The Kaohsiung journal of medical sciences最新文献

Y-Box-Binding Protein 1 Facilitates the Proliferation and Osteogenic Differentiation of Periodontal Ligament Stem Cells Through the Transcriptional Activation of FGF2-Mediated Akt/GSK3β/β-Catenin Signaling. y - box结合蛋白1通过fgf2介导的Akt/GSK3β/β-Catenin信号通路的转录激活促进牙周韧带干细胞的增殖和成骨分化。

IF 3.1

The Kaohsiung journal of medical sciences Pub Date : 2025-07-30 DOI: 10.1002/kjm2.70079

Yun-Hao Xi, Chang-Shun Li, Pin-Lin Wu, Xiao-Yang Zhou, Qian-Wen Li, Cheng-Hui Shen

{"title":"Y-Box-Binding Protein 1 Facilitates the Proliferation and Osteogenic Differentiation of Periodontal Ligament Stem Cells Through the Transcriptional Activation of FGF2-Mediated Akt/GSK3β/β-Catenin Signaling.","authors":"Yun-Hao Xi, Chang-Shun Li, Pin-Lin Wu, Xiao-Yang Zhou, Qian-Wen Li, Cheng-Hui Shen","doi":"10.1002/kjm2.70079","DOIUrl":"https://doi.org/10.1002/kjm2.70079","url":null,"abstract":"Periodontal ligament stem cells (PDLSCs) are derived from periodontal tissue and can differentiate into osteoblasts, which are ideal materials for alveolar bone repair and periodontal tissue regeneration. In this study, we aimed to explore the effects of Y-box binding protein 1 (YB-1) on the osteogenic differentiation and proliferation of PDLSCs and its underlying mechanism. hPDLSC proliferation was detected by CCK-8 and EdU assays. The osteogenic differentiation of hPDLSCs was clarified using alkaline phosphatase (ALP) activity detection and Alizarin red S (ARS) staining. The expression levels of osteogenic differentiation-related factors, Akt/GSK3β/β-catenin pathway-related factors, YB-1, and fibroblast growth factor 2 (FGF2) were evaluated using qPCR and Western blotting. The interplay between YB-1 and FGF2 was clarified using ChIP and dual-luciferase reporter gene assays. YB-1 expression was markedly decreased in periodontitis clinical tissues but increased in hPDLSCs during osteogenic differentiation. Moreover, silencing YB-1 suppressed the osteogenic differentiation and proliferation of hPDLSCs. In addition, YB-1 promotes hPDLSC proliferation and osteogenic differentiation in a manner dependent on the activation of the Akt/GSK3β/β-catenin signaling pathway, which is mediated by FGF2 transcriptional activation. Furthermore, the inhibitory effects of YB-1 knockdown on the osteogenic differentiation and proliferation of hPDLSCs were antagonized by human recombinant FGF2. Taken together, our findings revealed that YB-1 facilitates hPDLSC proliferation and osteogenic differentiation through increasing the level of FGF2 via transcriptional regulation, thereby activating the Akt/GSK3β/β-catenin pathway.","PeriodicalId":94244,"journal":{"name":"The Kaohsiung journal of medical sciences","volume":" ","pages":"e70079"},"PeriodicalIF":3.1,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144746629","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

GNPAT/USP30 Stabilizes DRP1 Protein to Promote Mitochondrial Fission and Functional Damage in COPD Progression. GNPAT/USP30稳定DRP1蛋白促进COPD进展中的线粒体分裂和功能损伤

The Kaohsiung journal of medical sciences Pub Date : 2025-07-25 DOI: 10.1002/kjm2.70080

Xin-Gui Cheng, Yun-Chan Liu, Fei Chen, Ji-Wei Li, Xiao-Zhou Yao, Qing-Yun Chen

{"title":"GNPAT/USP30 Stabilizes DRP1 Protein to Promote Mitochondrial Fission and Functional Damage in COPD Progression.","authors":"Xin-Gui Cheng, Yun-Chan Liu, Fei Chen, Ji-Wei Li, Xiao-Zhou Yao, Qing-Yun Chen","doi":"10.1002/kjm2.70080","DOIUrl":"https://doi.org/10.1002/kjm2.70080","url":null,"abstract":"Our previous study revealed the role of glycerol phosphate O-acyltransferase (GNPAT) in regulating chronic obstructive pulmonary disease (COPD). However, its further mechanisms remained unclear. In this study, COPD models were established by exposing mice to cigarette smoke particulates. H&E staining and immunohistochemistry assays were performed on COPD tissue. A549 cells were stimulated with 5% cigarette smoke extract (CSE) and transfected with GNPAT, ubiquitin-specific protease 30 (USP30), and dynamin-related protein 1 (DRP1) plasmids. Cell viability, cell apoptosis, lactate dehydrogenase (LDH) release, ATP production, and reactive oxygen species (ROS) levels were determined using commercial kits. Quantitative real-time PCR and western blotting were used to evaluate mRNA and protein expression. Mitochondrial morphology was examined by transmission electron microscopy. A co-immunoprecipitation assay determined the binding relationships among GNPAT, USP30, and DRP1. Our results showed that GNPAT and DRP1 were highly expressed in the COPD model mice. CSE promoted mitochondrial fission, mitochondrial dysfunction, and cell apoptosis, which were further enhanced by treatment with a mitochondrial fission inducer (TA9). GNPAT promoted mitochondrial fission, mitochondrial dysfunction, and cell apoptosis by enhancing DPR1 protein stability, which depended on USP30. DRP1 enhanced mitochondrial fission, mitochondrial dysfunction, and cell apoptosis, which were both reversed by GNPAT/USP30 inhibition. Collectively, our present study found that GNPAT recruited USP30 and stabilized DRP1, thereby mediating mitochondrial fission and mitochondrial dysfunction that contributed to cell apoptosis in COPD. This study suggests a promising therapeutic biomarker for COPD.","PeriodicalId":94244,"journal":{"name":"The Kaohsiung journal of medical sciences","volume":" ","pages":"e70080"},"PeriodicalIF":0.0,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144710354","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Inhibition of miR-499a-5p Ameliorates Apoptotic and Autophagic Damage in Hypoxic Cardiomyocytes H9c2 Through Upregulation of ARGLU1. 抑制miR-499a-5p通过上调ARGLU1改善缺氧心肌细胞H9c2的凋亡和自噬损伤

The Kaohsiung journal of medical sciences Pub Date : 2025-07-22 DOI: 10.1002/kjm2.70059

Sha Wang, Hui-Jun Wang, Shuo Pan

{"title":"Inhibition of miR-499a-5p Ameliorates Apoptotic and Autophagic Damage in Hypoxic Cardiomyocytes H9c2 Through Upregulation of ARGLU1.","authors":"Sha Wang, Hui-Jun Wang, Shuo Pan","doi":"10.1002/kjm2.70059","DOIUrl":"https://doi.org/10.1002/kjm2.70059","url":null,"abstract":"Myocardial infarction (MI), the most prevalent form of acute coronary syndrome, is often accompanied by cardiomyocyte apoptosis. In addition to apoptosis, autophagy plays a critical role in determining cardiomyocyte survival during MI. This study aimed to elucidate the regulatory role of miR-499a-5p in cardiomyocyte apoptosis and autophagy under hypoxic conditions. An MI mouse model was established via ligation of the left anterior descending coronary artery, and RT-qPCR was used to assess miR-499a-5p expression levels in cardiac tissues from MI and sham-operated mice. Masson's trichrome staining was employed to evaluate cardiac fibrosis, and echocardiography was conducted to assess cardiac functional parameters. For in vitro experiments, TUNEL assays and flow cytometry analyses were used to measure apoptosis and autophagy. A luciferase reporter assay confirmed the direct binding between miR-499a-5p and arginine and glutamate rich 1 (ARGLU1). Western blot analysis was used to quantify protein levels of apoptotic markers, autophagy-related proteins, and ARGLU1. The results demonstrated that MI mice developed significant cardiac fibrosis and functional impairment, along with increased miR-499a-5p expression. In H9c2 cells, knockdown of miR-499a-5p significantly reduced hypoxia-induced apoptosis and autophagy, whereas miR-499a-5p overexpression exacerbated these processes. Moreover, ARGLU1 was identified as a direct target of miR-499a-5p and was negatively regulated by it. Silencing ARGLU1 enhanced hypoxia-induced apoptosis and autophagy and reversed the protective effects observed with miR-499a-5p knockdown. In summary, miR-499a-5p inhibition mitigates hypoxia-induced injury in H9c2 cells by reducing apoptosis and autophagy through the upregulation of ARGLU1, suggesting a potential therapeutic target for MI.","PeriodicalId":94244,"journal":{"name":"The Kaohsiung journal of medical sciences","volume":" ","pages":"e70059"},"PeriodicalIF":0.0,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144692934","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Long Noncoding RNA TOB1-AS1 Represses Cervical Cancer Cell Proliferation, Invasion, and Migration via the MicroRNA-27a-3p/Thioredoxin-Interacting Protein Molecular Axis. 长链非编码RNA to1 - as1通过MicroRNA-27a-3p/硫氧还蛋白相互作用蛋白分子轴抑制宫颈癌细胞增殖、侵袭和迁移。

The Kaohsiung journal of medical sciences Pub Date : 2025-07-16 DOI: 10.1002/kjm2.70076

Yang Wang, You-Xiang Hou, Li Xie, Yi-La Xia, Yi-Na Wang

{"title":"Long Noncoding RNA TOB1-AS1 Represses Cervical Cancer Cell Proliferation, Invasion, and Migration via the MicroRNA-27a-3p/Thioredoxin-Interacting Protein Molecular Axis.","authors":"Yang Wang, You-Xiang Hou, Li Xie, Yi-La Xia, Yi-Na Wang","doi":"10.1002/kjm2.70076","DOIUrl":"https://doi.org/10.1002/kjm2.70076","url":null,"abstract":"Cervical cancer (CC) remains a major global health concern, particularly due to its aggressive nature and limited treatment options in advanced stages. Long noncoding RNA (lncRNA) TOB1-AS1 has been proposed as a tumor suppressor, yet its regulatory mechanism in CC remains unclear. This study aimed to elucidate the role of TOB1-AS1 in CC progression through the miR-27a-3p/thioredoxin-interacting protein (TXNIP) molecular axis. Functional gain- and loss-of-function assays were conducted to assess the effects of TOB1-AS1, miR-27a-3p, and TXNIP on cell proliferation, invasion, migration, and apoptosis. RT-qPCR, Western blotting, dual-luciferase reporter assays, and in vivo xenograft models were used to validate interactions and phenotypic outcomes. TOB1-AS1 was found to be downregulated in CC cells. Its overexpression suppressed proliferation, invasion, and migration, while enhancing apoptosis. Mechanistically, TOB1-AS1 functioned as a competing endogenous RNA (ceRNA) by sponging miR-27a-3p, thereby restoring TXNIP expression. Modulating miR-27a-3p or TXNIP levels partially reversed the effects of TOB1-AS1. In vivo, TOB1-AS1 overexpression significantly inhibited tumor growth and altered miR-27a-3p and TXNIP expression profiles. These findings suggest that lncRNA TOB1-AS1 acted as a ceRNA of miR-27a-3p to upregulate TXNIP, thereby suppressing CC cell proliferation, invasion and migration.","PeriodicalId":94244,"journal":{"name":"The Kaohsiung journal of medical sciences","volume":" ","pages":"e70076"},"PeriodicalIF":0.0,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144644495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Response to Integration of the Comprehensive Physical Examination and Diagnostic Tools in Clinical Cardiology. 综合体格检查与诊断工具在临床心脏病学中的整合反应。

The Kaohsiung journal of medical sciences Pub Date : 2025-07-13 DOI: 10.1002/kjm2.70075

Yu-Shien Kao, Yi-Hsun Chen, I-Chen Wu

引用次数: 0

Dynamics of Cardiometabolic Risk Factors Are Linked to the Risk of Hypertension and Diabetes in MASLD. 心脏代谢危险因素的动态与MASLD患者高血压和糖尿病的风险相关。

The Kaohsiung journal of medical sciences Pub Date : 2025-07-12 DOI: 10.1002/kjm2.70077

Chin-I Shih, Ming-Lun Yeh, Yi-Hung Lin, Ping-Tsung Shih, Kuan-Ta Wu, Meng-Hsuan Hsieh, Jeng-Fu Yang, Yi-Yu Chen, Po-Cheng Liang, Yu-Ju Wei, Pei-Chien Tsai, Ya-Yun Cheng, Ming-Yen Hsieh, Chih-Wen Wang, Chung-Feng Huang, Jee-Fu Huang, Chia-Yen Dai, Chi-Kung Ho, Wan-Long Chuang, Vincent Wai-Sun Wong, Wei-Ting Chang, Ming-Lung Yu

{"title":"Dynamics of Cardiometabolic Risk Factors Are Linked to the Risk of Hypertension and Diabetes in MASLD.","authors":"Chin-I Shih, Ming-Lun Yeh, Yi-Hung Lin, Ping-Tsung Shih, Kuan-Ta Wu, Meng-Hsuan Hsieh, Jeng-Fu Yang, Yi-Yu Chen, Po-Cheng Liang, Yu-Ju Wei, Pei-Chien Tsai, Ya-Yun Cheng, Ming-Yen Hsieh, Chih-Wen Wang, Chung-Feng Huang, Jee-Fu Huang, Chia-Yen Dai, Chi-Kung Ho, Wan-Long Chuang, Vincent Wai-Sun Wong, Wei-Ting Chang, Ming-Lung Yu","doi":"10.1002/kjm2.70077","DOIUrl":"https://doi.org/10.1002/kjm2.70077","url":null,"abstract":"This study investigates the impact of cardiometabolic risk factors (CMRF) on the prevalence and incidence of hypertension (HTN) and diabetes mellitus (DM) in individuals with metabolic dysfunction-associated steatotic liver disease (MASLD) and nonsteatotic liver disease (non-SLD), using both cross-sectional and longitudinal data. A total of 32,569 Taiwanese adults without viral hepatitis or significant alcohol consumption who underwent health checkups from 1999 to 2013 were analyzed cross-sectionally. Among them, 27,109 individuals free of HTN and DM at baseline and within 1 year of enrollment were followed longitudinally. Participants were classified into four groups based on hepatic steatosis assessed by ultrasound and presence of CMRF: healthy control (non-SLD/CMRF-), simple SLD (SLD/CMRF-), non-SLD/CMRF+, and MASLD. MASLD patients exhibited markedly higher annual incidence rates of HTN and DM (19.7 and 6.3 per 1000 person-years) compared to non-SLD individuals (HTN: 9.0; DM: 0.6 per 1000 person-years). The risk of incident HTN and DM increased progressively with the number of CMRF, with adjusted hazard ratios (aHR) ranging from 2.02 to 15.53 for HTN and from 2.92 to 82.38 for DM. Regression of cardiometabolic dysfunction decreased the risk of HTN and/or DM, and vice versa. The presence of CMRF significantly increased the likelihood of developing HTN and DM in both SLD and non-SLD groups, with aHRs up to 7.48 for HTN and 15.38 for DM. In conclusion, MASLD is strongly associated with increased prevalence and incidence of HTN and DM, and the burden and trajectory of CMRF critically modulate these risks.","PeriodicalId":94244,"journal":{"name":"The Kaohsiung journal of medical sciences","volume":" ","pages":"e70077"},"PeriodicalIF":0.0,"publicationDate":"2025-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144621599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

GATA1 Transcriptionally Upregulates LMCD1, Promoting Ferroptosis in Sepsis-Associated Acute Kidney Injury Through the Hippo/YAP Pathway. GATA1转录上调LMCD1，通过Hippo/YAP通路促进脓毒症相关急性肾损伤中的铁凋亡。

The Kaohsiung journal of medical sciences Pub Date : 2025-07-12 DOI: 10.1002/kjm2.70071

You-Qi Zhang, Wei-Xia Peng, You-Fu Li, Peng Lu, Hui Liu, Wen-Guang Liu

{"title":"GATA1 Transcriptionally Upregulates LMCD1, Promoting Ferroptosis in Sepsis-Associated Acute Kidney Injury Through the Hippo/YAP Pathway.","authors":"You-Qi Zhang, Wei-Xia Peng, You-Fu Li, Peng Lu, Hui Liu, Wen-Guang Liu","doi":"10.1002/kjm2.70071","DOIUrl":"https://doi.org/10.1002/kjm2.70071","url":null,"abstract":"Sepsis-associated acute kidney injury (SA-AKI) is associated with morbidity and mortality. Ferroptosis is associated with the pathophysiology of SA-AKI. Here, we investigated the role of LIM and cysteine-rich domain 1 (LMCD1) in the regulation of ferroptosis during SA-AKI progression. SA-AKI models were established by CLP and LPS treatments. Hematoxylin and eosin (HE) and (PAS) staining were conducted to examine renal pathological changes. ELISA was used to measure serum creatinine and BUN levels. Lipid ROS levels in cells were examined using flow cytometry. MDA, GSH, SOD, and Fe2+ levels in the cells were measured using appropriate kits. Molecular interactions were analyzed using ChIP, a dual-luciferase reporter gene, and Co-IP assays. GATA1 knockdown inhibits LPS-induced cell injury, oxidative stress, and ferroptosis in HK-2 cells by transcriptionally inhibiting LMCD1 expression. Moreover, LMCD1 activates the Hippo/YAP pathway by promoting CUL3-mediated Nrf2 ubiquitination degradation. LMCD1 knockdown alleviates CLP-induced AKI in mice by inhibiting ferroptosis. Taken together, LMCD1 transcriptionally activated by GATA1 promotes ferroptosis during SA-AKI progression by activating the Hippo/YAP pathway and facilitating CUL3-mediated Nrf2 ubiquitination degradation.","PeriodicalId":94244,"journal":{"name":"The Kaohsiung journal of medical sciences","volume":" ","pages":"e70071"},"PeriodicalIF":0.0,"publicationDate":"2025-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144621600","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mechanism of KDM5C-Mediated H3K4me3 Demethylation of HOXC-AS3 in the Proliferation of Colorectal Cancer Cells. kdm5c介导的HOXC-AS3 H3K4me3去甲基化在结直肠癌细胞增殖中的作用机制

The Kaohsiung journal of medical sciences Pub Date : 2025-07-08 DOI: 10.1002/kjm2.70068

Hong Li, Da-Min Li, Zhan Wang, Jie Hou

{"title":"Mechanism of KDM5C-Mediated H3K4me3 Demethylation of HOXC-AS3 in the Proliferation of Colorectal Cancer Cells.","authors":"Hong Li, Da-Min Li, Zhan Wang, Jie Hou","doi":"10.1002/kjm2.70068","DOIUrl":"https://doi.org/10.1002/kjm2.70068","url":null,"abstract":"Colorectal cancer (CRC) ranks as the third most prevalent malignancy and the second leading cause of cancer-related mortality worldwide. This study explored the role of lysine-specific histone demethylase 5C (KDM5C) in CRC progression. Expression levels of KDM5C, HOXC-AS3, and discs large MAGUK scaffold protein 4 (DLG4) were evaluated. Following the KDM5C knockdown, cell proliferation assays were conducted. The recruitment of KDM5C and histone H3 lysine 4 tri-methylation (H3K4me3) to the HOXC-AS3 promoter region was investigated. Furthermore, the subcellular distribution of HOXC-AS3 was assessed using nuclear-cytoplasmic fractionation and RNA fluorescence in situ hybridization (RNA-FISH). The interactions between HOXC-AS3, YTH domain-containing protein 1 (YTHDC1), and DLG4 were detected. The stability of DLG4 mRNA was evaluated, and the functional roles of HOXC-AS3 and DLG4 in CRC cells were examined through combined experimental analyses. KDM5C expression was elevated in CRC cells, whereas HOXC-AS3 and DLG4 levels were notably reduced. Silencing KDM5C resulted in suppressed cell proliferation. Mechanistically, KDM5C inhibited HOXC-AS3 expression by demethylating H3K4me3 at its promoter. HOXC-AS3 promoted DLG4 mRNA stability by recruiting the RNA-binding protein YTHDC1. Combined experimental results indicated that overexpression of HOXC-AS3 or DLG4 reduced the inhibitory effect of KDM5C downregulation on CRC cells. In conclusion, KDM5C promotes CRC cell proliferation by demethylating H3K4me3, repressing HOXC-AS3 expression. The reduced HOXC-AS3 levels impair the recruitment of YTHDC1, leading to decreased DLG4 expression.","PeriodicalId":94244,"journal":{"name":"The Kaohsiung journal of medical sciences","volume":" ","pages":"e70068"},"PeriodicalIF":0.0,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144593265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Ginsenoside Rg1 Restores Sirt2/Foxo1 Expression and Alleviates Autism-Like Behaviors in a Valproic Acid Induced Male Mouse Model. 在丙戊酸诱导的雄性小鼠模型中，人参皂苷Rg1恢复Sirt2/Foxo1表达并减轻自闭症样行为

The Kaohsiung journal of medical sciences Pub Date : 2025-07-07 DOI: 10.1002/kjm2.70078

Fan-Xu Song, Qing-Wei Wu, Wei Pan, Li-Jun Liu, Xin Li, Xue Zhou, Zong-Yao Yu, Xin Ning, Lan-Min Guo

{"title":"Ginsenoside Rg1 Restores Sirt2/Foxo1 Expression and Alleviates Autism-Like Behaviors in a Valproic Acid Induced Male Mouse Model.","authors":"Fan-Xu Song, Qing-Wei Wu, Wei Pan, Li-Jun Liu, Xin Li, Xue Zhou, Zong-Yao Yu, Xin Ning, Lan-Min Guo","doi":"10.1002/kjm2.70078","DOIUrl":"https://doi.org/10.1002/kjm2.70078","url":null,"abstract":"This study investigated whether Ginsenoside Rg1 (Rg1) alleviates autism-like behaviors in mice prenatally exposed to valproic acid (VPA) via Sirt2/Foxo1 signaling. Pregnant C57BL/6J mice received a single intraperitoneal injection of VPA (600 mg/kg) on embryonic Day 12.5 to establish an autism model. At 8 weeks of age, male offspring were randomly divided into four groups: Normal, VPA, VPA + Rg1 (5 mg/kg), and VPA + Rg1 (10 mg/kg). Rg1 was administered once daily for 28 days. Behavioral assessments included grooming, rearing, locomotor activity, social interaction, novel object recognition, open field, and marble-burying tests. Molecular assays measured Sirt2/Foxo1 expression, inflammatory cytokines, oxidative stress markers in the hippocampus and prefrontal cortex. Nissl staining was performed to evaluate neuronal integrity in the prefrontal cortex and hippocampus. Rg1 administration significantly ameliorated core autism-like behaviors in VPA-exposed mice, including deficits in social interaction, recognition memory, and anxiety- and compulsive-like behaviors, as well as excessive grooming and marble-burying. VPA reduced Sirt2/Foxo1 expression, increased levels of interleukin (IL)-1β, IL-6, tumor necrosis factor-α (TNF-α), and malondialdehyde (MDA), and decreased superoxide dismutase (SOD) activity in both brain regions. Rg1 treatment reversed these alterations in a dose-responsive manner, with the 10 mg/kg dose yielding more pronounced behavioral and molecular improvements than the 5 mg/kg dose. Nissl staining revealed significant neuronal loss in VPA-exposed mice, which was partially restored by Rg1 treatment. These findings suggest that Rg1 alleviates VPA-induced behavioral and neuropathological abnormalities, potentially via Sirt2/Foxo1-mediated regulation of neuroinflammation and oxidative stress, and may represent a promising therapeutic strategy for autism spectrum disorder.","PeriodicalId":94244,"journal":{"name":"The Kaohsiung journal of medical sciences","volume":" ","pages":"e70078"},"PeriodicalIF":0.0,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144586031","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Rhaponitin Reverses Cisplatin Resistance and Impairs Cancer Stemness Through HIF-1α/MCT4/Wnt Pathway in Tongue Squamous Cell Carcinoma. Rhaponitin通过HIF-1α/MCT4/Wnt通路逆转舌鳞状细胞癌顺铂耐药并损害癌干性

The Kaohsiung journal of medical sciences Pub Date : 2025-07-03 DOI: 10.1002/kjm2.70069

Yuan Wu, Xiao-Wen Wan, Lin Jiang, Wei Wang, Jia-Jun Zhu, Yi-Sen Shao

{"title":"Rhaponitin Reverses Cisplatin Resistance and Impairs Cancer Stemness Through HIF-1α/MCT4/Wnt Pathway in Tongue Squamous Cell Carcinoma.","authors":"Yuan Wu, Xiao-Wen Wan, Lin Jiang, Wei Wang, Jia-Jun Zhu, Yi-Sen Shao","doi":"10.1002/kjm2.70069","DOIUrl":"https://doi.org/10.1002/kjm2.70069","url":null,"abstract":"Rhaponitin (Rha) possesses anti-tumor activity and mediates the transcriptional activity of hypoxia-inducible factor (HIF)-1α that affects cisplatin (Cis) resistance. However, whether Rha can lessen Cis resistance in tongue squamous cell carcinoma (TSCC) by mediating HIF-1α activity is unclear. Cis-resistant SCC9 (SCC9-CisR) cells were treated with Cis, Rha, or Cis plus Rha to explore the effect of Rha on Cis resistance using a cell counting kit-8, flow cytometry, and tumor sphere formation assays. Stemness markers CD44 and SOX2 and HIF-1α mRNA levels were detected by quantitative PCR. The GSE115119 database and plugin iRegulon were employed to select target genes mediated by HIF-1α. Protein levels of HIF-1α, monocarboxylate transporter 4 (MCT4), and the Wnt/β-catenin pathway were measured by western blot. Subcutaneous xenograft models were constructed to explore the efficacy of Rha in combating Cis resistance. Rha repressed the growth and stemness of SCC9-CisR cells in vitro and in vivo. HIF-1α protein levels were markedly elevated in SCC9-CisR cells, yet Rha treatment attenuated the transcriptional activity of HIF-1α but not HIF-1α mRNA levels. Rha plus Cis repressed the viability and stemness of SCC9-CisR cells, but not HIF-1α-knockdown SCC9-CisR cells, compared with Cis alone. Rha-induced stemness inhibition and apoptosis in SCC9-CisR cells were overridden after HIF-1α overexpression. Rha inhibited the Wnt/β-catenin signaling by regulating the HIF-1α/MCT4 axis. In conclusion, Rha reduced cell stemness and enhanced Cis sensitivity in TSCC, which was achieved possibly via suppressing the Wnt/β-catenin signaling through mediation of the HIF-1α/MCT4 axis.","PeriodicalId":94244,"journal":{"name":"The Kaohsiung journal of medical sciences","volume":" ","pages":"e70069"},"PeriodicalIF":0.0,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144562452","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0