Excessive neuroinflammation mediated by microglia has a detrimental effect on the progression of ischemic stroke. Eriocalyxin B (EriB) was found with a neuroprotective effect in mice with Parkinson's disease via the suppression of microglial overactivation. This study aimed to investigate the roles of EriB in permanent middle cerebral artery occlusion (pMCAO) mice. The pMCAO was induced in the internal carotid artery of the mice by the intraluminal filament method, and EriB (10 mg/kg) was administered immediately after surgery by intraperitoneal injection. The behavior score, 2,3,5-triphenyltetrazole chloride staining, Nissl staining, TUNEL, immunohistochemistry, immunofluorescence, PCR, ELISA, and immunoblotting revealed that EriB administration reduced brain infarct and neuron death and ameliorated neuroinflammation and microglia overactivation in pMCAO mice, manifested by alterations of TUNEL-positive cell numbers, ionized calcium binding adaptor molecule 1 (Iba-1)-positive cell numbers, and expression of tumor necrosis factor-α, interleukin 6, IL-1β, inducible nitric oxide synthase, and arginase 1. In addition, EriB suppressed ischemia-induced activation of nuclear factor kappa B (NF-κB) signaling in the brain penumbra, suggesting the involvement of NF-κB in EriB function. In conclusion, EriB exerted anti-inflammatory effects in ischemia stroke by regulating the NF-κB signaling pathway, and this may provide insights into the neuroprotective effect of EriB in the treatment of ischemic stroke.
{"title":"Eriocalyxin B alleviated ischemic cerebral injury by limiting microglia-mediated excessive neuroinflammation in mice.","authors":"Yanqiang Chen, Cong Zhang, Liming Zhao, Rong Chen, Peipei Zhang, Junxia Li, Xueping Zhang, Xiangjian Zhang","doi":"10.1538/expanim.23-0070","DOIUrl":"10.1538/expanim.23-0070","url":null,"abstract":"<p><p>Excessive neuroinflammation mediated by microglia has a detrimental effect on the progression of ischemic stroke. Eriocalyxin B (EriB) was found with a neuroprotective effect in mice with Parkinson's disease via the suppression of microglial overactivation. This study aimed to investigate the roles of EriB in permanent middle cerebral artery occlusion (pMCAO) mice. The pMCAO was induced in the internal carotid artery of the mice by the intraluminal filament method, and EriB (10 mg/kg) was administered immediately after surgery by intraperitoneal injection. The behavior score, 2,3,5-triphenyltetrazole chloride staining, Nissl staining, TUNEL, immunohistochemistry, immunofluorescence, PCR, ELISA, and immunoblotting revealed that EriB administration reduced brain infarct and neuron death and ameliorated neuroinflammation and microglia overactivation in pMCAO mice, manifested by alterations of TUNEL-positive cell numbers, ionized calcium binding adaptor molecule 1 (Iba-1)-positive cell numbers, and expression of tumor necrosis factor-α, interleukin 6, IL-1β, inducible nitric oxide synthase, and arginase 1. In addition, EriB suppressed ischemia-induced activation of nuclear factor kappa B (NF-κB) signaling in the brain penumbra, suggesting the involvement of NF-κB in EriB function. In conclusion, EriB exerted anti-inflammatory effects in ischemia stroke by regulating the NF-κB signaling pathway, and this may provide insights into the neuroprotective effect of EriB in the treatment of ischemic stroke.</p>","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10877152/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41233601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01DOI: 10.1538/expanim.23-0065e
Zhen Li, Mengfan He, Danqing Dai, Xiaofei Gao, Huazheng Liang and Lize Xiong Exp. Anim. 73(1), 109-123, 2024 https://doi.org/10.1538/expanim.23-0065 In the original publication of the article, the Funding section was incomplete. The correct Funding information is provided below: Funding This work was supported by a grant from the Shanghai Commission of Science and Technology (201409003500), Major Project of National Natural Science Foundation of China (No. 82293640, No. 82293643), Key Project of National Natural Science Foundation of China (No. 82130121), the second round of the three-year action plan for "strengthening and promoting Traditional Chinese Medicine" of Hongkou District (HKGYQYXM-2022-06), and Scientific and technological innovation 2030 - major project of Brain Science and Brain-Like Intelligence Technology (2021ZD0202804) to Dr. Lize Xiong, a grant from the National Natural Science Foundation of China (No.81974535) to Dr. Huazheng Liang, and the Talent Promotion Program of Shanghai Fourth People's Hospital Affiliated to Tongji University School of Medicine (SY-XKZT-2019-3006) and the Discipline Promotion Program of Shanghai Fourth People's Hospital Affiliated to Tongji University School of Medicine (SY-XKZT-2019-1012) to Dr. Zhen Li.
{"title":"Errata: Middle aged CAMKII-Cre:Cbs<sup>fl/fl</sup> mice: a new model for studying perioperative neurocognitive disorders.","authors":"","doi":"10.1538/expanim.23-0065e","DOIUrl":"10.1538/expanim.23-0065e","url":null,"abstract":"<p><p>Zhen Li, Mengfan He, Danqing Dai, Xiaofei Gao, Huazheng Liang and Lize Xiong Exp. Anim. 73(1), 109-123, 2024 https://doi.org/10.1538/expanim.23-0065 In the original publication of the article, the Funding section was incomplete. The correct Funding information is provided below: Funding This work was supported by a grant from the Shanghai Commission of Science and Technology (201409003500), Major Project of National Natural Science Foundation of China (No. 82293640, No. 82293643), Key Project of National Natural Science Foundation of China (No. 82130121), the second round of the three-year action plan for \"strengthening and promoting Traditional Chinese Medicine\" of Hongkou District (HKGYQYXM-2022-06), and Scientific and technological innovation 2030 - major project of Brain Science and Brain-Like Intelligence Technology (2021ZD0202804) to Dr. Lize Xiong, a grant from the National Natural Science Foundation of China (No.81974535) to Dr. Huazheng Liang, and the Talent Promotion Program of Shanghai Fourth People's Hospital Affiliated to Tongji University School of Medicine (SY-XKZT-2019-3006) and the Discipline Promotion Program of Shanghai Fourth People's Hospital Affiliated to Tongji University School of Medicine (SY-XKZT-2019-1012) to Dr. Zhen Li.</p>","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11091357/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140862635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-11-09Epub Date: 2023-06-01DOI: 10.1538/expanim.23-0019
Yuemei Luo, Juan Yang, Lijia Zhang, Zhenzhen Tai, Hao Huang, Zucai Xu, Haiqing Zhang
Epilepsy is the most common chronic disorder in the nervous system, mainly characterized by recurrent, periodic, unpredictable seizures. Post-translational modifications (PTMs) are important protein functional regulators that regulate various physiological and pathological processes. It is significant for cell activity, stability, protein folding, and localization. Phosphoglycerate kinase (PGK) 1 has traditionally been studied as an important adenosine triphosphate (ATP)-generating enzyme of the glycolytic pathway. PGK1 catalyzes the reversible transfer of a phosphoryl group from 1, 3-bisphosphoglycerate (1, 3-BPG) to ADP, producing 3-phosphoglycerate (3-PG) and ATP. In addition to cell metabolism regulation, PGK1 is involved in multiple biological activities, including angiogenesis, autophagy, and DNA repair. However, the exact role of PGK1 succinylation in epilepsy has not been thoroughly investigated. The expression of PGK1 succinylation was analyzed by Immunoprecipitation. Western blots were used to assess the expression of PGK1, angiostatin, and vascular endothelial growth factor (VEGF) in a rat model of lithium-pilocarpine-induced acute epilepsy. Behavioral experiments were performed in a rat model of lithium-pilocarpine-induced acute epilepsy. ELISA method was used to measure the level of S100β in serum brain biomarkers' integrity of the blood-brain barrier. The expression of the succinylation of PGK1 was decreased in a rat model of lithium-pilocarpine-induced acute epilepsy compared with the normal rats in the hippocampus. Interestingly, the lysine 15 (K15), and the arginine (R) variants of lentivirus increased the susceptibility in a rat model of lithium-pilocarpine-induced acute epilepsy, and the K15 the glutamate (E) variants, had the opposite effect. In addition, the succinylation of PGK1 at K15 affected the expression of PGK1 succinylation but not the expression of PGK1total protein. Furthermore, the study found that the succinylation of PGK1 at K15 may affect the level of angiostatin and VEGF in the hippocampus, which also affects the level of S100β in serum. In conclusion, the mutation of the K15 site of PGK1 may alter the expression of the succinylation of PGK1 and then affect the integrity of the blood-brain barrier through the angiostatin / VEGF pathway altering the activity of epilepsy, which may be one of the new mechanisms of treatment strategies.
{"title":"Phosphoglycerate kinase (PGK) 1 succinylation modulates epileptic seizures and the blood-brain barrier.","authors":"Yuemei Luo, Juan Yang, Lijia Zhang, Zhenzhen Tai, Hao Huang, Zucai Xu, Haiqing Zhang","doi":"10.1538/expanim.23-0019","DOIUrl":"10.1538/expanim.23-0019","url":null,"abstract":"<p><p>Epilepsy is the most common chronic disorder in the nervous system, mainly characterized by recurrent, periodic, unpredictable seizures. Post-translational modifications (PTMs) are important protein functional regulators that regulate various physiological and pathological processes. It is significant for cell activity, stability, protein folding, and localization. Phosphoglycerate kinase (PGK) 1 has traditionally been studied as an important adenosine triphosphate (ATP)-generating enzyme of the glycolytic pathway. PGK1 catalyzes the reversible transfer of a phosphoryl group from 1, 3-bisphosphoglycerate (1, 3-BPG) to ADP, producing 3-phosphoglycerate (3-PG) and ATP. In addition to cell metabolism regulation, PGK1 is involved in multiple biological activities, including angiogenesis, autophagy, and DNA repair. However, the exact role of PGK1 succinylation in epilepsy has not been thoroughly investigated. The expression of PGK1 succinylation was analyzed by Immunoprecipitation. Western blots were used to assess the expression of PGK1, angiostatin, and vascular endothelial growth factor (VEGF) in a rat model of lithium-pilocarpine-induced acute epilepsy. Behavioral experiments were performed in a rat model of lithium-pilocarpine-induced acute epilepsy. ELISA method was used to measure the level of S100β in serum brain biomarkers' integrity of the blood-brain barrier. The expression of the succinylation of PGK1 was decreased in a rat model of lithium-pilocarpine-induced acute epilepsy compared with the normal rats in the hippocampus. Interestingly, the lysine 15 (K15), and the arginine (R) variants of lentivirus increased the susceptibility in a rat model of lithium-pilocarpine-induced acute epilepsy, and the K15 the glutamate (E) variants, had the opposite effect. In addition, the succinylation of PGK1 at K15 affected the expression of PGK1 succinylation but not the expression of PGK1total protein. Furthermore, the study found that the succinylation of PGK1 at K15 may affect the level of angiostatin and VEGF in the hippocampus, which also affects the level of S100β in serum. In conclusion, the mutation of the K15 site of PGK1 may alter the expression of the succinylation of PGK1 and then affect the integrity of the blood-brain barrier through the angiostatin / VEGF pathway altering the activity of epilepsy, which may be one of the new mechanisms of treatment strategies.</p>","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2023-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10658094/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9553293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-11-09Epub Date: 2023-06-13DOI: 10.1538/expanim.23-0052
Nergis Akbaş, Bahadır Süleyman, Renad Mammadov, Mine Gülaboğlu, Emin Murat Akbaş, Halis Süleyman
Felodipine is a calcium channel blocker with antioxidant and anti-inflammatory properties. Researchers have stated that oxidative stress and inflammation also play a role in the pathophysiology of gastric ulcers caused by nonsteroidal anti-inflammatory drugs. The aim of this study was to investigate the antiulcer effect of felodipine on indomethacin-induced gastric ulcers in Wistar rats and compare it with that of famotidine. The antiulcer activities of felodipine (5 mg/kg) and famotidine were investigated biochemically and macroscopically in animals treated with felodipine (5 mg/kg) and famotidine in combination with indomethacin. The results were compared with those of the healthy control group and the group administered indomethacin alone. It was observed that felodipine suppressed the indomethacin-induced malondialdehyde increase (P<0.001); reduced the decrease in total glutathione amount (P<0.001), reduced the decrease superoxide dismutase (P<0.001), and catalase activities (P<0.001); and significantly inhibited ulcers (P<0.001) at the tested dose compared with indomethacin alone. Felodipine at a dose of 5 mg/kg reduced the indomethacin-induced decrease in cyclooxygenase-1 activity (P<0.001) but did not cause a significant reduction in the decrease in cyclooxygenase-2 activity. The antiulcer efficacy of felodipine was demonstrated in this experimental model. These data suggest that felodipine may be useful in the treatment of nonsteroidal anti-inflammatory drug-induced gastric injury.
{"title":"Effect of felodipine on indomethacin-induced gastric ulcers in rats.","authors":"Nergis Akbaş, Bahadır Süleyman, Renad Mammadov, Mine Gülaboğlu, Emin Murat Akbaş, Halis Süleyman","doi":"10.1538/expanim.23-0052","DOIUrl":"10.1538/expanim.23-0052","url":null,"abstract":"<p><p>Felodipine is a calcium channel blocker with antioxidant and anti-inflammatory properties. Researchers have stated that oxidative stress and inflammation also play a role in the pathophysiology of gastric ulcers caused by nonsteroidal anti-inflammatory drugs. The aim of this study was to investigate the antiulcer effect of felodipine on indomethacin-induced gastric ulcers in Wistar rats and compare it with that of famotidine. The antiulcer activities of felodipine (5 mg/kg) and famotidine were investigated biochemically and macroscopically in animals treated with felodipine (5 mg/kg) and famotidine in combination with indomethacin. The results were compared with those of the healthy control group and the group administered indomethacin alone. It was observed that felodipine suppressed the indomethacin-induced malondialdehyde increase (P<0.001); reduced the decrease in total glutathione amount (P<0.001), reduced the decrease superoxide dismutase (P<0.001), and catalase activities (P<0.001); and significantly inhibited ulcers (P<0.001) at the tested dose compared with indomethacin alone. Felodipine at a dose of 5 mg/kg reduced the indomethacin-induced decrease in cyclooxygenase-1 activity (P<0.001) but did not cause a significant reduction in the decrease in cyclooxygenase-2 activity. The antiulcer efficacy of felodipine was demonstrated in this experimental model. These data suggest that felodipine may be useful in the treatment of nonsteroidal anti-inflammatory drug-induced gastric injury.</p>","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2023-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10658091/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9636158","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-11-09Epub Date: 2023-06-19DOI: 10.1538/expanim.23-0036
Baojun Fu, Jingjing Jiang, Yuqiong Huang
Neuropathic pain (NP) is caused by diseases or dysfunction of nervous system and has a considerable negative impact on patients' quality of life. Opioid analgesics can be used for NP treatment. However, the effect of dezocine on NC remains unknown. In this study, we aimed to investigate the analgesic and intestinal effects of various doses of dezocine in rats with chronic constriction injuries (CCI). 100 rats were equally divided into 5 groups: the low (D1 group), medium (D2 group), and high (D3 group) doses of dezocine, and sham operation and model groups. The effects of dezocine on pain, analgesic effect, pain response, and tension and contraction frequencies of intestinal smooth muscles were assessed. With an increase in the dezocine dosage, the cumulative pain scores of rats decreased and analgesic effect significantly increased; mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) improved in varying degrees. The expression of the NP-related proteins glial fibrillary acidic protein (GFAP) and connexin 43 (Cx43) was also improved by dezocine treatment. The results of western blot and ELISA showed that IL-6, and monocyte chemotactic protein-1 (MCP-1) levels also decreased significantly with an increase in the dezocine dose, indicated that dezocine alleviated the inflammatory microenvironment. The dezocine exhibited no significant effect on the tension or contraction frequencies of intestinal smooth muscles of rats. In conclusion, the analgesic effect of dezocine on rats with CCI is dose-dependent and has little effect on the tension or contraction frequencies of intestinal smooth muscles. Our research proved the analgesic effect of dezocine in rats with CCI, and provided further insights into new therapies for NP treatment.
{"title":"The analgesic effects of dezocine in rats with chronic constriction injuries.","authors":"Baojun Fu, Jingjing Jiang, Yuqiong Huang","doi":"10.1538/expanim.23-0036","DOIUrl":"10.1538/expanim.23-0036","url":null,"abstract":"<p><p>Neuropathic pain (NP) is caused by diseases or dysfunction of nervous system and has a considerable negative impact on patients' quality of life. Opioid analgesics can be used for NP treatment. However, the effect of dezocine on NC remains unknown. In this study, we aimed to investigate the analgesic and intestinal effects of various doses of dezocine in rats with chronic constriction injuries (CCI). 100 rats were equally divided into 5 groups: the low (D1 group), medium (D2 group), and high (D3 group) doses of dezocine, and sham operation and model groups. The effects of dezocine on pain, analgesic effect, pain response, and tension and contraction frequencies of intestinal smooth muscles were assessed. With an increase in the dezocine dosage, the cumulative pain scores of rats decreased and analgesic effect significantly increased; mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) improved in varying degrees. The expression of the NP-related proteins glial fibrillary acidic protein (GFAP) and connexin 43 (Cx43) was also improved by dezocine treatment. The results of western blot and ELISA showed that IL-6, and monocyte chemotactic protein-1 (MCP-1) levels also decreased significantly with an increase in the dezocine dose, indicated that dezocine alleviated the inflammatory microenvironment. The dezocine exhibited no significant effect on the tension or contraction frequencies of intestinal smooth muscles of rats. In conclusion, the analgesic effect of dezocine on rats with CCI is dose-dependent and has little effect on the tension or contraction frequencies of intestinal smooth muscles. Our research proved the analgesic effect of dezocine in rats with CCI, and provided further insights into new therapies for NP treatment.</p>","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2023-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10658089/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10013631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A tetanus outbreak occurred during 2014-2015 in the rhesus macaques reared in an open enclosure in our facility. As the soil of the facility was suspected to be contaminated with Clostridium tetani spores, there was a risk of further tetanus occurring among the macaques. To protect them from tetanus, a tetanus toxoid vaccination was recommended; however, the vaccinated elderly animals might not be effectively protected due to insufficient humoral immune responses. Hence, we evaluated the dynamics of antibody responses among rhesus macaques of all age groups vaccinated with two-dose tetanus toxoid at a 1-year interval during a 3-year follow-up study. The vaccination developed anti-tetanus toxin-specific antibodies in animals of all age groups, the antibody levels peaked 1 year after the second vaccination, and the peak levels decreased with age. However, the levels among elderly individuals (aged ≥13 years) were still higher than the threshold level, which was supposed to protect them from tetanus development. Although the rhesus macaques in our facility had a risk of occasional exposure to the spores due to the outbreak, no incidence of tetanus has ever occurred to date. These results indicate that the vaccination protocol is effective in protecting not only younger but also older animals from tetanus.
{"title":"Annual two-dose tetanus toxoid vaccination induces protective humoral immunity to all age groups of rhesus macaques.","authors":"Megumi Murata, Anastasiia Kovba, Akihisa Kaneko, Mayumi Morimoto, Akiyo Ishigami, Takayoshi Natsume, Ayaka Washizaki, Takako Miyabe-Nishiwaki, Juri Suzuki, Hirofumi Akari","doi":"10.1538/expanim.23-0040","DOIUrl":"10.1538/expanim.23-0040","url":null,"abstract":"<p><p>A tetanus outbreak occurred during 2014-2015 in the rhesus macaques reared in an open enclosure in our facility. As the soil of the facility was suspected to be contaminated with Clostridium tetani spores, there was a risk of further tetanus occurring among the macaques. To protect them from tetanus, a tetanus toxoid vaccination was recommended; however, the vaccinated elderly animals might not be effectively protected due to insufficient humoral immune responses. Hence, we evaluated the dynamics of antibody responses among rhesus macaques of all age groups vaccinated with two-dose tetanus toxoid at a 1-year interval during a 3-year follow-up study. The vaccination developed anti-tetanus toxin-specific antibodies in animals of all age groups, the antibody levels peaked 1 year after the second vaccination, and the peak levels decreased with age. However, the levels among elderly individuals (aged ≥13 years) were still higher than the threshold level, which was supposed to protect them from tetanus development. Although the rhesus macaques in our facility had a risk of occasional exposure to the spores due to the outbreak, no incidence of tetanus has ever occurred to date. These results indicate that the vaccination protocol is effective in protecting not only younger but also older animals from tetanus.</p>","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2023-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10658093/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9583648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-11-09Epub Date: 2023-07-06DOI: 10.1538/expanim.23-0021
Xiulong Xie, Zhenlan Niu, Linlin Wang, Xiaofei Zhou, Xingyan Yu, Hongyan Jing, Yi Yang
CD36 (also known as scavenger receptor B2) is a multifunctional receptor that mediates lipid uptake, advanced oxidation protein products, and immunological recognition, and has roles in lipid accumulation, apoptosis, as well as in metastatic colonization in cancer. CD36 is involved in tumor immunity, metastatic invasion, and therapy resistance through various molecular mechanisms. Targeting CD36 has emerged as an effective strategy for tumor immunotherapy. In this study, we have successfully generated a novel hCD36 mouse (Unless otherwise stated, hCD36 mouse below refer to homozygous hCD36 mouse) strain where the sequences encoding the extracellular domains of the mouse Cd36 gene were replaced with the corresponding human sequences. The results showed that the hCD36 mice only expressed human CD36, and the proportion of each lymphocyte was not significantly changed compared with wild-type mice. Furthermore, CD36 monoclonal antibody could significantly inhibit tumor growth after treatment. Therefore, the hCD36 mouse represent a validated preclinical mouse model for the evaluation of tumor immunotherapy targeting CD36.
{"title":"Humanized CD36 (hCD36) mouse model supports the preclinical evaluation of therapeutic candidates targeting CD36.","authors":"Xiulong Xie, Zhenlan Niu, Linlin Wang, Xiaofei Zhou, Xingyan Yu, Hongyan Jing, Yi Yang","doi":"10.1538/expanim.23-0021","DOIUrl":"10.1538/expanim.23-0021","url":null,"abstract":"<p><p>CD36 (also known as scavenger receptor B2) is a multifunctional receptor that mediates lipid uptake, advanced oxidation protein products, and immunological recognition, and has roles in lipid accumulation, apoptosis, as well as in metastatic colonization in cancer. CD36 is involved in tumor immunity, metastatic invasion, and therapy resistance through various molecular mechanisms. Targeting CD36 has emerged as an effective strategy for tumor immunotherapy. In this study, we have successfully generated a novel hCD36 mouse (Unless otherwise stated, hCD36 mouse below refer to homozygous hCD36 mouse) strain where the sequences encoding the extracellular domains of the mouse Cd36 gene were replaced with the corresponding human sequences. The results showed that the hCD36 mice only expressed human CD36, and the proportion of each lymphocyte was not significantly changed compared with wild-type mice. Furthermore, CD36 monoclonal antibody could significantly inhibit tumor growth after treatment. Therefore, the hCD36 mouse represent a validated preclinical mouse model for the evaluation of tumor immunotherapy targeting CD36.</p>","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2023-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10658083/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9752575","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The liver is a key organ governing body energy metabolism. Dietary fats influence energy metabolism and mitochondrial functioning. Crocodile oil (CO) is rich in mono- and polyunsaturated fatty acids that contain natural anti-inflammatory and healing properties. Our study examined how CO affects the expressions of liver proteins involved in energy metabolism in rats. Twenty-one male Sprague Dawley rats were divided into three groups and underwent oral gavage with 3 ml/kg of sterile water (N group), CO (CO group), or palm oil (PO group) for 7 weeks. Body weight, energy intake, liver weight, liver indexes, blood lipid profiles, and liver-energy intermediates were measured. The liver proteome was analyzed using shotgun proteomics, and the functions and network interactions of several candidate proteins were predicted using the STITCH v.5.0 software. Body weights, energy intake, liver contents, and lipid profiles did not differ between the groups. However, hepatic oxaloacetate and malate levels were significantly higher in the CO group than in the PO group. Targeted proteomics reveals that 22 out of 1,790 unique proteins in the CO group were involved in energy-generating pathways, including the tricarboxylic acid cycle and oxidative phosphorylation (OXPHOS), and were correlated with the AMP-activated protein kinase signaling pathway. Cluster analysis of 59 differentially expressed proteins showed that OXPHOS-associated proteins were upregulated in the CO group and that three glycolytic metabolism-related proteins were downregulated in the CO group. CO may enhance hepatic energy metabolism by regulating the expressions of energy expenditure-related proteins.
{"title":"Targeted proteomic analysis reveals that crocodile oil from Crocodylus siamensis may enhance hepatic energy metabolism in rats.","authors":"Wirasak Fungfuang, Krittika Srisuksai, Pitchaya Santativongchai, Sawanya Charoenlappanit, Narumon Phaonakrop, Sittiruk Roytrakul, Phitsanu Tulayakul, Kongphop Parunyakul","doi":"10.1538/expanim.23-0009","DOIUrl":"10.1538/expanim.23-0009","url":null,"abstract":"<p><p>The liver is a key organ governing body energy metabolism. Dietary fats influence energy metabolism and mitochondrial functioning. Crocodile oil (CO) is rich in mono- and polyunsaturated fatty acids that contain natural anti-inflammatory and healing properties. Our study examined how CO affects the expressions of liver proteins involved in energy metabolism in rats. Twenty-one male Sprague Dawley rats were divided into three groups and underwent oral gavage with 3 ml/kg of sterile water (N group), CO (CO group), or palm oil (PO group) for 7 weeks. Body weight, energy intake, liver weight, liver indexes, blood lipid profiles, and liver-energy intermediates were measured. The liver proteome was analyzed using shotgun proteomics, and the functions and network interactions of several candidate proteins were predicted using the STITCH v.5.0 software. Body weights, energy intake, liver contents, and lipid profiles did not differ between the groups. However, hepatic oxaloacetate and malate levels were significantly higher in the CO group than in the PO group. Targeted proteomics reveals that 22 out of 1,790 unique proteins in the CO group were involved in energy-generating pathways, including the tricarboxylic acid cycle and oxidative phosphorylation (OXPHOS), and were correlated with the AMP-activated protein kinase signaling pathway. Cluster analysis of 59 differentially expressed proteins showed that OXPHOS-associated proteins were upregulated in the CO group and that three glycolytic metabolism-related proteins were downregulated in the CO group. CO may enhance hepatic energy metabolism by regulating the expressions of energy expenditure-related proteins.</p>","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2023-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10658085/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9318537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hypertension and atherosclerosis are often found in one patient causing serious cardiovascular events. An animal model simultaneously expressing hypertension and atherosclerosis would be useful to study such a complex risk status. We therefore attempted to introduce a null mutation of the apolipoprotein E (ApoE) gene into the spontaneously hypertensive rat (SHR) using CRISPR/Cas9 to establish a genetic model for atherosclerosis with hypertension. We successfully established SHRApoE(-/-) having a 13-bps deletion in the 5'-end of ApoE gene. Deletion of ApoE protein was confirmed by Western blotting. Blood pressure of SHRApoE(-/-) was comparable to that of SHR. Feeding the rats with high fat high cholesterol diet (HFD) caused a significant increase in LDL cholesterol as well as in triglyceride in SHRApoE(-/-). After 8 weeks of HFD loading, superficial fat deposition was observed both in the aorta and the mesenteric arteries of SHRApoE(-/-) instead of mature atheromatous lesions found in humans. In addition, a null mutation of peroxiredoxin 2 (Prdx2) was introduced into SHRApoE(-/-) to examine the effect of increased oxidative stress on the development of atherosclerosis. SHR with the double depletion of ApoE and Prdx2 did not show mature atheroma either. Further, salt loading did not promote development of atheroma although it accelerated the development of fat deposition. These results indicated that when compared with ApoE-knockout mice, SHRApoE(-/-) was more resistant to atherosclerosis even though they have severe hypertension.
{"title":"Apolipoprotein E-depletion accelerates arterial fat deposition in the spontaneously hypertensive rat.","authors":"Hiroyuki Matsuo, Kohei Kawakami, Hiroki Ohara, Takehito Kaneko, Tomoji Mashimo, Takaya Yamada, Toru Nabika","doi":"10.1538/expanim.23-0012","DOIUrl":"10.1538/expanim.23-0012","url":null,"abstract":"<p><p>Hypertension and atherosclerosis are often found in one patient causing serious cardiovascular events. An animal model simultaneously expressing hypertension and atherosclerosis would be useful to study such a complex risk status. We therefore attempted to introduce a null mutation of the apolipoprotein E (ApoE) gene into the spontaneously hypertensive rat (SHR) using CRISPR/Cas9 to establish a genetic model for atherosclerosis with hypertension. We successfully established SHR<sup>ApoE(-/-)</sup> having a 13-bps deletion in the 5'-end of ApoE gene. Deletion of ApoE protein was confirmed by Western blotting. Blood pressure of SHR<sup>ApoE(-/-)</sup> was comparable to that of SHR. Feeding the rats with high fat high cholesterol diet (HFD) caused a significant increase in LDL cholesterol as well as in triglyceride in SHR<sup>ApoE(-/-)</sup>. After 8 weeks of HFD loading, superficial fat deposition was observed both in the aorta and the mesenteric arteries of SHR<sup>ApoE(-/-)</sup> instead of mature atheromatous lesions found in humans. In addition, a null mutation of peroxiredoxin 2 (Prdx2) was introduced into SHR<sup>ApoE(-/-)</sup> to examine the effect of increased oxidative stress on the development of atherosclerosis. SHR with the double depletion of ApoE and Prdx2 did not show mature atheroma either. Further, salt loading did not promote development of atheroma although it accelerated the development of fat deposition. These results indicated that when compared with ApoE-knockout mice, SHR<sup>ApoE(-/-)</sup> was more resistant to atherosclerosis even though they have severe hypertension.</p>","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2023-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10658095/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9790544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Administration in a lipid emulsion can modify the pharmacodynamics of drugs via a process known as lipid resuscitation. However, the detailed mechanism remains unclear. We studied the volume and another pharmacodynamic effect, the lipid sink, using propofol and thiamylal. Male adult mice (ddY) were intravenously administered 10 ml/kg propofol or thiamylal diluted with physiological saline, 10% soybean oil, or 20% soybean oil. The 50% effective dose (ED50) for achieving hypnosis was calculated using probit analysis. To investigate the volume effect, 0, 10, or 20 ml/kg of saline or soybean oil was administered, either simultaneously or beforehand. Next, a two- or three-fold dose of the anesthetics was administered and the durations of anesthesia were measured. Finally, at 30 s after the first injection, supplemental soybean oil was administered. The mean (± SE) ED50 values of propofol and thiamylal were 5.79 mg/kg (0.61) and 8.83 mg/kg (0.84), respectively. Lipid dilution increased the ED50 values of both anesthetics. After injection of a dose two-fold the ED50 value, the respective mean (± SD) durations of anesthesia were 125 ± 35 s and 102 ± 38 s. Supplemental administration of soybean oil significantly shortened the duration of anesthesia of propofol, but not that of thiamylal. The results indicate that administration of a lipid emulsion vitiated the anesthetic effect of propofol by reducing the non-emulsified free fraction in the aqueous phase, which may elucidate the lipid resuscitation likely caused by the lipid sink mechanism.
{"title":"Administration of lipid emulsion reduced the hypnotic potency of propofol more than that of thiamylal in mice.","authors":"Michiko Higashi, Saori Taharabaru, Yushi U Adachi, Maiko Satomoto, Takahiro Tamura, Naoyuki Matsuda, Aiji Sato-Boku, Masahiro Okuda","doi":"10.1538/expanim.23-0010","DOIUrl":"10.1538/expanim.23-0010","url":null,"abstract":"<p><p>Administration in a lipid emulsion can modify the pharmacodynamics of drugs via a process known as lipid resuscitation. However, the detailed mechanism remains unclear. We studied the volume and another pharmacodynamic effect, the lipid sink, using propofol and thiamylal. Male adult mice (ddY) were intravenously administered 10 ml/kg propofol or thiamylal diluted with physiological saline, 10% soybean oil, or 20% soybean oil. The 50% effective dose (ED<sub>50</sub>) for achieving hypnosis was calculated using probit analysis. To investigate the volume effect, 0, 10, or 20 ml/kg of saline or soybean oil was administered, either simultaneously or beforehand. Next, a two- or three-fold dose of the anesthetics was administered and the durations of anesthesia were measured. Finally, at 30 s after the first injection, supplemental soybean oil was administered. The mean (± SE) ED<sub>50</sub> values of propofol and thiamylal were 5.79 mg/kg (0.61) and 8.83 mg/kg (0.84), respectively. Lipid dilution increased the ED<sub>50</sub> values of both anesthetics. After injection of a dose two-fold the ED<sub>50</sub> value, the respective mean (± SD) durations of anesthesia were 125 ± 35 s and 102 ± 38 s. Supplemental administration of soybean oil significantly shortened the duration of anesthesia of propofol, but not that of thiamylal. The results indicate that administration of a lipid emulsion vitiated the anesthetic effect of propofol by reducing the non-emulsified free fraction in the aqueous phase, which may elucidate the lipid resuscitation likely caused by the lipid sink mechanism.</p>","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2023-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10658092/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9572313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}