Animal models and experimental medicine最新文献

{"title":"Single-cell sequencing reveals the features of adaptive immune responses in the liver of a mouse model of dengue fever","authors":"Yizhen Yuan,&nbsp;Qian Chen,&nbsp;Zhe Li,&nbsp;Fangzhou Cai,&nbsp;Dan Li,&nbsp;Wei Wang","doi":"10.1002/ame2.12454","DOIUrl":"10.1002/ame2.12454","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Dengue fever, an acute insect-borne infectious disease caused by the dengue virus (DENV), poses a great challenge to global public health. Hepatic involvement is the most common complication of severe dengue and is closely related to the occurrence and development of disease. However, the features of adaptive immune responses associated with liver injury in severe dengue are not clear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We used single-cell sequencing to examine the liver tissues of mild or severe dengue mice model to analyze the changes in immune response of T cells in the liver after dengue virus infection, and the immune interaction between macrophages and T cells. Flow cytometry was used to detect T cells and macrophages in mouse liver and blood to verify the single-cell sequencing results.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our result showed CTLs were significantly activated in the severe liver injury group but the immune function-related signal pathway was down-regulated. The reason may be that the excessive immune response in the severe group at the late stage of DENV infection induces the polarization of macrophages into M2 type, and the macrophages then inhibit T cell immunity through the TGF-β signaling pathway. In addition, the increased proportion of Treg cells suggested that Th17/Treg homeostasis was disrupted in the livers of severe liver injury mice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>In this study, single-cell sequencing and flow cytometry revealed the characteristic changes of T cell immune response and the role of macrophages in the liver of severe dengue fever mice. Our study provides a better understanding of the pathogenesis of liver injury in dengue fever patients.</p>\u0000 </section>\u0000 </div>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":"8 1","pages":"30-43"},"PeriodicalIF":0.0,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ame2.12454","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141581809","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 transcriptome of MHV-infected RAW264.7 cells offers an alternative model for macrophage innate immunity research","authors":"Yun Liu,&nbsp;Ting-Ting Feng,&nbsp;Wei Tong,&nbsp;Zhi Guo,&nbsp;Xia Li,&nbsp;Qi Kong,&nbsp;Zhi-Guang Xiang","doi":"10.1002/ame2.12443","DOIUrl":"10.1002/ame2.12443","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Macrophages are the primary innate immune cells encountered by the invading coronaviruses, and their abilities to initiate inflammatory reactions, to maintain the immunity homeostasis by differential polarization, to train the innate immune system by epigenic modification have been reported in laboratory animal research.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In the current in vitro research, murine macrophage RAW 264.7 cell were infected by mouse hepatitis virus, a coronavirus existed in mouse. At 3-, 6-, 12-, 24-, and 48-h post infection (<i>hpi.</i>), the attached cells were washed with PBS and harvested in Trizol reagent. Then The harvest is subjected to transcriptome sequencing.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The transcriptome analysis showed the immediate (3 <i>hpi.</i>) up regulation of DEGs related to inflammation, like <i>Il1b</i> and <i>Il6</i>. DEGs related to M2 differential polarization, like <i>Irf4</i> showed up regulation at 24 <i>hpi</i>., the late term after viral infection. In addition, DEGs related to metabolism and histone modification, like <i>Ezh2</i> were detected, which might correlate with the trained immunity of macrophages.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The current in vitro viral infection study showed the key innated immunity character of macrophages, which suggested the replacement value of viral infection cells model, to reduce the animal usage in preclinical research.</p>\u0000 </section>\u0000 </div>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":"8 1","pages":"57-66"},"PeriodicalIF":0.0,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ame2.12443","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141592398","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":"Applications and advancements in animal models for antiviral research on mosquito-borne arboviruses","authors":"Megan Caifeng Tang,&nbsp;Ka Heng Wong,&nbsp;Adzzie Shazleen Azman,&nbsp;Rafidah Lani","doi":"10.1002/ame2.12471","DOIUrl":"10.1002/ame2.12471","url":null,"abstract":"<p>Vector-borne diseases caused by arthropod-borne viruses (arboviruses) are a considerable challenge to public health globally. Mosquito-borne arboviruses, such as Chikungunya, Dengue, and Zika viruses, cause a range of human illnesses and may be fatal. Currently, efforts to control these diseases still face challenges due to growing vector resistance towards insecticides, urbanization, and limited effective antiviral treatments and vaccines. Animal models are crucial in antiviral research on mosquito-borne arboviruses, playing a role in understanding disease mechanisms, vaccine development, and toxicity testing, but the application of animal models still faces the challenges of ethical considerations and animal-to-human translational success. Genetically engineered mouse models, hamster models and non-human primate (NHP) are currently used in arbovirus research, but new models such as tree shrews and novel humanized mice are emerging. In the context of Malaysian research, the use of long-tailed macaques as potential NHP models for arbovirus research is possible; however, it faces the ethical dilemma of using an endangered species for scientific purposes. Overall, animal models play a crucial role in advancing infectious disease research, but a balance between medical research and species conservation must be upheld.</p>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":"7 5","pages":"673-684"},"PeriodicalIF":0.0,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ame2.12471","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141581808","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":"Epidural pressure measurement using a fiber-optic sensor (proof-of-principle in vivo animal trial)","authors":"Susanne Barz,&nbsp;Marvin Friedemann,&nbsp;Sebastian Voigt,&nbsp;Markus Melloh,&nbsp;Thomas Barz","doi":"10.1002/ame2.12469","DOIUrl":"10.1002/ame2.12469","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>An increase in epidural pressure around the stenosis has been observed in patients with lumbar spinal stenosis (LSS) with positive signs of sedimentation or redundant nerve roots. Further analysis of the pressure conditions in the stenotic area would be of great interest. We hypothesized that it would be possible to determine the physiological parameters of the epidural pulse wave and its course in pathological stenosis as a basis for objective identification of LSS based on pressure using a new measuring method with continuous spatial and temporal resolution.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We performed a single-case proof-of-principle in vivo animal trial and used a newly developed hybrid pressure-measurement probe with a fiber-tip Fabry–Pérot interferometer and several fiber Bragg gratings (FBG).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>With reproducible precision, we determined the mean epidural pressure to be 7.5 mmHg and the peak-to-peak value to be 4–5 mmHg. When analyzing the pressure measured by an FBG array, both the heart and respiratory rates can be precisely determined. This study was the first to measure the pulse wave velocity of the cerebrospinal fluid pressure wave as 0.97 m/s using the newly developed pressure probe. A simulated LSS was detected in real time and located exactly.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The developed fiber-optic pressure sensor probe enables a new objective measurement of epidural pressure. We confirmed our hypothesis that physiological parameters of the epidural pulse wave can be determined and that it is possible to identify an LSS.</p>\u0000 </section>\u0000 </div>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":"7 5","pages":"769-776"},"PeriodicalIF":0.0,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ame2.12469","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141565300","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":"Effect of macrophage-to-myofibroblast transition on silicosis","authors":"Fei Geng,&nbsp;Jingrou Xu,&nbsp;Xichen Ren,&nbsp;Ying Zhao,&nbsp;Yuhao Cai,&nbsp;Yaqian Li,&nbsp;Fuyu Jin,&nbsp;Tian Li,&nbsp;Xuemin Gao,&nbsp;Wenchen Cai,&nbsp;Hong Xu,&nbsp;Zhongqiu Wei,&nbsp;Na Mao,&nbsp;Ying Sun,&nbsp;Fang Yang","doi":"10.1002/ame2.12470","DOIUrl":"10.1002/ame2.12470","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The aim was to explore the effect of macrophage polarization and macrophage-to-myofibroblast transition (MMT) in silicosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Male Wistar rats were divided into a control group and a silicosis group developed using a HOPE MED 8050 dynamic automatic dusting system. Murine macrophage MH-S cells were randomly divided into a control group and an SiO₂ group. The pathological changes in lung tissue were observed using hematoxylin and eosin (HE) and Van Gieson (VG) staining. The distribution and location of macrophage marker (F4/80), M1 macrophage marker (iNOS), M2 macrophage marker (CD206), and myofibroblast marker (α-smooth muscle actin [α-SMA]) were detected using immunohistochemical and immunofluorescent staining. The expression changes in iNOS, Arg, α-SMA, vimentin, and type I collagen (Col I) were measured using Western blot.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The results of HE and VG staining showed obvious silicon nodule formation and the distribution of thick collagen fibers in the lung tissue of the silicosis group. Macrophage marker F4/80 increased gradually from 8 to 32 weeks after exposure to silica. Immunohistochemical and immunofluorescent staining results revealed that there were more iNOS-positive cells and some CD206-positive cells in the lung tissue of the silicosis group at 8 weeks. More CD206-positive cells were found in the silicon nodules of the lung tissues in the silicosis group at 32 weeks. Western blot analysis showed that the expressions of Inducible nitric oxide synthase and Arg protein in the lung tissues of the silicosis group were upregulated compared with those of the control group. The results of immunofluorescence staining showed the co-expression of F4/80, α-SMA, and Col I, and CD206 and α-SMA were co-expressed in the lung tissue of the silicosis group. The extracted rat alveolar lavage fluid revealed F4/80⁺α-SMA⁺, CD206⁺α-SMA⁺, and F4/80⁺α-SMA⁺Col I⁺ cells using immunofluorescence staining. Similar results were also found in MH-S cells induced by SiO₂.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The development of silicosis is accompanied by macrophage polarization and MMT.</p>\u0000 </section>\u0000 </div>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":"8 2","pages":"363-371"},"PeriodicalIF":0.0,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ame2.12470","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141560537","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":"Ultra-high-performance liquid chromatography-quadrupole time-of-flight-mass spectrometry-characterized extract of Aerides odorata Lour alleviates paracetamol-induced hepatotoxicity in animal model evidenced by biochemical, molecular, and computational studies","authors":"A. M. Abu Ahmed,&nbsp;Md. Atiar Rahman,&nbsp;Farjana Sharmen,&nbsp;A. S. M. Ali Reza,&nbsp;Md. Shahidul Islam,&nbsp;Md. Mamunur Rashid,&nbsp;Md. Khalid Juhani Rafi,&nbsp;Tanvir Ahmed Siddiqui,&nbsp;Md. Muzahid Ahmed Ezaj,&nbsp;Srabonti Saha,&nbsp;Md. Nazim Uddin,&nbsp;Walla Alelwani","doi":"10.1002/ame2.12452","DOIUrl":"10.1002/ame2.12452","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;Many kinds of orchids have significant health benefits although adequate research on their biological functions is yet to be carried out. This study investigated the paracetamol-induced liver damage–protecting effect of epiphytic &lt;i&gt;Aerides odorata&lt;/i&gt; methanol extract (AODE).&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;The protective effects of AODE were studied by analyzing its effect on liver function parameters, messenger RNA (mRNA) expression, and tissue histopathological architecture. The results were confirmed by ligand–receptor interaction of molecular docking and multitarget interaction of network pharmacological analyses.&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;AODE significantly (&lt;i&gt;p&lt;/i&gt; &lt; 0.05) minimized the dose-dependent increase in acid phosphatase, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, γ-glutamyl transferase, lactate dehydrogenase, and total bilirubin compared to the reference drug silymarin. Malondialdehyde level decreased, and the antioxidant genes catalase (&lt;i&gt;CAT&lt;/i&gt;), superoxide dismutase (&lt;i&gt;SOD&lt;/i&gt;), &lt;i&gt;β-actin&lt;/i&gt;, paraoxonase-1 (&lt;i&gt;PON1&lt;/i&gt;), and phosphofructokinase-1 (&lt;i&gt;PFK-1&lt;/i&gt;) were upregulated in AODE-treated paracetamol-intoxicated rats. A total of 376 compounds comprising phenols and flavonoids were identified using ultra-high-performance liquid chromatography-quadrupole time-of-flight-mass spectrometry (UPLC-qTOF-MS). The online toxicity assessment using SwissADME and admetSAR exhibited drug-like, nontoxic, and potential pharmacological properties. Additionally, in silico analysis showed that isoacteoside, one of the identified compounds, exhibited the best docking score (−11.42) with the liver protein human pituitary adenylate cyclase-1 (Protein Data Bank ID: 3N94). Furthermore, network pharmacology analysis identified the top 10 hub genes, namely &lt;i&gt;AKT1&lt;/i&gt; (protein kinase B), &lt;i&gt;CTNNB1&lt;/i&gt; (catenin beta-1), &lt;i&gt;SRC&lt;/i&gt; (proto-oncogene c-Src), &lt;i&gt;TNF&lt;/i&gt; (tumor necrosis factor), &lt;i&gt;EGFR&lt;/i&gt; (epidermal growth factor receptor), &lt;i&gt;HSP90AA1&lt;/i&gt; (&lt;b&gt;heat shock protein 90α&lt;/b&gt;), &lt;i&gt;MAPK3&lt;/i&gt; (mitogen-activated protein kinase 3), &lt;i&gt;STAT3&lt;/i&gt; (signal transducer and activator of transcription 3), &lt;i&gt;CASP3&lt;/i&gt; (caspase protein), and &lt;i&gt;ESR1&lt;/i&gt; (estrogen receptor 1), which are responsible for hepatoprotective activity.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Conclusion&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;The findings demonstrate that AODE could be a novel hepatoprotective target in drug-induced liver damage with a further single compound–based animal study.&lt;/p&gt;\u0000 ","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":"7 4","pages":"497-522"},"PeriodicalIF":0.0,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11369029/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141560539","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":"Mechanistic study of the effect of flexible fixation and load-bearing stress environment on fracture healing and shaping","authors":"Xingfu Li,&nbsp;Zhenhan Deng,&nbsp;Wei Lu","doi":"10.1002/ame2.12448","DOIUrl":"10.1002/ame2.12448","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The biomechanical environment created by suture-button fixation Latarjet is conducive to the healing and shaping of the transplanted coracoid, but its mechanism remains unclear. The latest research has found that the absence of stem cell chemokine (CXCL12) impeded bone regeneration in Sonic Hedgehog (SHH)-deficient animals. However, whether the biomechanical environment affects SHH and CXCL12 function has not been studied.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Rat fracture models were constructed to simulate stress environments under non-load-bearing and load-bearing conditions. The fracture healing and shaping, as well as the expression levels of SHH and CXCL12, were assessed through gross viewing, micro-computed tomography (micro-CT), and histochemical staining.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Under flexible fixation, the relative bone volume (BV/TV) of rats exposed to the load-bearing stress environment was significantly higher than that of rats under a non-load-bearing stress environment (<i>p</i> ≤ 0.05). Adverse bone shaping was not observed in rats subjected to flexible fixation. The levels of SHH and CXCL12 in load-bearing rats exhibited significant elevation (<i>p</i> ≤ 0.05). Under a load-bearing stress environment, no significant difference was observed in the BV/TV between the flexible fixation group and the rigid fixation group (<i>p</i> ≥ 0.05), but there was excessive hyperplasia of the fracture callus in the rigid fixation group. The levels of SHH and CXCL12 in rats subjected to rigid fixation were significantly elevated (<i>p</i> ≤ 0.05).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Flexible fixation and load-bearing stress environment may contribute to bone healing and shaping by influencing the levels of SHH and CXCL12, suggested that this mechanism may be relevant to the healing and shaping of the transplanted coracoid after suture-button fixation Latarjet.</p>\u0000 </section>\u0000 </div>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":"7 6","pages":"816-823"},"PeriodicalIF":0.0,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11680484/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141560538","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":"Developments in the study of Chinese herbal medicine's assessment index and action mechanism for diabetes mellitus","authors":"Xin-Yue Liu,&nbsp;Han-Wen Zheng,&nbsp;Feng-Zhong Wang,&nbsp;Tul-Wahab Atia,&nbsp;Bei Fan,&nbsp;Qiong Wang","doi":"10.1002/ame2.12455","DOIUrl":"10.1002/ame2.12455","url":null,"abstract":"<p>In traditional Chinese medicine (TCM), based on various pathogenic symptoms and the ‘golden chamber’ medical text, <i>Huangdi Neijing</i>, diabetes mellitus falls under the category ‘collateral disease’. TCM, with its wealth of experience, has been treating diabetes for over two millennia. Different antidiabetic Chinese herbal medicines reduce blood sugar, with their effective ingredients exerting unique advantages. As well as a glucose lowering effect, TCM also regulates bodily functions to prevent diabetes associated complications, with reduced side effects compared to western synthetic drugs. Chinese herbal medicine is usually composed of polysaccharides, saponins, alkaloids, flavonoids, and terpenoids. These active ingredients reduce blood sugar via various mechanism of actions that include boosting endogenous insulin secretion, enhancing insulin sensitivity and adjusting key enzyme activity and scavenging free radicals. These actions regulate glycolipid metabolism in the body, eventually achieving the goal of normalizing blood glucose. Using different animal models, a number of molecular markers are available for the detection of diabetes induction and the molecular pathology of the disease is becoming clearer. Nonetheless, there is a dearth of scientific data about the pharmacology, dose-effect relationship, and structure–activity relationship of TCM and its constituents. Further research into the efficacy, toxicity and mode of action of TCM, using different metabolic and molecular markers, is key to developing novel TCM antidiabetic formulations.</p>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":"7 4","pages":"433-443"},"PeriodicalIF":0.0,"publicationDate":"2024-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11369031/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141556189","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":"Cucurbitacins mitigate vascular neointimal hyperplasia by suppressing cyclin A2 expression and inhibiting VSMC proliferation","authors":"Ruqiang Yuan,&nbsp;Lei Qian,&nbsp;Hu Xu,&nbsp;Weijing Yun","doi":"10.1002/ame2.12457","DOIUrl":"10.1002/ame2.12457","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Restenosis frequently occurs after percutaneous angioplasty in patients with vascular occlusion and seriously threatens their health. Substantial evidence has revealed that preventing vascular smooth muscle cell proliferation using a drug-eluting stent is an effective approach to improve restenosis. Cucurbitacins have been demonstrated to exert an anti-proliferation effect in various tumors and a hypotensive effect. This study aims to investigate the role of cucurbitacins extracted from <i>Cucumis melo</i> L. (CuECs) and cucurbitacin B (CuB) on restenosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>C57BL/6 mice were subjected to left carotid artery ligation and subcutaneously injected with CuECs or CuB for 4 weeks. Hematoxylin–Eosin, immunofluorescence and immunohistochemistry staining were used to evaluate the effect of CuECs and CuB on neointimal hyperplasia. Western blot, real-time PCR, flow cytometry analysis, EdU staining and cellular immunofluorescence assay were employed to measure the effects of CuECs and CuB on cell proliferation and the cell cycle in vitro. The potential interactions of CuECs with cyclin A2 were performed by molecular docking.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The results demonstrated that both CuECs and CuB exhibited significant inhibitory effects on neointimal hyperplasia and proliferation of vascular smooth muscle cells. Furthermore, CuECs and CuB mediated cell cycle arrest at the S phase. Autodocking analysis demonstrated that CuB, CuD, CuE and CuI had high binding energy for cyclin A2. Our study also showed that CuECs and CuB dramatically inhibited FBS-induced cyclin A2 expression. Moreover, the expression of cyclin A2 in CuEC- and CuB-treated neointima was downregulated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>CuECs, especially CuB, exert an anti-proliferation effect in VSMCs and may be potential drugs to prevent restenosis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":"7 4","pages":"397-407"},"PeriodicalIF":0.0,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11369011/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141545688","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":"Elimination of GGTA1, CMAH, β4GalNT2 and CIITA genes in pigs compromises human versus pig xenogeneic immune reactions","authors":"Jing Xu,&nbsp;Jilong Ren,&nbsp;Kai Xu,&nbsp;Minghui Fang,&nbsp;Meina Ka,&nbsp;Fei Xu,&nbsp;Xin Wang,&nbsp;Jing Wang,&nbsp;Zhiqiang Han,&nbsp;Guihai Feng,&nbsp;Ying Zhang,&nbsp;Tang Hai,&nbsp;Wei Li,&nbsp;Zheng Hu","doi":"10.1002/ame2.12461","DOIUrl":"10.1002/ame2.12461","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Pig organ xenotransplantation is a potential solution for the severe organ shortage in clinic, while immunogenic genes need to be eliminated to improve the immune compatibility between humans and pigs. Current knockout strategies are mainly aimed at the genes causing hyperacute immune rejection (HAR) that occurs in the first few hours while adaptive immune reactions orchestrated by CD4 T cell thereafter also cause graft failure, in which process the MHC II molecule plays critical roles.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Thus, we generate a 4-gene (<i>GGTA1, CMAH, β4GalNT2,</i> and <i>CIITA</i>) knockout pig by CRISPR/Cas9 and somatic cell nuclear transfer to compromise HAR and CD4 T cell reactions simultaneously.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We successfully obtained 4KO piglets with deficiency in all alleles of genes, and at cellular and tissue levels. Additionally, the safety of our animals after gene editing was verified by using whole-genome sequencing and karyotyping. Piglets have survived for more than one year in the barrier, and also survived for more than 3 months in the conventional environment, suggesting that the piglets without MHC II can be raised in the barrier and then gradually mated in the conventional environment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>4KO piglets have lower immunogenicity, are safe in genomic level, and are easier to breed than the model with both MHC I and II deletion.</p>\u0000 </section>\u0000 </div>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":"7 4","pages":"584-590"},"PeriodicalIF":0.0,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ame2.12461","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141499917","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}