Subsequently to the publication of the above paper, an interested reader drew to the authors' attention that, for the cell migration and invasion assay experiments shown in Fig. 2 on p. 6322, the 'HeLa/miR‑378 inhibitor' panels in Fig. 2B and C appeared to contain overlapping sections of data, such that these data panels were apparently derived from the same original source to show the results of purportedly different experiments. The authors have re‑examined their original data, and realize that Fig. 2C was inadvertently assembled incorrectly. The revised version of Fig. 2, now containing the correct data for the 'HeLa/miR‑378 inhibitor' experiment in Fig. 2C, is shown on the next page. Note that this error did not adversely affect either the results or the overall conclusions reported in this study. All the authors agree with the publication of this corrigendum, and are grateful to the Editor of Molecular Medicine Reports for allowing them the opportunity to publish this. They also wish to apologize to the readership of the Journal for any inconvenience caused. [Molecular Medicine Reports 17: 6319‑6326, 2018; DOI: 10.3892/mmr.2018.8645].
{"title":"[Corrigendum] MicroRNA‑378 enhances migration and invasion in cervical cancer by directly targeting autophagy‑related protein 12.","authors":"Dongmei Tan, Chao Zhou, Sai Han, Xuetao Hou, Shufang Kang, Youzhong Zhang","doi":"10.3892/mmr.2024.13366","DOIUrl":"https://doi.org/10.3892/mmr.2024.13366","url":null,"abstract":"<p><p>Subsequently to the publication of the above paper, an interested reader drew to the authors' attention that, for the cell migration and invasion assay experiments shown in Fig. 2 on p. 6322, the 'HeLa/miR‑378 inhibitor' panels in Fig. 2B and C appeared to contain overlapping sections of data, such that these data panels were apparently derived from the same original source to show the results of purportedly different experiments. The authors have re‑examined their original data, and realize that Fig. 2C was inadvertently assembled incorrectly. The revised version of Fig. 2, now containing the correct data for the 'HeLa/miR‑378 inhibitor' experiment in Fig. 2C, is shown on the next page. Note that this error did not adversely affect either the results or the overall conclusions reported in this study. All the authors agree with the publication of this corrigendum, and are grateful to the Editor of <i>Molecular Medicine Reports</i> for allowing them the opportunity to publish this. They also wish to apologize to the readership of the Journal for any inconvenience caused. [Molecular Medicine Reports 17: 6319‑6326, 2018; DOI: 10.3892/mmr.2018.8645].</p>","PeriodicalId":18818,"journal":{"name":"Molecular medicine reports","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470269","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Diabetic wounds represent a significant complication of diabetes and present a substantial challenge to global public health. Macrophages are crucial effector cells that play a pivotal role in the pathogenesis of diabetic wounds, through their polarization into distinct functional phenotypes. The field of epigenetics has emerged as a rapidly advancing research area, as this phenomenon has the potential to markedly affect gene expression, cellular differentiation, tissue development and susceptibility to disease. Understanding epigenetic mechanisms is crucial to further exploring disease pathogenesis. A growing body of scientific evidence has highlighted the pivotal role of epigenetics in the regulation of macrophage phenotypes. Various epigenetic mechanisms, such as DNA methylation, histone modification and non‑coding RNAs, are involved in the modulation of macrophage phenotype differentiation in response to the various environmental stimuli present in diabetic wounds. The present review provided an overview of the various changes that take place in macrophage phenotypes and functions within diabetic wounds and discussed the emerging role of epigenetic modifications in terms of regulating macrophage plasticity in diabetic wounds. It is hoped that this synthesis of information will facilitate the elucidation of diabetic wound pathogenesis and the identification of potential therapeutic targets.
糖尿病伤口是糖尿病的一个重要并发症,对全球公共卫生构成巨大挑战。巨噬细胞是重要的效应细胞,它们通过极化形成不同的功能表型,在糖尿病伤口的发病机制中发挥着关键作用。表观遗传学领域已成为一个快速发展的研究领域,因为这种现象有可能显著影响基因表达、细胞分化、组织发育和对疾病的易感性。了解表观遗传学机制对于进一步探索疾病的发病机理至关重要。越来越多的科学证据凸显了表观遗传学在调控巨噬细胞表型中的关键作用。各种表观遗传学机制,如 DNA 甲基化、组蛋白修饰和非编码 RNA,都参与了巨噬细胞表型分化的调控,以应对糖尿病伤口中存在的各种环境刺激。本综述概述了糖尿病伤口中巨噬细胞表型和功能发生的各种变化,并讨论了表观遗传修饰在调节糖尿病伤口中巨噬细胞可塑性方面的新作用。希望这些信息的综述将有助于阐明糖尿病伤口的发病机制和确定潜在的治疗靶点。
{"title":"Epigenetic regulatory mechanism of macrophage polarization in diabetic wound healing (Review).","authors":"Jielin Song, Yuqing Wu, Yunli Chen, Xu Sun, Zhaohui Zhang","doi":"10.3892/mmr.2024.13367","DOIUrl":"https://doi.org/10.3892/mmr.2024.13367","url":null,"abstract":"<p><p>Diabetic wounds represent a significant complication of diabetes and present a substantial challenge to global public health. Macrophages are crucial effector cells that play a pivotal role in the pathogenesis of diabetic wounds, through their polarization into distinct functional phenotypes. The field of epigenetics has emerged as a rapidly advancing research area, as this phenomenon has the potential to markedly affect gene expression, cellular differentiation, tissue development and susceptibility to disease. Understanding epigenetic mechanisms is crucial to further exploring disease pathogenesis. A growing body of scientific evidence has highlighted the pivotal role of epigenetics in the regulation of macrophage phenotypes. Various epigenetic mechanisms, such as DNA methylation, histone modification and non‑coding RNAs, are involved in the modulation of macrophage phenotype differentiation in response to the various environmental stimuli present in diabetic wounds. The present review provided an overview of the various changes that take place in macrophage phenotypes and functions within diabetic wounds and discussed the emerging role of epigenetic modifications in terms of regulating macrophage plasticity in diabetic wounds. It is hoped that this synthesis of information will facilitate the elucidation of diabetic wound pathogenesis and the identification of potential therapeutic targets.</p>","PeriodicalId":18818,"journal":{"name":"Molecular medicine reports","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470271","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The nuclear receptor subfamily 4 group A member 1 (NR4A1) gene plays a crucial role in both osteoporosis and adipogenesis. The present study investigated the mechanisms by which NR4A1 influences osteoblastogenesis and adipogenesis in human bone marrow‑derived mesenchymal stem cells (BMD‑MSCs). NR4A1 was overexpressed or knocked down in mouse MC3T3‑E1 osteoblast cells and 3T3‑L1 adipocyte cells, as well as in PCS‑500‑012, a BMD‑MSC line. The alkaline phosphatase (ALP) assay and Alizarin Red S staining were performed using MC3T3‑E1 and BMD‑MSCs to assess ALP activity and mineralization, while Oil Red O staining was used to assess the lipid content in 3T3‑L1 cells and BMD‑MSCs. Total RNA was isolated from control, NR4A1‑overexpressing and NR4A1 small interfering RNA (siRNA; siNR4A1)‑treated BMD‑MSCs. RNA sequencing (RNA‑seq) was performed to identify differentially expressed genes, followed by ingenuity pathway analysis (IPA) to determine the role of NR4A1 in osteoblastogenesis and adipogenesis. NR4A1 or Nr4a1 knockdown tended to increase ALP activity and significantly increased calcification in BMD‑MSCs (P<0.005) and MC3T3‑E1 cells (P<0.005), respectively. By contrast, NR4A1 or Nr4a1 overexpression significantly decreased ALP activity and calcification. NR4A1 or Nr4a1 knockdown and overexpression significantly decreased and increased adipogenesis, respectively, in BMD‑MSCs (P<0.005 and <0.05, respectively) and 3T3‑L1 cells (P<0.005 in both). Treatments of BMD‑MSCs with an NR4A1 antagonist, 1,1‑bis(3'‑indolyl)‑1‑(p‑hydroxyphenyl) methane and siNR4A1 showed similar results. RNA‑seq and IPA in control, NR4A1 knockdown and NR4A1 overexpressing cells indicated that Notch signaling mediated the effects of NR4A1 in osteoblastogenesis and adipogenesis. Expression of mastermind‑like transcriptional coactivator 3 was reduced in the Notch signaling pathway in cells treated with siNR4A1. In conclusion, NR4A1 suppressed osteoblastogenesis and promotes adipogenesis in human BMD‑MSCs. The present study also suggested that NR4A1 plays a role in the progression of osteoporosis and adipogenesis by modulating the Notch signaling cascade.
核受体 4 亚家族 A 组 1(NR4A1)基因在骨质疏松症和脂肪生成中都起着至关重要的作用。本研究探讨了NR4A1影响人骨髓间充质干细胞(BMD-MSCs)成骨和成脂的机制。研究人员在小鼠 MC3T3-E1 成骨细胞、3T3-L1 脂肪细胞以及 BMD 间充质干细胞 PCS-500-012 株系中过表达或敲除了 NR4A1。利用碱性磷酸酶(ALP)测定和茜素红 S 染色法对 MC3T3-E1 和 BMD-MSCs 进行了检测,以评估 ALP 活性和矿化度;而油红 O 染色法则用于评估 3T3-L1 细胞和 BMD-MSCs 中的脂质含量。从对照组、NR4A1缺失组和NR4A1小干扰RNA(siRNA;siNR4A1)处理的BMD-间充质干细胞中分离总RNA。进行了 RNA 测序(RNA-seq)以确定差异表达基因,然后进行了巧妙通路分析(IPA)以确定 NR4A1 在成骨细胞生成和脂肪生成中的作用。NR4A1或Nr4a1敲除会增加ALP活性,并显著增加BMD-间充质干细胞的钙化(PNR4A1或Nr4a1过表达会显著降低ALP活性和钙化)。NR4A1或Nr4a1的敲除和过表达分别明显降低和增加了BMD-间充质干细胞的脂肪生成(PsiNR4A1显示了类似的结果)。对照组、NR4A1敲除和NR4A1过表达细胞的RNA-seq和IPA表明,Notch信号介导了NR4A1在成骨细胞生成和脂肪生成中的作用。siNR4A1 处理的细胞中,Notch 信号通路中的类主控转录辅激活子 3 的表达减少。总之,NR4A1抑制了人BMD-间充质干细胞的成骨细胞生成,促进了其脂肪生成。本研究还表明,NR4A1 通过调节 Notch 信号级联在骨质疏松症和脂肪生成过程中发挥作用。
{"title":"Orphan nuclear receptor NR4A1 regulates both osteoblastogenesis and adipogenesis in human mesenchymal stem cells.","authors":"Yilan Jin, Youngho Son, Insun Song, Yoon-Sok Chung, Yong Jun Choi","doi":"10.3892/mmr.2024.13368","DOIUrl":"https://doi.org/10.3892/mmr.2024.13368","url":null,"abstract":"<p><p>The nuclear receptor subfamily 4 group A member 1 (<i>NR4A1</i>) gene plays a crucial role in both osteoporosis and adipogenesis. The present study investigated the mechanisms by which NR4A1 influences osteoblastogenesis and adipogenesis in human bone marrow‑derived mesenchymal stem cells (BMD‑MSCs). <i>NR4A1</i> was overexpressed or knocked down in mouse MC3T3‑E1 osteoblast cells and 3T3‑L1 adipocyte cells, as well as in PCS‑500‑012, a BMD‑MSC line. The alkaline phosphatase (ALP) assay and Alizarin Red S staining were performed using MC3T3‑E1 and BMD‑MSCs to assess ALP activity and mineralization, while Oil Red O staining was used to assess the lipid content in 3T3‑L1 cells and BMD‑MSCs. Total RNA was isolated from control, <i>NR4A1</i>‑overexpressing and <i>NR4A1</i> small interfering RNA (siRNA; <i>siNR4A1</i>)‑treated BMD‑MSCs. RNA sequencing (RNA‑seq) was performed to identify differentially expressed genes, followed by ingenuity pathway analysis (IPA) to determine the role of <i>NR4A1</i> in osteoblastogenesis and adipogenesis. <i>NR4A1</i> or <i>Nr4a1</i> knockdown tended to increase ALP activity and significantly increased calcification in BMD‑MSCs (P<0.005) and MC3T3‑E1 cells (P<0.005), respectively. By contrast, <i>NR4A1</i> or <i>Nr4a1</i> overexpression significantly decreased ALP activity and calcification. <i>NR4A1</i> or <i>Nr4a1</i> knockdown and overexpression significantly decreased and increased adipogenesis, respectively, in BMD‑MSCs (P<0.005 and <0.05, respectively) and 3T3‑L1 cells (P<0.005 in both). Treatments of BMD‑MSCs with an NR4A1 antagonist, 1,1‑bis(3'‑indolyl)‑1‑(p‑hydroxyphenyl) methane and <i>siNR4A1</i> showed similar results. RNA‑seq and IPA in control, <i>NR4A1</i> knockdown and <i>NR4A1</i> overexpressing cells indicated that Notch signaling mediated the effects of <i>NR4A1</i> in osteoblastogenesis and adipogenesis. Expression of mastermind‑like transcriptional coactivator 3 was reduced in the Notch signaling pathway in cells treated with <i>siNR4A1</i>. In conclusion, <i>NR4A1</i> suppressed osteoblastogenesis and promotes adipogenesis in human BMD‑MSCs. The present study also suggested that <i>NR4A1</i> plays a role in the progression of osteoporosis and adipogenesis by modulating the Notch signaling cascade.</p>","PeriodicalId":18818,"journal":{"name":"Molecular medicine reports","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470272","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-01Epub Date: 2024-10-18DOI: 10.3892/mmr.2024.13369
Pan Cai, Shichang Yan, Yan Lu, Xiaoxiao Zhou, Xiuhui Wang, Minghui Wang, Zhifeng Yin
Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that one of the data panels in Fig. 3A on p. 6, showing how carnosol inhibits RANKL-induced osteoclastogenesis in the early stage of differentiation, was strikingly similar to data that had already been submitted for publication in another article in the journal Annals of Translational Medicine written by different authors at different research institutes. Owing to the fact that the contentious data in the above article had already been submitted for publication prior to its submission to Molecular Medicine Reports, the Editor has decided that this paper should be retracted from the Journal. After having been in contact with the authors, they accepted the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused. [26: 225, 2022; DOI: 10.3892/mmr.2022.12741].
{"title":"[Retracted] Carnosol inhibits osteoclastogenesis <i>in vivo</i> and <i>in vitro</i> by blocking the RANKL‑induced NF‑κB signaling pathway.","authors":"Pan Cai, Shichang Yan, Yan Lu, Xiaoxiao Zhou, Xiuhui Wang, Minghui Wang, Zhifeng Yin","doi":"10.3892/mmr.2024.13369","DOIUrl":"https://doi.org/10.3892/mmr.2024.13369","url":null,"abstract":"<p><p>Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that one of the data panels in Fig. 3A on p. 6, showing how carnosol inhibits RANKL-induced osteoclastogenesis in the early stage of differentiation, was strikingly similar to data that had already been submitted for publication in another article in the journal <i>Annals of Translational Medicine</i> written by different authors at different research institutes. Owing to the fact that the contentious data in the above article had already been submitted for publication prior to its submission to <i>Molecular Medicine Reports</i>, the Editor has decided that this paper should be retracted from the Journal. After having been in contact with the authors, they accepted the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused. [26: 225, 2022; DOI: 10.3892/mmr.2022.12741].</p>","PeriodicalId":18818,"journal":{"name":"Molecular medicine reports","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01Epub Date: 2024-10-04DOI: 10.3892/mmr.2024.13347
Xiaolei Zhang, Shizhen Wang, Yongting Qin, Hang Guo
The present study aimed to investigate the role of microRNA (miR)‑221‑3p in endothelial progenitor cells (EPCs) treated with lipoprotein(a) [LP(a)]. EPCs were identified using immunofluorescence assays and miR‑221‑3p levels were measured using reverse transcription‑quantitative PCR. EPC migration was detected using Transwell assays, proliferation was measured by staining with 5‑ethynyl‑2'‑deoxyuridine and adhesion was assessed by microscopy. Flow cytometry was used to measure apoptosis and protein expression was detected using western blotting. A dual‑luciferase reporter assay was used to confirm the target interactions. The proliferation, migration, adhesion and angiogenesis of EPCs were decreased, and apoptosis was increased after treatment with LP(a). These effects were weakened by transfection with miR‑221‑3p inhibitor. The negative effects of LP(a) on EPCs were also weakened by overexpression of silent information regulator 1 (SIRT1). Inhibition of the RAF/MEK/ERK signaling pathway blocked the effects of SIRT1 overexpression. In conclusion, miR‑221‑3p inhibitor transfection activated the RAF/MEK/ERK signaling pathway through SIRT1, promoted the proliferation, migration, adhesion and angiogenesis of EPCs, and reduced apoptosis.
{"title":"Downregulation of microRNA‑221‑3p promotes angiogenesis of lipoprotein(a)‑injured endothelial progenitor cells by targeting silent information regulator 1 to activate the RAF/MEK/ERK signaling pathway.","authors":"Xiaolei Zhang, Shizhen Wang, Yongting Qin, Hang Guo","doi":"10.3892/mmr.2024.13347","DOIUrl":"10.3892/mmr.2024.13347","url":null,"abstract":"<p><p>The present study aimed to investigate the role of microRNA (miR)‑221‑3p in endothelial progenitor cells (EPCs) treated with lipoprotein(a) [LP(a)]. EPCs were identified using immunofluorescence assays and miR‑221‑3p levels were measured using reverse transcription‑quantitative PCR. EPC migration was detected using Transwell assays, proliferation was measured by staining with 5‑ethynyl‑2'‑deoxyuridine and adhesion was assessed by microscopy. Flow cytometry was used to measure apoptosis and protein expression was detected using western blotting. A dual‑luciferase reporter assay was used to confirm the target interactions. The proliferation, migration, adhesion and angiogenesis of EPCs were decreased, and apoptosis was increased after treatment with LP(a). These effects were weakened by transfection with miR‑221‑3p inhibitor. The negative effects of LP(a) on EPCs were also weakened by overexpression of silent information regulator 1 (SIRT1). Inhibition of the RAF/MEK/ERK signaling pathway blocked the effects of SIRT1 overexpression. In conclusion, miR‑221‑3p inhibitor transfection activated the RAF/MEK/ERK signaling pathway through SIRT1, promoted the proliferation, migration, adhesion and angiogenesis of EPCs, and reduced apoptosis.</p>","PeriodicalId":18818,"journal":{"name":"Molecular medicine reports","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11462396/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142372279","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01Epub Date: 2024-09-27DOI: 10.3892/mmr.2024.13339
Quanjun Niu, Junhang Hao, Zhen Li, Huiping Zhang
Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease whose etiology is not fully understood. Defective peripheral immune tolerance and subsequent mis‑differentiation and aberrant infiltration of synovium by various immune cells, especially helper T (Th) cells, play an important role in the development of RA. There are significant sex differences in RA, but the results of studies on the effects of sex hormones on RA have been difficult to standardize and hormone replacement therapy has been limited by the potential for serious side effects. Existing research has amply demonstrated that cellular immune responses are largely determined by sex and that sex hormones play a key role in Th cell responses. Based on the aforementioned background and the plasticity of Th cells, it is reasonable to hypothesize that the action of sex hormones on Th cells will hopefully become a therapeutic target for RA. The present review discussed the role of various Th cell subsets in the pathogenesis of RA and also explored the role of sex hormones on the phenotype and function of these aberrantly regulated immune cells in RA as well as other pathologic effects on RA.
类风湿性关节炎(RA)是一种慢性自身免疫性炎症,其病因尚未完全明了。外周免疫耐受性缺陷以及随后的各种免疫细胞,尤其是辅助性 T 细胞(Th)的错误分化和异常浸润滑膜在 RA 的发病中起着重要作用。RA 存在明显的性别差异,但有关性激素对 RA 影响的研究结果难以标准化,激素替代疗法也因可能产生严重副作用而受到限制。现有研究充分证明,细胞免疫反应在很大程度上取决于性别,而性激素在Th细胞反应中起着关键作用。基于上述背景和Th细胞的可塑性,我们有理由假设性激素对Th细胞的作用有望成为RA的治疗靶点。本综述讨论了各种 Th 细胞亚群在 RA 发病机制中的作用,还探讨了性激素对 RA 中这些异常调控的免疫细胞的表型和功能的作用,以及对 RA 的其他病理影响。
{"title":"Helper T cells: A potential target for sex hormones to ameliorate rheumatoid arthritis? (Review).","authors":"Quanjun Niu, Junhang Hao, Zhen Li, Huiping Zhang","doi":"10.3892/mmr.2024.13339","DOIUrl":"10.3892/mmr.2024.13339","url":null,"abstract":"<p><p>Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease whose etiology is not fully understood. Defective peripheral immune tolerance and subsequent mis‑differentiation and aberrant infiltration of synovium by various immune cells, especially helper T (Th) cells, play an important role in the development of RA. There are significant sex differences in RA, but the results of studies on the effects of sex hormones on RA have been difficult to standardize and hormone replacement therapy has been limited by the potential for serious side effects. Existing research has amply demonstrated that cellular immune responses are largely determined by sex and that sex hormones play a key role in Th cell responses. Based on the aforementioned background and the plasticity of Th cells, it is reasonable to hypothesize that the action of sex hormones on Th cells will hopefully become a therapeutic target for RA. The present review discussed the role of various Th cell subsets in the pathogenesis of RA and also explored the role of sex hormones on the phenotype and function of these aberrantly regulated immune cells in RA as well as other pathologic effects on RA.</p>","PeriodicalId":18818,"journal":{"name":"Molecular medicine reports","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11450432/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142381281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01Epub Date: 2024-09-27DOI: 10.3892/mmr.2024.13335
Kebin Huang, Bingwei Dong, Yueyue Wang, Tao Tian, Biying Zhang
Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that certain of the flow cytometric analysis data shown in Fig. 4B on p. 7834 were strikingly similar to data that had already been submitted for publication in different form in another article written by different authors at different research institutes. Owing to the fact that the contentious data in the above article had already been submitted for publication prior to its submission to Molecular Medicine Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 12: 7830‑7836, 2015; DOI: 10.3892/mmr.2015.4455].
{"title":"[Retracted] MicroRNA‑519 enhances HL60 human acute myeloid leukemia cell line proliferation by reducing the expression level of RNA‑binding protein human antigen R.","authors":"Kebin Huang, Bingwei Dong, Yueyue Wang, Tao Tian, Biying Zhang","doi":"10.3892/mmr.2024.13335","DOIUrl":"10.3892/mmr.2024.13335","url":null,"abstract":"<p><p>Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that certain of the flow cytometric analysis data shown in Fig. 4B on p. 7834 were strikingly similar to data that had already been submitted for publication in different form in another article written by different authors at different research institutes. Owing to the fact that the contentious data in the above article had already been submitted for publication prior to its submission to <i>Molecular Medicine Reports</i>, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 12: 7830‑7836, 2015; DOI: 10.3892/mmr.2015.4455].</p>","PeriodicalId":18818,"journal":{"name":"Molecular medicine reports","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11443597/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142350368","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01Epub Date: 2024-10-18DOI: 10.3892/mmr.2024.13361
Lan Li, Xiao-Ying Mang, Ke-Wei Jiang, Ying Zhao, Yu-Rong Chen
The present study aimed to investigate the effect of swimming training on the angiogenesis of endothelial progenitor cells (EPCs) in type 2 diabetes mellitus (T2DM) rats by upregulating the insulin‑like growth factor 1 (IGF1) expression and to reveal its potential mechanism of action. Male Sprague‑Dawley rats were divided into the Control, Model, Model train, Model train + short interfering (si)‑NC and Model train + si‑IGF1 groups. Serum glucose levels were measured using the oral glucose tolerance test. EPCs were isolated from the bone marrow cavity and identified through morphological observation and immunofluorescence staining. The expression of IGF‑1 mRNA in rat serum and EPCs was analyzed by reverse transcription‑quantitative PCR. The fasting insulin levels in serum were assessed by ELISA. Cell Counting Kit‑8, scratch assay and tube formation assay were used to determine the cell viability, migration and tube formation of rat EPCs, and western blotting was employed to measure the expression levels of IGF1, phosphoinositide 3‑kinase (PI3K), phosphorylated‑PI3K, protein kinase B (AKT) and phosphorylated‑AKT. The present study demonstrated that swimming training significantly decreased the glucose levels and homeostatic model assessment of insulin resistance scores, but increased the fasting insulin levels and IGF1 mRNA expression. Microscopic observation and immunofluorescence identification suggested that EPCs were successfully isolated. In addition, swimming training markedly elevated the levels of IGF1 and promoted cell viability, migration and tube formation in rat EPCs. Furthermore, IGF1 knockdown experiments indicated that swimming training might play a regulatory role by elevating the IGF1 expression to activate the PI3K/AKT pathway. Overall, swimming training promoted the angiogenesis of EPCs in T2DM rats and its potential mechanism may be related to the upregulation of IGF1 expression and the activation of the PI3K/AKT pathway.
{"title":"Swimming training promotes angiogenesis of endothelial progenitor cells by upregulating IGF1 expression and activating the PI3K/AKT pathway in type 2 diabetic rats.","authors":"Lan Li, Xiao-Ying Mang, Ke-Wei Jiang, Ying Zhao, Yu-Rong Chen","doi":"10.3892/mmr.2024.13361","DOIUrl":"https://doi.org/10.3892/mmr.2024.13361","url":null,"abstract":"<p><p>The present study aimed to investigate the effect of swimming training on the angiogenesis of endothelial progenitor cells (EPCs) in type 2 diabetes mellitus (T2DM) rats by upregulating the insulin‑like growth factor 1 (IGF1) expression and to reveal its potential mechanism of action. Male Sprague‑Dawley rats were divided into the Control, Model, Model train, Model train + short interfering (si)‑NC and Model train + si‑IGF1 groups. Serum glucose levels were measured using the oral glucose tolerance test. EPCs were isolated from the bone marrow cavity and identified through morphological observation and immunofluorescence staining. The expression of IGF‑1 mRNA in rat serum and EPCs was analyzed by reverse transcription‑quantitative PCR. The fasting insulin levels in serum were assessed by ELISA. Cell Counting Kit‑8, scratch assay and tube formation assay were used to determine the cell viability, migration and tube formation of rat EPCs, and western blotting was employed to measure the expression levels of IGF1, phosphoinositide 3‑kinase (PI3K), phosphorylated‑PI3K, protein kinase B (AKT) and phosphorylated‑AKT. The present study demonstrated that swimming training significantly decreased the glucose levels and homeostatic model assessment of insulin resistance scores, but increased the fasting insulin levels and IGF1 mRNA expression. Microscopic observation and immunofluorescence identification suggested that EPCs were successfully isolated. In addition, swimming training markedly elevated the levels of IGF1 and promoted cell viability, migration and tube formation in rat EPCs. Furthermore, IGF1 knockdown experiments indicated that swimming training might play a regulatory role by elevating the IGF1 expression to activate the PI3K/AKT pathway. Overall, swimming training promoted the angiogenesis of EPCs in T2DM rats and its potential mechanism may be related to the upregulation of IGF1 expression and the activation of the PI3K/AKT pathway.</p>","PeriodicalId":18818,"journal":{"name":"Molecular medicine reports","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470268","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01Epub Date: 2024-10-18DOI: 10.3892/mmr.2024.13363
Huixiang Wang, Xiaoli Zhao, Chengxiang Ni, Yuyang Dai, Yan Guo
Following the publication of this article, a concerned reader drew to the Editor's attention that the experimental design of the western blot assay experiments portrayed in Fig. 5A on p. 7804, and the overall organization of this figure, may have been flawed, as mitochondrial and cytosolic proteins were featured in the figure with only one set of supporting control western blot data; in this scenario, the proteins would necessarily have needed to have been obtained from two separate cell samples in different experiments, and blotted on to separate gels. Moreover, there was also a concern that certain of the gels featured possible breaks in their continuity/splicing events, such that the protein bands in the figure were not shown consecutively, as they would have appeared, in the affected slices. After having conducted an internal investigation, the Editor of Molecular Medicine Reports agrees with the reader that there were anomalies associated with the presentation of Fig. 5. Therefore, on the grounds of a lack of confidence in the presented data, the Editor has decided that the article should be retracted from the publication. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused, and we also thank the reader for bringing this matter to our attention. [Molecular Medicine Reports 17: 7797‑7806, 2018; DOI: 10.3892/mmr.2018.8823].
这篇文章发表后,一位读者提请编辑注意,第 7804 页图 5A 中描绘的 Western 印迹分析实验的实验设计以及该图的整体组织可能存在缺陷,因为图中线粒体和细胞膜蛋白质仅有一组支持对照的 Western 印迹数据;在这种情况下,蛋白质必然需要在不同的实验中从两个不同的细胞样本中获得,并在不同的凝胶上印迹。此外,还有人担心某些凝胶的连续性/拼接事件可能会出现断裂,因此图中的蛋白质条带并不是连续显示的,因为它们本来就会出现在受影响的切片中。经过内部调查,《分子医学报告》编辑同意读者的观点,即图 5 的显示存在异常。因此,由于对所提供的数据缺乏信心,编辑决定将该文章撤稿。作者被要求解释这些问题,但编辑部没有收到回复。对于给读者带来的不便,编辑深表歉意,我们也感谢读者将此事告知我们。[Molecular Medicine Reports 17: 7797-7806, 2018; DOI: 10.3892/mmr.2018.8823]。
{"title":"[Retracted] Zearalenone regulates endometrial stromal cell apoptosis and migration via the promotion of mitochondrial fission by activation of the JNK/Drp1 pathway.","authors":"Huixiang Wang, Xiaoli Zhao, Chengxiang Ni, Yuyang Dai, Yan Guo","doi":"10.3892/mmr.2024.13363","DOIUrl":"https://doi.org/10.3892/mmr.2024.13363","url":null,"abstract":"<p><p>Following the publication of this article, a concerned reader drew to the Editor's attention that the experimental design of the western blot assay experiments portrayed in Fig. 5A on p. 7804, and the overall organization of this figure, may have been flawed, as mitochondrial and cytosolic proteins were featured in the figure with only one set of supporting control western blot data; in this scenario, the proteins would necessarily have needed to have been obtained from two separate cell samples in different experiments, and blotted on to separate gels. Moreover, there was also a concern that certain of the gels featured possible breaks in their continuity/splicing events, such that the protein bands in the figure were not shown consecutively, as they would have appeared, in the affected slices. After having conducted an internal investigation, the Editor of <i>Molecular Medicine Reports</i> agrees with the reader that there were anomalies associated with the presentation of Fig. 5. Therefore, on the grounds of a lack of confidence in the presented data, the Editor has decided that the article should be retracted from the publication. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused, and we also thank the reader for bringing this matter to our attention. [Molecular Medicine Reports 17: 7797‑7806, 2018; DOI: 10.3892/mmr.2018.8823].</p>","PeriodicalId":18818,"journal":{"name":"Molecular medicine reports","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01Epub Date: 2024-10-11DOI: 10.3892/mmr.2024.13352
Ingridy Izabella Vieira Cardoso, Marcela Nunes Rosa, Daniel Antunes Moreno, Letícia Maria Barbosa Tufi, Lorrayne Pereira Ramos, Larissa Alessandra Bourdeth Pereira, Lenilson Silva, Janaina Mello Soares Galvão, Isabela Cristiane Tosi, André Van Helvoort Lengert, Marcelo Cavalcanti Da Cruz, Silvia Aparecida Teixeira, Rui Manuel Reis, Luiz Fernando Lopes, Mariana Tomazini Pinto
Germ cell tumors (GCTs) constitute diverse neoplasms arising in the gonads or extragonadal locations. Testicular GCTs (TGCTs) are the predominant solid tumors in adolescents and young men. Despite cisplatin serving as the primary therapeutic intervention for TGCTs, 10‑20% of patients with advanced disease demonstrate resistance to cisplatin‑based chemotherapy, and epithelial‑mesenchymal transition (EMT) is a potential contributor to this resistance. EMT is regulated by various factors, including the snail family transcriptional repressor 2 (SLUG) transcriptional factor, and, to the best of our knowledge, remains unexplored within TGCTs. Therefore, the present study investigated the EMT transcription factor SLUG in TGCTs. In silico analyses were performed to investigate the expression of EMT markers in TGCTs. In addition, a cisplatin‑resistant model for TGCTs was developed using the NTERA‑2 cell line, and a mouse model was also established. Subsequently, EMT was assessed both in vitro and in vivo within the cisplatin‑resistant models using quantitative PCR and western blot analyses. The results of the in silico analysis showed that the different histologies exhibited distinct expression profiles for EMT markers. Seminomas exhibited a lower expression of EMT markers, whereas embryonal carcinomas and mixed GCT demonstrated high expression. Notably, patients with lower SLUG expression had longer median progression‑free survival (46.4 months vs. 28.0 months, P=0.022). In the in vitro analysis, EMT‑associated genes [fibronectin; vimentin (VIM); actin, α2, smooth muscle; collagen type I α1; transforming growth factor‑β1; and SLUG] were upregulated in the cisplatin‑resistant NTERA‑2 (NTERA‑2R) cell line after 72 h of cisplatin treatment. Consistent with this finding, the NTERA‑2R mouse model demonstrated a significant upregulation in the expression levels of VIM and SLUG. In conclusion, the present findings suggested that SLUG may serve a crucial role in connecting EMT with the development of cisplatin resistance, and targeting SLUG may be a putative therapeutic strategy to mitigate cisplatin resistance.
生殖细胞瘤(GCTs)是发生在性腺或性腺外部位的多种肿瘤。睾丸生殖细胞瘤(TGCT)是青少年和年轻男性最主要的实体肿瘤。尽管顺铂是TGCTs的主要治疗手段,但10-20%的晚期患者对顺铂化疗产生了耐药性,而上皮-间质转化(EMT)是导致耐药性的潜在因素。EMT受多种因素调控,包括蜗牛家族转录抑制因子2(SLUG)转录因子。因此,本研究调查了TGCTs中的EMT转录因子SLUG。研究人员进行了硅学分析,以调查TGCTs中EMT标记物的表达情况。此外,还利用 NTERA-2 细胞系建立了顺铂耐药的 TGCTs 模型,并建立了小鼠模型。随后,利用定量 PCR 和 Western 印迹分析评估了顺铂耐药模型中的体外和体内 EMT。硅学分析的结果显示,不同组织学的EMT标记物表现出不同的表达谱。精原细胞瘤的EMT标记物表达量较低,而胚胎癌和混合型GCT的表达量较高。值得注意的是,SLUG表达较低的患者中位无进展生存期更长(46.4个月对28.0个月,P=0.022)。在体外分析中,顺铂耐药的NTERA-2(NTERA-2R)细胞系在顺铂处理72小时后,EMT相关基因[纤连蛋白;波形蛋白(VIM);肌动蛋白,α2,平滑肌;胶原蛋白I型α1;转化生长因子-β1;和SLUG]上调。与这一发现相一致的是,NTERA-2R 小鼠模型也显示出 VIM 和 SLUG 表达水平的显著上调。总之,本研究结果表明,SLUG可能在EMT与顺铂耐药性的发展之间起着至关重要的作用,靶向SLUG可能是缓解顺铂耐药性的一种治疗策略。
{"title":"Cisplatin‑resistant germ cell tumor models: An exploration of the epithelial‑mesenchymal transition regulator <i>SLUG</i>.","authors":"Ingridy Izabella Vieira Cardoso, Marcela Nunes Rosa, Daniel Antunes Moreno, Letícia Maria Barbosa Tufi, Lorrayne Pereira Ramos, Larissa Alessandra Bourdeth Pereira, Lenilson Silva, Janaina Mello Soares Galvão, Isabela Cristiane Tosi, André Van Helvoort Lengert, Marcelo Cavalcanti Da Cruz, Silvia Aparecida Teixeira, Rui Manuel Reis, Luiz Fernando Lopes, Mariana Tomazini Pinto","doi":"10.3892/mmr.2024.13352","DOIUrl":"10.3892/mmr.2024.13352","url":null,"abstract":"<p><p>Germ cell tumors (GCTs) constitute diverse neoplasms arising in the gonads or extragonadal locations. Testicular GCTs (TGCTs) are the predominant solid tumors in adolescents and young men. Despite cisplatin serving as the primary therapeutic intervention for TGCTs, 10‑20% of patients with advanced disease demonstrate resistance to cisplatin‑based chemotherapy, and epithelial‑mesenchymal transition (EMT) is a potential contributor to this resistance. EMT is regulated by various factors, including the snail family transcriptional repressor 2 (<i>SLUG</i>) transcriptional factor, and, to the best of our knowledge, remains unexplored within TGCTs. Therefore, the present study investigated the EMT transcription factor <i>SLUG</i> in TGCTs. <i>In silico</i> analyses were performed to investigate the expression of EMT markers in TGCTs. In addition, a cisplatin‑resistant model for TGCTs was developed using the NTERA‑2 cell line, and a mouse model was also established. Subsequently, EMT was assessed both <i>in vitro</i> and <i>in vivo</i> within the cisplatin‑resistant models using quantitative PCR and western blot analyses. The results of the <i>in silico</i> analysis showed that the different histologies exhibited distinct expression profiles for EMT markers. Seminomas exhibited a lower expression of EMT markers, whereas embryonal carcinomas and mixed GCT demonstrated high expression. Notably, patients with lower <i>SLUG</i> expression had longer median progression‑free survival (46.4 months vs. 28.0 months, P=0.022). In the <i>in vitro</i> analysis, EMT‑associated genes [fibronectin; vimentin (<i>VIM</i>); actin, α2, smooth muscle; collagen type I α1; transforming growth factor‑β1; and <i>SLUG</i>] were upregulated in the cisplatin‑resistant NTERA‑2 (NTERA‑2R) cell line after 72 h of cisplatin treatment. Consistent with this finding, the NTERA‑2R mouse model demonstrated a significant upregulation in the expression levels of VIM and SLUG. In conclusion, the present findings suggested that <i>SLUG</i> may serve a crucial role in connecting EMT with the development of cisplatin resistance, and targeting <i>SLUG</i> may be a putative therapeutic strategy to mitigate cisplatin resistance.</p>","PeriodicalId":18818,"journal":{"name":"Molecular medicine reports","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11484538/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142400778","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}