Griselda A. Cabral-Pacheco, V. Flores-Morales, I. Garza-Veloz, Miriam Damián‑Sandoval, Rosa Martínez‑Flores, M. Martínez-Vázquez, Iván Delgado-Enciso, I. Rodríguez-Sánchez, Margarita L. Martinez-Fierro
{"title":"Evaluation of dapsone and its synthetic derivative DDS‑13 in cancer in vitro","authors":"Griselda A. Cabral-Pacheco, V. Flores-Morales, I. Garza-Veloz, Miriam Damián‑Sandoval, Rosa Martínez‑Flores, M. Martínez-Vázquez, Iván Delgado-Enciso, I. Rodríguez-Sánchez, Margarita L. Martinez-Fierro","doi":"10.3892/etm.2023.12335","DOIUrl":"https://doi.org/10.3892/etm.2023.12335","url":null,"abstract":"","PeriodicalId":12285,"journal":{"name":"Experimental and therapeutic medicine","volume":"45 6","pages":""},"PeriodicalIF":2.7,"publicationDate":"2023-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138602378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yuli Hu, Jie Zhang, Ya Lin, Yi Lin, Rui Jin, Qianqian Zhu, Yi Ma
{"title":"Serine and arginine rich splicing factor 1‑regulated microtubule interacting and trafficking domain containing 1 affects colorectal cancer progression and ferroptosis","authors":"Yuli Hu, Jie Zhang, Ya Lin, Yi Lin, Rui Jin, Qianqian Zhu, Yi Ma","doi":"10.3892/etm.2023.12334","DOIUrl":"https://doi.org/10.3892/etm.2023.12334","url":null,"abstract":"","PeriodicalId":12285,"journal":{"name":"Experimental and therapeutic medicine","volume":"33 8","pages":""},"PeriodicalIF":2.7,"publicationDate":"2023-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138601351","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tanise Telles, B. May, Mauricio Pimentel, Bruna Pereira, Michael Andrades, L. Rohde, Kátia Dos Santos
{"title":"Non‑synonymous polymorphisms in the HRC and ADRB1 genes may be associated with all‑cause death in patients with non‑ischemic heart failure","authors":"Tanise Telles, B. May, Mauricio Pimentel, Bruna Pereira, Michael Andrades, L. Rohde, Kátia Dos Santos","doi":"10.3892/etm.2023.12337","DOIUrl":"https://doi.org/10.3892/etm.2023.12337","url":null,"abstract":"","PeriodicalId":12285,"journal":{"name":"Experimental and therapeutic medicine","volume":"12 8","pages":""},"PeriodicalIF":2.7,"publicationDate":"2023-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138604068","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tao Ding, Yi Zhu, Zhong-Man Zhang, Yue Zou, Di An, Wei Li, Xu-Feng Chen
Kodamaea ohmeri (K. ohmeri) is an ascosporogenic species of yeast that belongs to the genus Ascosporogenous and the family of Saccharomycetaceae. It has recently been found to cause various types of infections, particularly in critically ill immunocompromised patients. The present study describes a case of hospital-acquired pneumonia caused by K. ohmeri during veno-arterial extracorporeal membrane oxygenation. The fungal culture turned negative after the administration of caspofungin and amphotericin B. Extracorporeal membrane oxygenation (ECMO) is an adjunctive medical technique that provides temporary cardiopulmonary support for patients. Previous observations have suggested that the immune function of patients will typically decline during the use of ECMO, rendering infection to be one of the main complications of ECMO. K. ohmeri is a rare pathogenic fungus, particularly in immunocompromised individuals with vascular catheters, while amphotericin B is the most common antifungal therapy administered to treat K. ohmeri infections. It is important to raise awareness of rare fungal infections and actively treat them.
Kodamaea ohmeri（K. ohmeri）是一种腹孢子源性酵母菌，属于腹孢子源属和酵母科。最近发现它可引起各种类型的感染，尤其是在免疫力低下的重症患者中。本研究描述了一例在静脉-动脉体外膜氧合过程中由 K. ohmeri 引起的医院获得性肺炎。体外膜肺氧合（ECMO）是一种辅助医疗技术，可为患者提供临时心肺支持。以往的观察表明，在使用 ECMO 期间，患者的免疫功能通常会下降，从而使感染成为 ECMO 的主要并发症之一。K. ohmeri 是一种罕见的致病真菌，尤其是在使用血管导管的免疫功能低下患者中，而两性霉素 B 是治疗 K. ohmeri 感染最常用的抗真菌疗法。提高人们对罕见真菌感染的认识并积极治疗非常重要。
{"title":"Hospital‑acquired pneumonia caused by Kodamaea ohmeri during extracorporeal membrane oxygenation treatment: A case report and literature review.","authors":"Tao Ding, Yi Zhu, Zhong-Man Zhang, Yue Zou, Di An, Wei Li, Xu-Feng Chen","doi":"10.3892/etm.2023.12331","DOIUrl":"https://doi.org/10.3892/etm.2023.12331","url":null,"abstract":"<i>Kodamaea ohmeri</i> (<i>K. ohmeri</i>) is an ascosporogenic species of yeast that belongs to the genus <i>Ascosporogenous</i> and the family of Saccharomycetaceae. It has recently been found to cause various types of infections, particularly in critically ill immunocompromised patients. The present study describes a case of hospital-acquired pneumonia caused by <i>K. ohmeri</i> during veno-arterial extracorporeal membrane oxygenation. The fungal culture turned negative after the administration of caspofungin and amphotericin B. Extracorporeal membrane oxygenation (ECMO) is an adjunctive medical technique that provides temporary cardiopulmonary support for patients. Previous observations have suggested that the immune function of patients will typically decline during the use of ECMO, rendering infection to be one of the main complications of ECMO. <i>K. ohmeri</i> is a rare pathogenic fungus, particularly in immunocompromised individuals with vascular catheters, while amphotericin B is the most common antifungal therapy administered to treat <i>K. ohmeri</i> infections. It is important to raise awareness of rare fungal infections and actively treat them.","PeriodicalId":12285,"journal":{"name":"Experimental and therapeutic medicine","volume":"2 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2023-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138825752","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yu Sun, Jin Dong, Xiaohong Chai, Jingping Wang, Bao Li, Jinjing Yang
Cardiac hypertrophy, characterized by cardiomyocyte enlargement, is an adaptive response of the heart to certain hypertrophic stimuli; however, prolonged hypertrophy results in cardiac dysfunction and can ultimately cause heart failure. The present study evaluated the role of semaphorin-3A (Sema3A), a neurochemical inhibitor, in cardiac hypertrophy, utilizing an isoproterenol (ISO) induced H9c2 cell model. Cells were stained with rhodamine-phalloidin to assess the cell surface area and reverse transcription-quantitative PCR was performed to quantify mRNA expression levels of Sema3A, brain natriuretic factor (BNF) and β-myosin heavy chain (β-MHC). The protein expression levels of the autophagy-related proteins light chain 3 (LC3), p62 and Beclin-1, and the Akt/mTOR signaling pathway associated proteins Akt, phosphorylated (p)-Akt, mTOR, p-mTOR, 4E-binding protein 1 (4EBP1) and p-4EBP1 were semi-quantified using western blotting. Rapamycin, a canonical autophagy inducer, was administered to H9c2 cells to elucidate the regulatory mechanism of Sema3A. The results indicated significantly increased cell surface area and elevated BNF and β-MHC mRNA expression levels, increased LC3II/I ratio and Beclin-1 protein expression levels and significantly decreased p62 protein expression levels after treatment of H9c2 cardiomyocytes with ISO for 24 h. Sema3A overexpression improved ISO-induced hypertrophy in H9c2 cells, indicated by decreased cell surface area and reduced BNF and β-MHC mRNA expression levels. Moreover, Sema3A overexpression inhibited ISO-induced autophagy in H9c2 cells, indicated by decreased LC3II/I ratio and Beclin-1 protein expression levels and increased p62 protein expression levels. The autophagy activator rapamycin partially inhibited the protective effect of Sema3A on ISO-induced hypertrophy. Sema3A overexpression suppressed the decrease of the protein expression levels of p-Akt, mTOR and their downstream target 4EBP1, which is induced by ISO. Collectively, these results suggested Sema3A prevented ISO-induced cardiac hypertrophy by inhibiting autophagy via the Akt/mTOR signaling pathway.
{"title":"Semaphorin‑3A alleviates cardiac hypertrophy by regulating autophagy.","authors":"Yu Sun, Jin Dong, Xiaohong Chai, Jingping Wang, Bao Li, Jinjing Yang","doi":"10.3892/etm.2023.12326","DOIUrl":"https://doi.org/10.3892/etm.2023.12326","url":null,"abstract":"Cardiac hypertrophy, characterized by cardiomyocyte enlargement, is an adaptive response of the heart to certain hypertrophic stimuli; however, prolonged hypertrophy results in cardiac dysfunction and can ultimately cause heart failure. The present study evaluated the role of semaphorin-3A (Sema3A), a neurochemical inhibitor, in cardiac hypertrophy, utilizing an isoproterenol (ISO) induced H9c2 cell model. Cells were stained with rhodamine-phalloidin to assess the cell surface area and reverse transcription-quantitative PCR was performed to quantify mRNA expression levels of Sema3A, brain natriuretic factor (BNF) and β-myosin heavy chain (β-MHC). The protein expression levels of the autophagy-related proteins light chain 3 (LC3), p62 and Beclin-1, and the Akt/mTOR signaling pathway associated proteins Akt, phosphorylated (p)-Akt, mTOR, p-mTOR, 4E-binding protein 1 (4EBP1) and p-4EBP1 were semi-quantified using western blotting. Rapamycin, a canonical autophagy inducer, was administered to H9c2 cells to elucidate the regulatory mechanism of Sema3A. The results indicated significantly increased cell surface area and elevated BNF and β-MHC mRNA expression levels, increased LC3II/I ratio and Beclin-1 protein expression levels and significantly decreased p62 protein expression levels after treatment of H9c2 cardiomyocytes with ISO for 24 h. Sema3A overexpression improved ISO-induced hypertrophy in H9c2 cells, indicated by decreased cell surface area and reduced BNF and β-MHC mRNA expression levels. Moreover, Sema3A overexpression inhibited ISO-induced autophagy in H9c2 cells, indicated by decreased LC3II/I ratio and Beclin-1 protein expression levels and increased p62 protein expression levels. The autophagy activator rapamycin partially inhibited the protective effect of Sema3A on ISO-induced hypertrophy. Sema3A overexpression suppressed the decrease of the protein expression levels of p-Akt, mTOR and their downstream target 4EBP1, which is induced by ISO. Collectively, these results suggested Sema3A prevented ISO-induced cardiac hypertrophy by inhibiting autophagy via the Akt/mTOR signaling pathway.","PeriodicalId":12285,"journal":{"name":"Experimental and therapeutic medicine","volume":"31 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2023-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138827004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Methotrexate-related other iatrogenic immunodeficiency-associated lymphoproliferative disorder (MTX-OIIA-LPD) is prone to extranodal involvement but rarely involves the central nervous system (CNS). The present study reports a case of MTX-OIIA-LPD of the CNS discovered during medication-related osteonecrosis of the jaw (MRONJ) treatment in a 76-year-old woman with rheumatoid arthritis (RA). The chief complaint of the patient was bone exposure and pain in the right mandibular molar. The patient had been receiving MTX for RA and alendronate sodium hydrate for osteoporosis, followed by denosumab. Treatment was initiated based on a diagnosis of MRONJ. However, the patient experienced lightheadedness and floating dizziness afterwards. Examinations revealed scattered neoplastic lesions in the brain. The histopathological diagnosis was diffuse large B-cell lymphoma. A systemic search also revealed adrenal involvement. Since the patient was taking MTX, a diagnosis of MTX-OIIA-LPD was made and MTX was discontinued. Chemotherapeutic agents were administered since the central lesions became symptomatic. The MTX-OIIA-LPD lesions in the brain and adrenal glands completely resolved 8 months after onset. The physical condition of the patient improved, and the bone-exposed areas became epithelialized. Reports on MTX-LPD in the oral and maxillofacial region are few, which may delay its diagnosis. Therefore, biopsy of oral lesions in patients with MRONJ who are taking MTX and collaboration with related diagnostic departments, such as rheumatology and hematology, must be done to initiate the diagnosis and treatment of extraoral MTX-LPD.
甲氨蝶呤相关的其他先天性免疫缺陷相关淋巴组织增生性疾病（MTX-OIIA-LPD）容易累及结节外，但很少累及中枢神经系统（CNS）。本研究报告了一例中枢神经系统MTX-OIIA-LPD病例，患者是一名76岁的类风湿性关节炎（RA）女性患者，在接受药物相关性颌骨坏死（MRONJ）治疗期间被发现。患者的主诉是右下颌臼齿骨质暴露和疼痛。患者一直在接受 MTX 治疗 RA 和阿仑膦酸钠水合物治疗骨质疏松症，之后又接受了地诺单抗治疗。治疗是根据 MRONJ 诊断开始的。然而，患者随后出现了头晕和漂浮感。检查发现脑部有散在的肿瘤病变。组织病理学诊断为弥漫大 B 细胞淋巴瘤。系统检查还发现肾上腺受累。由于患者正在服用MTX，因此诊断为MTX-OIIA-LPD，并停用了MTX。由于中心病变已出现症状，因此使用了化疗药物。脑部和肾上腺的 MTX-OIIA-LPD 病变在发病 8 个月后完全消退。患者的身体状况有所改善，骨头暴露部位也上了一层皮。有关口腔和颌面部 MTX-LPD 的报道很少，这可能会延误诊断。因此，必须对正在服用MTX的MRONJ患者的口腔病变进行活检，并与风湿病学和血液学等相关诊断部门合作，以启动口腔外MTX-LPD的诊断和治疗。
{"title":"Methotrexate‑related other iatrogenic immunodeficiency‑associated lymphoproliferative disorder in the CNS and medication‑related osteonecrosis of the jaw occurring simultaneously: A case report.","authors":"Tomoki Kato, Chisaki Mizumoto, Fuminori Inoue, Takuma Watanabe, Shigeki Yamanaka, Shizuko Fukuhara, Kazumasa Nakao","doi":"10.3892/etm.2023.12329","DOIUrl":"https://doi.org/10.3892/etm.2023.12329","url":null,"abstract":"Methotrexate-related other iatrogenic immunodeficiency-associated lymphoproliferative disorder (MTX-OIIA-LPD) is prone to extranodal involvement but rarely involves the central nervous system (CNS). The present study reports a case of MTX-OIIA-LPD of the CNS discovered during medication-related osteonecrosis of the jaw (MRONJ) treatment in a 76-year-old woman with rheumatoid arthritis (RA). The chief complaint of the patient was bone exposure and pain in the right mandibular molar. The patient had been receiving MTX for RA and alendronate sodium hydrate for osteoporosis, followed by denosumab. Treatment was initiated based on a diagnosis of MRONJ. However, the patient experienced lightheadedness and floating dizziness afterwards. Examinations revealed scattered neoplastic lesions in the brain. The histopathological diagnosis was diffuse large B-cell lymphoma. A systemic search also revealed adrenal involvement. Since the patient was taking MTX, a diagnosis of MTX-OIIA-LPD was made and MTX was discontinued. Chemotherapeutic agents were administered since the central lesions became symptomatic. The MTX-OIIA-LPD lesions in the brain and adrenal glands completely resolved 8 months after onset. The physical condition of the patient improved, and the bone-exposed areas became epithelialized. Reports on MTX-LPD in the oral and maxillofacial region are few, which may delay its diagnosis. Therefore, biopsy of oral lesions in patients with MRONJ who are taking MTX and collaboration with related diagnostic departments, such as rheumatology and hematology, must be done to initiate the diagnosis and treatment of extraoral MTX-LPD.","PeriodicalId":12285,"journal":{"name":"Experimental and therapeutic medicine","volume":"14 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2023-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138825753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Parkinson's disease (PD) is the second most common neurodegenerative disease after Alzheimer's disease (AD). Icariside II (ICS II) is known to confer notable therapeutic effects against a variety of neurodegenerative diseases, such as AD. Therefore, the present study aimed to evaluate the possible effects of ICS II on 1-methyl-4-phenylpyridinium (MPP+)-induced SK-N-SH cell injury, in addition to understanding the underlying mechanism of action. The MPP+-induced SK-N-SH cell model was used to simulate PD in vitro. The viability and mitochondrial membrane potential of SK-N-SH cells were detected by MTT assay and JC-1 staining, respectively. Lactate dehydrogenase (LDH) release, ATP levels and complex I activity in treated SK-N-SH cells were measured using LDH activity, ATP and Complex I assay kits, respectively. The protein expression levels of histone deacetylase 2 (HDAC2) and γ-H2A histone family member X and the copy number of mitochondrial DNA were measured by western blotting or reverse transcription-quantitative PCR, respectively. Autodock 4.2 was used to predict the molecular docking site of ICS II on HDAC2. The results of the present study demonstrated that ICS II mitigated SK-N-SH cytotoxicity induced by MPP+. Specifically, ICS II alleviated DNA damage and restored mitochondrial function in SK-N-SH cells treated with MPP+. In addition, ICS II reduced the HDAC2 protein expression levels in MPP+-induced SK-N-SH cells. However, overexpression of HDAC2 reversed the protective effects of ICS II on DNA damage and mitochondrial dysfunction in MPP+-induced SK-N-SH cells. In conclusion, the results of the present study suggest that ICS II can protect dopaminergic neurons from MPP+-induced neurotoxicity by downregulating HDAC2 expression to restore mitochondrial function.
帕金森病（PD）是仅次于阿尔茨海默病（AD）的第二大常见神经退行性疾病。已知淫羊藿苷 II（ICS II）对多种神经退行性疾病（如阿尔兹海默病）具有显著的治疗效果。因此，本研究除了了解其潜在的作用机制外，还旨在评估伊卡里苷 II 对 1-甲基-4-苯基吡啶鎓（MPP+）诱导的 SK-N-SH 细胞损伤可能产生的影响。MPP+诱导的SK-N-SH细胞模型用于体外模拟PD。MTT试验和JC-1染色法分别检测了SK-N-SH细胞的活力和线粒体膜电位。使用 LDH 活性、ATP 和复合物 I 检测试剂盒分别检测了经处理的 SK-N-SH 细胞的乳酸脱氢酶（LDH）释放量、ATP 水平和复合物 I 活性。组蛋白去乙酰化酶 2（HDAC2）和γ-H2A 组蛋白家族成员 X 的蛋白表达水平以及线粒体 DNA 的拷贝数分别通过 Western 印迹法或反转录定量 PCR 法进行测定。使用 Autodock 4.2 预测了 ICS II 与 HDAC2 的分子对接位点。本研究结果表明，ICS II 可减轻 MPP+ 诱导的 SK-N-SH 细胞毒性。具体来说，ICS II减轻了MPP+对SK-N-SH细胞的DNA损伤并恢复了线粒体功能。此外，ICS II 还降低了 MPP+ 诱导的 SK-N-SH 细胞中 HDAC2 蛋白的表达水平。然而，在 MPP+ 诱导的 SK-N-SH 细胞中，HDAC2 的过表达逆转了 ICS II 对 DNA 损伤和线粒体功能障碍的保护作用。总之，本研究的结果表明，ICS II 可通过下调 HDAC2 的表达来恢复线粒体功能，从而保护多巴胺能神经元免受 MPP+ 诱导的神经毒性的影响。
{"title":"Icariside II protects dopaminergic neurons from 1‑methyl‑4‑phenylpyridinium‑induced neurotoxicity by downregulating HDAC2 to restore mitochondrial function.","authors":"Wenbo Fan, Jianwu Zhou","doi":"10.3892/etm.2023.12328","DOIUrl":"https://doi.org/10.3892/etm.2023.12328","url":null,"abstract":"Parkinson's disease (PD) is the second most common neurodegenerative disease after Alzheimer's disease (AD). Icariside II (ICS II) is known to confer notable therapeutic effects against a variety of neurodegenerative diseases, such as AD. Therefore, the present study aimed to evaluate the possible effects of ICS II on 1-methyl-4-phenylpyridinium (MPP<sup>+</sup>)-induced SK-N-SH cell injury, in addition to understanding the underlying mechanism of action. The MPP<sup>+</sup>-induced SK-N-SH cell model was used to simulate PD <i>in vitro</i>. The viability and mitochondrial membrane potential of SK-N-SH cells were detected by MTT assay and JC-1 staining, respectively. Lactate dehydrogenase (LDH) release, ATP levels and complex I activity in treated SK-N-SH cells were measured using LDH activity, ATP and Complex I assay kits, respectively. The protein expression levels of histone deacetylase 2 (HDAC2) and γ-H2A histone family member X and the copy number of mitochondrial DNA were measured by western blotting or reverse transcription-quantitative PCR, respectively. Autodock 4.2 was used to predict the molecular docking site of ICS II on HDAC2. The results of the present study demonstrated that ICS II mitigated SK-N-SH cytotoxicity induced by MPP<sup>+</sup>. Specifically, ICS II alleviated DNA damage and restored mitochondrial function in SK-N-SH cells treated with MPP<sup>+</sup>. In addition, ICS II reduced the HDAC2 protein expression levels in MPP<sup>+</sup>-induced SK-N-SH cells. However, overexpression of HDAC2 reversed the protective effects of ICS II on DNA damage and mitochondrial dysfunction in MPP<sup>+</sup>-induced SK-N-SH cells. In conclusion, the results of the present study suggest that ICS II can protect dopaminergic neurons from MPP<sup>+</sup>-induced neurotoxicity by downregulating HDAC2 expression to restore mitochondrial function.","PeriodicalId":12285,"journal":{"name":"Experimental and therapeutic medicine","volume":"31 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2023-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138826974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","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 event that often leads to severe disability, and effective treatments for SCI are currently limited. The present study investigated the potential effects and specific mechanisms of melatonin treatment in SCI. Mice were divided into Sham (Sham), Vehicle (Veh), Melatonin (Mel), and Melatonin + 4-phenyl-2-propionamidotetralin (4P-PDOT) (Mel + 4PP) groups based on randomized allocation. The expression of MT2 and the nuclear factor-erythroid 2-related factor 2 (Nrf2)/Keap1 signaling pathways were examined, along with oxidative stress indicators, inflammatory factors and GFAP-positive cells near the injury site. The polarization of microglial cells in different inflammatory microenvironments was also observed. Cell survival, motor function recovery and spinal cord tissue morphology were assessed using staining and Basso Mouse Scale scores. On day 7 after SCI, the results revealed that melatonin treatment increased MT2 protein expression and activated the Nrf2/Keap1 signaling pathway. It also reduced GFAP-positive cells, mitigated oxidative stress, and suppressed inflammatory responses around the injury site. Furthermore, melatonin treatment promoted the polarization of microglia toward the M2 type, increased the number of neutrophil-positive cells, and modulated the transcription of Bax and Bcl2 in the injured spinal cord. Melatonin treatment alleviated the severity of spinal injuries and facilitated functional recovery in mice with SCI. Notably, blocking MT2 with 4P-PDOT partially reversed the neuroprotective effects of melatonin in SCI, indicating that the activation of the MT2/Nrf2/Keap1 signaling pathway contributes to the neuroprotective properties of melatonin in SCI. The therapeutic and translational potentials of melatonin in SCI warrant further investigation.
{"title":"Melatonin exerts neuroprotective effects in mice with spinal cord injury by activating the Nrf2/Keap1 signaling pathway via the MT2 receptor.","authors":"Liyan Yan, Xiaonan Han, Mingkang Zhang, Hongwei Kou, Hongjian Liu, Tian Cheng","doi":"10.3892/etm.2023.12325","DOIUrl":"https://doi.org/10.3892/etm.2023.12325","url":null,"abstract":"Spinal cord injury (SCI) is a devastating event that often leads to severe disability, and effective treatments for SCI are currently limited. The present study investigated the potential effects and specific mechanisms of melatonin treatment in SCI. Mice were divided into Sham (Sham), Vehicle (Veh), Melatonin (Mel), and Melatonin + 4-phenyl-2-propionamidotetralin (4P-PDOT) (Mel + 4PP) groups based on randomized allocation. The expression of MT2 and the nuclear factor-erythroid 2-related factor 2 (Nrf2)/Keap1 signaling pathways were examined, along with oxidative stress indicators, inflammatory factors and GFAP-positive cells near the injury site. The polarization of microglial cells in different inflammatory microenvironments was also observed. Cell survival, motor function recovery and spinal cord tissue morphology were assessed using staining and Basso Mouse Scale scores. On day 7 after SCI, the results revealed that melatonin treatment increased MT2 protein expression and activated the Nrf2/Keap1 signaling pathway. It also reduced GFAP-positive cells, mitigated oxidative stress, and suppressed inflammatory responses around the injury site. Furthermore, melatonin treatment promoted the polarization of microglia toward the M2 type, increased the number of neutrophil-positive cells, and modulated the transcription of Bax and Bcl2 in the injured spinal cord. Melatonin treatment alleviated the severity of spinal injuries and facilitated functional recovery in mice with SCI. Notably, blocking MT2 with 4P-PDOT partially reversed the neuroprotective effects of melatonin in SCI, indicating that the activation of the MT2/Nrf2/Keap1 signaling pathway contributes to the neuroprotective properties of melatonin in SCI. The therapeutic and translational potentials of melatonin in SCI warrant further investigation.","PeriodicalId":12285,"journal":{"name":"Experimental and therapeutic medicine","volume":"2 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2023-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138825995","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nesidioblastosis is a rare cause of hyperinsulinemic hypoglycemia in adults and its clinical features are similar to those of insulinoma with recurrent hypoglycemic attacks. The present study reports the case of a 48-year-old man who visited the Affiliated Hospital of Zunyi Medical University (Zunyi, China) with a 5-year history of recurrent hypoglycemic symptoms such as dizziness and palpitations. Abdominal magnetic resonance imaging (MRI) showed a mass of ~1.2x1.0 cm in the head of the pancreas, which was suspected to be an insulinoma. For confirmation, the patient underwent both fluorine-18-fluorodeoxyglucose (18F-FDG) and gallium-68-labeled 1,4,7,10-tetraazacyclododecane-1,4,7,10-teraacetic acid-d-Phel-Tyr3-Thr8-OC (68Ga-DOTATATE) positron emission tomography/computed tomography (PET/CT), which showed a moderately increased uptake of 18F-FDG but no uptake of 68Ga-DOTATATE in the corresponding lesion. The patient subsequently underwent surgery to remove the lesion, which was pathologically confirmed as a pancreatic nesidioblastosis. This case showed that nesidioblastosis should be considered a differential diagnosis for insulinoma and that dual nuclear tracer PET/CT imaging is helpful for differentiating between the two. If conventional imaging techniques such as ultrasound, CT and MRI cannot identify the cause of hypoglycemia in future cases, dual-nuclide tracer PET/CT imaging should be considered.
{"title":"Diagnosis of pancreatic focal nesidioblastosis assisted by dual‑nuclide tracer positron emission tomography/computed tomography: A case report.","authors":"Guangwen Zhu, Liting Xie, Xianwen Hu","doi":"10.3892/etm.2023.12330","DOIUrl":"https://doi.org/10.3892/etm.2023.12330","url":null,"abstract":"Nesidioblastosis is a rare cause of hyperinsulinemic hypoglycemia in adults and its clinical features are similar to those of insulinoma with recurrent hypoglycemic attacks. The present study reports the case of a 48-year-old man who visited the Affiliated Hospital of Zunyi Medical University (Zunyi, China) with a 5-year history of recurrent hypoglycemic symptoms such as dizziness and palpitations. Abdominal magnetic resonance imaging (MRI) showed a mass of ~1.2x1.0 cm in the head of the pancreas, which was suspected to be an insulinoma. For confirmation, the patient underwent both fluorine-18-fluorodeoxyglucose (<sup>18</sup>F-FDG) and gallium-68-labeled 1,4,7,10-tetraazacyclododecane-1,4,7,10-teraacetic acid-d-Phel-Tyr3-Thr8-OC (<sup>68</sup>Ga-DOTATATE) positron emission tomography/computed tomography (PET/CT), which showed a moderately increased uptake of <sup>18</sup>F-FDG but no uptake of <sup>68</sup>Ga-DOTATATE in the corresponding lesion. The patient subsequently underwent surgery to remove the lesion, which was pathologically confirmed as a pancreatic nesidioblastosis. This case showed that nesidioblastosis should be considered a differential diagnosis for insulinoma and that dual nuclear tracer PET/CT imaging is helpful for differentiating between the two. If conventional imaging techniques such as ultrasound, CT and MRI cannot identify the cause of hypoglycemia in future cases, dual-nuclide tracer PET/CT imaging should be considered.","PeriodicalId":12285,"journal":{"name":"Experimental and therapeutic medicine","volume":"240 1 1","pages":""},"PeriodicalIF":2.7,"publicationDate":"2023-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138826065","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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