Animal models and experimental medicine最新文献

{"title":"Intratracheal instillation for the testing of pulmonary toxicity in mice-Effects of instillation devices and feed type on inflammation.","authors":"Niels Hadrup, Michael Guldbrandsen, Eva Terrida, Katja M S Bendtsen, Karin S Hougaard, Nicklas R Jacobsen, Ulla Vogel","doi":"10.1002/ame2.12503","DOIUrl":"https://doi.org/10.1002/ame2.12503","url":null,"abstract":"<p><strong>Background: </strong>Inhalation exposure is the gold standard when assessing pulmonary toxicity. However, it typically requires substantial amounts of test material. Intratracheal instillation is an alternative administration technique, where the test substance is suspended in a liquid vehicle and deposited into the lung via the trachea. Instillation requires minimal test material, delivers an exact dose deep into the lung, and is less labor-intensive than inhalation exposures. However, one shortcoming is that the procedure may induce short-term inflammation. To minimize this, we tested different modifications of the technique to identify the potential for refinement.</p><p><strong>Methods: </strong>First, we tested whether previous findings of increased inflammation could be confirmed. Next, we tested whether instillation with a disposable 1 mL syringe with ball-tipped steel-needle (Disposable-syringe/steel-needle) induced less inflammation than the use of our standard set-up, a 250 μL reusable glass syringe with a disposable plastic catheter (Glass-syringe/plastic-catheter). Finally, we tested if access to pelleted and liquid feed prior to instillation affected inflammation. We evaluated inflammation by neutrophil numbers in bronchoalveolar fluid 24 h post-exposure.</p><p><strong>Results: </strong>Vehicle-instilled mice showed a small increase in neutrophil numbers compared to untreated mice. Neutrophil numbers were slightly elevated in the groups instilled with Disposable-syringe/steel-needle; an interaction with feed type indicated that the increase in neutrophils was more pronounced in combination with feed pellets compared to liquid feed. We found no difference between the feed types when using the Glass-syringe/plastic-catheter combination.</p><p><strong>Conclusion: </strong>The Glass-syringe/plastic-catheter combination induced the least exposure-related inflammation, confirming this as a preferred instillation procedure.</p>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142928341","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}

{"title":"The N-terminal domain of gasdermin D induces liver fibrosis by reprogrammed lipid metabolism","authors":"Xue Wang,&nbsp;Chunyou Ning,&nbsp;Xingyi Cheng,&nbsp;Zhengzhong Wu,&nbsp;Dongbo Wu,&nbsp;Xuemei Ding,&nbsp;Cunxiang Ju,&nbsp;Zhihang Zhou,&nbsp;Lingfeng Wan,&nbsp;Wei Zhao,&nbsp;Peiliang Shi","doi":"10.1002/ame2.12506","DOIUrl":"10.1002/ame2.12506","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The emerging incidence of pathogenic liver conditions is turning into a major concern for global health. Induction of pyroptosis in hepatocytes instigates cellular disintegration, which in turn liberates substantial quantities of pro-inflammatory intracellular substances, thereby accelerating the advancement of liver fibrosis. Consequently, directing therapeutic efforts towards inhibiting pyroptosis could potentially serve as an innovative approach in managing inflammation related chronic hepatic disorders.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>GSDMD-NT^ki/wt mice and Alb-cre^ki/wt mice were generated using CRISPR/Cas9 technology. After crossing the two strains together, we induced conditional cell death by doxycycline to construct a mouse model of liver fibrosis. We analyzed differentially expressed genes by RNA sequencing and explored their biological functions. The efficacy of obeticholic acid (OCA) in the treatment of liver fibrosis was assessed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Doxycycline-treated GSDMD-NT^ki/wt × Alb-cre^ki/wt mice showed severe liver damage, vacuolation of hepatocytes, increased collagen fibers, and accumulation of lipid droplets. The expression of liver fibrosis related genes was greatly increased in the doxycycline-treated mouse liver compared with untreated mouse liver. RNA-sequencing showed that upregulated differentially expressed genes were involved in inflammatory responses, cell activation, and metabolic processes. Treatment with OCA alleviated the liver fibrosis, with reduced ALT and AST levels seen in the GSDMD-NT^ki/wt × Alb-cre^ki/wt mice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>We successfully constructed a novel mouse model for liver fibrosis. This GSDMD-NT-induced fibrosis may be mediated by abnormal lipid metabolism. Our results demonstrated that we successfully constructed a mouse model of liver fibrosis, and GSDMD-NT induced fibrosis by mediating lipid metabolism.</p>\u0000 </section>\u0000 </div>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":"8 1","pages":"114-125"},"PeriodicalIF":0.0,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ame2.12506","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142900619","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":"Generation of transgenic chicken through ovarian injection","authors":"Jinghua Jiang,&nbsp;Caiying Wang,&nbsp;Xuguang Du,&nbsp;Fei Gao,&nbsp;Sen Wu","doi":"10.1002/ame2.12514","DOIUrl":"10.1002/ame2.12514","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Traditional DNA microinjection methods used in mammals are difficult to apply to avian species due to their unique reproductive characteristics. Genetic manipulation in chickens, particularly involving immature follicles within living ovaries, has not been extensively explored. This study seeks to establish an efficient method for generating transgenic chickens through ovarian injection, potentially bypassing the challenges associated with primordial germ cell (PGC) manipulation and fertilized egg microinjection.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Hens were anesthetized and underwent a surgical procedure to access the ovary for DNA injection into immature follicles. The study used liposomes to deliver GFP-expressing plasmids at various dosages. After injection, hens recovered, and their eggs were fertilized through artificial insemination.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Transgenic chickens were successfully generated in one generation without needing G0 founders. The injection of 20 μg plasmid yielded the highest transgenic efficiency at 12.1%. GFP-positive embryos were confirmed through microscopy, and successful transgene expression was validated at the tissue level using immunostaining. TERT and GFP elements introduced in the G1 generation resulted in 4.1% positive transgene rates, as confirmed by PCR and Southern blotting.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This ovarian injection method offers a promising alternative for avian genetic manipulation, bypassing complex PGC procedures and enabling direct generation of G1 transgenic chickens. This technique simplifies the transgenic process for chickens and has the potential to be adapted for other avian species, especially those without established PGCs culture systems.</p>\u0000 </section>\u0000 </div>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":"8 1","pages":"187-193"},"PeriodicalIF":0.0,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ame2.12514","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142900617","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":"Isoproterenol mechanisms in inducing myocardial fibrosis and its application as an experimental model for the evaluation of therapeutic potential of phytochemicals and pharmaceuticals","authors":"Lujain Bader Eddin,&nbsp;Mohamed Fizur Nagoor Meeran,&nbsp;Niraj Kumar Jha,&nbsp;Samer N. Goyal,&nbsp;Shreesh Ojha","doi":"10.1002/ame2.12496","DOIUrl":"10.1002/ame2.12496","url":null,"abstract":"<p>Cardiac injury initiates repair mechanisms and results in cardiac remodeling and fibrosis, which appears to be a leading cause of cardiovascular diseases. Cardiac fibrosis is characterized by the accumulation of extracellular matrix proteins, mainly collagen in the cardiac interstitium. Many experimental studies have demonstrated that fibrotic injury in the heart is reversible; therefore, it is vital to understand different molecular mechanisms that are involved in the initiation, progression, and resolution of cardiac fibrosis to enable the development of antifibrotic agents. Of the many experimental models, one of the recent models that has gained renewed interest is isoproterenol (ISP)–induced cardiac fibrosis. ISP is a synthetic catecholamine, sympathomimetic, and nonselective β-adrenergic receptor agonist. The overstimulated and sustained activation of β-adrenergic receptors has been reported to induce biochemical and physiological alterations and ultimately result in cardiac remodeling. ISP has been used for decades to induce acute myocardial infarction. However, the use of low doses and chronic administration of ISP have been shown to induce cardiac fibrosis; this practice has increased in recent years. Intraperitoneal or subcutaneous ISP has been widely used in preclinical studies to induce cardiac remodeling manifested by fibrosis and hypertrophy. The induced oxidative stress with subsequent perturbations in cellular signaling cascades through triggering the release of free radicals is considered the initiating mechanism of myocardial fibrosis. ISP is consistently used to induce fibrosis in laboratory animals and in cardiomyocytes isolated from animals. In recent years, numerous phytochemicals and synthetic molecules have been evaluated in ISP-induced cardiac fibrosis. The present review exclusively provides a comprehensive summary of the pathological biochemical, histological, and molecular mechanisms of ISP in inducing cardiac fibrosis and hypertrophy. It also summarizes the application of this experimental model in the therapeutic evaluation of natural as well as synthetic compounds to demonstrate their potential in mitigating myocardial fibrosis and hypertrophy.</p>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":"8 1","pages":"67-91"},"PeriodicalIF":0.0,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ame2.12496","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142848590","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 decrease in zinc-finger E-box-binding homeobox-1 could accelerate steroid-induced osteonecrosis of the femoral head by repressing type-H vessel formation via Wnt/β-catenin pathway","authors":"Guangyang Zhang,&nbsp;Yuanqing Cai,&nbsp;Jialin Liang,&nbsp;Zhaopu Jing,&nbsp;Wang Wei,&nbsp;Leifeng Lv,&nbsp;Xiaoqian Dang,&nbsp;Qichun Song","doi":"10.1002/ame2.12507","DOIUrl":"10.1002/ame2.12507","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Zinc-finger E-box-binding homeobox-1 (<i>ZEB1</i>) is predominantly found in type-H vessels. However, the roles of <i>ZEB1</i> and type-H vessels in steroid-induced osteonecrosis of the femoral head (SONFH) are unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Human femoral heads were collected to detect the expression of <i>ZEB1</i> and the levels of type-H vessels. Then, the SONFH model was developed by injecting C57BL/6 mice with lipopolysaccharide and methylprednisolone. Micro-computed tomography, angiography, double calcein labeling, immunofluorescence, immunohistochemistry, quantitative real-time polymerase chain reaction, and Western blotting were performed to detect the expression of <i>ZEB1</i>, the <i>Wnt/β-catenin</i> pathway, type-H vessels, and the extent to which <i>ZEB1</i> mediates angiogenesis and osteogenesis. Human umbilical vein endothelial cells were also used to explore the relationship between <i>ZEB1</i> and the <i>Wnt/β-catenin</i> pathway.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We found that <i>ZEB1</i> expression and the formation of type-H vessels decreased in SONFH patients and in a mouse model. The number of vascular endothelial growth factors in the femoral heads also decreased. Moreover, the bone mineral density, trabecular number, mineral apposition rate, and expression of genes related to osteogenesis decreased. After <i>ZEB1</i> knockdown, angiogenesis and osteogenesis decreased. However, the numbers of type-H vessels and the extent of angiogenesis and osteogenesis improved after activation of the <i>Wnt/β-catenin</i> pathway.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The ZEB1 expression decreased in SONFH, causing a decrease in type-H vessel, and it mediated angiogenesis and osteogenesis by regulating the <i>Wnt/β-catenin</i> pathway, ultimately accelerating the process of SONFH.</p>\u0000 </section>\u0000 </div>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":"7 6","pages":"802-815"},"PeriodicalIF":0.0,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11680474/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142840559","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":"Initial pig developmental stage influences intestinal organoid growth but not cellular composition","authors":"Camille Duchesne,&nbsp;Gwénaëlle Randuineau,&nbsp;Laurence Le Normand,&nbsp;Véronique Romé,&nbsp;Samia Laraqui,&nbsp;Alexis Pierre Arnaud,&nbsp;Gaëlle Boudry","doi":"10.1002/ame2.12512","DOIUrl":"10.1002/ame2.12512","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Intestinal organoids are promising tools in the context of animal experiment reduction but a thorough characterization of the impact of the origin of intestinal stem cells (ISC) on organoid phenotype is needed to routinely use this cellular model. Our objective was to evaluate the effect of ISC donor age on the growth, morphology and cellular composition of intestinal organoids derived from pig.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Organoids were derived from jejunal and colonic ISC obtained from 1-, 7-, 28-, 36- and 180-day-old pigs and passaged three times.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We first confirmed by qPCR that the expression of 18% of the &gt;80 studied genes related to various intestinal functions differed between jejunal and colonic organoids after two passages (<i>p</i> &lt; 0.05). Growth and morphology of organoids depended on intestinal location (greater number and larger organoids derived from colonic than jejunal ISC, <i>p</i> &lt; 0.05) but also pig age. Indeed, when ISC were derived from young piglets, the ratio of organoids to spheroids was greater (<i>p</i> &lt; 0.05), spheroids were larger during the primary culture but smaller after two passages (<i>p</i> &lt; 0.05) and organoids were smaller after one passage (<i>p</i> &gt; 0.05) compared to ISC from older pigs. Finally, no difference in cellular composition, evaluated by immunostaining of markers of the major intestinal cell types (absorptive, enteroendocrine and goblet cells) was observed between organoids originating from 7- or 180-day-old pigs, but differences between intestinal site origins were noticed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>In conclusion, while the age of the tissue donor affected organoid growth and morphology, it did not influence the phenotype.</p>\u0000 </section>\u0000 </div>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":"7 6","pages":"944-954"},"PeriodicalIF":0.0,"publicationDate":"2024-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11680479/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142831193","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":"Deficiency of DEK proto-oncogene alleviates allergic rhinitis by inhibiting RhoA/Ezrin-mediated mitochondrial fission.","authors":"Longzhu Dai, Yongde Jin, Jingmei Chai, Jianing Yang, Jiangang Wang, Mu Chen, Liangchang Li, Chongyang Wang, Guanghai Yan","doi":"10.1002/ame2.12523","DOIUrl":"https://doi.org/10.1002/ame2.12523","url":null,"abstract":"<p><strong>Background: </strong>Allergic rhinitis (AR) is a kind of immune disease mediated by IgE. We are intrigued by the potential role of DEK proto-oncogene (DEK) in inflammation-related diseases. We investigated the effects and mechanisms of DEK in treating AR, aiming to identify potential new treatment targets for AR.</p><p><strong>Methods: </strong>The AR mouse model was induced by house dust mite (HDM) (1 mg/mL). HNEpCs stimulated by HDM (1 mg/mL) were pretreated for 24 h with or without DEK lentivirus. The effect of DEK knockout or knockdown on AR was evaluated in vitro and in vivo using western blotting, ELISA, flow cytometry, real-time quantitative PCR, immunohistochemistry, HE staining, PAS staining, Diff staining, and immunofluorescence.</p><p><strong>Results: </strong>After DEK knockdown, the inflammatory response of AR mice was reduced. In addition, DEK deletion mitigated nasal tissue damage and mitochondrial division. Our further studies showed that DEK deletion or inhibition led to the down-regulation of RhoA activity and decreased phosphorylation of Ezrin and Drp1 proteins, and inhibited mitochondrial division. Overall, DEK deficiency mitigated AR by down-regulating RhoA/Ezrin/Drp1 pathway activity.</p><p><strong>Conclusion: </strong>DEK alleviates AR through RhoA/Ezrin/Drp1 signaling pathway, which provides a new perspective for developing improved therapies and understanding the pathogenesis of AR.</p>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142820224","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}

{"title":"Chondrogenic commitment of human umbilical cord blood and umbilical cord-derived mesenchymal stem cells induced by the supernatant of chondrocytes: A comparison study","authors":"Xingfu Li,&nbsp;Zhenhan Deng,&nbsp;Wei Lu","doi":"10.1002/ame2.12515","DOIUrl":"10.1002/ame2.12515","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Native cartilage has low capacity for regeneration because it has very few progenitor cells. Human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) and human umbilical cord-derived MSCs (hUC-MSCs) have been employed as promising sources of stem cells for cartilage injury repair. Reproduction of hyaline cartilage from MSCs remains a challenging endeavor. The paracrine factors secreted by chondrocytes possess the capability to induce chondrogenesis from MSCs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The conditioned medium derived from chondrocytes was utilized to induce chondrogenic differentiation of hUCB-MSCs and hUC-MSCs. The expression levels of collagen type I alpha 1 chain (<i>Col1a1</i>), collagen type II alpha 1 chain (<i>Col2a1</i>), and SRY-box transcription factor 9 (<i>SOX9</i>) were assessed through quantitative real-time polymerase chain reaction (qRT-PCR), Western blot (WB), and immunofluorescence (IF) assays. To elucidate the mechanism of differentiation, the concentration of transforming growth factor-β1 (TGF-β1) in the conditioned medium of chondrocytes was quantified using enzyme-linked immunosorbent assay (ELISA). Meanwhile, the viability of cells was assessed using Cell Counting Kit-8 (CCK-8) assays.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The expression levels of <i>Col2a1</i> and <i>SOX9</i> were found to be higher in induced hUC-MSCs compared to those in induced hUCB-MSCs. The conditioned medium of chondrocytes contained TGF-β1. The CCK-8 assays revealed that the proliferation rate of hUC-MSCs was significantly higher compared to that of hUCB-MSCs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The chondrogenic potential and proliferation capacity of hUC-MSCs surpass those of hUCB-MSCs, thereby establishing hUC-MSCs as a superior source of seed cells for cartilage tissue engineering.</p>\u0000 </section>\u0000 </div>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":"7 6","pages":"793-801"},"PeriodicalIF":0.0,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11680488/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142796711","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":"Improving dexamethasone drug loading and efficacy in treating rheumatoid arthritis via liposome: Focusing on inflammation and molecular mechanisms","authors":"Mohammad Yasin Zamanian,&nbsp;Hamidreza Zafari,&nbsp;Maria K. Osminina,&nbsp;Alla A. Skakodub,&nbsp;Raed Fanoukh Aboqader Al-Aouadi,&nbsp;Maryam Golmohammadi,&nbsp;Nikta Nikbakht,&nbsp;Iman Fatemi","doi":"10.1002/ame2.12518","DOIUrl":"10.1002/ame2.12518","url":null,"abstract":"<p>Rheumatoid arthritis (RA) is a chronic autoimmune disease that affects approximately 0.46% of the global population. Conventional therapeutics for RA, including disease-modifying antirheumatic drugs (DMARDs), nonsteroidal anti-inflammatory drugs (NSAIDs), and corticosteroids, frequently result in unintended adverse effects. Dexamethasone (DEX) is a potent glucocorticoid used to treat RA due to its anti-inflammatory and immunosuppressive properties. Liposomal delivery of DEX, particularly when liposomes are surface-modified with targeting ligands like peptides or sialic acid, can improve drug efficacy by enhancing its distribution to inflamed joints and minimizing toxicity. This study investigates the potential of liposomal drug delivery systems to enhance the efficacy and targeting of DEX in the treatment of RA. Results from various studies demonstrate that liposomal DEX significantly inhibits arthritis progression in animal models, reduces joint inflammation and damage, and alleviates cartilage destruction compared to free DEX. The liposomal formulation also shows better hemocompatibility, fewer adverse effects on body weight and immune organ index, and a longer circulation time with higher bioavailability. The anti-inflammatory mechanism is associated with the downregulation of pro-inflammatory cytokines like tumor necrosis factor-α (TNF-α) and B-cell–activating factor (BAFF), which are key players in the pathogenesis of RA. Additionally, liposomal DEX can induce the expression of anti-inflammatory cytokines like interleukin-10 (IL-10), which has significant anti-inflammatory and immunoregulatory properties. The findings suggest that liposomal DEX represents a promising candidate for effective and safe RA therapy, with the potential to improve the management of this debilitating disease by providing targeted delivery and sustained release of the drug.</p>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":"8 1","pages":"5-19"},"PeriodicalIF":0.0,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ame2.12518","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142775619","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 a user-friendly CSDS cage apparatus for studying depressive-like behaviors in rodents","authors":"Hao Zhang,&nbsp;Dongmei Gao,&nbsp;Minghu Hu,&nbsp;Wanqing Zhou,&nbsp;Muxuan Han,&nbsp;Ya Sun,&nbsp;Yang Zhang,&nbsp;Jieqiong Wang,&nbsp;Mingzhou Gao","doi":"10.1002/ame2.12510","DOIUrl":"10.1002/ame2.12510","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Previously, a chronic social defeat stress (CSDS) model has been widely-adopted for assessing depressive-like behaviors in animals. However, there is still room for improvement in the CSDS model to safeguard study accuracy and the welfare of lab rodents. Our study team developed a novel, standardized apparatus to induce CSDS in rodents and assessed the model's practical adaptability.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>An innovative CSDS cage apparatus and water bottle was designed. To evaluate the effectiveness of the newly developed tools, a variety of animal models, including the tail suspension test (TST), sucrose preference test, forced swimming test (FST), novelty-suppressed feeding test, female urine sniffing test, and open field test (OFT), were adopted to assess depressive-like behaviors in mice. Fluoxetine treatment was also administered to observe the reversal effect, as part of the validation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The CSDS cage apparatus resulted in the manifestation of depressive-like behaviors in the model mice. Significant reductions in sucrose preference and urine sniffing time were observed, while the OFT revealed decreased central zone total distance, residence time, and frequency of entry. Moreover, increased immobility was found in the FST and TST. Fluoxetine treatment was found to successfully reverse the modeling effect.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The CSDS cage apparatus was validated for enhanced usability and addressed the previous challenges of water bottle leakage and lab rodent welfare issues. The consistent results from multiple behavioral tests also supported real-world application of the apparatus, offering researchers a promising alternative to conventional rodent cages.</p>\u0000 </section>\u0000 </div>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":"8 1","pages":"179-186"},"PeriodicalIF":0.0,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ame2.12510","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142775618","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}