Animal models and experimental medicine最新文献

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Cistanche tubulosa improves peripheral neuropathy in MPTP-induced PD mice based on regulation of m6A methylation. 肉苁梗通过调节m6A甲基化改善mptp诱导的PD小鼠周围神经病变。
Animal models and experimental medicine Pub Date : 2025-07-11 DOI: 10.1002/ame2.70039
Yatan Li, Wei Jia, Junhua Hu, Borui Zhang, Xinxin Qi, Jianhua Yang, Xinling Yang
{"title":"Cistanche tubulosa improves peripheral neuropathy in MPTP-induced PD mice based on regulation of m6A methylation.","authors":"Yatan Li, Wei Jia, Junhua Hu, Borui Zhang, Xinxin Qi, Jianhua Yang, Xinling Yang","doi":"10.1002/ame2.70039","DOIUrl":"https://doi.org/10.1002/ame2.70039","url":null,"abstract":"<p><strong>Background: </strong>This study aimed to discover whether Cistanche tubulosa affects the AKT/CASP3 pathway by regulating m6A methylation, to exert a protective effect against peripheral nerve injury in a Parkinson's Disease (PD) mouse model.</p><p><strong>Methods: </strong>In this study, network pharmacology analysis and the molecular docking virtual screening technique was used to filter Acteoside (Act), a potential neuroprotective agent of active components in Cistanche tubulosa. A PD-related peripheral neuropathy mouse model was established by MPTP induction, followed by 21 days treatment of oral Act (25, 50, and 100 mg kg<sup>-1</sup>). Pole climbing, automatic avoidance ability and hot plate sensory tests were evaluated to determine behavioral changes caused by central and peripheral nerve injury. The pathological alterations of dorsal root ganglion tissue and the protein levels of IL-6, AKT, and CASP3 under Act intervention, as well as the dynamic changes of FTO, METTL3, and YTHDF2 which are closely related to m6A methylation, were comprehensively analyzed to observe the peripheral nerve protective efficacy of Act.</p><p><strong>Results: </strong>The results showed that peripheral neuropathy occurring with PD in the mouse model, which could be verified by behavioral tests and pathological histological changes. In addition to the previously established protective effect of Act on dopaminergic neurons in substantia nigra (SN), extensive follow-up studies demonstrated that Act effectively induced m6A methylation, which could further regulate the AKT/CASP3 pathway to play a therapeutic role. In this study, medium and high doses of Act played more obvious therapeutic roles.</p><p><strong>Conclusion: </strong>These findings suggest that Act may regulate the severity of peripheral nerve injury under the activation of the AKT/CASP3 signaling pathway by balancing the methylation level of m6A. These results provide a theoretical basis and experimental evidence for further research on the protective effect of Cistanche tubulosa on both the central and peripheral nerves in the treatment of PD.</p>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144610547","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Harnessing the multidimensional bioactivity of Chaetomorpha aerea: Integrative phytochemical profiling with in vitro, in vivo, and in silico insights. 利用毛茛的多维生物活性:综合植物化学分析与体外,体内和计算机见解。
Animal models and experimental medicine Pub Date : 2025-07-11 DOI: 10.1002/ame2.70064
Md Mahmudul Hasan, Md Abdul Alim, Md Safayat Hossen Momen, Md Shahidul Islam, Sajjad Hossen Chowdhury, Mohammad Rashed, Fahmina Hoque, S M Moazzem Hossen
{"title":"Harnessing the multidimensional bioactivity of Chaetomorpha aerea: Integrative phytochemical profiling with in vitro, in vivo, and in silico insights.","authors":"Md Mahmudul Hasan, Md Abdul Alim, Md Safayat Hossen Momen, Md Shahidul Islam, Sajjad Hossen Chowdhury, Mohammad Rashed, Fahmina Hoque, S M Moazzem Hossen","doi":"10.1002/ame2.70064","DOIUrl":"https://doi.org/10.1002/ame2.70064","url":null,"abstract":"<p><strong>Background: </strong>Chaetomorpha aerea, a marine green alga, has drawn attention because of its rich phytochemical constituents and therapeutic benefits. Using an integrated approach that combined in vitro, in vivo, and in silico approaches, this work examined the antioxidant, anti-inflammatory, and antidiabetic qualities of acetone extract of C. aerea (AECA).</p><p><strong>Methods: </strong>Total phenolic and flavonoid concentrations of AECA were measured. Antioxidant activity was assessed using the DPPH and ABTS free radical scavenging assays. In vitro protein denaturation and in vivo carrageenan-induced paw edema models were employed to evaluate the anti-inflammatory potential, whereas antidiabetic activity was assessed using in vitro α-amylase inhibition and in vivo oral glucose tolerance test (OGTT). Molecular docking and ADME/T analysis were employed to further analyze bioactive compounds identified using gas chromatography-mass spectrometry (GC-MS).</p><p><strong>Result: </strong>Antioxidant activity demonstrated a minimum inhibitory concentration (IC<sub>50</sub>) of 107.44 μg/mL for DPPH and 118.23 μg/mL for ABTS. In vitro anti-inflammatory assays indicated a suppression of protein denaturation at a concentration of 102 μg/mL (IC<sub>50</sub>), where AECA (400 mg/kg) resulted in a 27% reduction in paw edema at 6 h in the mouse model. In vitro antidiabetic test indicated α-amylase inhibition with an IC<sub>50</sub> value of 70.72 μg/mL, and in the OGTT, a significant lowering of blood glucose was recorded at 120 min in mice. Strong binding affinities were observed for stigmasta-5,24(28)-dien-3-ol, identified using GC-MS, with values of -9.9 kcal/mol for α-amylase and - 8.0 kcal/mol for cyclooxygenase-2.</p><p><strong>Conclusion: </strong>C. aerea serves as an effective natural remedy for oxidative stress, inflammation, and hyperglycemia. These findings advocate for further clinical and mechanistic investigations to optimize therapeutic efficacy.</p>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144610581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Sheep femoral artery occlusion is well tolerated and does not result in ischemia. 绵羊股动脉闭塞具有良好的耐受性,不会导致缺血。
Animal models and experimental medicine Pub Date : 2025-07-11 DOI: 10.1002/ame2.70065
Timothy Shiraev, Ziyu Wang, Lakshay Seth, Lisa Partel, Innes K Wise, Hugh Paterson, John O'Sullivan, Sean Lal, Anthony S Weiss, Paul Bannon, Robert D Hume
{"title":"Sheep femoral artery occlusion is well tolerated and does not result in ischemia.","authors":"Timothy Shiraev, Ziyu Wang, Lakshay Seth, Lisa Partel, Innes K Wise, Hugh Paterson, John O'Sullivan, Sean Lal, Anthony S Weiss, Paul Bannon, Robert D Hume","doi":"10.1002/ame2.70065","DOIUrl":"https://doi.org/10.1002/ame2.70065","url":null,"abstract":"<p><strong>Objective: </strong>Sheep are commonly used as large animal pre-clinical models for investigating cardiovascular therapies, interventions, anatomy and physiology. Further, novel small diameter vascular grafts are frequently tested via implantation into sheep carotid arteries (CAs). This is because, unlike humans, acute occlusion of one or both sheep CAs is not associated with morbidity or mortality and thus provides safer experimental testing, with reduced ethical constraints, animal numbers and costs. However, to date there has been no evidence regarding sheep tolerance of femoral artery (FA) occlusion.</p><p><strong>Methods: </strong>In this study, seven sheep underwent CA graft surgery, with digital subtraction angiography (DSA) of the CAs performed every 2 months via femoral access, for a total of 8 months. Four months into the study, the left FA of two sheep became inaccessible due to a suspected FA occlusion. Thus, femoral angiography was performed, followed by FA dissection, FA histology and retrospective analysis of both veterinarian animal monitoring and pain scores.</p><p><strong>Results: </strong>FA angiography and histology confirmed complete left FA occlusion in two sheep. Retrospective animal monitoring demonstrated sheep with occluded FAs did not display increased pain scores or deleterious effects on their gait or wellbeing.</p><p><strong>Conclusion: </strong>Our data shows that sheep tolerate FA occlusion with no symptoms, similar to their cerebral circulation, making them an appropriate model for assessing small diameter femoral graft interposition studies and testing other cardiovascular interventions.</p>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144610582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Systematic review of the subcutaneous air pouch model using monosodium urate and calcium pyrophosphate and recommendations for studying crystal-related arthropathies. 系统回顾了使用尿酸钠和焦磷酸钙的皮下气囊模型,以及对研究晶体相关关节病的建议。
Animal models and experimental medicine Pub Date : 2025-07-11 DOI: 10.1002/ame2.70058
Wenu Hewage, Josif Vidimce, Ryan G Shiels, Michael Morgan, Andrew C Bulmer
{"title":"Systematic review of the subcutaneous air pouch model using monosodium urate and calcium pyrophosphate and recommendations for studying crystal-related arthropathies.","authors":"Wenu Hewage, Josif Vidimce, Ryan G Shiels, Michael Morgan, Andrew C Bulmer","doi":"10.1002/ame2.70058","DOIUrl":"https://doi.org/10.1002/ame2.70058","url":null,"abstract":"<p><p>The subcutaneous air pouch model has been used extensively to study the pathophysiology of inflammatory conditions such as joint diseases and the potential efficacy of pharmacological treatments in vivo. Delivery of air between the subcutaneous and dermal layer of the intra-scapular zone of the rodent generates an environment analogous to the synovial joint space. Introduction of monosodium urate crystals or calcium pyrophosphate crystals into the air space produces a sterile acute inflammatory response mimicking clinical gout and pseudogout, respectively. The inflammatory response can be quantitatively and robustly evaluated by measuring leukocyte infiltration, inflammatory cytokine production, eicosanoid release, complement activation and reactive oxygen species generation. Despite the utility of this model, great variation exists within the literature regarding the design, sampling time points, and endpoints measured. This systematic review summarizes the current literature on the subcutaneous air pouch model studying monosodium urate or calcium pyrophosphate crystals and provides recommendations for standardizing and improving the reliability and validity of this model. Standardizing the experimental approach would improve inter-study comparability, increase the internal validity of studies and reproducibility of results, and ultimately improve the understanding of gout and pseudogout and accelerate the discovery of new pharmacological therapies.</p>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144610583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A Drosophila model of prion disease and its metabolic changes in the brain. 朊病毒疾病的果蝇模型及其在大脑中的代谢变化。
Animal models and experimental medicine Pub Date : 2025-07-09 DOI: 10.1002/ame2.70048
Dongdong Wang, Zhixin Sun, Pei Wen, Mengyang Zhao, Yuheng He, Fengting Gou, Jingjing Wang, Qing Fan, Xueyuan Li, Tianying Ma, Xiaoyu Wang, Wen Li, Sen Chen, Deming Zhao, Lifeng Yang
{"title":"A Drosophila model of prion disease and its metabolic changes in the brain.","authors":"Dongdong Wang, Zhixin Sun, Pei Wen, Mengyang Zhao, Yuheng He, Fengting Gou, Jingjing Wang, Qing Fan, Xueyuan Li, Tianying Ma, Xiaoyu Wang, Wen Li, Sen Chen, Deming Zhao, Lifeng Yang","doi":"10.1002/ame2.70048","DOIUrl":"https://doi.org/10.1002/ame2.70048","url":null,"abstract":"<p><strong>Background: </strong>Prion diseases (PrDs) are fatal transmissible neurodegenerative disorders caused by misfolded prion protein, which is highly expressed in the brain. Drosophila has been employed as a model system for studying mammalian neurodegenerative diseases.</p><p><strong>Methods: </strong>Drosophila transgenic for hamster prion protein (HaPrP) was generated by Valium20 transformation. Locomotion, longevity, protease resistance, and histology were assessed, and nontargeted metabolomics analyses were performed to investigate the changes in Drosophila metabolism with the HaPrP expression and metformin treatment.</p><p><strong>Results: </strong>The Drosophila model exhibited pan-neuronal expression of HaPrP, with expression levels increasing with age. Flies displayed reduced climbing ability, shortened lifespan, and vacuolar structures in the brain. Additionally, HaPrP expressed in older flies demonstrated resistance to digestion by 5 μg/mL Proteinase K. The Drosophila model also displayed alterations in protein, lipid, and carbohydrate metabolism. We hypothesize that glutamate, N-acetylaspartate, ceramide, phosphatidylethanolamine, dihydroxyacetone phosphate, ribose-5-phosphate, and pyruvate are key metabolites potentially related to PrDs. Metformin improved locomotor activity, reduced PrP<sup>res</sup> formation, and ameliorated mitochondrial dysfunction in flies, which may be associated with alterations in succinate, pyruvate, choline, and sphingomyelin levels.</p><p><strong>Conclusions: </strong>We generated a Drosophila model of PrDs that recapitulates key pathological features observed in mammals. Preliminary applications have demonstrated that the Drosophila model is suitable for PrDs research and the high-throughput screening of potential therapeutic compounds.</p>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144593159","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Long noncoding RNA GCH1 mediates mitophagy via the PTEN-induced kinase 1/Parkin pathway to drive chondrocyte dysfunction and cartilage degeneration in osteoarthritis. 长链非编码RNA GCH1通过pten诱导的激酶1/Parkin途径介导线粒体自噬,驱动骨关节炎的软骨细胞功能障碍和软骨退变。
Animal models and experimental medicine Pub Date : 2025-07-09 DOI: 10.1002/ame2.70057
Gang Zeng, Yujun Sun, Taihe Liu, Wenzhou Liu, Yanbo Chen, Jionglin Wu, Jiayuan Zheng, Weidong Song, Yue Ding
{"title":"Long noncoding RNA GCH1 mediates mitophagy via the PTEN-induced kinase 1/Parkin pathway to drive chondrocyte dysfunction and cartilage degeneration in osteoarthritis.","authors":"Gang Zeng, Yujun Sun, Taihe Liu, Wenzhou Liu, Yanbo Chen, Jionglin Wu, Jiayuan Zheng, Weidong Song, Yue Ding","doi":"10.1002/ame2.70057","DOIUrl":"https://doi.org/10.1002/ame2.70057","url":null,"abstract":"<p><strong>Background: </strong>Osteoarthritis (OA) is a common degenerative joint disease characterized by the progressive degradation of articular cartilage. Mitochondrial dysfunction and autophagy, including mitophagy, have been implicated in OA pathogenesis. Long noncoding RNAs (lncRNA) are emerging as key regulators in various cellular processes, but their roles in OA, particularly in chondrocytes, remain poorly understood. This study explores the involvement of lncRNA-GCH1 in regulating mitophagy and its impact on chondrocyte function and cartilage degradation in OA.</p><p><strong>Methods: </strong>Primary chondrocytes were isolated from the cartilage tissues of OA patients and healthy controls. lncRNA-GCH1 expression was assessed using RNA-seq, reverse transcription quantitative polymerase chain reaction, and RNA fluorescence in situ hybridization. Functional assays, including Cell Counting Kit-8 (CCK-8), colony formation, flow cytometry, and Western blotting, were used to evaluate the effects of lncRNA-GCH1 knockdown on chondrocyte proliferation, apoptosis, cell cycle, and mitophagy. Mitochondrial function was assessed by measuring adenosine triphosphate production, reactive oxygen species levels, and mitochondrial membrane potential. In vivo, a murine OA model was used to examine the impact of lncRNA-GCH1 knockdown on cartilage degradation.</p><p><strong>Results: </strong>lncRNA-GCH1 was upregulated in OA chondrocytes and localized in the cytoplasm. Knockdown of lncRNA-GCH1 enhanced cell proliferation and arrested cell cycle in G0/G1. It also suppressed mitophagy, improved mitochondrial function, and reduced matrix-degrading enzyme expression-effects that were reversed by rapamycin treatment. Meanwhile, lncRNA-GCH1 knockdown reduced PTEN-induced kinase 1 (PINK1) aggregation and in vivo local inhibition of PINK1 diminished cartilage degradation.</p><p><strong>Conclusion: </strong>lncRNA-GCH1 regulates mitophagy in OA chondrocytes, influencing mitochondrial function and matrix degradation. Targeting lncRNA-GCH1 may offer a potential therapeutic approach for OA treatment.</p>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144602526","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Changes in hemodynamics of pulmonary artery using Flowire in a canine model of acute pulmonary thromboembolism. 用Flowire观察犬急性肺血栓栓塞模型肺动脉血流动力学的变化。
Animal models and experimental medicine Pub Date : 2025-07-08 DOI: 10.1002/ame2.70061
Tomohiko Yoshida, Katsuhiro Matsuura, Akiko Uemura, Ryou Tanaka
{"title":"Changes in hemodynamics of pulmonary artery using Flowire in a canine model of acute pulmonary thromboembolism.","authors":"Tomohiko Yoshida, Katsuhiro Matsuura, Akiko Uemura, Ryou Tanaka","doi":"10.1002/ame2.70061","DOIUrl":"https://doi.org/10.1002/ame2.70061","url":null,"abstract":"<p><strong>Background: </strong>Pulmonary hypertension (PH) is a life-threatening condition that can be triggered by pulmonary thromboembolism (PTE), which causes abrupt increases in pulmonary artery pressure and resistance. Although Doppler echocardiography is a useful screening tool, its ability to accurately reflect rapid hemodynamic changes during acute PTE remains limited. The Flowire catheter allows for real-time assessment of intravascular flow and may offer better insight into these changes.</p><p><strong>Aims: </strong>The aims were to investigate changes in pulmonary artery hemodynamics measured using a Flowire catheter and to validate the accuracy of Doppler echocardiography in assessing these changes in dogs with acute pulmonary thromboembolism (PTE).</p><p><strong>Methods: </strong>Hemodynamic and echocardiographic data were obtained from 10 anesthetized female beagles using a Flowire catheter and echocardiography at three preload conditions: baseline, bolus loading, and an acute pulmonary hypertension state induced by a 300-μm dextran microsphere injection.</p><p><strong>Results: </strong>With increases in pulmonary artery pressure and pulmonary vascular resistance, the proximal and distal pulmonary artery flow peak measured using the Flowire catheter significantly decreased during the acute pulmonary hypertension period. Echocardiography did not accurately capture these hemodynamic changes and tended to overestimate pulmonary artery flow peak in the distal pulmonary artery.</p><p><strong>Conclusion: </strong>Doppler echocardiography has limitations in accurately reflecting complex hemodynamic changes during acute PTE. In contrast, Flowire catheterization provides additional and precise local hemodynamic information.</p>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144593160","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Therapeutic targeting of myeloid cells in liver fibrosis: Mechanisms and clinical prospects. 髓细胞在肝纤维化中的靶向治疗:机制和临床前景。
Animal models and experimental medicine Pub Date : 2025-07-08 DOI: 10.1002/ame2.70053
Yue Wang, Yiming Liu, Dan Chen, Leiming Liu, Leimin Sun, Lingling Zhang
{"title":"Therapeutic targeting of myeloid cells in liver fibrosis: Mechanisms and clinical prospects.","authors":"Yue Wang, Yiming Liu, Dan Chen, Leiming Liu, Leimin Sun, Lingling Zhang","doi":"10.1002/ame2.70053","DOIUrl":"https://doi.org/10.1002/ame2.70053","url":null,"abstract":"<p><p>Liver fibrosis, a hallmark pathological endpoint of chronic aging-related liver diseases, remains a clinical challenge with limited therapeutic options. In healthy liver, myeloid cells constitute <5% of total hepatic immune cells, primarily comprising tissue-resident Kupffer cells. However, during aging or chronic injury, bone marrow-derived myeloid cell recruitment increases by two- to threefold in murine fibrotic models, reaching 15%-20% of intrahepatic immune populations. These infiltrating myeloid subsets exhibit functional plasticity, dynamically differentiating into pro-inflammatory macrophages or fibrosis-promoting Kupffer-like cells, contingent upon chemokine gradients (e.g., CCL2/CCR2 axis) and damage-associated molecular patterns (DAMPs). This review systematically examines the regulatory mechanisms of myeloid cells in liver fibrogenesis, with particular emphasis on their developmental origins, hepatic recruitment dynamics, functional heterogeneity, and pathogenic contributions to fibrosis. Furthermore, signaling pathways involving myeloid cells in liver fibrosis and therapeutic approaches modulating their differentiation and recruitment are discussed in this review.</p>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144593161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Achieving scalable expansion of therapeutic porcine hepatocytes in vivo through serial transplantation. 通过连续移植实现治疗性猪肝细胞在体内的可扩展扩展。
Animal models and experimental medicine Pub Date : 2025-06-30 DOI: 10.1002/ame2.70052
Zhiqiang Han, Xin Wang, Dawei Yu, Jing Wang, Ke Sun, Siqi Wang, Ying Zhang, Guihai Feng, Wei Li, Tang Hai, Jilong Ren
{"title":"Achieving scalable expansion of therapeutic porcine hepatocytes in vivo through serial transplantation.","authors":"Zhiqiang Han, Xin Wang, Dawei Yu, Jing Wang, Ke Sun, Siqi Wang, Ying Zhang, Guihai Feng, Wei Li, Tang Hai, Jilong Ren","doi":"10.1002/ame2.70052","DOIUrl":"https://doi.org/10.1002/ame2.70052","url":null,"abstract":"<p><p>The clinical application of hepatocyte transplantation has been significantly hindered by the scarcity of primary hepatocytes and the functional immaturity of in vitro-produced hepatocytes. By performing serial allogeneic hepatocyte transplantation in CRISPR/Cas9-mediated Fah-knockout pigs, we successfully achieved large-scale expansion of hepatocytes while maintaining their authentic biological characteristics. Particularly, the established model enables sustained in vivo liver reconstruction, concurrently ameliorating hepatic fibrosis and demonstrating functional microenvironmental remodeling. Moreover, through comprehensive single-cell transcriptomic profiling of 52 418 hepatocytes across transplant generations (F0-F2), we discovered that the cellular composition of these transplanted hepatocytes is similar to that of wild-type hepatocytes. The regenerated liver exhibits all six major hepatic cell types identical to the wild-type counterparts, with the characteristic lobular zonation patterns well preserved. Our research provides valuable insights into the large-scale expansion of physiologically functional hepatocytes in vivo without compromising their biological properties. This finding holds great promise for advancing the clinical application of human hepatocyte transplantation, potentially offering more effective treatment options for patients with liver diseases.</p>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144531608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Diosgenin ameliorates silica-induced tuberculosis in rats. 薯蓣皂苷元改善大鼠二氧化硅诱发结核。
Animal models and experimental medicine Pub Date : 2025-06-30 DOI: 10.1002/ame2.70055
Williams Asamoah Adu, Selase Ativui, Michael Ofori, George Owusu, Cynthia Amaning Danquah, Paul Poku Sampene Ossei
{"title":"Diosgenin ameliorates silica-induced tuberculosis in rats.","authors":"Williams Asamoah Adu, Selase Ativui, Michael Ofori, George Owusu, Cynthia Amaning Danquah, Paul Poku Sampene Ossei","doi":"10.1002/ame2.70055","DOIUrl":"https://doi.org/10.1002/ame2.70055","url":null,"abstract":"<p><strong>Background: </strong>Silicosis is an occupational lung disease that is caused by chronic exposure to silica dust. Silica-exposed workers are at higher risk of developing TB, resulting in lung fibrosis and significant respiratory dysfunction. Diosgenin is a steroidal saponin that has been shown to exert a therapeutic effect on lung injury. Therefore, we investigated the potential efficacy of diosgenin in treating silicotuberculosis by evaluating its effectiveness against Mycobacterium smegmatis, as well as its antifibrotic and antioxidant effects in silica-induced TB in rats.</p><p><strong>Methods: </strong>Silicosis was induced by intratracheal instillation of 50 mg/kg crystalline silica in Sprague-Dawley rats. Rats were grouped into 7 (10 per group). Different doses of diosgenin (1, 10, and 20 mg/kg) and saline were administered for 30 days. Afterwards, five rats from each group were sacrificed, and the five remaining rats in each group, except the control, received Mycobacterium smegmatis. Treatment continued until the 50th day, and the animals were sacrificed at the end of the experiment. The result was analyzed using a one-way analysis of variance (ANOVA) with GraphPad Prism.</p><p><strong>Results: </strong>At a half-maximal inhibition concentration of 0.006043 μg/mL, diosgenin inhibited the growth of Mycobacterium smegmatis. Oxidative stress markers such as malondialdehyde were significantly reduced. The health-enhancing effects of catalase and superoxide dismutase were elevated. Additionally, histological findings demonstrated a significant improvement in respiratory function following diosgenin treatment.</p><p><strong>Conclusion: </strong>Diosgenin treatment inhibited the growth of Mycobacterium smegmatis, leading to a reduction in the susceptibility of rats to infection and improved pulmonary function through its antioxidant effect.</p>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144531609","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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