and mRNAs. This provides novel in vivo experimental evidence for understanding the pathogenesis of PN in patients.</p>\u0000 </section>\u0000 </div>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":"9 7","pages":"1353-1363"},"PeriodicalIF":3.4,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13394499/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147724986","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":"Development of a loop-mediated isothermal amplification-lateral flow dipstick (LAMP-LFD) assay and on-site rapid detection evaluation for Rodentibacter heylii and Rodentibacter pneumotropicus","authors":"Huiqiong Yan,&nbsp;Sisi Chen,&nbsp;Yuhan Gan,&nbsp;Jing Xing,&nbsp;Yufang Feng,&nbsp;Xin Wen,&nbsp;Jie Fang,&nbsp;Jiangtao Du,&nbsp;Shasang Zhou,&nbsp;Honggang Guo,&nbsp;Xiaoyin Jin,&nbsp;Zhiyuan Wang,&nbsp;Junhao Tao,&nbsp;Lingqun Lu,&nbsp;Qingming Kong,&nbsp;Huazhong Ying,&nbsp;Wei Han,&nbsp;Fangwei Dai","doi":"10.1002/ame2.70214","DOIUrl":"10.1002/ame2.70214","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p><i>Rodentibacter pneumotropicus</i> and <i>Rodentibacter heylii</i> are important exclusion pathogens in specific pathogen-free (SPF) laboratory animals. However, routine detection methods such as traditional bacterial culture remain labor-intensive and time-consuming. The loop-mediated isothermal amplification-lateral flow dipstick (LAMP–LFD) assay provides a self-contained format for nucleic acid testing that combines speed, sensitivity, and specificity while minimizing aerosol contamination, making it well-suited for point-of-need applications.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>This study aimed to develop a streamlined, on-site detection platform capable of rapidly identifying both pathogens with high analytical accuracy, operational simplicity, and suitability for routine laboratory surveillance.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A LAMP–LFD system was established for the detection of the two pathogens using primers designed against the conserved 16S–23S rRNA ITS region. The assay's specificity, sensitivity, repeatability, and limit of detection (LoD) were evaluated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The assay achieved detection limits of 1 × 10⁻⁴ ng/μL for <i>R. pneumotropicus</i> and 1 × 10⁻⁵ ng/μL for <i>R. heylii</i>, demonstrating significantly higher sensitivity than PCR. No cross-reactivity was observed with 15 non-target bacteria. Among 28 infected samples, the method detected 19 positives, compared with 21 by multiplex PCR and 23 by qPCR. In 842 laboratory animal samples, culture-based, qPCR, and LAMP–LFD detected 2, 41, and 37 positive samples, respectively. The LoDs were 10² and 10¹ CFU/mL in fecal samples and 10¹ and 10⁰ CFU/mL in throat swab samples for <i>R. pneumotropicus</i> and <i>R. heylii</i>, respectively.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This method provides an approach for monitoring the health status of laboratory mice by enabling the detection of these two target pathogens.</p>\u0000 </section>\u0000 </div>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":"9 7","pages":"1395-1408"},"PeriodicalIF":3.4,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13394658/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148058828","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":"ApoE- and Cfh-deficient mice exhibit structural and molecular features of human early–intermediate retinal degeneration","authors":"Sergio Recalde,&nbsp;Maite Moreno Orduña,&nbsp;Jaione Bezunartea,&nbsp;Idoia Belza,&nbsp;Ainara Chas,&nbsp;Laura Fernández-Sánchez,&nbsp;Nicolás Cuenca Navarro,&nbsp;Alfredo García-Layana,&nbsp;Patricia Fernández-Robredo,&nbsp;María Hernández","doi":"10.1002/ame2.70243","DOIUrl":"10.1002/ame2.70243","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Age-related macular degeneration (AMD) is a multifactorial retinal disease in which alterations in lipid metabolism and dysregulation of the complement system play a central role. The aim of this study was to characterize a novel double-knockout (DK) mouse model deficient in apolipoprotein E and complement factor H (ApoE^−/–Cfh^−/−) as an experimental model of early and intermediate AMD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>ApoE^−/–Cfh^−/− mice and wild-type controls underwent comprehensive morphological, ultrastructural, biochemical, and molecular analyses. Retinal and retinal pigment epithelium (RPE) integrity, Bruch's membrane (BM) morphology, lipid accumulation, complement activation, angiogenic signaling, and synaptic organization were evaluated using histology, electron microscopy, immunohistochemistry, biochemical assays, and gene expression analyses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>DK mice exhibited significant RPE thinning, disruption of tight junctions, vacuolization, and BM thickening (<i>p</i> &lt; 0.05). Lipid accumulation and plasma lipid levels significantly increased compared with controls (<i>p</i> &lt; 0.01). Complement activation was significantly enhanced, as evidenced by increased C5b-9 deposition (<i>p</i> &lt; 0.01). In addition, DK mice exhibited increased vascular endothelial growth factor expression (<i>p</i> &lt; 0.05), altered matrix metalloproteinase activity (<i>p</i> &lt; 0.05), and significant synaptic disorganization between photoreceptors and second-order neurons (<i>p</i> &lt; 0.05).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The ApoE^−/–Cfh^−/− mouse reproduces key molecular and structural features of early and intermediate retinal degeneration with statistically significant alterations. Although it does not progress to advanced disease stages, it represents a valuable model to investigate several factors of AMD pathogenesis and evaluate therapeutic strategies targeting early disease mechanisms.</p>\u0000 </section>\u0000 </div>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":"9 7","pages":"1420-1435"},"PeriodicalIF":3.4,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13394217/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148364321","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":"Animal models of idiopathic membranous nephropathy: Recent advances and future perspectives","authors":"Qiuying Liu,&nbsp;Huixian Bian,&nbsp;Jianhua Liu,&nbsp;Lina Wu,&nbsp;Zhijie Zhang,&nbsp;Hongli Zhao,&nbsp;Xiaosong Qin","doi":"10.1002/ame2.70221","DOIUrl":"10.1002/ame2.70221","url":null,"abstract":"<p>Idiopathic membranous nephropathy (IMN) is one of the main causes of adult nephrotic syndrome. A subset of untreated or inadequately treated patients eventually progress to end-stage renal disease (ESRD), posing a significant clinical challenge. Although the discovery of novel podocyte target antigens has deepened our understanding of IMN pathogenesis, the precise molecular mechanisms remain incompletely elucidated, and effective targeted therapies are still lacking. Animal models play an irreplaceable role in uncovering IMN pathogenesis and developing effective therapies. In recent years, with a deeper understanding of IMN, researchers have successfully established various animal models, including Heymann nephritis (HN), cationic bovine serum albumin (C-BSA), Aminopeptidase A (APA), thrombospondin type 1 domain-containing 7A (THSD7A)-related, and phospholipase A2 receptor (PLA2R)-related IMN models. These models have substantially advanced the simulation of pathological human IMN features. Notably, the development of human PLA2R1-related animal models marks a landmark breakthrough in this field, as these models are the first to recapitulate the immunopathological processes driven by a key human autoantigen in experimental animals. However, current animal models have their own limitations and still cannot fully replicate the complex pathological process of human IMN. This review summarizes recent progress in animal IMN models, analyzes their methods, pathological features, strengths, and limitations, and discusses future directions. Future model development should integrate advanced multi-omics and artificial intelligence (AI) to achieve greater accessibility and precision, enabling the construction of multidimensional models encompassing genetics, environment, and immunity, thereby enabling a leap from “disease simulation” to “personalized treatment”.</p>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":"9 7","pages":"1325-1337"},"PeriodicalIF":3.4,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13394600/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148347618","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":"Phenotypic profiling of pristane-induced mimicking human systemic lupus erythematosus in Macaca fascicularis","authors":"Jonny Jonny,&nbsp;Soetojo Wirjopranoto,&nbsp;Chairul A. Nidom,&nbsp;I Ketut Sudiana,&nbsp;Terawan A. Putranto,&nbsp;Elisa D. Pratiwi,&nbsp;Tiza W. Mawaddah,&nbsp;Astria N. Nidom,&nbsp;Reviany V. Nidom,&nbsp;Setyarina Indrasari,&nbsp;Irma Y. Rosytania,&nbsp;Hiqmah Y. Yana,&nbsp;Sanindita Kusumastuti","doi":"10.1002/ame2.70162","DOIUrl":"10.1002/ame2.70162","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The development of nonhuman primate models that replicate human systemic lupus erythematosus (SLE) remains limited. This study aimed to develop a pristane-induced SLE model in <i>Macaca fascicularis</i> and evaluate its capacity to mimic human-like clinical and laboratory immunological alterations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>An experimental, single-arm investigation was performed using six female <i>M. fascicularis</i> (2–3 years old, 3–4 kg), which received a single intraperitoneal pristane injection (5 mL/kg body weight) to induce SLE and were monitored biweekly.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Throughout the 24-week study period, all macaques developed hallmark SLE-like changes without requiring a booster, including a pronounced increase in antinuclear antibody titers (<i>p</i> = 0.002), with anti-dsDNA positivity detected at the study endpoint. Significant decline was observed in hemoglobin, leukocyte, and lymphocyte count (<i>p</i> &lt; 0.05), reflecting hematologic perturbations consistent with human SLE. Physiologic deterioration, manifested as hyperthermia and weight loss, also emerged early (<i>p</i> = 0.001). Biochemical assessment demonstrated mild hepatic and renal dysfunction marked by elevated serum glutamic pyruvic transaminase (SGPT) and urea concentrations (<i>p</i> &lt; 0.05). Uniform proteinuria further indicated renal involvement, although the absence of hematuria suggests a spectrum of renal injury that may be less severe than that observed in advanced human SLE and may require longer observation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Overall, the reproducibility of autoantibody elevation and multisystem involvement demonstrates the model's translational potential. This nonhuman primate model offers a significant framework for investigating SLE pathogenesis and assessing novel therapy approaches.</p>\u0000 </section>\u0000 </div>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":"9 7","pages":"1302-1309"},"PeriodicalIF":3.4,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13393505/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147464482","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":"Evaluation of quantitative muscle MRI and an intelligent phenotyping housing system as advanced phenotyping methods in a mouse model of calpain 3-deficient muscular dystrophy","authors":"Nicolina Südkamp,&nbsp;Marlena Rohm,&nbsp;Gabriele Russo,&nbsp;Xavier Helluy,&nbsp;Abdulhadi Kocabas,&nbsp;Martijn Froeling,&nbsp;Felix Kleefeld,&nbsp;Denise Manahan-Vaughan,&nbsp;Tobias Ruck,&nbsp;Frank Jacobsen,&nbsp;Matthias Vorgerd,&nbsp;Johannes Forsting,&nbsp;Lara Schlaffke","doi":"10.1002/ame2.70193","DOIUrl":"10.1002/ame2.70193","url":null,"abstract":"<p>Calpainopathy is a rare genetic myopathy without causal treatment available. Recent advances have produced promising treatment strategies, including genetic treatment and immunomodulation, that are currently being tested pre-clinically in murine models. Traditional behavioral assays frequently fail to detect early motor deficits in corresponding mouse models. Thus, this study investigated whether more sophisticated measures, such as quantitative magnetic resonance imaging (qMRI) and automated motor assessments can reveal early pathological changes in a mouse model of calpainopathy, particularly in the subclinical stages. In this study, <i>Calpain 3</i>-deficient mice (Capn3-deficient) and wild-type controls underwent a standardized qMRI protocol on a 7T scanner at 5 and 15 months of age. Fat fraction (FF), water T2 relaxation time (wT2), and diffusion metrics were analyzed across selected hindlimb muscles. Additionally, voluntary motor activity was monitored using an intelligent phenotyping housing system. Motor activity assays revealed minimal and inconsistent genotype effects. Sex significantly affected qMRI measures, altering fat distribution and wT2 at 5 and 15 months. At 5 months, no significant differences were detected between genotypes. At 15 months, Capn3-deficient mice exhibited elevated wT2 in the soleus and gastrocnemius muscles, correlating with endomysial immune cell infiltration. Diffusion parameters and FF remained unchanged. Taken together, the results show that muscle qMRI, particularly T2 mapping, can sensitively detect subclinical muscle changes in aging Capn3-deficient mice, pointing towards inflammatory processes. Pronounced sex differences and measurement variability underscore the need for larger, sex-balanced cohorts. Extending follow-up beyond 15 months will likely increase sensitivity for later-stage pathology.</p>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":"9 7","pages":"1469-1479"},"PeriodicalIF":3.4,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13394435/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147629470","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":"GS-9620 alleviates psoriasis-like inflammation by regulating autophagy in keratinocytes","authors":"Yansi Lyu,&nbsp;Wei Zhou,&nbsp;Pei Zhang,&nbsp;Chen Lin,&nbsp;Xin Wen,&nbsp;Zigang Zhao,&nbsp;Guoqiang Zhang,&nbsp;Qian Zhang,&nbsp;Si Chen","doi":"10.1002/ame2.70222","DOIUrl":"10.1002/ame2.70222","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Psoriasis is an immune-driven dermatosis marked by keratinocyte hyperproliferation. GS-9620, a TLR7 agonist, previously mitigated EV71-triggered inflammation in mice; here we probe its anti-psoriatic potential and mechanisms.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>IMQ-induced psoriasis-like mice were treated with GS-9620 or MTX; severity was tracked by PASI and histology. Skin/spleen cytokines (IL-1β, IL-6, IL-18, HMGB1, TNF-α) were quantified via ELISA; immune subsets were quantified by flow cytometry. Autophagy proteins (ATG5/12/16 L1) and NLRP3 were assessed by IHC/Western blot. In vitro, M5-stimulated primary keratinocytes were treated with GS-9620 ± autophagy modulators, followed by cytokine and protein analyses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>GS-9620 markedly reduced erythema, scaling and epidermal thickness, lowered skin and systemic cytokines, and decreased splenic CD3⁺/CD4⁺IL-17A⁺ cells. It restored ATG5/12/16 L1 expression while suppressing NLRP3 both in lesions and in M5-stimulated keratinocytes, leading to diminished IL-1β, IL-6, IL-18, HMGB1 and TNF-α release.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>GS-9620 alleviates psoriasis by enhancing autophagy and dampening NLRP3-mediated inflammation, offering a promising therapeutic avenue.</p>\u0000 </section>\u0000 </div>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":"9 7","pages":"1364-1372"},"PeriodicalIF":3.4,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13394422/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148213723","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 novel mouse model of chronic Pseudomonas aeruginosa infection inducing bronchiectasis-like phenotype","authors":"Heng Yang,&nbsp;Yang Liu,&nbsp;Yuqing Wang,&nbsp;Yuhua Wen,&nbsp;Yan Chen,&nbsp;Rui Fan,&nbsp;Jiayan Xu,&nbsp;Shunlian Hu,&nbsp;Hao Qian,&nbsp;Rui Jiang,&nbsp;Weijun Cao,&nbsp;Jinfu Xu","doi":"10.1002/ame2.70245","DOIUrl":"10.1002/ame2.70245","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Given the need to translate basic research into human therapies, the development and refinement of clinically relevant animal models for bronchiectasis are critically important. To date, there are no well-established animal models for bronchiectasis. Thus, our aim was to develop a novel animal model that accurately recapitulates bronchiectasis-like pathologies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>To address this question, clinical strains of chronic <i>Pseudomonas aeruginosa</i> (CPA) were embedded in agar beads in vitro; then CPA-loaded agar beads and papain were repeatedly instilled intratracheally in female C57BL/6 J mice. Experimental assessments included micro-computed tomography (micro-CT) imaging, histological analysis, immune cell infiltration, cytokines, and lung function parameter measurements to evaluate structural damage, immune responses, and lung function impairments in the mouse model.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In this mouse model, we observed that lung micro-CT imaging revealed significant bronchiectasis, with visible airways in the periphery, cylindrical airway expansion, and an airway-to-artery ratio &gt; 1. Histopathology highlighted immune cell infiltration around the trachea, including lymphocytes, neutrophils, and monocytes, along with Periodic acid–Schiff staining-positive hypermucinous secretion. Compared to controls, the bronchiectasis group exhibited elevated pro-inflammatory cytokines in bronchoalveolar lavage fluid and worse lung function.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our study presented a novel mouse model that better replicated the bronchiectasis-like phenotype than the CPA airway infection model, showing the advantages of the “CPA-loaded agar beads and papain”–driven approach in optimizing the disease models. The model mimicked the progression of bronchiectasis closely and could be used for studies on disease pathogenesis as well as the evaluation of novel therapies in the near future.</p>\u0000 </section>\u0000 </div>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":"9 7","pages":"1409-1419"},"PeriodicalIF":3.4,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13394506/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148364382","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":"Humanized immune system animal models and their recent applications","authors":"Nicolas Skuli,&nbsp;Rudra B. Amin,&nbsp;A’ishah Bakayoko,&nbsp;Marisa Kruidenier,&nbsp;Sahara Aqui,&nbsp;Sarah J. Skuli,&nbsp;Terence P. Gade","doi":"10.1002/ame2.70212","DOIUrl":"10.1002/ame2.70212","url":null,"abstract":"<p>Human or humanized immune system (HIS) animal models have emerged as indispensable tools for studying human biology and disease in vivo. By engrafting human hematopoietic and hematopoietic stem cells (HSC) into immunodeficient hosts, these models have enabled the development of a functional HIS, allowing the study of immune responses, disease mechanisms, and therapeutic interventions in a physiologically relevant setting. HIS models have broad applications across cancer research, infectious disease, regenerative medicine, and immunotherapy development. This review provides a comprehensive overview of the current landscape of HIS model generation, including HSC-based approaches, host strain selection, and recent advances involving genetically engineered mouse models expressing human cytokines and human leukocyte antigen molecules. We evaluated the strengths and limitations of these models, including issues with incomplete immune reconstitution and species-specific incompatibilities. We also discuss their increasing role in preclinical drug development and explore emerging innovations such as multitissue humanization and genome-editing strategies. As HIS models continue to evolve, they provide strong opportunities to bridge basic research and clinical translation.</p>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":"9 7","pages":"1310-1324"},"PeriodicalIF":3.4,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13394990/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147847419","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":"Chrysin alleviates pressure overload–induced myocardial remodeling through regulating the PI3K/AKT/NRF2 pathway–mediated oxidative stress response","authors":"Yijia Wang,&nbsp;Xing Feng,&nbsp;Shuhui Zhao,&nbsp;Yuchong Fu,&nbsp;Ao Zhang,&nbsp;Xiaofeng Shen,&nbsp;Bowen Yu,&nbsp;Yihao Wang,&nbsp;Jiahui Lin,&nbsp;Bing Zhang,&nbsp;Weiping Ji,&nbsp;Lianpin Wu,&nbsp;Xiaoling Guo","doi":"10.1002/ame2.70230","DOIUrl":"10.1002/ame2.70230","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Oxidative stress plays a pivotal role in the pathogenesis of heart failure and is closely linked to myocardial remodeling, which includes myocardial hypertrophy and fibrosis. Chrysin (CHR) has multiple medicinal effects such as antioxidant, anti-inflammatory, and anti-apoptosis. This research seeks to investigate whether CHR can protect against pressure overload–induced myocardial remodeling and to explore the underlying mechanism.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Transverse aortic constriction (TAC) surgery was conducted to establish a model of cardiac hypertrophy on male C57BL/6J mice. A model of cardiomyocyte hypertrophy in H9C2 cells induced by angiotensin II (Ang II) was also established.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The results showed that CHR significantly improved survival and cardiac function, reduced myocardial hypertrophy and fibrosis, inhibited the expression of inflammatory mediators TNF-α and IL-1β, suppressed cell apoptosis rate, downregulated the levels of Bcl-2 Associated X protein (BAX) and Cleaved-Caspase-3, and upregulated B-cell lymphoma/leukemia 2 (BCL-2) expression in TAC surgical mice or Ang II-treated H9C2 cells. CHR could also upregulate the levels of antioxidant enzymes SOD1 and HO-1 by mediating the nuclear translocation and expression of NRF2 to counteract oxidative stress response. The further mechanism investigation utilizing bioinformatics analysis and western blot revealed that the disease of heart failure is associated with the phosphatidylinositol‑3‑kinase (PI3K)/serine/threonine-protein kinase B (AKT) signaling pathway.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Collectively, our findings demonstrated that CHR might exert the improvement effects on pressure overload–induced myocardial remodeling with hypertrophy and fibrosis through regulating the PI3K/AKT/NRF2 pathway–mediated oxidative stress response to alleviate myocardial cell inflammation and apoptosis, suggesting that CHR may be a promising therapeutic agent for cardiac diseases induced by pressure overload.</p>\u0000 </section>\u0000 </div>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":"9 7","pages":"1373-1394"},"PeriodicalIF":3.4,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13394667/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148240791","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}