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.
Methods
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 (hpi.), the attached cells were washed with PBS and harvested in Trizol reagent. Then The harvest is subjected to transcriptome sequencing.
Results
The transcriptome analysis showed the immediate (3 hpi.) up regulation of DEGs related to inflammation, like Il1b and Il6. DEGs related to M2 differential polarization, like Irf4 showed up regulation at 24 hpi., the late term after viral infection. In addition, DEGs related to metabolism and histone modification, like Ezh2 were detected, which might correlate with the trained immunity of macrophages.
Conclusions
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.
{"title":"The transcriptome of MHV-infected RAW264.7 cells offers an alternative model for macrophage innate immunity research","authors":"Yun Liu, Ting-Ting Feng, Wei Tong, Zhi Guo, Xia Li, Qi Kong, 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}
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.
{"title":"Applications and advancements in animal models for antiviral research on mosquito-borne arboviruses","authors":"Megan Caifeng Tang, Ka Heng Wong, Adzzie Shazleen Azman, 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}
Susanne Barz, Marvin Friedemann, Sebastian Voigt, Markus Melloh, Thomas Barz
Background
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.
Methods
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).
Results
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.
Conclusions
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.
{"title":"Epidural pressure measurement using a fiber-optic sensor (proof-of-principle in vivo animal trial)","authors":"Susanne Barz, Marvin Friedemann, Sebastian Voigt, Markus Melloh, 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}
Fei Geng, Jingrou Xu, Xichen Ren, Ying Zhao, Yuhao Cai, Yaqian Li, Fuyu Jin, Tian Li, Xuemin Gao, Wenchen Cai, Hong Xu, Zhongqiu Wei, Na Mao, Ying Sun, Fang Yang
Background
The aim was to explore the effect of macrophage polarization and macrophage-to-myofibroblast transition (MMT) in silicosis.
Methods
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.
Results
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.
Conclusions
The development of silicosis is accompanied by macrophage polarization and MMT.
背景：目的是探讨巨噬细胞极化和巨噬细胞向肌成纤维细胞转化（MMT）对矽肺的影响：目的：探讨巨噬细胞极化和巨噬细胞向肌成纤维细胞转化（MMT）对矽肺的影响：雄性 Wistar 大鼠分为对照组和使用 HOPE MED 8050 动态自动除尘系统开发的矽肺组。将小鼠巨噬细胞 MH-S 随机分为对照组和二氧化硅组。使用苏木精、伊红（HE）和范吉森（VG）染色法观察肺组织的病理变化。采用免疫组化和免疫荧光染色法检测巨噬细胞标记物（F4/80）、M1巨噬细胞标记物（iNOS）、M2巨噬细胞标记物（CD206）和肌成纤维细胞标记物（α-平滑肌肌动蛋白[α-SMA]）的分布和位置。采用 Western 印迹法测定 iNOS、Arg、α-SMA、波形蛋白和 I 型胶原（Col I）的表达变化：结果：HE和VG染色结果显示，矽肺组肺组织中有明显的硅结节形成和粗胶原纤维分布。巨噬细胞标记物F4/80在接触二氧化硅后8周至32周逐渐增加。免疫组化和免疫荧光染色结果显示，8周时，矽肺组的肺组织中有更多的iNOS阳性细胞和一些CD206阳性细胞。32 周时，在矽肺组肺组织的硅结节中发现了更多的 CD206 阳性细胞。Western blot 分析显示，与对照组相比，矽肺组肺组织中诱导型一氧化氮合酶和 Arg 蛋白的表达上调。免疫荧光染色结果显示，F4/80、α-SMA和Col I在矽肺组肺组织中同时表达，CD206和α-SMA在矽肺组肺组织中同时表达。用免疫荧光染色法检测大鼠肺泡灌洗液，发现F4/80+α-SMA+、CD206+α-SMA+和F4/80+α-SMA+Col I+细胞。在二氧化硅诱导的 MH-S 细胞中也发现了类似的结果：结论：矽肺的发展伴随着巨噬细胞极化和MMT。
{"title":"Effect of macrophage-to-myofibroblast transition on silicosis","authors":"Fei Geng, Jingrou Xu, Xichen Ren, Ying Zhao, Yuhao Cai, Yaqian Li, Fuyu Jin, Tian Li, Xuemin Gao, Wenchen Cai, Hong Xu, Zhongqiu Wei, Na Mao, Ying Sun, 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 SiO<sub>2</sub> 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<sup>+</sup>α-SMA<sup>+</sup>, CD206<sup>+</sup>α-SMA<sup>+</sup>, and F4/80<sup>+</sup>α-SMA<sup>+</sup>Col I<sup>+</sup> cells using immunofluorescence staining. Similar results were also found in MH-S cells induced by SiO<sub>2</sub>.</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}
A. M. Abu Ahmed, Md. Atiar Rahman, Farjana Sharmen, A. S. M. Ali Reza, Md. Shahidul Islam, Md. Mamunur Rashid, Md. Khalid Juhani Rafi, Tanvir Ahmed Siddiqui, Md. Muzahid Ahmed Ezaj, Srabonti Saha, Md. Nazim Uddin, Walla Alelwani
<div> <section> <h3> Background</h3> <p>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 <i>Aerides odorata</i> methanol extract (AODE).</p> </section> <section> <h3> Methods</h3> <p>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.</p> </section> <section> <h3> Results</h3> <p>AODE significantly (<i>p</i> < 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 (<i>CAT</i>), superoxide dismutase (<i>SOD</i>), <i>β-actin</i>, paraoxonase-1 (<i>PON1</i>), and phosphofructokinase-1 (<i>PFK-1</i>) 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 <i>AKT1</i> (protein kinase B), <i>CTNNB1</i> (catenin beta-1), <i>SRC</i> (proto-oncogene c-Src), <i>TNF</i> (tumor necrosis factor), <i>EGFR</i> (epidermal growth factor receptor), <i>HSP90AA1</i> (<b>heat shock protein 90α</b>), <i>MAPK3</i> (mitogen-activated protein kinase 3), <i>STAT3</i> (signal transducer and activator of transcription 3), <i>CASP3</i> (caspase protein), and <i>ESR1</i> (estrogen receptor 1), which are responsible for hepatoprotective activity.</p> </section> <section> <h3> Conclusion</h3> <p>The findings demonstrate that AODE could be a novel hepatoprotective target in drug-induced liver damage with a further single compound–based animal study.</p>
{"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, Md. Atiar Rahman, Farjana Sharmen, A. S. M. Ali Reza, Md. Shahidul Islam, Md. Mamunur Rashid, Md. Khalid Juhani Rafi, Tanvir Ahmed Siddiqui, Md. Muzahid Ahmed Ezaj, Srabonti Saha, Md. Nazim Uddin, Walla Alelwani","doi":"10.1002/ame2.12452","DOIUrl":"10.1002/ame2.12452","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>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 <i>Aerides odorata</i> methanol extract (AODE).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>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.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>AODE significantly (<i>p</i> < 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 (<i>CAT</i>), superoxide dismutase (<i>SOD</i>), <i>β-actin</i>, paraoxonase-1 (<i>PON1</i>), and phosphofructokinase-1 (<i>PFK-1</i>) 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 <i>AKT1</i> (protein kinase B), <i>CTNNB1</i> (catenin beta-1), <i>SRC</i> (proto-oncogene c-Src), <i>TNF</i> (tumor necrosis factor), <i>EGFR</i> (epidermal growth factor receptor), <i>HSP90AA1</i> (<b>heat shock protein 90α</b>), <i>MAPK3</i> (mitogen-activated protein kinase 3), <i>STAT3</i> (signal transducer and activator of transcription 3), <i>CASP3</i> (caspase protein), and <i>ESR1</i> (estrogen receptor 1), which are responsible for hepatoprotective activity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The findings demonstrate that AODE could be a novel hepatoprotective target in drug-induced liver damage with a further single compound–based animal study.</p>\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}
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.
Methods
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.
Results
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 (p ≤ 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 (p ≤ 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 (p ≥ 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 (p ≤ 0.05).
Conclusions
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.
{"title":"Mechanistic study of the effect of flexible fixation and load-bearing stress environment on fracture healing and shaping","authors":"Xingfu Li, Zhenhan Deng, 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}
Xin-Yue Liu, Han-Wen Zheng, Feng-Zhong Wang, Tul-Wahab Atia, Bei Fan, Qiong Wang
In traditional Chinese medicine (TCM), based on various pathogenic symptoms and the ‘golden chamber’ medical text, Huangdi Neijing, 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.
{"title":"Developments in the study of Chinese herbal medicine's assessment index and action mechanism for diabetes mellitus","authors":"Xin-Yue Liu, Han-Wen Zheng, Feng-Zhong Wang, Tul-Wahab Atia, Bei Fan, 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}
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 Cucumis melo L. (CuECs) and cucurbitacin B (CuB) on restenosis.
Methods
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.
Results
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.
Conclusions
CuECs, especially CuB, exert an anti-proliferation effect in VSMCs and may be potential drugs to prevent restenosis.
{"title":"Cucurbitacins mitigate vascular neointimal hyperplasia by suppressing cyclin A2 expression and inhibiting VSMC proliferation","authors":"Ruqiang Yuan, Lei Qian, Hu Xu, 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}
Jing Xu, Jilong Ren, Kai Xu, Minghui Fang, Meina Ka, Fei Xu, Xin Wang, Jing Wang, Zhiqiang Han, Guihai Feng, Ying Zhang, Tang Hai, Wei Li, Zheng Hu
Background
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.
Methods
Thus, we generate a 4-gene (GGTA1, CMAH, β4GalNT2, and CIITA) knockout pig by CRISPR/Cas9 and somatic cell nuclear transfer to compromise HAR and CD4 T cell reactions simultaneously.
Results
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.
Conclusions
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.
背景：猪器官异种移植是解决临床上器官严重短缺问题的一种潜在方法，但需要消除免疫原性基因以改善人与猪之间的免疫相容性。目前的基因敲除策略主要针对导致超急性免疫排斥反应（HAR）的基因，这种排斥反应发生在最初几小时，而此后由 CD4 T 细胞协调的适应性免疫反应也会导致移植失败，在这一过程中，MHC II 分子起着关键作用：因此，我们通过 CRISPR/Cas9 和体细胞核移植技术产生了 4 个基因（GGTA1、CMAH、β4GalNT2 和 CIITA）敲除猪，以同时影响 HAR 和 CD4 T 细胞反应：结果：我们成功地获得了在细胞和组织水平上所有等位基因都缺乏的 4KO 仔猪。此外，我们还通过全基因组测序和核型分析验证了基因编辑后动物的安全性。仔猪在屏障中存活了一年多，在常规环境中也存活了 3 个多月，这表明没有 MHC II 的仔猪可以在屏障中饲养，然后逐渐在常规环境中交配：结论：与同时缺失 MHC I 和 II 的模型相比，4KO 仔猪的免疫原性更低、基因组水平更安全、更容易繁殖。
{"title":"Elimination of GGTA1, CMAH, β4GalNT2 and CIITA genes in pigs compromises human versus pig xenogeneic immune reactions","authors":"Jing Xu, Jilong Ren, Kai Xu, Minghui Fang, Meina Ka, Fei Xu, Xin Wang, Jing Wang, Zhiqiang Han, Guihai Feng, Ying Zhang, Tang Hai, Wei Li, 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}
This review compiles information from the literature on the chemical composition, pharmacological effects, and molecular mechanisms of earthworm extract (EE) and suggests possibilities for clinical translation of EE. We also consider future trends and concerns in this domain. We summarize the bioactive components of EE, including G-90, lysenin, lumbrokinase, antimicrobial peptides, earthworm serine protease (ESP), and polyphenols, and detail the antitumor, antithrombotic, antiviral, antibacterial, anti-inflammatory, analgesic, antioxidant, wound-healing, antifibrotic, and hypoglycemic activities and mechanisms of action of EE based on existing in vitro and in vivo studies. We further propose the potential of EE for clinical translation in anticancer and lipid-modifying therapies, and its promise as source of a novel agent for wound healing and resistance to antibiotic tolerance. The earthworm enzyme lumbrokinase embodies highly effective anticoagulant and thrombolytic properties and has the advantage of not causing bleeding phenomena due to hyperfibrinolysis. Its antifibrotic properties can reduce the excessive accumulation of extracellular matrix. The glycolipoprotein extract G-90 can effectively scavenge reactive oxygen groups and protect cellular tissues from oxidative damage. Earthworms have evolved a well-developed defense mechanism to fight against microbial infections, and the bioactive agents in EE have shown good antibacterial, fungal, and viral properties in in vitro and in vivo experiments and can alleviate inflammatory responses caused by infections, effectively reducing pain. Recent studies have also highlighted the role of EE in lowering blood glucose. EE shows high medicinal value and is expected to be a source of many bioactive compounds.
本综述汇编了有关蚯蚓提取物（EE）的化学成分、药理作用和分子机制的文献信息，并提出了将蚯蚓提取物应用于临床的可能性。我们还考虑了这一领域的未来趋势和关注点。我们总结了蚯蚓提取物的生物活性成分，包括 G-90、溶血素、腰激酶、抗菌肽、蚯蚓丝氨酸蛋白酶 (ESP) 和多酚，并根据现有的体外和体内研究详细介绍了蚯蚓提取物的抗肿瘤、抗血栓、抗病毒、抗菌、抗炎、镇痛、抗氧化、伤口愈合、抗纤维化和降血糖活性及其作用机制。我们进一步提出了 EE 在抗癌和调脂疗法中的临床转化潜力，以及作为伤口愈合和抗生素耐受性新型药物来源的前景。蚯蚓酶腰激酶具有高效的抗凝和溶栓特性，而且不会因纤维蛋白溶解亢进而导致出血现象。其抗纤维化特性可减少细胞外基质的过度积聚。糖脂蛋白提取物 G-90 能有效清除活性氧基团，保护细胞组织免受氧化损伤。蚯蚓进化出了一套完善的抵御微生物感染的防御机制，而 EE 中的生物活性物质在体外和体内实验中都表现出了良好的抗菌、抗真菌和抗病毒特性，可以缓解感染引起的炎症反应，有效减轻疼痛。最近的研究还强调了 EE 在降低血糖方面的作用。EE 具有很高的药用价值，有望成为许多生物活性化合物的来源。
{"title":"Pharmacological effects of bioactive agents in earthworm extract: A comprehensive review","authors":"Zihan Zhu, Xinyi Deng, Wenqing Xie, Hengzhen Li, Yusheng Li, Zhenhan Deng","doi":"10.1002/ame2.12465","DOIUrl":"10.1002/ame2.12465","url":null,"abstract":"<p>This review compiles information from the literature on the chemical composition, pharmacological effects, and molecular mechanisms of earthworm extract (EE) and suggests possibilities for clinical translation of EE. We also consider future trends and concerns in this domain. We summarize the bioactive components of EE, including G-90, lysenin, lumbrokinase, antimicrobial peptides, earthworm serine protease (ESP), and polyphenols, and detail the antitumor, antithrombotic, antiviral, antibacterial, anti-inflammatory, analgesic, antioxidant, wound-healing, antifibrotic, and hypoglycemic activities and mechanisms of action of EE based on existing in vitro and in vivo studies. We further propose the potential of EE for clinical translation in anticancer and lipid-modifying therapies, and its promise as source of a novel agent for wound healing and resistance to antibiotic tolerance. The earthworm enzyme lumbrokinase embodies highly effective anticoagulant and thrombolytic properties and has the advantage of not causing bleeding phenomena due to hyperfibrinolysis. Its antifibrotic properties can reduce the excessive accumulation of extracellular matrix. The glycolipoprotein extract G-90 can effectively scavenge reactive oxygen groups and protect cellular tissues from oxidative damage. Earthworms have evolved a well-developed defense mechanism to fight against microbial infections, and the bioactive agents in EE have shown good antibacterial, fungal, and viral properties in in vitro and in vivo experiments and can alleviate inflammatory responses caused by infections, effectively reducing pain. Recent studies have also highlighted the role of EE in lowering blood glucose. EE shows high medicinal value and is expected to be a source of many bioactive compounds.</p>","PeriodicalId":93869,"journal":{"name":"Animal models and experimental medicine","volume":"7 5","pages":"653-672"},"PeriodicalIF":0.0,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ame2.12465","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141494555","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}
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