Pub Date : 2024-05-03Epub Date: 2023-11-29DOI: 10.1538/expanim.23-0092
Haiqing Zhang, Zunlin Zhou, Jiyao Qin, Juan Yang, Hao Huang, Xiaoyan Yang, Zhong Luo, Yongsu Zheng, Yan Peng, Ya Chen, Zucai Xu
Transmembrane protein (TMEM230) is located in secretory/recycling vesicles, including synaptic vesicles in neurons. However, the functional relationship between TMEM230 and epilepsy is still a mystery. The aims of this study were to investigate the expression of TMEM230 in patients with temporal lobe epilepsy (TLE) and two different mice models of chronic epilepsy, and to determine the probable roles of TMEM230 in epilepsy. Our results showed that TMEM230 expression was increased in the temporal neocortex of epileptic patients and the hippocampus and cortex of epileptic mice compared with that in the control tissues. Moreover, TMEM230 was mainly expressed in the neurons in both humans and mice epileptic brain. TMEM230 co-localized with glutamate vesicular transporter 1 (VGLUT-1), but not with vesicular γ-aminobutyric acid (GABA) transporter (VGAT). Mechanistically, coimmunoprecipitation confirmed that TMEM230 interacted with VGLUT-1, but not with VGAT in the hippocampus of epileptic mice. Lentivirus mediated overexpression of TMEM230 increased mice susceptibility to epilepsy and behavioural phenotypes of epileptic seizures during the kainite (KA)-induced chronic phase of epileptic seizures and the pentylenetetrazole (PTZ) kindling process, whereas lentivirus-mediated TMEM230 downregulation had the opposite effect. These results shed light on the functions of TMEM230 in neurons, suggesting that TMEM230 may play a critical role in the regulation of epileptic activity via influencing excitatory neurotransmission.
{"title":"Transmembrane protein modulates seizure in epilepsy: evidence from temporal lobe epilepsy patients and mouse models.","authors":"Haiqing Zhang, Zunlin Zhou, Jiyao Qin, Juan Yang, Hao Huang, Xiaoyan Yang, Zhong Luo, Yongsu Zheng, Yan Peng, Ya Chen, Zucai Xu","doi":"10.1538/expanim.23-0092","DOIUrl":"10.1538/expanim.23-0092","url":null,"abstract":"<p><p>Transmembrane protein (TMEM230) is located in secretory/recycling vesicles, including synaptic vesicles in neurons. However, the functional relationship between TMEM230 and epilepsy is still a mystery. The aims of this study were to investigate the expression of TMEM230 in patients with temporal lobe epilepsy (TLE) and two different mice models of chronic epilepsy, and to determine the probable roles of TMEM230 in epilepsy. Our results showed that TMEM230 expression was increased in the temporal neocortex of epileptic patients and the hippocampus and cortex of epileptic mice compared with that in the control tissues. Moreover, TMEM230 was mainly expressed in the neurons in both humans and mice epileptic brain. TMEM230 co-localized with glutamate vesicular transporter 1 (VGLUT-1), but not with vesicular γ-aminobutyric acid (GABA) transporter (VGAT). Mechanistically, coimmunoprecipitation confirmed that TMEM230 interacted with VGLUT-1, but not with VGAT in the hippocampus of epileptic mice. Lentivirus mediated overexpression of TMEM230 increased mice susceptibility to epilepsy and behavioural phenotypes of epileptic seizures during the kainite (KA)-induced chronic phase of epileptic seizures and the pentylenetetrazole (PTZ) kindling process, whereas lentivirus-mediated TMEM230 downregulation had the opposite effect. These results shed light on the functions of TMEM230 in neurons, suggesting that TMEM230 may play a critical role in the regulation of epileptic activity via influencing excitatory neurotransmission.</p>","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11091352/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138458806","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 : 2024-05-03Epub Date: 2024-01-11DOI: 10.1538/expanim.23-0113
Xinpeng Wang, Linguo Xie, Chunyu Liu
C-C chemokine receptor type 2 (CCR2) is a monocyte chemokine associated with oxidative stress and inflammation. Kidney stones (KS) are composed of calcium oxalate (CaOx), which trigger renal oxidative stress and inflammatory. This study aims to evaluate the effects of CCR2 on KS in vivo and in vitro. Eight-week-old male C57BL/6J mice were intraperitoneally injected with glyoxylate (GOX) daily to establish a KS model, and along with CCR2 antagonist (INCB3344) treatment on days 2, 4, and 6. The results showed that CCR2 antagonist reduced renal injury markers (blood urea nitrogen and serum creatinine), alleviated renal tubular injury and CaOx crystal deposition. CCR2 antagonist also decreased CCR2 expression induced by GOX treatment and increased Nrf2 expression. GOX treatment promoted malondialdehyde (MDA) production, decreased glutathione (GSH) content, and inhibited catalase (CAT) and superoxide dismutase (SOD) activity, however, CCR2 antagonist attenuated the above effects of GOX. CCR2 antagonist had inhibitory effects on GOX-induced inflammatory cytokine expression (IL1B, IL6 and MCP1), and inhibited apoptosis by increasing Bcl-2 expression and decreasing Bax and cleaved-caspase 3 expression. In vitro experiments were performed by co-culture model of CaOx-induced damaged HK-2 cells and macrophage-like THP-1 cells. CCR2 antagonist inhibited CaOx-induced THP-1 cell M1 polarization by decreasing the TNF-α, IL6 and iNOS levels, and further alleviated CaOx-induced oxidative stress damage, inflammatory response and apoptosis of HK-2 cells. The study suggests that CCR2 antagonist may be resistant to CaOx crystals-induced oxidative stress and inflammation by inhibiting macrophage M1 polarization.
{"title":"CCR2 antagonist attenuates calcium oxalate-induced kidney oxidative stress and inflammation by regulating macrophage activation.","authors":"Xinpeng Wang, Linguo Xie, Chunyu Liu","doi":"10.1538/expanim.23-0113","DOIUrl":"10.1538/expanim.23-0113","url":null,"abstract":"<p><p>C-C chemokine receptor type 2 (CCR2) is a monocyte chemokine associated with oxidative stress and inflammation. Kidney stones (KS) are composed of calcium oxalate (CaOx), which trigger renal oxidative stress and inflammatory. This study aims to evaluate the effects of CCR2 on KS in vivo and in vitro. Eight-week-old male C57BL/6J mice were intraperitoneally injected with glyoxylate (GOX) daily to establish a KS model, and along with CCR2 antagonist (INCB3344) treatment on days 2, 4, and 6. The results showed that CCR2 antagonist reduced renal injury markers (blood urea nitrogen and serum creatinine), alleviated renal tubular injury and CaOx crystal deposition. CCR2 antagonist also decreased CCR2 expression induced by GOX treatment and increased Nrf2 expression. GOX treatment promoted malondialdehyde (MDA) production, decreased glutathione (GSH) content, and inhibited catalase (CAT) and superoxide dismutase (SOD) activity, however, CCR2 antagonist attenuated the above effects of GOX. CCR2 antagonist had inhibitory effects on GOX-induced inflammatory cytokine expression (IL1B, IL6 and MCP1), and inhibited apoptosis by increasing Bcl-2 expression and decreasing Bax and cleaved-caspase 3 expression. In vitro experiments were performed by co-culture model of CaOx-induced damaged HK-2 cells and macrophage-like THP-1 cells. CCR2 antagonist inhibited CaOx-induced THP-1 cell M1 polarization by decreasing the TNF-α, IL6 and iNOS levels, and further alleviated CaOx-induced oxidative stress damage, inflammatory response and apoptosis of HK-2 cells. The study suggests that CCR2 antagonist may be resistant to CaOx crystals-induced oxidative stress and inflammation by inhibiting macrophage M1 polarization.</p>","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11091353/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139416687","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 : 2024-05-03Epub Date: 2024-01-20DOI: 10.1538/expanim.23-0158
Masaki Watanabe, Yuko Nikaido, Nobuya Sasaki
Proper administration of anesthesia is indispensable for the ethical treatment of lab animals in biomedical research. Therefore, selecting an effective anesthesia protocol is pivotal for the design and success of experiments. Hence, continuous development and refinement of anesthetic agents are imperative to improve research outcomes and elevate animal welfare. "Balanced anesthesia" involves using multiple drugs to optimize efficacy while minimizing side effects. The medetomidine, midazolam, and butorphanol, called MMB, and medetomidine, alfaxalone, and butorphanol, called MAB, are popular in Japan. However, the drawbacks of midazolam, including its extended recovery time, and the narrow safety margin of MAB, have prompted research for suitable alternatives. This study replaced midazolam in the MMB combination with remimazolam (RMZ), which is noted for its ultra-short half-life. The resulting combination, called MRB, was effective in providing a wider safety margin compared to MAB while maintaining an anesthesia depth equivalent level to that of MMB in mice. Notably, MRB consistently exhibited better recovery scores after antagonist administration in contrast to MMB. Furthermore, the re-sedation phenomenon observed with MMB was not observed with MRB. The rapid metabolism of RMZ enables reliable anesthesia induction, circumventing the complications linked to MAB. Overall, MRB excelled in providing extended surgical anesthesia and swift post-antagonist recovery. These results highlight the potential of RMZ for broader animal research applications.
在生物医学研究中,正确实施麻醉对于合乎道德地对待实验动物是不可或缺的。因此,选择有效的麻醉方案对实验的设计和成功至关重要。因此,不断开发和改进麻醉剂对改善研究成果和提高动物福利至关重要。"平衡麻醉 "是指使用多种药物,在优化药效的同时将副作用降至最低。在日本,美托咪定、咪达唑仑和丁吗啡醇(称为 MMB)以及美托咪定、阿法沙隆和丁吗啡醇(称为 MAB)很受欢迎。然而,咪达唑仑的缺点(包括恢复时间较长)和 MAB 的安全范围较窄,促使人们研究合适的替代品。这项研究将 MMB 组合中的咪达唑仑替换为瑞咪唑仑(RMZ),后者以其超短的半衰期而著称。由此产生的组合称为 MRB,与 MAB 相比,它能有效提供更宽的安全范围,同时在小鼠体内保持与 MMB 相当的麻醉深度。值得注意的是,与 MMB 相比,MRB 在施用拮抗剂后始终表现出更好的恢复评分。此外,在使用 MMB 时观察到的重新镇静现象在 MRB 上没有观察到。RMZ 的快速新陈代谢实现了可靠的麻醉诱导,避免了与 MAB 相关的并发症。总体而言,MRB 在延长手术麻醉时间和麻醉后迅速恢复方面表现出色。这些结果凸显了 RMZ 在更广泛的动物研究应用中的潜力。
{"title":"Validation of the anesthetic effect of a mixture of remimazolam, medetomidine, and butorphanol in three mouse strains.","authors":"Masaki Watanabe, Yuko Nikaido, Nobuya Sasaki","doi":"10.1538/expanim.23-0158","DOIUrl":"10.1538/expanim.23-0158","url":null,"abstract":"<p><p>Proper administration of anesthesia is indispensable for the ethical treatment of lab animals in biomedical research. Therefore, selecting an effective anesthesia protocol is pivotal for the design and success of experiments. Hence, continuous development and refinement of anesthetic agents are imperative to improve research outcomes and elevate animal welfare. \"Balanced anesthesia\" involves using multiple drugs to optimize efficacy while minimizing side effects. The medetomidine, midazolam, and butorphanol, called MMB, and medetomidine, alfaxalone, and butorphanol, called MAB, are popular in Japan. However, the drawbacks of midazolam, including its extended recovery time, and the narrow safety margin of MAB, have prompted research for suitable alternatives. This study replaced midazolam in the MMB combination with remimazolam (RMZ), which is noted for its ultra-short half-life. The resulting combination, called MRB, was effective in providing a wider safety margin compared to MAB while maintaining an anesthesia depth equivalent level to that of MMB in mice. Notably, MRB consistently exhibited better recovery scores after antagonist administration in contrast to MMB. Furthermore, the re-sedation phenomenon observed with MMB was not observed with MRB. The rapid metabolism of RMZ enables reliable anesthesia induction, circumventing the complications linked to MAB. Overall, MRB excelled in providing extended surgical anesthesia and swift post-antagonist recovery. These results highlight the potential of RMZ for broader animal research applications.</p>","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11091355/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139511922","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}
Disturbances in sleep-wake and circadian rhythms may reportedly precede the onset of cognitive symptoms in the early stages of Alzheimer's disease (AD); however, the underlying mechanisms of these AD-induced sleep disturbances remain unelucidated. To specifically evaluate the involvement of amyloid beta (Aβ) oligomers in AD-induced sleep disturbances, we examined circadian and sleep phenotypes using an Aβ-GFP transgenic (Aβ-GFP Tg) mouse characterized by intracellular accumulation of Aβ oligomers. The circadian rhythm and free-running period of wheel running activity were identical between Aβ-GFP Tg and littermate wild-type mice. The durations of rapid eye movement (REM) sleep were elongated in Aβ-GFP Tg mice; however, the durations of non-REM sleep and wakefulness were unaffected. The Aβ-GFP Tg mice exhibited shifts in the electroencephalogram (EEG) power spectra toward higher frequencies in the inactive light phase. These findings suggest that the intracellular accumulation of Aβ oligomers might be associated with sleep quality; however, its impact on circadian systems is limited.
{"title":"Circadian and sleep phenotypes in a mouse model of Alzheimer's disease characterized by intracellular accumulation of amyloid β oligomers.","authors":"Tomoyuki Sato, Tomoyo Ochiishi, Sayaka Higo-Yamamoto, Katsutaka Oishi","doi":"10.1538/expanim.23-0104","DOIUrl":"10.1538/expanim.23-0104","url":null,"abstract":"<p><p>Disturbances in sleep-wake and circadian rhythms may reportedly precede the onset of cognitive symptoms in the early stages of Alzheimer's disease (AD); however, the underlying mechanisms of these AD-induced sleep disturbances remain unelucidated. To specifically evaluate the involvement of amyloid beta (Aβ) oligomers in AD-induced sleep disturbances, we examined circadian and sleep phenotypes using an Aβ-GFP transgenic (Aβ-GFP Tg) mouse characterized by intracellular accumulation of Aβ oligomers. The circadian rhythm and free-running period of wheel running activity were identical between Aβ-GFP Tg and littermate wild-type mice. The durations of rapid eye movement (REM) sleep were elongated in Aβ-GFP Tg mice; however, the durations of non-REM sleep and wakefulness were unaffected. The Aβ-GFP Tg mice exhibited shifts in the electroencephalogram (EEG) power spectra toward higher frequencies in the inactive light phase. These findings suggest that the intracellular accumulation of Aβ oligomers might be associated with sleep quality; however, its impact on circadian systems is limited.</p>","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11091359/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138801034","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}
IL-19 is a member of IL-10 family and is mainly produced by macrophages. Acute pancreatitis (AP) is an inflammatory disease characterized by acinar cell injury and necrosis. In the present study, the role of IL-19 in AP and AP-associated lung injury in mice was explored using L-arginine-induced pancreatitis. Experimental pancreatitis was induced by intraperitoneal injection of L-arginine in wild-type (WT) and IL-19 gene-deficient (IL-19 KO) mice. Among the mice treated with L-arginine, the serum amylase level was significantly increased in the IL-19 KO mice, and interstitial edema, analyzed using hematoxylin and eosin-stained sections, was aggravated mildly in IL-19 KO mice compared with WT mice. Furthermore, the mRNA expression of tumor necrosis factor-α was significantly upregulated in IL-19 KO mice treated with L-arginine compared with WT mice treated with L-arginine. IL-19 mRNA was equally expressed in the pancreases of both control and L-arginine-treated WT mice. The conditions of lung alveoli were then evaluated in WT and IL-19 KO mice treated with L-arginine. In mice with L-arginine-induced pancreatitis, the alveolar area was remarkedly decreased, and expression of lung myeloperoxidase was significantly increased in IL-19 KO mice compared with WT mice. In the lungs, the mRNA expression of IL-6 and inducible nitric oxide synthase was significantly increased in IL-19 KO mice compared with WT mice. In summary, IL-19 was proposed to alleviate L-arginine-induced pancreatitis by regulating TNF-α production and to protect against AP-related lung injury by inhibiting neutrophil migration.
{"title":"Functional role of IL-19 in a mouse model of L-arginine-induced pancreatitis and related lung injury.","authors":"Naoshige Ono, Joji Horikoshi, Takeshi Izawa, Kazuhiro Nishiyama, Miyuu Tanaka, Takashi Fujita, Mitsuru Kuwamura, Yasu-Taka Azuma","doi":"10.1538/expanim.23-0094","DOIUrl":"10.1538/expanim.23-0094","url":null,"abstract":"<p><p>IL-19 is a member of IL-10 family and is mainly produced by macrophages. Acute pancreatitis (AP) is an inflammatory disease characterized by acinar cell injury and necrosis. In the present study, the role of IL-19 in AP and AP-associated lung injury in mice was explored using L-arginine-induced pancreatitis. Experimental pancreatitis was induced by intraperitoneal injection of L-arginine in wild-type (WT) and IL-19 gene-deficient (IL-19 KO) mice. Among the mice treated with L-arginine, the serum amylase level was significantly increased in the IL-19 KO mice, and interstitial edema, analyzed using hematoxylin and eosin-stained sections, was aggravated mildly in IL-19 KO mice compared with WT mice. Furthermore, the mRNA expression of tumor necrosis factor-α was significantly upregulated in IL-19 KO mice treated with L-arginine compared with WT mice treated with L-arginine. IL-19 mRNA was equally expressed in the pancreases of both control and L-arginine-treated WT mice. The conditions of lung alveoli were then evaluated in WT and IL-19 KO mice treated with L-arginine. In mice with L-arginine-induced pancreatitis, the alveolar area was remarkedly decreased, and expression of lung myeloperoxidase was significantly increased in IL-19 KO mice compared with WT mice. In the lungs, the mRNA expression of IL-6 and inducible nitric oxide synthase was significantly increased in IL-19 KO mice compared with WT mice. In summary, IL-19 was proposed to alleviate L-arginine-induced pancreatitis by regulating TNF-α production and to protect against AP-related lung injury by inhibiting neutrophil migration.</p>","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11091360/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138498137","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 : 2024-05-03Epub Date: 2023-11-10DOI: 10.1538/expanim.23-0068
Rui Dai, Yun Xiang, Rui Fang, Hai-Han Zheng, Qing-Song Zhao, Yan Wang
Asthma is the most common chronic disease in the respiratory system of children caused by abnormal immunity that responses to common antigens. Lonicerin exerts anti-inflammatory activity in other inflammatory models through targeting enhancer of zeste homolog 2 (EZH2) that is related to asthma. We sought to explore the role and mechanism of lonicerin in regulating allergic airway inflammation. Mice were intraperitoneally injected 10 µg ovalbumin (OVA) on postnatal day 5 (P5) and P10, and then inhaled 3% aerosolized OVA for 10 min every day on P18-20, to establish asthmatic mice model. Lonicerin (10 or 30 mg/kg) was given to mice by intragastric administration on P16-P20. Notably, the administration of lonicerin amended infiltration of inflammatory cells and mucus hypersecretion. OVA-specific IgE level, inflammatory cell count and inflammatory cytokines in asthmatic mice were reduced after lonicerin treatment. Moreover, it suppressed the activity of EZH2 and activation of nuclear factor-kappa B (NF-κB) as evidenced by decreasing tri-methylation of histone H3 at lysine 27 and reducing nuclear translocation of NF-κB p65. In a word, Lonicerin may attenuate asthma by inhibiting EZH2/NF-κB signaling pathway.
{"title":"Lonicerin alleviates ovalbumin-induced asthma of mice via inhibiting enhancer of zeste homolog 2/nuclear factor-kappa B signaling pathway.","authors":"Rui Dai, Yun Xiang, Rui Fang, Hai-Han Zheng, Qing-Song Zhao, Yan Wang","doi":"10.1538/expanim.23-0068","DOIUrl":"10.1538/expanim.23-0068","url":null,"abstract":"<p><p>Asthma is the most common chronic disease in the respiratory system of children caused by abnormal immunity that responses to common antigens. Lonicerin exerts anti-inflammatory activity in other inflammatory models through targeting enhancer of zeste homolog 2 (EZH2) that is related to asthma. We sought to explore the role and mechanism of lonicerin in regulating allergic airway inflammation. Mice were intraperitoneally injected 10 µg ovalbumin (OVA) on postnatal day 5 (P5) and P10, and then inhaled 3% aerosolized OVA for 10 min every day on P18-20, to establish asthmatic mice model. Lonicerin (10 or 30 mg/kg) was given to mice by intragastric administration on P16-P20. Notably, the administration of lonicerin amended infiltration of inflammatory cells and mucus hypersecretion. OVA-specific IgE level, inflammatory cell count and inflammatory cytokines in asthmatic mice were reduced after lonicerin treatment. Moreover, it suppressed the activity of EZH2 and activation of nuclear factor-kappa B (NF-κB) as evidenced by decreasing tri-methylation of histone H3 at lysine 27 and reducing nuclear translocation of NF-κB p65. In a word, Lonicerin may attenuate asthma by inhibiting EZH2/NF-κB signaling pathway.</p>","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11091354/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89717533","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}
Several artificial intelligence (AI) systems have been developed for glomerular pathology analysis in clinical settings. However, the application of AI systems in nonclinical fields remains limited. In this study, we trained a convolutional neural network model, which is an AI algorithm, to classify the severity of Tensin 2 (TNS2)-deficient nephropathy into seven categories. A dataset consisting of 803 glomerular images was generated from kidney sections of TNS2-deficient and wild-type mice. Manual evaluations of the images were conducted to assess their glomerular injury scores. The trained AI achieved approximately 70% accuracy in predicting the glomerular injury score for TNS2-deficient nephropathy. However, the AI achieved approximately 100% accuracy when considering predictions within one score of the true label as correct. The AI's predicted mean score closely matched the true mean score. In conclusion, while the AI model may not replace human judgment entirely, it can serve as a reliable second assessor in scoring glomerular injury, offering potential benefits in enhancing the accuracy and objectivity of such assessments.
{"title":"Automated scoring of glomerular injury in TNS2-deficient nephropathy.","authors":"Shuji Shimada, Kyosuke Tanimoto, Hayato Sasaki, Takumi Taga, Takeru Sasaki, Tomomi Imagawa, Nobuya Sasaki","doi":"10.1538/expanim.24-0001","DOIUrl":"https://doi.org/10.1538/expanim.24-0001","url":null,"abstract":"Several artificial intelligence (AI) systems have been developed for glomerular pathology analysis in clinical settings. However, the application of AI systems in nonclinical fields remains limited. In this study, we trained a convolutional neural network model, which is an AI algorithm, to classify the severity of Tensin 2 (TNS2)-deficient nephropathy into seven categories. A dataset consisting of 803 glomerular images was generated from kidney sections of TNS2-deficient and wild-type mice. Manual evaluations of the images were conducted to assess their glomerular injury scores. The trained AI achieved approximately 70% accuracy in predicting the glomerular injury score for TNS2-deficient nephropathy. However, the AI achieved approximately 100% accuracy when considering predictions within one score of the true label as correct. The AI's predicted mean score closely matched the true mean score. In conclusion, while the AI model may not replace human judgment entirely, it can serve as a reliable second assessor in scoring glomerular injury, offering potential benefits in enhancing the accuracy and objectivity of such assessments.","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140680657","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tianjiao Sheng, Lei Wang, Simeng Yan, Qiuyu Wei, Xiao Geng, Weiru Lan, Yan Chen, Yuedong Liu, Na Li
Ulcerative colitis (UC) is characterized by overactive inflammatory response, impaired intestinal mucosal barrier and disrupted gut microbiota. Youhua Kuijie formula is a classic empirical prescription based on the pathogenesis of UC. The present study was designed to verify the protective effect of Youhua Kuijie Formula on DSS-induced UC in mice and uncover the related mechanism. Youhua Kuijie Formula were orally administrated to UC mice induced by DSS dissolved in drinking water for ten days. The protective effect of Youhua Kuijie Formula was evidenced by reduced pathological symptoms accompanied by palliative inflammatory response and relatively intact intestinal barrier. The data from 16S rRNA gene sequencing and GC-MS untargeted metabolomics indicated that the supplement of Youhua Kuijie Formula restructured gut microbiota community structure, and thereby modulated the metabolic profiles in UC mice. The analysis of pathway enrichment analysis suggested the major alterations in metabolic pathway were related to protein digestion and absorption. Besides, the results of the following experiments suggested that Youhua Kuijie Formula treatment increased adenosine monophosphate-activated protein kinase (AMPK) activation, decreased mechanistic target of rapamycin (mTOR) phosphorylation, and thereby reversing autophagy deficiency in the intestinal tract of UC mice. Collectively, our results demonstrated that the regulation of AMPK/mTOR was involved in Youhua Kuijie Formula administration mediated protective effect on UC.
{"title":"Involvement of gut microbiota recovery and autophagy induction in Youhua Kuijie Formula's protection against experimental ulcerative colitis.","authors":"Tianjiao Sheng, Lei Wang, Simeng Yan, Qiuyu Wei, Xiao Geng, Weiru Lan, Yan Chen, Yuedong Liu, Na Li","doi":"10.1538/expanim.23-0166","DOIUrl":"https://doi.org/10.1538/expanim.23-0166","url":null,"abstract":"Ulcerative colitis (UC) is characterized by overactive inflammatory response, impaired intestinal mucosal barrier and disrupted gut microbiota. Youhua Kuijie formula is a classic empirical prescription based on the pathogenesis of UC. The present study was designed to verify the protective effect of Youhua Kuijie Formula on DSS-induced UC in mice and uncover the related mechanism. Youhua Kuijie Formula were orally administrated to UC mice induced by DSS dissolved in drinking water for ten days. The protective effect of Youhua Kuijie Formula was evidenced by reduced pathological symptoms accompanied by palliative inflammatory response and relatively intact intestinal barrier. The data from 16S rRNA gene sequencing and GC-MS untargeted metabolomics indicated that the supplement of Youhua Kuijie Formula restructured gut microbiota community structure, and thereby modulated the metabolic profiles in UC mice. The analysis of pathway enrichment analysis suggested the major alterations in metabolic pathway were related to protein digestion and absorption. Besides, the results of the following experiments suggested that Youhua Kuijie Formula treatment increased adenosine monophosphate-activated protein kinase (AMPK) activation, decreased mechanistic target of rapamycin (mTOR) phosphorylation, and thereby reversing autophagy deficiency in the intestinal tract of UC mice. Collectively, our results demonstrated that the regulation of AMPK/mTOR was involved in Youhua Kuijie Formula administration mediated protective effect on UC.","PeriodicalId":12102,"journal":{"name":"Experimental Animals","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140727299","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Spinal cord injury (SCI) is a devastating disease characterized by neuronal apoptosis. Gli-similar 3 (GLIS3), a transcriptional factor, was involved in cell apoptosis and associated with the transcription of downstream target genes related to neuronal function. However, the function of GLIS3 in SCI remains unknown. Therefore, we used the mouse model of SCI to explore the role of GLIS3 in SCI. The results showed that GLIS3 expression was significantly increased in spinal cord tissues of SCI mice, and GLIS3 overexpression promoted the functional recovery, reserved histological changes, and inhibited neuronal apoptosis after SCI. Through online tools, the potential target genes of GLIS3 were analyzed and we found that Mps one binder kinase activator 1b (Mob1b) had a strong association with SCI among these genes. MOB1b is a core component of Hippo signaling pathway, which was reported to inhibit cell apoptosis. MOB1b expression was significantly increased in mice at 7 days post-SCI and GLIS3 overexpression further increased its expression. Dual-luciferase reporter assay revealed that GLIS3 bound to the promoter of Mob1b and promoted its transcription. In conclusion, our findings reveal that the compensatory increase of GLIS3 promotes functional recovery after SCI through inhibiting neuronal apoptosis by transcriptionally regulating MOB1b. Our study provides a novel target for functional recovery after SCI.
{"title":"The compensatory increase of Gli-similar 3 inhibited neuronal apoptosis through regulating Mps one binder kinase activator 1b (MOB1b): a possible strategy for the functional recovery after spinal cord injury.","authors":"Hong-Bo Yang, Ying Li, Xiu-Hai Li, Qing-Ming Yan, Xian-Zhang Han, Jian Cao, Hong-Peng Sang, Jin-Long Li","doi":"10.1538/expanim.23-0041","DOIUrl":"10.1538/expanim.23-0041","url":null,"abstract":"<p><p>Spinal cord injury (SCI) is a devastating disease characterized by neuronal apoptosis. Gli-similar 3 (GLIS3), a transcriptional factor, was involved in cell apoptosis and associated with the transcription of downstream target genes related to neuronal function. However, the function of GLIS3 in SCI remains unknown. Therefore, we used the mouse model of SCI to explore the role of GLIS3 in SCI. The results showed that GLIS3 expression was significantly increased in spinal cord tissues of SCI mice, and GLIS3 overexpression promoted the functional recovery, reserved histological changes, and inhibited neuronal apoptosis after SCI. Through online tools, the potential target genes of GLIS3 were analyzed and we found that Mps one binder kinase activator 1b (Mob1b) had a strong association with SCI among these genes. MOB1b is a core component of Hippo signaling pathway, which was reported to inhibit cell apoptosis. MOB1b expression was significantly increased in mice at 7 days post-SCI and GLIS3 overexpression further increased its expression. Dual-luciferase reporter assay revealed that GLIS3 bound to the promoter of Mob1b and promoted its transcription. In conclusion, our findings reveal that the compensatory increase of GLIS3 promotes functional recovery after SCI through inhibiting neuronal apoptosis by transcriptionally regulating MOB1b. Our study provides a novel target for functional recovery after SCI.</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/PMC10877155/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9992686","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}
Animals frequently eat less after a test-article treatment in nonclinical toxicological studies, and it can be difficult to distinguish test article-derived toxicities from secondary changes related to this reduced food intake. Therefore, in this study, we restricted the food intake of cynomolgus monkeys (Cambodian, male, n=2 or 3, 48 ± 3 months old) to 25% of the control for two weeks and evaluated the effects on toxicological parameters (general conditions, body weight, electrocardiography, urinalysis, hematology, blood chemistry, bone marrow analysis, pathological examination). After 2 weeks, the monkeys exhibited decreases in bone marrow erythropoiesis (e.g., decreases in reticulocytes and bone marrow erythrocytes), as well as glycogenesis induction (e.g., increase in aspartate aminotransferase (AST)) and malnutrition (e.g., decrease in triglyceride and systemic adipocytes atrophy). Additionally, histopathological analysis revealed granuloma and inflammatory cell infiltration in coronary fat, which had never been found in previous food restriction studies using other animal species. These findings will enable researchers to more accurately evaluate the toxicological risks of test articles that simultaneously induce food intake reduction.
{"title":"Effects of two weeks of food restriction on toxicological parameters in cynomolgus monkeys.","authors":"Nozomi Fujisawa, Tomochika Matsushita, Saori Matsuo, Mayumi Hiranuma, Hiroko Azabu, Ryota Saito, Shun-Ichiro Komatsu, Atsuhiko Kato, Naoto Toyota, Junko Taketo, Hiromi Suzuki","doi":"10.1538/expanim.23-0017","DOIUrl":"10.1538/expanim.23-0017","url":null,"abstract":"<p><p>Animals frequently eat less after a test-article treatment in nonclinical toxicological studies, and it can be difficult to distinguish test article-derived toxicities from secondary changes related to this reduced food intake. Therefore, in this study, we restricted the food intake of cynomolgus monkeys (Cambodian, male, n=2 or 3, 48 ± 3 months old) to 25% of the control for two weeks and evaluated the effects on toxicological parameters (general conditions, body weight, electrocardiography, urinalysis, hematology, blood chemistry, bone marrow analysis, pathological examination). After 2 weeks, the monkeys exhibited decreases in bone marrow erythropoiesis (e.g., decreases in reticulocytes and bone marrow erythrocytes), as well as glycogenesis induction (e.g., increase in aspartate aminotransferase (AST)) and malnutrition (e.g., decrease in triglyceride and systemic adipocytes atrophy). Additionally, histopathological analysis revealed granuloma and inflammatory cell infiltration in coronary fat, which had never been found in previous food restriction studies using other animal species. These findings will enable researchers to more accurately evaluate the toxicological risks of test articles that simultaneously induce food intake reduction.</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/PMC10877149/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10176958","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}