Animal models and experimental medicine最新文献

{"title":"Refining OVCAR-3 xenograft models of peritoneal carcinomatosis in nu/nu mice: Comparative intraperitoneal implantation strategies and the role of basement membrane matrix.","authors":"M Teresa Perelló-Trias, Antonio Jose Serrano-Muñoz, Juan J Segura-Sampedro, Adriana M Quintero-Duarte, Joana M Ramis, Marta Monjo","doi":"10.1002/ame2.70280","DOIUrl":"10.1002/ame2.70280","url":null,"abstract":"<p><strong>Background: </strong>Ovarian cancer (OC) is often diagnosed at advanced stages, with extensive peritoneal carcinomatosis (PC) and poor prognosis. Although intraperitoneal drug delivery systems (iDDS) are promising for targeting residual microscopic disease after cytoreductive surgery, reproducible murine PC models remain limited. We compared two OVCAR-3-based intraperitoneal engraftment strategies (diffuse vs. localized) and assessed the impact of inoculum density and basement membrane extract (BME) supplementation to identify a robust model for iDDS evaluation.</p><p><strong>Methods: </strong>Immunodeficient female nu/nu mice were engrafted with luciferase-expressing OVCAR-3 cells. For localized implantation, 1 × 10⁶ or 4 × 10⁶ cells were implanted into the preperitoneal space behind the rectus abdominis; after assessment, the 1 × 10⁶ group was tested with basement membrane extract (BME). In the intraperitoneal dissemination model, 1 × 10⁶ cells were injected with BME to promote diffuse peritoneal spread. Tumor progression was monitored weekly using bioluminescence imaging (BLI), and animals were sacrificed for macroscopic, histological, and immunohistochemical analyses.</p><p><strong>Results: </strong>In the localized model, no differences were detected between 1 × 10⁶ and 4 × 10⁶ cells; therefore, 1 × 10⁶ was selected for subsequent experiments. BME increased early tumor volume and attenuated the initial BLI decline, but signal and tomographic measurements progressively decreased. Histology revealed extracellular matrix remodeling, apoptosis, and tumor regression, indicating limited long-term viability. In contrast, the intraperitoneal injection model generated a clinically relevant dissemination pattern. After an initial decrease, BLI increased steadily, and necropsy confirmed tumor nodules along abdominal organ surfaces.</p><p><strong>Conclusions: </strong>The intraperitoneal injection model with BME more accurately reproduced human PC progression and distribution, providing a platform for preclinical testing of localized iDDS.</p>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13527296/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148868212","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":"Single-cell atlas of neuroglial dynamics in SNCA-A53T Parkinson's disease mouse model","authors":"Binqing Qin,&nbsp;Zichu Fu,&nbsp;Xuanxuan Zou,&nbsp;Senmao Chai,&nbsp;Jingjing Weng,&nbsp;Puqing Wang,&nbsp;Xiaodong Sun,&nbsp;Ming Sang","doi":"10.1002/ame2.70252","DOIUrl":"10.1002/ame2.70252","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Parkinson's disease (PD) is a neurodegenerative disorder characterized by progressive degeneration of midbrain substantia nigra dopaminergic neurons, resulting in striatal dopamine depletion and motor dysfunction. While this pathological cascade is well-established, its underlying mechanisms remain elusive.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>To further investigate the pathological mechanisms of PD, we performed single-cell RNA sequencing of the midbrain and striatum from Hua-Syn (SNCA*A53T) transgenic (A53T) mice as a PD model.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Analysis of 22 865 midbrain and 32 117 striatal cells revealed cell-type-specific risk association. Glial populations (astrocytes, microglia, oligodendrocytes) showed significant enrichment for PD-risk genes. Variance-based clustering identified PD-enriched subclusters exhibiting upregulated inflammatory pathways, apoptotic pathways, proteostasis disruption, glutamatergic signaling dysregulation, and mitochondrial respiratory chain defects. Transcriptional regulation analysis identified genes associated with PD specific activity, including <i>Rorb</i> and <i>Foxc1</i> in the midbrain and <i>Dbx2</i> and <i>Klf13</i> in the striatum. Cell–cell interactions showed that cell-to-cell signaling was enhanced, and the SEMA and CCL neuroinflammatory axes were specifically activated in the PD group.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our integrative analysis delineates the cellular and molecular architecture of the pathological process triggered by the expression of A53T mutant α-synuclein, and provides a framework for targeted therapeutic development.</p>\u0000 </section>\u0000 </div>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":"9 8","pages":"1613-1632"},"PeriodicalIF":3.4,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13394255/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148451024","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":"Age-associated immune dysregulation links to disease severity in macrolide-resistant Mycoplasma pneumoniae pneumonia: Insights from a comparative juvenile–adult mouse model","authors":"Xuejun Li,&nbsp;Yudong Wang,&nbsp;Liyong Liu,&nbsp;Mengmeng Gong,&nbsp;Jinlong Wang,&nbsp;Yuqing Cao,&nbsp;Zhixin Sun,&nbsp;Fanliang Meng,&nbsp;Qiuyan Wang,&nbsp;Hongji Wu,&nbsp;Fei Zhao,&nbsp;Yan Ma,&nbsp;Yibai Xiong","doi":"10.1002/ame2.70231","DOIUrl":"10.1002/ame2.70231","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;Macrolide-resistant &lt;i&gt;mycoplasma pneumoniae&lt;/i&gt; (MRMP) infections are more common and severe in children, indicating that age-related immune dysregulation affects disease outcomes, yet the underlying mechanisms remain unclear and suitable pediatric models are lacking. This study compared juvenile and adult mice with MRMP infection to identify age-dependent immune features linked to lung injury and establish a relevant animal model for pediatric research.&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;Three-week-old (juvenile) and 8-week-old (adult) BALB/c mice were infected with MRMP. Pathological phenotypes included lung index, bacterial load, and lung histopathology scores. Serum inflammatory storm profiles were characterized using the Olink 48-plex assay. High-dimensional immune mapping of the spleen was performed by cytometry by time-of-flight mass spectrometry (CyTOF). Integrated analyses including sparse partial least squares-discriminant analysis (sPLS-DA), correlation heatmaps, and KEGG pathway enrichment were created to explore associations among differential immune subsets, inflammatory mediators, and &lt;i&gt;M. pneumoniae&lt;/i&gt; pneumonia (MPP) phenotypes.&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;No statistically significant differences in bacterial load were observed among the MRMP-infected juvenile (Juv+MRMP) and MRMP-infected adult (Ad+MRMP) groups (&lt;i&gt;p&lt;/i&gt; &gt; 0.05). However, the Juv+MRMP group exhibited significantly higher lung indices and more severe pulmonary histopathological damage, indicating a dissociation between bacterial burden and tissue injury. Olink analysis revealed significantly higher levels of serum chemokines (CCL2, CCL12, CCL22) and proinflammatory cytokines (IL-17A, IL-1β, IL-27) in the Juv+MRMP group than in the Ad+MRMP group. CyTOF analysis revealed a starkly different immune landscape: Juvenile mice exhibited excessive innate immune activation, with significant increases in neutrophil and monocyte infiltration, as well as elevated proportions of M2 macrophages and NK cells (&lt;i&gt;p&lt;/i&gt; &lt; 0.05); while adaptive immune responses were impaired, characterized by reduced proportions of CD4&lt;sup&gt;+&lt;/sup&gt; T cells and Treg cells, and maintained a high reserve of naïve Th cells compared with those in adult mice, along with elevated proportions of activated Tc cells (CD69&lt;sup&gt;+&lt;/sup&gt; Tc) (&lt;i&gt;p&lt;/i&gt; &lt; 0.05). Correlation analysis revealed that age and infection status are key factors driving host immune variability. M2 macrophages and NK cells were potentially associated with lung tissue pathology scores. Pathogen load correlates with both initial immune cells (CD24&lt;sup&gt;+&lt;/sup&gt; naïve ","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":"9 8","pages":"1489-1506"},"PeriodicalIF":3.4,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13416119/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148610826","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":"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":"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}