Animal models and experimental medicine最新文献

{"title":"Development of a chronic compression spinal cord injury model in neonatal and adult rats","authors":"Reggie Ridlen,&nbsp;Victoria Marsters,&nbsp;Elizabeth Clarke,&nbsp;Kristine McGrath,&nbsp;Catherine A. Gorrie","doi":"10.1002/ame2.12484","DOIUrl":"10.1002/ame2.12484","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Spinal cord injury presents a significant burden globally, with traumatic spinal cord injury being the predominant cause historically. However, nontraumatic spinal cord injury (NTSCI) is emerging as a significant contributor, particularly in developed nations, yet it remains poorly understood due to underreporting and misclassification. NTSCI, spanning various etiologies such as bony growths, vascular conditions, infections, neoplastic conditions, and immune disorders, poses unique challenges in diagnosis and treatment, often resulting in lifelong morbidity. This study addresses the lack of suitable animal models for NTSCI research, especially in neonatal animals.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Utilizing a solid spacer approach, we developed a compression NTSCI model applicable to both neonatal and adult Sprague–Dawley rats.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Through anatomical measurements and in vivo experiments, we confirmed the feasibility and safety of the spacer insertion procedure and observed no acute off-target effects.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The versatility of this model lies in its adaptability to different ages of rats, offering a cost-effective and reproducible means to induce graded injuries. Moreover, behavioral assessments demonstrated observable hindlimb function, validating the model's utility for studying functional outcomes. Although challenges persist, particularly in accounting for spinal column growth in neonatal animals, this model fills a crucial gap in pediatric NTSCI research. By providing a platform to investigate pathophysiological mechanisms and test potential treatments, it offers promising avenues for advancing our understanding and management of pediatric NTSCI.</p>\u0000 </section>\u0000 </div>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":"7 5","pages":"758-768"},"PeriodicalIF":0.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ame2.12484","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142303179","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":"Ischemia-reperfusion injury after spinal cord decompressive surgery-An in vivo rat model.","authors":"Boyu Zhang, Zhefeng Jin, Pengren Luo, He Yin, Xin Chen, Bowen Yang, Xiaokuan Qin, LiGuo Zhu, Bo Xu, Guoliang Ma, Dian Zhang","doi":"10.1002/ame2.12485","DOIUrl":"https://doi.org/10.1002/ame2.12485","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Although decompression surgery is the optimal treatment for patients with severe degenerative cervical myelopathy (DCM), some individuals experience no improvement or even a decline in neurological function after surgery, with spinal cord ischemia-reperfusion injury (SCII) identified as the primary cause. Spinal cord compression results in local ischemia and blood perfusion following decompression is fundamental to SCII. However, owing to inadequate perioperative blood flow monitoring, direct evidence regarding the occurrence of SCII after decompression is lacking. The objective of this study was to establish a suitable animal model for investigating the underlying mechanism of spinal cord ischemia-reperfusion injury following decompression surgery for degenerative cervical myelopathy (DCM) and to elucidate alterations in neurological function and local blood flow within the spinal cord before and after decompression.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Twenty-four Sprague-Dawley rats were allocated to three groups: the DCM group (cervical compression group, with implanted compression material in the spinal canal, n = 8), the DCM-D group (cervical decompression group, with removal of compression material from the spinal canal 4 weeks after implantation, n = 8), and the SHAM group (sham operation, n = 8). Von Frey test, forepaw grip strength, and gait were assessed within 4 weeks post-implantation. Spinal cord compression was evaluated using magnetic resonance imaging. Local blood flow in the spinal cord was monitored during the perioperative decompression. The rats were sacrificed 1 week after decompression to observe morphological changes in the compressed or decompressed segments of the spinal cord. Additionally, NeuN expression and the oxidative damage marker 8-oxoG DNA were analyzed.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Following spinal cord compression, abnormal mechanical pain worsened, and a decrease in forepaw grip strength was observed within 1-4 weeks. Upon decompression, the abnormal mechanical pain subsided, and forepaw grip strength was restored; however, neither reached the level of the sham operation group. Decompression leads to an increase in the local blood flow, indicating improved perfusion of the spinal cord. The number of NeuN-positive cells in the spinal cord of rats in the DCM-D group exceeded that in the DCM group but remained lower than that in the SHAM group. Notably, a higher level of 8-oxoG DNA expression was observed, suggesting oxidative stress following spinal cord decompression.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;This model is deemed suitable for analyzing the underlying mechanism of SCII following decompressive cervical laminectomy, as we posit that the obtained results are comparable to the clinical progression of degenerative cervical myelopathy (DCM) post-decompression and exhibit analogous neurological alterations. Notably, this model revealed ischemic reperfusion in the spinal cord aft","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142121310","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":"Targeting STAT3 signaling pathway by curcumin and its analogues for breast cancer: A narrative review","authors":"Maryam Golmohammadi,&nbsp;Mohammad Yassin Zamanian,&nbsp;Ahmed Muzahem Al-Ani,&nbsp;Thaer L. Jabbar,&nbsp;Ali Kamil Kareem,&nbsp;Zeinab Hashem Aghaei,&nbsp;Hossein Tahernia,&nbsp;Ahmed Hjazi,&nbsp;Saad Abdul-ridh Jissir,&nbsp;Elham Hakimizadeh","doi":"10.1002/ame2.12491","DOIUrl":"10.1002/ame2.12491","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Breast cancer (BC) continues to be a significant global health issue, with a rising number of cases requiring ongoing research and innovation in treatment strategies. Curcumin (CUR), a natural compound derived from Curcuma longa, and similar compounds have shown potential in targeting the STAT3 signaling pathway, which plays a crucial role in BC progression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>The aim of this study was to investigate the effects of curcumin and its analogues on BC based on cellular and molecular mechanisms.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials &amp; Methods</h3>\u0000 \u0000 <p>The literature search conducted for this study involved utilizing the Scopus, ScienceDirect, PubMed, and Google Scholar databases in order to identify pertinent articles.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>This narrative review explores the potential of CUR and similar compounds in inhibiting STAT3 activation, thereby suppressing the proliferation of cancer cells, inducing apoptosis, and inhibiting metastasis. The review demonstrates that CUR directly inhibits the phosphorylation of STAT3, preventing its movement into the nucleus and its ability to bind to DNA, thereby hindering the survival and proliferation of cancer cells. CUR also enhances the effectiveness of other therapeutic agents and modulates the tumor microenvironment by affecting tumor-associated macrophages (TAMs). CUR analogues, such as hydrazinocurcumin (HC), FLLL11, FLLL12, and GO-Y030, show improved bioavailability and potency in inhibiting STAT3, resulting in reduced cell proliferation and increased apoptosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>CUR and its analogues hold promise as effective adjuvant treatments for BC by targeting the STAT3 signaling pathway. These compounds provide new insights into the mechanisms of action of CUR and its potential to enhance the effectiveness of BC therapies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":"7 6","pages":"853-867"},"PeriodicalIF":0.0,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11680487/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142115837","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":"An overview of different methods to establish a murine premature ovarian failure model","authors":"Negar Pouladvand,&nbsp;Mahnaz Azarnia,&nbsp;Hadis Zeinali,&nbsp;Rouhollah Fathi,&nbsp;Somayeh Tavana","doi":"10.1002/ame2.12477","DOIUrl":"10.1002/ame2.12477","url":null,"abstract":"<p>Premature ovarian failure (POF)is defined as the loss of normal ovarian function before the age of 40 and is characterized by increased gonadotropin levels and decreased estradiol levels and ovarian reserve, often leading to infertility. The incomplete understanding of the pathogenesis of POF is a major impediment to the development of effective treatments for this disease, so the use of animal models is a promising option for investigating and identifying the molecular mechanisms involved in POF patients and developing therapeutic agents. As mice and rats are the most commonly used models in animal research, this review article considers studies that used murine POF models. In this review based on the most recent studies, first, we introduce 10 different methods for inducing murine POF models, then we demonstrate the advantages and disadvantages of each one, and finally, we suggest the most practical method for inducing a POF model in these animals. This may help researchers find the method of creating a POF model that is most appropriate for their type of study and suits the purpose of their research.</p>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":"7 6","pages":"835-852"},"PeriodicalIF":0.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11680483/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142115836","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to “Overexpression of ACE2 ameliorates Aβ-induced blood–brain barrier damage and angiogenesis by inhibiting NF-κB/VEGF/VEGFR2 pathway”","authors":"","doi":"10.1002/ame2.12489","DOIUrl":"10.1002/ame2.12489","url":null,"abstract":"<p>Xueling Zhang, Yu Zhang, Ling Zhang*, Chuan Qin*, <i>Anim Models Exp Med</i>. 2023;6:237–244.</p><p>In Figure 2A, the picture of immune blot for GAPDH was misplaced. The correct picture has been added to the updated Figure 2A.</p><p>In figure 6A, the picture of immune blot for GAPDH was misplaced and the molecular weight of VEGFa was mistakenly marked. The correct picture has been added to the updated Figure 6A.</p><p>In Figure 8A, the picture of immune blot for GAPDH was misplaced. The correct picture has been added to the updated Figure 8A.</p><p>We apologize for these errors.</p>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":"7 6","pages":"966-967"},"PeriodicalIF":0.0,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11680481/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142037982","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 comprehensive view on the fisetin impact on colorectal cancer in animal models: Focusing on cellular and molecular mechanisms","authors":"Mohammad Yasin Zamanian,&nbsp;Niloofar Taheri,&nbsp;Montather F. Ramadan,&nbsp;Yasser Fakri Mustafa,&nbsp;Safa Alkhayyat,&nbsp;Klunko Nataliya Sergeevna,&nbsp;Hashem O. Alsaab,&nbsp;Ahmed Hjazi,&nbsp;Farnoosh Molavi Vasei,&nbsp;Siamak Daneshvar","doi":"10.1002/ame2.12476","DOIUrl":"10.1002/ame2.12476","url":null,"abstract":"<p>Flavonoids, including fisetin, have been linked to a reduced risk of colorectal cancer (CRC) and have potential therapeutic applications for the condition. Fisetin, a natural flavonoid found in various fruits and vegetables, has shown promise in managing CRC due to its diverse biological activities. It has been found to influence key cell signaling pathways related to inflammation, angiogenesis, apoptosis, and transcription factors. The results of this study demonstrate that fisetin induces colon cancer cell apoptosis through multiple mechanisms. It impacts the p53 pathway, leading to increased levels of p53 and decreased levels of murine double minute 2, contributing to apoptosis induction. Fisetin also triggers the release of important components in the apoptotic process, such as second mitochondria-derived activator of caspase/direct inhibitor of apoptosis-binding protein with low pI and cytochrome c. Furthermore, fisetin inhibits the cyclooxygenase-2 and wingless-related integration site (Wnt)/epidermal growth factor receptor/nuclear factor kappa B signaling pathways, reducing Wnt target gene expression and hindering colony formation. It achieves this by regulating the activities of cyclin-dependent kinase 2 and cyclin-dependent kinase 4, reducing retinoblastoma protein phosphorylation, decreasing cyclin E levels, and increasing p21 levels, ultimately influencing E2 promoter binding factor 1 and cell division cycle 2 (CDC2) protein levels. Additionally, fisetin exhibits various effects on CRC cells, including inhibiting the phosphorylation of Y-box binding protein 1 and ribosomal S6 kinase, promoting the phosphorylation of extracellular signal-regulated kinase 1/2, and disrupting the repair process of DNA double-strand breaks. Moreover, fisetin serves as an adjunct therapy for the prevention and treatment of phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit α (PIK3CA)-mutant CRC, resulting in a reduction in phosphatidylinositol-3 kinase (PI3K) expression, Ak strain transforming phosphorylation, mTOR activity, and downstream target proteins in CRC cells with a PIK3CA mutation. These findings highlight the multifaceted potential of fisetin in managing CRC and position it as a promising candidate for future therapy development.</p>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":"7 5","pages":"591-605"},"PeriodicalIF":0.0,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ame2.12476","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141972455","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":"Fevogrit, a polyherbal medicine, mitigates endotoxin (lipopolysaccharide)-induced fever in Wistar rats by regulating pro-inflammatory cytokine levels.","authors":"Acharya Balkrishna, Sonam Sharma, Vivek Gohel, Rani Singh, Meenu Tomer, Rishabh Dev, Sandeep Sinha, Anurag Varshney","doi":"10.1002/ame2.12472","DOIUrl":"https://doi.org/10.1002/ame2.12472","url":null,"abstract":"<p><strong>Background: </strong>Fever is characterized by an upregulation of the thermoregulatory set-point after the body encounters any pathological challenge. It is accompanied by uncomfortable sickness behaviors and may be harmful in patients with other comorbidities. We have explored the impact of an Ayurvedic medicine, Fevogrit, in an endotoxin (lipopolysaccharide)-induced fever model in Wistar rats.</p><p><strong>Methods: </strong>Active phytoconstituents of Fevogrit were identified and quantified using ultra-high-performance liquid chromatography (UHPLC) platform. For the in-vivo study, fever was induced in male Wistar rats by the intraperitoneal administration of lipopolysaccharide (LPS), obtained from Escherichia coli. The animals were allocated to normal control, disease control, Paracetamol treated and Fevogrit treated groups. The rectal temperature of animals was recorded at different time points using a digital thermometer. At the 6-h time point, levels of TNF-α, IL-1β and IL-6 cytokines were analyzed in serum. Additionally, the mRNA expression of these cytokines was determined in hypothalamus, 24 h post-LPS administration.</p><p><strong>Results: </strong>UHPLC analysis of Fevogrit revealed the presence of picroside I, picroside II, vanillic acid, cinnamic acid, magnoflorine and cordifolioside A, as bioactive constituents with known anti-inflammatory properties. Fevogrit treatment efficiently reduces the LPS-induced rise in the rectal temperature of animals. The levels and gene expression of TNF-α, IL-1β and IL-6 in serum and hypothalamus, respectively, was also significantly reduced by Fevogrit treatment.</p><p><strong>Conclusion: </strong>The findings of the study demonstrated that Fevogrit can suppress LPS-induced fever by inhibiting peripheral or central inflammatory signaling pathways and could well be a viable treatment for infection-induced increase in body temperatures.</p>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141636092","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 activation of adenosine monophosphate–activated protein kinase inhibits the migration of tongue squamous cell carcinoma cells by targeting Claudin-1 via epithelial–mesenchymal transition","authors":"Xin-Yue Zhou,&nbsp;Qiu-Ming Liu,&nbsp;Zhuang Li,&nbsp;Xia-Yang Liu,&nbsp;Qi-Wei Zhao,&nbsp;Yu Wang,&nbsp;Feng-Hua Wu,&nbsp;Gang Zhao,&nbsp;Rui Sun,&nbsp;Xiao-Hong Guo","doi":"10.1002/ame2.12444","DOIUrl":"10.1002/ame2.12444","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The role of Claudin-1 in tongue squamous cell carcinoma (TSCC) metastasis needs further clarification, particularly its impact on cell migration. Herein, our study aims to investigate the role of Claudin-1 in TSCC cell migration and its underlying mechanisms.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>36 TSCC tissue samples underwent immunohistochemical staining for Claudin-1. Western blotting and immunofluorescence analyses were conducted to evaluate Claudin-1 expression and distribution in TSCC cells. Claudin-1 knockdown cell lines were established using short hairpin RNA transfection. Migration effects were assessed through wound healing assays. Furthermore, the expression of EMT-associated molecules was measured via western blotting.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Claudin-1 expression decreased as TSCC malignancy increased. Adenosine monophosphate–activated protein kinase (AMPK) activation led to increased Claudin-1 expression and membrane translocation, inhibiting TSCC cell migration and epithelial–mesenchymal transition (EMT). Conversely, Claudin-1 knockdown reversed these inhibitory effects on migration and EMT caused by AMPK activation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our results indicated that AMPK activation suppresses TSCC cell migration by targeting Claudin-1 and EMT pathways.</p>\u0000 </section>\u0000 </div>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":"7 5","pages":"606-616"},"PeriodicalIF":0.0,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ame2.12444","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141629430","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 cumulative analgesic effect of repeated electroacupuncture is modulated by Adora3 in the SCDH of mice with neuropathic pain.","authors":"Faisal Ayub Kiani, Hao Li, Panpan Guo, Qiulin Zhang, Mahmoud M Abouelfetouh, Mingxing Ding, Yi Ding","doi":"10.1002/ame2.12458","DOIUrl":"https://doi.org/10.1002/ame2.12458","url":null,"abstract":"<p><strong>Background: </strong>Existing remedial approaches for relieving neuropathic pain (NPP) are challenging and open the way for alternative therapeutic measures such as electroacupuncture (EA). The mechanism underlying the antinociceptive effects of repeated EA sessions, particularly concerning the regulation of the Adora3 receptor and its associated enzymes, has remained elusive.</p><p><strong>Methods: </strong>This study used a mouse model of spared nerve injury (SNI) to explore the cumulative analgesic effects of repeated EA at ST36 (Zusanli) and its impact on Adora3 regulation in the spinal cord dorsal horn (SCDH). Forty-eight male mice underwent SNI surgery for induction of neuropathic pain and were randomly assigned to the SNI, SNI + 2EA, SNI + 4EA, and SNI + 7EA groups. Spinal cord (L4-L6) was sampled for immunofluorescence, adenosine (ADO) detection and for molecular investigations following repeated EA treatment.</p><p><strong>Results: </strong>Following spared nerve injury (SNI), there was a significant decrease in mechanical withdrawal thresholds (PWTs) and thermal nociceptive withdrawal latency (TWL) in the ipsilateral hind paw on the third day post-surgery, while the contralateral hind paw PWTs showed no significant changes. On subsequent EA treatments, the SNI + EA groups led to a significant increase in pain thresholds (p < 0.05). Repeated EA sessions in SNI mice upregulated Adenosine A3 (Adora3) and cluster of differentiation-73 (CD73) expression while downregulating adenosine deaminase (ADA) and enhancing neuronal instigation in the SCDH. Colocalization analysis of Neun-treated cells revealed increased Adora3 expression, particularly in the SNI + 7EA group.</p><p><strong>Conclusions: </strong>In conclusion, cumulative electroacupuncture treatment reduced neuropathic pain by regulating Adora3 and CD73 expression, inhibiting ADA and most likely increasing neuronal activation in the SCDH. This study offers a promising therapeutic option for managing neuropathic pain, paving the way for further research.</p>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141592397","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":"Assessment of the piroxicam-incited model of synchronized colitis in T-cell receptor alpha chain-deficient mice","authors":"Maximo E. Lange,&nbsp;Danisa M. Bescucci,&nbsp;Valerie F. Boras,&nbsp;Tony Montina,&nbsp;G. Douglas Inglis","doi":"10.1002/ame2.12456","DOIUrl":"10.1002/ame2.12456","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>A multitude of mouse models are utilized to emulate and study intestinal inflammation. T-cell receptor alpha chain (TCRα)-deficient mice are used as a model of spontaneous colitis that has similarities with human ulcerative colitis. However, colitis is triggered late in the life of the mouse (age: 4–5 months), and inflammation does not develop at the same time in different mice. A previously conducted study reported that the administration of the drug piroxicam triggered predictable and early colitis in TCRα-deficient mice at the age of 6–8 weeks. However, a detailed characterization of ensuing inflammation was not provided.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted an in-depth examination of piroxicam-triggered colitis in TCRα-deficient mice, with emphasis on spatial histopathologic changes and analysis of expression of inflammatory markers. Furthermore, we tested amelioration of colitis with dexamethasone.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We confirmed that piroxicam induced a time-prescribed colitis and did so in the proximal colon as well as the cecum of TCRα-deficient mice. Piroxicam administration was observed to induce epithelial hyperplasia, goblet cell loss, and leukocyte infiltration with occasional ulceration. A Swiss roll technique was used to examine the colon and cecum in its entirety. Importantly, we observed that inflammation was multifocal segmental, with areas of tissue damage in between healthy tissue. In addition, we observed variability in the severity of inflammation among replicate animals and treatments, and that the administration of dexamethasone only partially ameliorated inflammation in the proximal colon.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Piroxicam consistently induced multifocal segmental colitis in the proximal colon and cecum, although the degree of inflammation was reduced in the latter. Importantly, spatial variability in inflammation in the large intestine and the inter-replicate variation in the severity of inflammation must be taken into consideration when utilizing this murine model of synchronized colitis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":"7 4","pages":"533-543"},"PeriodicalIF":0.0,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ame2.12456","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141592396","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}