Animal models and experimental medicine最新文献

{"title":"Adenosine monophosphate–activated protein kinase activation is associated with suppression of NLRP3 inflammasome–mediated neuroinflammation in a weight-drop model of traumatic brain injury in Sprague–Dawley rats","authors":"Triveni Kodi,&nbsp;Paka Sravan Kumar,&nbsp;Krishnadas Nandakumar,&nbsp;Anoop Kishore","doi":"10.1002/ame2.70288","DOIUrl":"10.1002/ame2.70288","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Traumatic brain injury (TBI) disrupts adenosine monophosphate–activated protein kinase (AMPK) signaling, impairs energy homeostasis, activates inflammatory pathways, and triggers neuroinflammation. AMPK activators such as metformin (MET), quercetin (QUE), resveratrol (RES), cinnamaldehyde (CIN), and berberine (BER) exhibit anti-inflammatory and neuroprotective properties. However, their role in modulating the nucleotide-binding oligomerization domain, leucine-rich repeat, and pyrin domain-containing protein 3 (NLRP3) inflammasome in TBI-induced neuroinflammation remains unclear. This study investigated the neuroprotective effects of AMPK activators in the weight-drop model of TBI, focusing on suppression of the NLRP3 inflammasome.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Rats received an intraperitoneal administration of AMPK activators—MET (100 mg/kg), QUE (15 mg/kg), RES (25 mg/kg), CIN (25 mg/kg), or BER (50 mg/kg)—from days −3 to 17. TBI was induced on day 1 using the weight-drop method (240 g from 1.5 m). Cognitive performance was evaluated using the novel object recognition test and Morris water maze. Neuroinflammatory markers, including nuclear factor kappa B (NF-κB), NLRP3, pro-caspase-1, interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and microglial polarization markers (CD86 and CD206), were assessed using Western blotting and enzyme-linked immunosorbent assay (ELISA). Oxidative stress and histopathological changes were also examined.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>TBI resulted in cognitive impairment, oxidative stress, and neuronal damage; reduced p-AMPK/AMPK ratio; decreased CD206 levels; and elevated the levels of NF-κB, CD86, TNF-α, and NLRP3 inflammasome components (NLRP3, pro-caspase-1, and IL-1β). Pretreatment with AMPK activators significantly improved cognitive deficits, attenuated oxidative stress and neuroinflammation, restored p-AMPK/AMPK ratio, promoted anti-inflammatory effects, and suppressed NLRP3 inflammasome activation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>AMPK activators exhibited neuroprotection in TBI by improving cognition and regulating oxidative stress, microglial activation, and NLRP3-mediated neuroinflammation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":"9 9","pages":"1849-1868"},"PeriodicalIF":3.4,"publicationDate":"2026-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13586698/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148993157","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":"Comparative analysis of TP53 gene in Tupaia belangeri subspecies (Tupaia belangeri yaoshanensis vs. Tupaia belangeri chinensis) and identification of mutations in spontaneous tumor cases","authors":"Yingying Cao,&nbsp;Haibo Tang,&nbsp;Liang Liang,&nbsp;Jing Leng,&nbsp;Weijian Huang","doi":"10.1002/ame2.70260","DOIUrl":"10.1002/ame2.70260","url":null,"abstract":"<p>The tree shrew (<i>Tupaia belangeri</i>) is an emerging animal model for human diseases, yet the status of the critical tumor suppressor <i>TP53</i> in its subspecies and spontaneous tumors is unknown. We sequenced the entire <i>TP53</i> coding region from two subspecies, <i>T. b. yaoshanensis</i> and <i>T. b. chinensis</i>, and analyzed two spontaneous sarcomas from <i>T. b. yaoshanensis</i> using histopathology, immunohistochemistry, and cDNA sequencing with clonal validation. <i>TP53</i> showed 99.5% nucleotide identity between subspecies, with a single fixed non-synonymous substitution (D42G) in <i>T. b. yaoshanensis</i> predicted to be functionally neutral. All residues corresponding to human cancer hotspots were strictly conserved, and structural modeling confirmed high similarity to human p53 (RMSD = 0.6 Å). Critically, we identified <i>TP53</i> sequence variants in both spontaneous tumors: a missense variant (Ser175Gly) in the DNA-binding domain of a liposarcoma and another (Met344Thr) in the tetramerization domain of a myxofibrosarcoma. Computational prediction suggested both missense variants are tolerated (SIFT scores 0.61 and 0.77), and their functional significance remains to be determined. This study provides preliminary evidence of <i>TP53</i> variants in spontaneous tree shrew tumors and reveals natural subspecies variation. The high conservation of p53 reinforces the tree shrew's relevance as a model for <i>TP53</i>-related cancer research, although further functional studies are needed.</p>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":"9 9","pages":"1901-1909"},"PeriodicalIF":3.4,"publicationDate":"2026-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13479160/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148765946","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":"Baseline podocyte-associated state and persistent cell–matrix transcriptional programs are associated with BALB/c substrain differences in adriamycin nephropathy","authors":"Ryuya Nakagawa,&nbsp;Masaki Watanabe,&nbsp;Koyuki Kawamoto,&nbsp;Momoka Hiratsuka,&nbsp;Takeru Sasaki,&nbsp;Nobuya Sasaki","doi":"10.1002/ame2.70281","DOIUrl":"10.1002/ame2.70281","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Adriamycin (ADR)-induced nephropathy is a widely used murine model of glomerular injury. Although strain-dependent susceptibility is well recognized, variation among closely related substrains remains insufficiently explored.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We compared early responses to ADR between two BALB/c substrains, BALB/cAJcl (AJcl) and BALB/cByJcl (ByJcl), focusing on baseline podocyte-associated features and early glomerular transcriptional programs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Following ADR administration, ByJcl mice developed significantly greater albuminuria at Day 7 compared with AJcl mice. At Day 7, ByJcl mice also showed lower WT1-positive nuclei counts and diminished nephrin immunoreactivity than AJcl mice; notably, these differences were already evident at baseline. Glomerulus-enriched RNA sequencing showed that extracellular matrix organization and integrin signaling were already enriched in ByJcl at baseline and remained enriched at Day 5, when coordinated suppression of podocyte-associated transcriptional programs was also evident.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Substrain-dependent differences in baseline podocyte-associated readouts and a pre-existing cell–matrix transcriptional state that persists after ADR are associated with divergent trajectories of ADR-induced injury. Because WT1-based counts cannot distinguish podocyte number from WT1 expression, these baseline differences are best described as an attenuated podocyte-associated state rather than a definitive reduction in podocyte number. Careful documentation of substrain origin is critical for experimental reproducibility in nephropathy research.</p>\u0000 </section>\u0000 </div>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":"9 9","pages":"1729-1742"},"PeriodicalIF":3.4,"publicationDate":"2026-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13501844/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148809589","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":"Correction to “Porcine kidney xenotransplantation: From primate models to clinical reality”","authors":"","doi":"10.1002/ame2.70284","DOIUrl":"10.1002/ame2.70284","url":null,"abstract":"<p>\u0000 <span>Guo, Z</span>, <span>Zhang, L</span>, <span>Deng, S</span>, <span>Qin, C</span>. <span>Porcine kidney xenotransplantation: from primate models to clinical reality</span>. <i>Animal Model Exp Med</i>. <span>2026</span>; <span>9</span>(<span>6</span>): <span>1142</span>-<span>1166</span>. doi:10.1002/ame2.70195\u0000 </p><p>2. We would like to add the following text to the Acknowledgments section:</p><p>We thank Thomas Binder for editing this manuscript. Thomas Binder is affiliated with the Institut für Transfusionsmedizin, Universitätsmedizin Rostock (UMR).</p><p>The corrected Acknowledgments section should read as follows:</p><p>\u0000 <b>ACKNOWLEDGMENTS</b>\u0000 </p><p>This work was supported by the CAMS Innovation Fund for Medical Sciences (CIFMS) (2025-I2M-FGS-005) and the Non-profit Central Research Institute Fund of the Chinese Academy of Medical Sciences (2023-PT180-01). We thank Thomas Binder for editing this manuscript. Thomas Binder is affiliated with the Institut für Transfusionsmedizin, Universitätsmedizin Rostock (UMR).</p><p>We apologize for these errors.</p>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":"9 9","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13483557/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148802992","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":"The diagnostic value of the circadian rhythm gene KLF10 in anxiety-depressive disorders and its neuroimmune regulatory mechanisms","authors":"Anlan Liu,&nbsp;Weifeng Guo,&nbsp;Jianxiang Li,&nbsp;Tiange Zhang,&nbsp;Dan Xu","doi":"10.1002/ame2.70276","DOIUrl":"10.1002/ame2.70276","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Anxiety-depressive disorder (ADD) is one of the important subtypes of depression, which has been shown to be closely related to neuroimmune abnormalities. Currently, specific biomarkers have not been identified as diagnostic, differential, and therapeutic targets. This study aimed to explore the molecular mechanisms and diagnostic biomarkers of ADD and elucidate its association with neuroinflammation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Differentially expressed circadian rhythm-related genes were screened. Key genes were identified by machine learning. An ADD rat model was established using chronic restraint stress combined with corticosterone administration. Using AAV virus tools for KLF-10 overexpression and knockout (KLF10-OE and shKLF10), depression-like and anxiety-like behaviors were evaluated through behavioral experiments, pathological changes in the hippocampus and amygdala were observed by Nissl staining, cytokine levels were detected by ELISA, molecular co-localization was performed by RNAscope ISH and immunofluorescence, and molecular expression of NF-κB/NLRP3 pathway was detected by Western blot and qRT PCR.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Nine circadian rhythm-related genes showed significant differential expression, with KLF10 identified as a diagnostic biomarker. KLF10 overexpression ameliorated depressive-like and anxiety-like behaviors, and reduced pro-inflammatory factors (IL-1β, TNF-α) and increased anti-inflammatory factors (IL-10, TGF-β) in both brain and serum, the treatment can be blocked by PMA. KLF10 suppressed IκB-α phosphorylation-mediated NF-κB nuclear translocation and inhibited downstream molecules.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>KLF10 mitigates hippocampal-amygdala neuroinflammation by downregulating the NF-κB/NLRP3 pathway, thereby alleviating a ADD symptoms, and represents a potential diagnostic biomarker and therapeutic target.</p>\u0000 </section>\u0000 </div>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":"9 9","pages":"1869-1883"},"PeriodicalIF":3.4,"publicationDate":"2026-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13456114/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148708808","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":"Adipose-derived mesenchymal stem cell injection into the KI10 acupoint mitigates cartilage damage in KOA rats through PGE2-mediated α7nAChR/NF-κB pathway","authors":"Mengwei Dong,&nbsp;Wenfang Li,&nbsp;Wanpeng Yang,&nbsp;Te Ba,&nbsp;Nan Nan,&nbsp;Yang Liu,&nbsp;Jing Han,&nbsp;Huiqin Hao","doi":"10.1002/ame2.70220","DOIUrl":"10.1002/ame2.70220","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Knee osteoarthritis (KOA) is a chronic joint disorder. Current treatment options offer limited benefit. Adipose-derived mesenchymal stem cells (ADSCs), known for their chondrogenic potential and anti-inflammatory and immunomodulatory functions, have gained growing interest in regenerative therapy. Acupoint interventions are widely recognized for analgesic and anti-inflammatory effects. Combining ADSCs with acupoint-targeted delivery may represent a novel therapeutic approach. This study evaluated the therapeutic efficacy and underlying mechanisms of ADSC injection into the KI10 acupoint in mitigating KOA-related cartilage damage.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>KOA models were established in male Sprague–Dawley rats, followed by ADSC injection into the KI10 acupoint. Pain, motor function, and joint structural changes were assessed through ethological testing, imaging, histopathology, transmission electron microscopy, and molecular analyses. TMT-based proteomics was used to identify mechanistic pathways, and the α7nAChR antagonist methyllycaconitine citrate (MLA) was used to validate the pathways.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>ADSC injection into the KI10 acupoint significantly reduced pain and improved motor performance in KOA rats. Imaging and histological analysis revealed significant decreases in synovial inflammation and cartilage degeneration. Transmission electron microscopy confirmed diminished chondrocyte injury. Proteomic analysis indicated activation of the cholinergic anti-inflammatory pathway, and MLA administration reversed these therapeutic benefits, verifying pathway involvement.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>ADSC injection into the KI10 acupoint effectively attenuates cartilage injury and inflammation in KOA by activating the PGE2-mediated α7nAChR/NF-κB signaling pathway. This combined strategy harnesses the complementary advantages of stem cell therapy and acupoint-targeted intervention, offering a promising therapeutic avenue for KOA.</p>\u0000 </section>\u0000 </div>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":"9 9","pages":"1828-1848"},"PeriodicalIF":3.4,"publicationDate":"2026-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13478736/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148763239","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":"Comparison of rat hypertrophic scar models: Caudal tension model with superior pathological consistency","authors":"Lingyi Zhan,&nbsp;Hong Xiang,&nbsp;Yaohui Kong,&nbsp;Yunfeng Lei,&nbsp;Shuqi Xiao,&nbsp;Shiqi Chen,&nbsp;Jiaming Li,&nbsp;Ziwei Li,&nbsp;Rui Ni,&nbsp;Dan Peng,&nbsp;Yao Liu","doi":"10.1002/ame2.70249","DOIUrl":"10.1002/ame2.70249","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Hypertrophic scars (HS) are a common fibrotic disorder in skin wound healing, characterized by excessive fibroblast proliferation and abnormal collagen deposition, with an incidence reaching 40%–70% in burn patients. Current treatments (e.g., corticosteroid injections) face challenges such as high recurrence rates and significant adverse effects, highlighting the urgent need for reliable animal models to investigate pathogenesis and develop novel therapies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Forty-eight male Sprague–Dawley (SD) rats were used to systematically compare modeling efficacy across auricular (3.5 mm corneal trephine), dorsal (linear incision/tension/full-thickness excision), and caudal (linear incision/tension) sites. Each subgroup contained 12 rats (<i>n</i> = 12/group). Scar formation was evaluated over 60 days via macroscopic observation, Vancouver Scar Scale (VSS) scoring, H&amp;E/Masson staining (fibroblast density/collagen deposition), and immunofluorescence α-smooth muscle actin (α-SMA), transforming growth factor beta (TGF-β), type I collagen/type III collagen (COL I/III).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The caudal tension group demonstrated optimal outcomes, with scar thickness (0.394 ± 0.006 mm), fibroblast density (1079 ± 118 cells/mm²), and collagen deposition (90.6% ± 2.4%) significantly higher than other groups (***<i>p</i> &lt; 0.001), alongside sustained upregulation of α-SMA and TGF-β. The auricular site was excluded due to rapid self-healing.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The tension method on the tail is a simple, stable, and clinically relevant HS model, effectively replicating human pathological features and providing an ideal platform for disease mechanism research and drug screening.</p>\u0000 </section>\u0000 </div>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":"9 9","pages":"1701-1711"},"PeriodicalIF":3.4,"publicationDate":"2026-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13394272/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148458089","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":"Establishment and characterization of mouse lymph node fibrosis models","authors":"Yaru Niu,&nbsp;Xu Guan,&nbsp;Jian Ma,&nbsp;Xin Zhang,&nbsp;Yihang Shi,&nbsp;Jinzhu Zhang,&nbsp;Leiqiong Gao,&nbsp;Wei Chen,&nbsp;Xishan Wang","doi":"10.1002/ame2.70261","DOIUrl":"10.1002/ame2.70261","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Lymph node (LN) fibrosis occurs in a variety of pathological conditions, including HIV infection, obesity, cancer, and tissue injury. Fibroblastic reticular cells (FRCs) play a critical role in maintaining LN architecture and immune homeostasis, whereas their dysregulation promotes extracellular matrix (ECM) deposition and immune dysfunction. Transforming growth factor-β1 (TGF-β1) is a key profibrotic cytokine. However, reliable and convenient animal models for investigating LN fibrosis remain limited.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This study comprehensively compared four induction methods: footpad injection of TGF-β1, lymphatic vessel ligation, inguinal subcutaneous injection of TGF-β1, and direct intra-LN injection of TGF-β1. Histological analysis, transcriptomic profiling, flow cytometric analysis, and safety evaluation were performed to assess fibrosis and immune alterations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among the four approaches, inguinal subcutaneous and intra-LN injection of TGF-β1 successfully induced LN fibrosis without causing significant injury to major organs. Notably, the intra-LN injection model induced fibrosis in both cortical and medullary regions of LNs. Comparing the transcriptomic data of fibrotic and non-fibrotic LNs demonstrated marked changes in fibrosis-related genes, including pro-fibrogenic mediators, collagens and basement membrane-related genes, and TGF-β1-associated signaling pathways. In two fibrotic models, we also noticed increased macrophage infiltration and a drop in CD8⁺ T cells, suggesting an immune suppressive microenvironment. Furthermore, inhibition of collagen cross-linking partially alleviated fibrotic remodeling in fibrotic LNs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>We established and characterized two mouse models of LN fibrosis induced by TGF-β1 administration. These models provide valuable tools for investigating the mechanisms of LN fibrosis and its impact on local immune regulation, and may facilitate the development of therapeutic strategies targeting fibrotic LNs.</p>\u0000 </section>\u0000 </div>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":"9 9","pages":"1782-1794"},"PeriodicalIF":3.4,"publicationDate":"2026-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13430925/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148665351","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 therapeutic effects of D-limonene following orchiopexy in the rat model of cryptorchidism","authors":"Arman Norouzi-Ghalehbala,&nbsp;Mohammadjavad Rezaei-Varmaziar,&nbsp;Majid Taati,&nbsp;Ali Soleimanzadeh,&nbsp;Abbas Raisi,&nbsp;Farshid Davoodi,&nbsp;Amir Ali Shahbazfar","doi":"10.1002/ame2.70253","DOIUrl":"10.1002/ame2.70253","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Cryptorchidism impairs spermatogenesis, causes infertility, and increases malignancy risk. Orchiopexy, the standard treatment, often fails to fully restore testicular function. This study evaluated the adjunctive effects of D-limonene in prepubertal rats with bilateral cryptorchidism.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Twenty-four male rats were allocated into four groups: sham-operated (SH), cryptorchid control with orchiopexy (CT), and two orchiopexy groups receiving low-dose (50 mg/kg, Lim-50) or high-dose (100 mg/kg, Lim-100) D-limonene. Assessments included oxidative stress markers in testicular tissue (total antioxidant capacity [TAC], malondialdehyde [MDA], superoxide dismutase [SOD], and glutathione peroxidase [GPx]), macroscopic indices (testicular index [TI], absolute testicular weight [TW], and testicular weight index [TWI]), histopathological parameters (Johnsen score [JS], epithelial height [EHS], and seminiferous tubule diameter [STD]), apoptosis-related proteins (Bax, Bcl-2, Caspase-3, and TNF-α), serum testosterone, and sperm parameters.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>D-limonene improved several indices of testicular injury following orchiopexy in cryptorchid rats. Both treatment doses increased TAC, while the higher dose more effectively reduced MDA and improved SOD activity. Testicular morphometric and histopathological parameters, including TW, TI, TWI, JS, EHS, and STD, were significantly improved. D-Limonene also decreased pro-apoptotic markers (Bax and Cleaved Caspase-3), increased anti-apoptotic markers (Bcl-2 and Pro-Caspase-3), reduced TNF-α expression and apoptotic cell counts, and enhanced serum testosterone and sperm quality. However, full normalization of all parameters was not achieved.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Adjunctive D-limonene administration following orchiopexy attenuated oxidative stress, inflammation, and apoptosis, and partially restored testicular structure and function in experimental cryptorchidism. These findings support D-limonene as a promising supplementary strategy with partial but meaningful protective effects.</p>\u0000 </section>\u0000 </div>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":"9 9","pages":"1884-1900"},"PeriodicalIF":3.4,"publicationDate":"2026-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13402648/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148594982","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":"Construction and evaluation of a chronic arthritis animal model induced by persistent activation of toll-like receptors via lipopolysaccharide stimulation","authors":"Fengming Li,&nbsp;Qiang Luo,&nbsp;Xinglin Wu,&nbsp;Yuxiao Chen,&nbsp;Xuemei Tang","doi":"10.1002/ame2.70290","DOIUrl":"10.1002/ame2.70290","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Systemic juvenile idiopathic arthritis (sJIA) is a chronic arthritis characterized primarily by systemic inflammatory responses. However, its pathogenesis remains incompletely understood and may be related to the activation of Toll-like receptors (TLRs). To overcome limitations of existing models, this study develops an animal model mimicking sJIA systemic inflammatory features via TLR4 activation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We integrated multi-center single-cell and bulk RNA-seq data from sJIA patients and healthy children to assess TLR pathway activity. Based on the analysis of differentially expressed TLR molecules, we identified TLR4 as an important factor. A chronic arthritis mouse model (LC) was constructed by introducing sustained TLR4 activation into the collagen-induced arthritis (CIA) model. The general condition, inflammation, and joint pathology were evaluated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In sJIA patients, TLR pathway activation, particularly in monocytes, was identified as a key feature. Bulk RNA-seq analysis revealed TLR4 expression was significantly upregulated in sJIA. The LC mouse model exhibited pronounced systemic inflammation, including fever, weight loss, splenomegaly, and elevated inflammatory cytokines (IL-18, TNF-α, IFN-γ). Immunofluorescence confirmed significant CD163⁺ macrophage infiltration in the liver of LC mice. Interestingly, despite the exacerbated systemic inflammation, the LC mice exhibited milder joint damage, lower arthritis scores, and less cartilage degradation compared to the CIA group, demonstrating a dissociation between systemic inflammation and joint pathology.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This study identifies sustained TLR4 activation as a critical driver of systemic inflammation in sJIA. The LC model effectively recapitulates systemic features of sJIA while revealing a dissociation between systemic inflammation and joint damage.</p>\u0000 </section>\u0000 </div>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":"9 9","pages":"1795-1812"},"PeriodicalIF":3.4,"publicationDate":"2026-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13602179/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149042556","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}