Korean Journal of Physiology & Pharmacology最新文献_第6页

Tasquinimod promotes the sensitivity of ovarian cancer cells to cisplatin by down-regulating the HDAC4/p21 pathway. 塔斯奎尼莫德通过下调 HDAC4/p21 通路促进卵巢癌细胞对顺铂的敏感性。

IF 1.6 4区医学

Korean Journal of Physiology & Pharmacology Pub Date : 2025-03-01 Epub Date: 2024-11-14 DOI: 10.4196/kjpp.24.132

Zhao Li, Ya-Hong Wu, Ye-Qing Guo, Xiao-Jia Min, Ying Lin

{"title":"Tasquinimod promotes the sensitivity of ovarian cancer cells to cisplatin by down-regulating the HDAC4/p21 pathway.","authors":"Zhao Li, Ya-Hong Wu, Ye-Qing Guo, Xiao-Jia Min, Ying Lin","doi":"10.4196/kjpp.24.132","DOIUrl":"10.4196/kjpp.24.132","url":null,"abstract":"To investigate whether Tasquinimod can influence cisplatin resistance in drug-resistant ovarian cancer (OC) cell lines by regulating histone deacetylase 4 (HDAC4) or p21, we explored its effects on the cell cycle, and associated mechanisms. RT-PCR and Western blot analyses, flow cytometry, CCK8 assay, and immunofluorescence were utilized to investigate the effects of Tasquinimod on gene expression, cell cycle, apoptosis, viability, and protein levels in OC cells. The results showed that Tasquinimod inhibited cell viability and promoted apoptosis in SKOV3/DDP (cisplatin) and A2780/DDP cells more effectively than DDP alone. In combination with cisplatin, Tasquinimod further enhanced cell apoptosis and reduced cell viability in these cell lines, an effect that could be reversed following HDAC4 overexpression. Tasquinimod treatment down-regulated HDAC4, Bcl-2, and cyclin D1, and CDK4 expression and up-regulated the cleaved-Caspase-3, and p21 expression in SKOV3/DDP and A2780/ DDP cells. Additionally, Tasquinimod inhibited DDP resistance in OC/DDP cells. These effects were similarly observed in OC mouse models treated with Tasquinimod. In conclusion, Tasquinimod can improve OC cells' sensitivity to DDP by down-regulating the HDAC4/p21 axis, offering insights into potential strategies for overcoming cisplatin resistance in OC.","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":" ","pages":"191-204"},"PeriodicalIF":1.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11842298/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142632834","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Monotropein resists atherosclerosis by reducing inflammation, oxidative stress, and abnormal proliferation and migration of vascular smooth muscle cells. 单肌蛋白通过减少炎症、氧化应激和血管平滑肌细胞的异常增殖和迁移来抵抗动脉粥样硬化。

IF 1.6 4区医学

Korean Journal of Physiology & Pharmacology Pub Date : 2025-03-01 DOI: 10.4196/kjpp.24.352

Hongliang Li, Bingqian Ye, Jiping Tian, Bofan Wang, Yiwen Zha, Shuying Zheng, Tan Ma, Wenwen Zhuang, Won Sun Park, Jingyan Liang

{"title":"Monotropein resists atherosclerosis by reducing inflammation, oxidative stress, and abnormal proliferation and migration of vascular smooth muscle cells.","authors":"Hongliang Li, Bingqian Ye, Jiping Tian, Bofan Wang, Yiwen Zha, Shuying Zheng, Tan Ma, Wenwen Zhuang, Won Sun Park, Jingyan Liang","doi":"10.4196/kjpp.24.352","DOIUrl":"10.4196/kjpp.24.352","url":null,"abstract":"Monotropein is a compound classified into iridoid which is found in herbaceous plants Morindae officinalis. It possesses anti-inflammatory, antioxidant, and anti-osteoarthritic activities. Previous study indicates that monotropein may have the potential to combat cardiovascular disease, although the related mechanism remains unclear. In this study, we constructed the model of atherosclerosis by oxidized low density lipoprotein-induced vascular smooth muscle cells and LDLR-/- mice given high-fat diet to investigate the effects of monotropein on atherosclerosis. Our results showed that monotropein treatment significantly reduced the area of atherosclerotic plaques and necrotic cores in mice, inhibited the proliferation and migration of vascular smooth muscle cells, and reduced inflammatory responses and oxidative stress, which in turn alleviated atherosclerosis. In addition, we found that monotropein reduced the expression levels of P-NF-κB and P-AP-1. In conclusion, our data suggest that monotropein inhibited the proliferation and migration of vascular smooth muscle cells by mediating the activity of NF-κB, AP-1, reducing the level of inflammation and oxidative stress, and thus resisting the development of atherosclerosis. These findings demonstrate the efficacious therapeutic impact of monotropein on atherosclerosis and elucidate its specific target.","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":"29 2","pages":"245-255"},"PeriodicalIF":1.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11842295/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143460811","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Microglial galectin-3 increases with aging in the mouse hippocampus. 小鼠海马小胶质半凝集素-3随着年龄的增长而增加。

IF 1.6 4区医学

Korean Journal of Physiology & Pharmacology Pub Date : 2025-03-01 Epub Date: 2025-01-14 DOI: 10.4196/kjpp.24.196

Hyun Joo Shin, So Jeong Lee, Hyeong Seok An, Ha Nyeoung Choi, Eun Ae Jeong, Jaewoong Lee, Kyung Eun Kim, Bong-Hoi Choi, Seung Pil Yun, Dawon Kang, Sang Soo Kang, Gu Seob Roh

{"title":"Microglial galectin-3 increases with aging in the mouse hippocampus.","authors":"Hyun Joo Shin, So Jeong Lee, Hyeong Seok An, Ha Nyeoung Choi, Eun Ae Jeong, Jaewoong Lee, Kyung Eun Kim, Bong-Hoi Choi, Seung Pil Yun, Dawon Kang, Sang Soo Kang, Gu Seob Roh","doi":"10.4196/kjpp.24.196","DOIUrl":"10.4196/kjpp.24.196","url":null,"abstract":"Microglial activation during aging is associated with neuroinflammation and cognitive impairment. Galectin-3 plays a crucial role in microglial activation and phagocytosis. However, the role of galectin-3 in the aged brain is not completely understood. In the present study, we investigated aging-related mechanisms and microglial galectin-3 expression in the mouse hippocampus using female 6-, 12-, and 24-month-old C57BL/6 mice. Western blot analysis revealed neurodegeneration, blood-brain barrier leakage, and increased levels of neuroinflammation-related proteins in 24-month-old mice compared to 6- and 12-month-old mice. Immunohistochemistry revealed an increase in activated microglia in the hippocampus of 24-month-old mice compared to 6- and 12-month-old mice. Furthermore, we found more galectin-3 and triggering receptor expressed on myeloid cells-2-positive microglia in 24-month-old mice compared to 6- and 12-month-old mice. Using primary mouse microglial cells, galectin -3 was also increased by lipopolysaccharide treatment. These findings suggest that galectin-3 may play an important role in microglial activation and neuroinflammation during brain aging.","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":" ","pages":"215-225"},"PeriodicalIF":1.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11842289/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142980688","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Toxicity and efficacy study of a combination of two retinoic acids in an ApoE knockout mouse model of atherosclerosis. 两种维甲酸复方制剂在载脂蛋白E基因敲除小鼠动脉粥样硬化模型中的毒性和疗效研究。

IF 1.6 4区医学

Korean Journal of Physiology & Pharmacology Pub Date : 2025-03-01 Epub Date: 2024-11-14 DOI: 10.4196/kjpp.24.165

Da Som Jeong, Ji-Young Lee, Hyo-Jeong Han, Soo Min Ko, Dong Hyun Lee, Yerin Lee, Young-Sik Park, Byong-Cheol Shin, Woo-Chan Son

{"title":"Toxicity and efficacy study of a combination of two retinoic acids in an ApoE knockout mouse model of atherosclerosis.","authors":"Da Som Jeong, Ji-Young Lee, Hyo-Jeong Han, Soo Min Ko, Dong Hyun Lee, Yerin Lee, Young-Sik Park, Byong-Cheol Shin, Woo-Chan Son","doi":"10.4196/kjpp.24.165","DOIUrl":"10.4196/kjpp.24.165","url":null,"abstract":"Atherosclerosis is a major contributor to cardiovascular disease, characterized by inflammation and lipid accumulation in arterial walls, leading to plaque formation. Elevated low-density lipoprotein cholesterol is a primary risk factor for atherosclerosis. All-trans retinoic acid (ATRA), a metabolite of vitamin A, has demonstrated anti-inflammatory effects and potential in regulating vascular injury. 9-cisretinoic acid (9cRA) is an active metabolite of vitamin A and activates the retinoid X receptor. This study investigates whether potassium retinoate (PA9RA), a synthetic combination of ATRA and 9cRA, offers superior efficacy in treating atherosclerosis compared to established treatments such as clopidogrel and atorvastatin. Male ApoE-/- mice were fed a Western-type diet and treated with PA9RA, clopidogrel, or atorvastatin for 10 weeks. The body weight, organ weight, serum biochemistry, and histopathology, including atherosclerotic lesion area and liver steatosis were assessed. PA9RA treatment led to a significant reduction in body weight and inguinal fat, with the 45 mg/kg/day dose showing marked efficacy in decreasing atherosclerotic lesion size and ameliorating liver steatosis. Histopathological evaluation revealed decreased foam cell formation and improved liver histology in PA9RA-treated groups compared to controls. Notable side effects included epidermal hyperplasia and gastric hyperplasia at high doses of PA9RA. PA9RA exhibits superior efficacy over clopidogrel and atorvastatin in ameliorating atherosclerosis and fatty liver in ApoE-/- mice. This study highlights PA9RA's potential as a promising therapeutic agent for atherosclerosis. Further research is needed to elucidate its mechanisms of action and assess long-term safety and efficacy.","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":" ","pages":"179-189"},"PeriodicalIF":1.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11842292/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142632840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Human induced pluripotent stem cell-cardiomyocytes for cardiotoxicity assessment: a comparative study of arrhythmiainducing drugs with multi-electrode array analysis. 用于心脏毒性评估的人诱导多能干细胞-心肌细胞：心律失常诱导药物与多电极阵列分析的比较研究。

IF 1.6 4区医学

Korean Journal of Physiology & Pharmacology Pub Date : 2025-03-01 DOI: 10.4196/kjpp.24.413

Na Kyeong Park, Yun-Gwi Park, Ji-Hee Choi, Hyung Kyu Choi, Sung-Hwan Moon, Soon-Jung Park, Seong Woo Choi

{"title":"Human induced pluripotent stem cell-cardiomyocytes for cardiotoxicity assessment: a comparative study of arrhythmiainducing drugs with multi-electrode array analysis.","authors":"Na Kyeong Park, Yun-Gwi Park, Ji-Hee Choi, Hyung Kyu Choi, Sung-Hwan Moon, Soon-Jung Park, Seong Woo Choi","doi":"10.4196/kjpp.24.413","DOIUrl":"10.4196/kjpp.24.413","url":null,"abstract":"Reliable preclinical models for assessing drug-induced cardiotoxicity are essential to reduce the high rate of drug withdrawals during development. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have emerged as a promising platform for such assessments due to their expression of cardiacspecific ion channels and electrophysiological properties. In this study, we investigated the effects of eight arrhythmogenic drugs-E4031, nifedipine, mexiletine, JNJ303, flecainide, moxifloxacin, quinidine, and ranolazine-on hiPSC-CMs derived from both healthy individuals and a long QT syndrome (LQTS) patient using multielectrode array systems. The results demonstrated dose-dependent changes in field potential duration and arrhythmogenic risk, with LQTS-derived hiPSC-CMs showing increased sensitivity to hERG channel blockers such as E4031. Furthermore, the study highlights the potential of hiPSC-CMs to model disease-specific cardiac responses, providing insights into genetic predispositions and personalized drug responses. Despite challenges related to the immaturity of hiPSC-CMs, their ability to recapitulate human cardiac electrophysiology makes them a valuable tool for preclinical cardiotoxicity assessments. This study underscores the utility of integrating patientderived hiPSC-CMs with advanced analytical platforms, such as multi-electrode array systems, to evaluate drug-induced electrophysiological changes. These findings reinforce the role of hiPSC-CMs in drug development, facilitating safer and more efficient screening methods while supporting precision medicine applications.","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":"29 2","pages":"257-269"},"PeriodicalIF":1.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11842287/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143460810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Differential expression of ORAI channels and STIM proteins in renal cell carcinoma subtypes: implications for metastasis and therapeutic targeting. 肾细胞癌亚型中 ORAI 通道和 STIM 蛋白的差异表达：对转移和靶向治疗的影响。

IF 1.6 4区医学

Korean Journal of Physiology & Pharmacology Pub Date : 2025-01-01 Epub Date: 2024-10-31 DOI: 10.4196/kjpp.24.126

Ji-Hee Kim, Kyu-Hee Hwang, Jiyeon Oh, Sung-Eun Kim, Mi-Young Lee, Tae Sic Lee, Seung-Kuy Cha

{"title":"Differential expression of ORAI channels and STIM proteins in renal cell carcinoma subtypes: implications for metastasis and therapeutic targeting.","authors":"Ji-Hee Kim, Kyu-Hee Hwang, Jiyeon Oh, Sung-Eun Kim, Mi-Young Lee, Tae Sic Lee, Seung-Kuy Cha","doi":"10.4196/kjpp.24.126","DOIUrl":"10.4196/kjpp.24.126","url":null,"abstract":"Renal cell carcinoma (RCC) presents significant clinical challenges, highlighting the importance of understanding its molecular mechanisms. While store-operated Ca2+ entry (SOCE) is known to play an essential role in tumorigenesis and metastasis, its specific implications across various RCC subtypes remain underexplored. This study analyzed SOCE-related mRNA profiles from the KIRC and KIRP projects in The Cancer Genome Atlas (TCGA) database, focusing on differential gene expression and overall survival outcomes. Functional studies in clear cell RCC (Caki-1) and papillary RCC cell lines (pRCC, Caki-2) revealed increased expression of Orai1 and Orai3, along with STIM1, exhibited in both subtypes, with decreased STIM2 and increased Orai2 expression in pRCC. Notably, Orai3 expression had a gender-specific impact on survival, particularly in females with pRCC, where it inversely correlated with STIM2 expression. Functional assays showed Orai3 dominance in Caki-2 and Orai1 in Caki- 1. Interestingly, 2-APB inhibited SOCE in Caki-1 but enhanced it in Caki-2, suggesting Orai3 as the primary SOCE channel in pRCC. Knockdown of Orai1 and Orai3 reduced cell migration and proliferation via regulating focal adhesion kinase (FAK) and Cyclin D1 in both cell lines. These findings highlight the critical roles of Orai1 and Orai3 in RCC metastasis, with Orai3 linked to poorer prognosis in females with pRCC. This study offers valuable insights into RCC diagnostics and potential therapeutic strategies targeting ORAI channels and STIM proteins.","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":" ","pages":"33-43"},"PeriodicalIF":1.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11694002/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142559472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Fine particulate matter induces osteoclast-mediated bone loss in mice. 细颗粒物会诱发小鼠破骨细胞介导的骨质流失。

IF 1.6 4区医学

Korean Journal of Physiology & Pharmacology Pub Date : 2025-01-01 Epub Date: 2024-10-31 DOI: 10.4196/kjpp.24.115

Hye Young Mun, Septika Prismasari, Jeong Hee Hong, Hana Lee, Doyong Kim, Han Sung Kim, Dong Min Shin, Jung Yun Kang

{"title":"Fine particulate matter induces osteoclast-mediated bone loss in mice.","authors":"Hye Young Mun, Septika Prismasari, Jeong Hee Hong, Hana Lee, Doyong Kim, Han Sung Kim, Dong Min Shin, Jung Yun Kang","doi":"10.4196/kjpp.24.115","DOIUrl":"10.4196/kjpp.24.115","url":null,"abstract":"Fine particulate matter (FPM) is a major component of air pollution and has emerged as a significant global health concern owing to its adverse health effects. Previous studies have investigated the correlation between bone health and FPM through cohort or review studies. However, the effects of FPM exposure on bone health are poorly understood. This study aimed to investigate the effects of FPM on bone health and elucidate these effects in vitro and in vivo using mice. Micro-CT analysis in vivo revealed FPM exposure decreased bone mineral density, trabecular bone volume/total volume ratio, and trabecular number in the femurs of mice, while increasing trabecular separation. Histological analysis showed that the FPM-treated group had a reduced trabecular area and an increased number of osteoclasts in the bone tissue. Moreover, in vitro studies revealed that low concentrations of FPM significantly enhanced osteoclast differentiation. These findings further support the notion that short-term FPM exposure negatively impacts bone health, providing a foundation for further research on this topic.","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":" ","pages":"9-19"},"PeriodicalIF":1.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11694009/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142559473","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Astragalus polysaccharide ameliorates diabetic retinopathy by inhibiting the SHH-Gli1-AQP1 signaling pathway in streptozotocin-induced type 2 diabetic rats. 黄芪多糖通过抑制链脲佐菌素诱导的2型糖尿病大鼠的SHH-Gli1-AQP1信号通路改善糖尿病视网膜病变

IF 1.6 4区医学

Korean Journal of Physiology & Pharmacology Pub Date : 2025-01-01 Epub Date: 2024-11-14 DOI: 10.4196/kjpp.23.251

Jingrong Qu, Bo Wang, Yulong Wang, Hao Li, Xiaomei An

{"title":"Astragalus polysaccharide ameliorates diabetic retinopathy by inhibiting the SHH-Gli1-AQP1 signaling pathway in streptozotocin-induced type 2 diabetic rats.","authors":"Jingrong Qu, Bo Wang, Yulong Wang, Hao Li, Xiaomei An","doi":"10.4196/kjpp.23.251","DOIUrl":"10.4196/kjpp.23.251","url":null,"abstract":"This study aims to investigate the effects of astragalus polysaccharide (APS) on diabetic retinopathy through the SHH-Gli1-AQP1 pathway. The anti-type 2 diabetes mellitus (T2DM) targets of APS were identified through comprehensive searches of drug and disease-related databases. A protein-protein interaction network was then constructed, followed by GO and KEGG enrichment analyses. Molecular docking simulations were performed to evaluate the interactions of APS and metformin with Gli1 and AQP1. An in vivo T2DM rat model was established via streptozotocin (STZ) injection and treated with metformin and varying doses of APS for 12 weeks. Histological changes in retinal cells were assessed using H&E and PAS staining. The expression levels of AQP1, Gli1, and SHH in the retina were measured using immunohistochemistry, Western blotting, immunofluorescence, and ELISA. Additionally, mRNA expression of AQP1, Gli1, and SHH was quantified by RT-qPCR. Bioinformatic analyses indicated that Gli1 and AQP1, key components of the SHH-Gli1- AQP1 signaling pathway, may be associated with T2DM. Subsequent experiments demonstrated that the STZ-induced T2DM rats exhibited significant retinal damage, which was notably mitigated by both APS and metformin treatments. Furthermore, the SHH-Gli1-AQP1 signaling pathway was found to be overactivated in STZ-induced T2DM rats. Treatment with APS and metformin significantly reduced the elevated expression levels of SHH, Gli1, and AQP1. APS effectively inhibits retinal damage of STZ-induced T2DM rats by restraining the SHH-Gli1-AQP1 signaling pathway.","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":" ","pages":"21-32"},"PeriodicalIF":1.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11694010/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142632817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mebendazole effectively overcomes imatinib resistance by dual-targeting BCR/ABL oncoprotein and β-tubulin in chronic myeloid leukemia cells. 甲苯达唑通过双重靶向慢性骨髓性白血病细胞中的BCR/ABL癌蛋白和β-微管蛋白，有效克服伊马替尼耐药性。

IF 1.6 4区医学

Korean Journal of Physiology & Pharmacology Pub Date : 2025-01-01 Epub Date: 2024-11-14 DOI: 10.4196/kjpp.24.176

Li Yang, Zhuanyun Du, Yuhang Peng, Wenyao Zhang, Wenli Feng, Ying Yuan

{"title":"Mebendazole effectively overcomes imatinib resistance by dual-targeting BCR/ABL oncoprotein and β-tubulin in chronic myeloid leukemia cells.","authors":"Li Yang, Zhuanyun Du, Yuhang Peng, Wenyao Zhang, Wenli Feng, Ying Yuan","doi":"10.4196/kjpp.24.176","DOIUrl":"10.4196/kjpp.24.176","url":null,"abstract":"To target the pivotal BCR/ABL oncoprotein in chronic myeloid leukemia (CML) cells, tyrosine kinase inhibitors (TKIs) are utilized as landmark achievements in CML therapy. However, TKI resistance and intolerance remain principal obstacles in the treatment of CML patients. In recent years, drug repositioning provided alternative and promising perspectives apart from the classical cancer therapies, and promoted anthelmintic mebendazole (MBZ) as an effective anti-cancer drug in various cancers. Here, we investigated the role of MBZ in CML treatment including imatinib-resistant CML cells. Our results proved that MBZ inhibited the proliferation and induced apoptosis in CML cells. We found that MBZ effectively suppressed BCR/ABL kinase activity and MEK/ERK signaling pathway by reducing p-BCR/ABL and p-ERK levels with ABL1 targeting ability. Meanwhile, MBZ directly targeted the colchicine-binding site of β-tubulin protein, hampered microtubule polymerization and induced mitosis arrest and mitotic catastrophe. In addition, MBZ increased DNA damage levels and hampered the accumulation of ataxia-telangiectasia mutated and DNA-dependent protein kinase into the nucleus. This work discovered that anthelmintic MBZ exerts remarkable anticancer effects in both imatinib-sensitive and imatinib-resistant CML cells in vitro and revealed mechanisms underlying. From the perspective of drug repositioning and multi-target therapeutic strategy, this study provides a promising option for CML treatment, especially in TKI-resistant or intolerant individuals.","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":" ","pages":"67-81"},"PeriodicalIF":1.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11694007/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142632823","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

p66shc deficiency attenuates high glucose-induced autophagy dysfunction in Schwann cells. p66shc 缺乏症可减轻高糖诱导的许旺细胞自噬功能障碍。

IF 1.6 4区医学

Korean Journal of Physiology & Pharmacology Pub Date : 2025-01-01 Epub Date: 2024-10-31 DOI: 10.4196/kjpp.24.155

Su-Jeong Choi, Giang-Huong Vu, Harsha Nagar, Seonhee Kim, Ikjun Lee, Shuyu Piao, Byeong Hwa Jeon, Kaikobad Irani, Sang-Ha Oh, Cuk-Seong Kim

{"title":"p66shc deficiency attenuates high glucose-induced autophagy dysfunction in Schwann cells.","authors":"Su-Jeong Choi, Giang-Huong Vu, Harsha Nagar, Seonhee Kim, Ikjun Lee, Shuyu Piao, Byeong Hwa Jeon, Kaikobad Irani, Sang-Ha Oh, Cuk-Seong Kim","doi":"10.4196/kjpp.24.155","DOIUrl":"10.4196/kjpp.24.155","url":null,"abstract":"Schwann cells are the most abundant cells in the peripheral nervous system, maintaining the development, function and regeneration of peripheral nerves. Defects in these Schwann cells injury response potentially contribute to the pathogenesis of diabetic peripheral neuropathy (DPN), a common complication of diabetes mellitus. The protein p66shc is essential in regulating oxidative stress responses, autophagy induction and cell survival, and is also vital in the development of DPN. In this study, we hypothesized that p66shc mediates high glucose-induced oxidative stress and autophagic dysfunction. In Schwann cells treated with high glucose; p66shc expression, levels of reactive oxygen species, autophagy impairment, and early apoptosis were elevated. Inhibition of p66shc gene expression by siRNA reversed high glucose-induced oxidative stress, autophagy impairment, and early apoptosis. We also demonstrated that the levels of p66shc was increased, while autophagy-related proteins p62 and LC3 (LC3-II/I) were suppressed in the sciatic nerve of streptozotocin-induced diabetes mice. P66shc-deficient mice exhibited the improvement in autophagy impairment after diabetes onset. Our findings suggest that the p66 plays a crucial role in Schwann cell dysfunction, identifying its potential as a therapeutic target.","PeriodicalId":54746,"journal":{"name":"Korean Journal of Physiology & Pharmacology","volume":" ","pages":"57-66"},"PeriodicalIF":1.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11694004/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142559475","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0