Cellular senescence, characterized by cell cycle arrest, can result in tissue dysfunction when senescent cells persist and accumulate. Periodontitis, a chronic inflammatory condition caused by the interaction between bacteria and the immune system of the host, primarily manifests as damage to periodontal tissues. Aging and inflammation are interlinked processes that exacerbate each other. The progression of localized chronic periodontal inflammation is often accelerated in conjunction with tissue and organ aging. The presence of senescent cells and release of inflammatory cytokines, immune modulators, growth factors and proteases that are associated with the senescence‑associated secretory phenotype contribute to the deterioration of periodontal tissues. The present review aimed to elucidate the mechanisms of cellular senescence and its potential impact on periodontitis, offering novel insights for modulating the inflammatory microenvironment of periodontal tissues.
{"title":"Cellular senescence: A new perspective on the suppression of periodontitis (Review).","authors":"Xue-Jing Lin, Qing Yuan, Jie Zhou, Yu-Lei Dong, Diwas Sunchuri, Zhu-Ling Guo","doi":"10.3892/mmr.2024.13362","DOIUrl":"https://doi.org/10.3892/mmr.2024.13362","url":null,"abstract":"<p><p>Cellular senescence, characterized by cell cycle arrest, can result in tissue dysfunction when senescent cells persist and accumulate. Periodontitis, a chronic inflammatory condition caused by the interaction between bacteria and the immune system of the host, primarily manifests as damage to periodontal tissues. Aging and inflammation are interlinked processes that exacerbate each other. The progression of localized chronic periodontal inflammation is often accelerated in conjunction with tissue and organ aging. The presence of senescent cells and release of inflammatory cytokines, immune modulators, growth factors and proteases that are associated with the senescence‑associated secretory phenotype contribute to the deterioration of periodontal tissues. The present review aimed to elucidate the mechanisms of cellular senescence and its potential impact on periodontitis, offering novel insights for modulating the inflammatory microenvironment of periodontal tissues.</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":"142470263","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.2024.13351
Ting Wei, Ruichun Li, Shiwen Guo, Chen Liang
Stigmasterol is a sterol compound found in various traditional Chinese medicines; however, its effects on glioma remain unclear. The present study aimed to investigate the effects of stigmasterol on the biological behaviors of glioblastoma (GBM) cells and to explore the underlying mechanisms. In vitro experiments assessed its effects on GBM cell proliferation, apoptosis, cell cycle progression, invasion, migration and vasculogenic mimicry (VM). The potential targets for stigmasterol in treating GBM were identified using databases and Venn diagram analysis, followed by enrichment analysis using R language. A prognostic model related to the target genes of stigmasterol was developed through univariate Cox regression and least absolute shrinkage and selection operator analyses. Stigmasterol was found to suppress the proliferation of GBM cells in a dose‑ and time‑dependent manner, to induce apoptosis, and to inhibit invasion, migration and VM formation. Additionally, 31 potential targets of stigmasterol were identified, linked to lipid metabolism and the G protein‑coupled receptor signaling pathway. Lipid metabolism assays revealed that stigmasterol significantly reduced free fatty acids and total cholesterol levels. Furthermore, two prognosis‑related target genes, fatty acid binding protein 5 and α‑1B adrenergic receptor, were selected, and the prognostic model effectively predicted GBM outcomes. Moreover, molecular docking revealed strong binding affinities between stigmasterol and the target proteins. Overall, these findings suggested that stigmasterol may exert anti‑glioma effects, which could be potentially mediated through the regulation of lipid metabolism.
豆固醇是一种存在于多种中药中的甾醇化合物,但它对胶质瘤的影响尚不清楚。本研究旨在研究豆固醇对胶质母细胞瘤(GBM)细胞生物学行为的影响,并探索其潜在机制。体外实验评估了它对 GBM 细胞增殖、凋亡、细胞周期进展、侵袭、迁移和血管生成模拟(VM)的影响。利用数据库和维恩图分析确定了麦角甾醇治疗 GBM 的潜在靶点,随后使用 R 语言进行了富集分析。通过单变量考克斯回归、最小绝对缩减和选择算子分析,建立了与豆固醇靶基因相关的预后模型。研究发现,豆固醇能以剂量和时间依赖的方式抑制 GBM 细胞的增殖,诱导细胞凋亡,抑制侵袭、迁移和 VM 的形成。此外,还发现了31个豆甾醇的潜在靶点,它们与脂质代谢和G蛋白偶联受体信号通路有关。脂质代谢测定显示,豆固醇能显著降低游离脂肪酸和总胆固醇水平。此外,还筛选出了两个与预后相关的靶基因,即脂肪酸结合蛋白5和α-1B肾上腺素能受体,该预后模型可有效预测GBM的预后。此外,分子对接显示豆固醇与靶蛋白之间有很强的结合亲和力。总之,这些研究结果表明,豆固醇可能通过调节脂质代谢发挥抗胶质瘤的作用。
{"title":"Stigmasterol exerts antiglioma effects by regulating lipid metabolism.","authors":"Ting Wei, Ruichun Li, Shiwen Guo, Chen Liang","doi":"10.3892/mmr.2024.13351","DOIUrl":"10.3892/mmr.2024.13351","url":null,"abstract":"<p><p>Stigmasterol is a sterol compound found in various traditional Chinese medicines; however, its effects on glioma remain unclear. The present study aimed to investigate the effects of stigmasterol on the biological behaviors of glioblastoma (GBM) cells and to explore the underlying mechanisms. <i>In vitro</i> experiments assessed its effects on GBM cell proliferation, apoptosis, cell cycle progression, invasion, migration and vasculogenic mimicry (VM). The potential targets for stigmasterol in treating GBM were identified using databases and Venn diagram analysis, followed by enrichment analysis using R language. A prognostic model related to the target genes of stigmasterol was developed through univariate Cox regression and least absolute shrinkage and selection operator analyses. Stigmasterol was found to suppress the proliferation of GBM cells in a dose‑ and time‑dependent manner, to induce apoptosis, and to inhibit invasion, migration and VM formation. Additionally, 31 potential targets of stigmasterol were identified, linked to lipid metabolism and the G protein‑coupled receptor signaling pathway. Lipid metabolism assays revealed that stigmasterol significantly reduced free fatty acids and total cholesterol levels. Furthermore, two prognosis‑related target genes, fatty acid binding protein 5 and α‑1B adrenergic receptor, were selected, and the prognostic model effectively predicted GBM outcomes. Moreover, molecular docking revealed strong binding affinities between stigmasterol and the target proteins. Overall, these findings suggested that stigmasterol may exert anti‑glioma effects, which could be potentially mediated through the regulation of lipid metabolism.</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/PMC11484536/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142372283","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: 2024-10-04DOI: 10.3892/mmr.2024.13345
Yaqi Li, Yixuan Chen, Peng Yu, Deju Zhang, Xiaoyi Tang, Zicheng Zhu, Fan Xiao, Wei Deng, Yang Liu, Zhaoying Tan, Jing Zhang, Shuchun Yu
The present study aimed to investigate the role of PI3K‑mediated ferroptosis signaling induced by mild therapeutic hypothermia (MTH), which was defined as a temperature of 34˚C, in protecting against myocardial ischemia-reperfusion (I/R) injury (MIRI). To meet this aim, H9C2 cells underwent hypoxia‑reperfusion (H/R) and/or MTH. The MTT assay was used to assess cell viability, cytotoxicity was measured using a lactate dehydrogenase cytotoxicity assay, and Annexin V‑FITC/PI flow cytometric analysis was used to analyze early and late cell apoptosis. In addition, 84 healthy adult male Sprague‑Dawley rats were randomly divided into seven groups (n=12), and underwent I/R and various treatments. Hemodynamics were monitored, and the levels of myocardial injury marker enzymes and oxidative stress markers in myocardial tissue were measured using ELISA. The expression levels of PI3K, AKT, transient receptor potential cation channel subfamily M member 7 (TRPM7), glutathione peroxidase 4 (GPX4) and acyl‑CoA synthetase long chain family member 4 (ACSL4) in animals and cells were measured using western blot analysis. These experiments revealed that MTH could effectively reduce myocardial infarct size, improve hemodynamic performance following MIRI and suppress myocardial apoptosis, thereby contributing to the recovery from H/R injury. Mechanistically, MTH was revealed to be able to activate the PI3K/AKT signaling pathway in cells, upregulating GPX4, and downregulating the expression levels of TRPM7 and ACSL4. Treatment with 2‑aminoethoxydiphenyl borate (an inhibitor of TRPM7) could further strengthen the myocardial protective effects of MTH, whereas treatment with erastin (promoter of ferroptosis) and wortmannin (inhibitor of PI3K) led to the effective elimination of the myocardial protective effects of MTH. Compared with in the I/R group, the PI3K/AKT activation level and the expression levels of GPX4 were both significantly increased, whereas the expression levels of TRPM7 and ACSL4 were significantly decreased in the I/R + MTH group. Taken together, the results of the present study indicated that MTH may activate the PI3K/AKT signaling pathway to inhibit TRPM7 and suppress ferroptosis induced by MIRI.
{"title":"Mild therapeutic hypothermic protection activates the PI3K/AKT signaling pathway to inhibit TRPM7 and suppress ferroptosis induced by myocardial ischemia‑reperfusion injury.","authors":"Yaqi Li, Yixuan Chen, Peng Yu, Deju Zhang, Xiaoyi Tang, Zicheng Zhu, Fan Xiao, Wei Deng, Yang Liu, Zhaoying Tan, Jing Zhang, Shuchun Yu","doi":"10.3892/mmr.2024.13345","DOIUrl":"10.3892/mmr.2024.13345","url":null,"abstract":"<p><p>The present study aimed to investigate the role of PI3K‑mediated ferroptosis signaling induced by mild therapeutic hypothermia (MTH), which was defined as a temperature of 34˚C, in protecting against myocardial ischemia-reperfusion (I/R) injury (MIRI). To meet this aim, H9C2 cells underwent hypoxia‑reperfusion (H/R) and/or MTH. The MTT assay was used to assess cell viability, cytotoxicity was measured using a lactate dehydrogenase cytotoxicity assay, and Annexin V‑FITC/PI flow cytometric analysis was used to analyze early and late cell apoptosis. In addition, 84 healthy adult male Sprague‑Dawley rats were randomly divided into seven groups (n=12), and underwent I/R and various treatments. Hemodynamics were monitored, and the levels of myocardial injury marker enzymes and oxidative stress markers in myocardial tissue were measured using ELISA. The expression levels of PI3K, AKT, transient receptor potential cation channel subfamily M member 7 (TRPM7), glutathione peroxidase 4 (GPX4) and acyl‑CoA synthetase long chain family member 4 (ACSL4) in animals and cells were measured using western blot analysis. These experiments revealed that MTH could effectively reduce myocardial infarct size, improve hemodynamic performance following MIRI and suppress myocardial apoptosis, thereby contributing to the recovery from H/R injury. Mechanistically, MTH was revealed to be able to activate the PI3K/AKT signaling pathway in cells, upregulating GPX4, and downregulating the expression levels of TRPM7 and ACSL4. Treatment with 2‑aminoethoxydiphenyl borate (an inhibitor of TRPM7) could further strengthen the myocardial protective effects of MTH, whereas treatment with erastin (promoter of ferroptosis) and wortmannin (inhibitor of PI3K) led to the effective elimination of the myocardial protective effects of MTH. Compared with in the I/R group, the PI3K/AKT activation level and the expression levels of GPX4 were both significantly increased, whereas the expression levels of TRPM7 and ACSL4 were significantly decreased in the I/R + MTH group. Taken together, the results of the present study indicated that MTH may activate the PI3K/AKT signaling pathway to inhibit TRPM7 and suppress ferroptosis induced by MIRI.</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/PMC11462392/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142372280","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: 2024-10-04DOI: 10.3892/mmr.2024.13349
Weiming Chen, Xiwei Hao, Binyi Yang, Yuezhen Zhang, Lingyun Sun, Yanan Hua, Li Yang, Jiabin Yu, Jing Zhao, Lin Hou, Hongting Lu
Following the publication of this article, an interested reader drew to the authors' attention that the forward and reverse primer sequences written for GAPDH in Table I on p. 3 were incorrect. Upon requesting an explanation of these errors from the authors, they realized that these sequences had been written incorrectly in the paper: The sequence of the forward primer in Table I should have been written as 5'‑CAG GAGGCATTGCTGATGAT‑3', and the reverse primer should have been written as 5'‑GAAGGCTGGGGCTCATTT‑3'. The Editorial Office also requested seeing proof of purchase of the primers used in this study from the authors. The authors are grateful to the Editor of Molecular Medicine Reports for allowing them the opportunity to publish this corrigendum, and all the authors agree with its publication. The authors also regret the inconvenience that these mistakes have caused. [Molecular Medicine Reports 23: 245, 2021; DOI: 10.3892/mmr.2021.11884].
本文发表后,一位感兴趣的读者提请作者注意,第 3 页表 I 中 GAPDH 的正反引物序列有误。在要求作者解释这些错误后,作者意识到论文中的这些序列写错了:表 I 中正向引物的序列应写成 5'-CAG GAGGCATTGCTGATGAT-3',反向引物应写成 5'-GAAGGCTGGGGCTCATTT-3'。编辑部还要求作者提供本研究所用引物的购买证明。作者感谢《分子医学报告》编辑允许他们有机会发表本更正,所有作者均同意发表本更正。作者也对这些错误造成的不便表示歉意。[分子医学报告 23: 245, 2021; DOI: 10.3892/mmr.2021.11884]。
{"title":"[Corrigendum] MYCN‑amplified neuroblastoma cell‑derived exosomal miR‑17‑5p promotes proliferation and migration of non‑MYCN amplified cells.","authors":"Weiming Chen, Xiwei Hao, Binyi Yang, Yuezhen Zhang, Lingyun Sun, Yanan Hua, Li Yang, Jiabin Yu, Jing Zhao, Lin Hou, Hongting Lu","doi":"10.3892/mmr.2024.13349","DOIUrl":"10.3892/mmr.2024.13349","url":null,"abstract":"<p><p>Following the publication of this article, an interested reader drew to the authors' attention that the forward and reverse primer sequences written for GAPDH in Table I on p. 3 were incorrect. Upon requesting an explanation of these errors from the authors, they realized that these sequences had been written incorrectly in the paper: The sequence of the forward primer in Table I should have been written as 5'‑CAG GAGGCATTGCTGATGAT‑3', and the reverse primer should have been written as 5'‑GAAGGCTGGGGCTCATTT‑3'. The Editorial Office also requested seeing proof of purchase of the primers used in this study from the authors. The authors are grateful to the Editor of <i>Molecular Medicine Reports</i> for allowing them the opportunity to publish this corrigendum, and all the authors agree with its publication. The authors also regret the inconvenience that these mistakes have caused. [Molecular Medicine Reports 23: 245, 2021; DOI: 10.3892/mmr.2021.11884].</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/PMC11465413/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142372276","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}
Paridis Rhizoma saponins (PRS) are significant components of Rhizoma Paridis and have inhibitory effects on various tumors, such as bladder, breast, liver and colon cancer. Polyphyllin II (PPII), one of the PRS, has an unclear effect on breast cancer. The present study aimed to explore the effect and mechanism of PPII in breast cancer. A network pharmacology approach was employed to predict the core components and breast cancer‑related targets of PRS. Moreover, a xenograft tumor model was established to determine the anti‑breast cancer effect of PPII in vivo. The viability of MDA‑MB‑231 cells was determined by a Cell Counting Kit‑8 assay. Apoptosis was analyzed using annexin V/PI double staining. Additionally, Transwell and scratch assays were performed to evaluate invasion and migration. The potential mechanism was predicted by Kyoto Encyclopedia of Genes and Genomes enrichment analysis and molecular docking analysis and verified by western blot analysis. The effect of PPII on aerobic glycolysis in breast cancer cells was detected by lactic acid and pyruvate kits and Western blotting of glycolytic rate‑limiting enzymes. Network pharmacology analysis revealed 26 core targets involved in breast cancer and that PPII was the core active component of PRS. The in vivo studies showed that PPII could inhibit the growth of breast cancer in mice. In vitro experiments confirmed that PPII induced cancer cell apoptosis and inhibited invasion and migration. Furthermore, PPII was capable of suppressing the expression of key proteins in the PI3K/Akt signaling pathway, reducing the generation of aerobic glycolytic products, and diminishing the protein expression levels of hexokinase 2 and pyruvate kinase M2. The results indicated that PPII inhibited aerobic glycolysis in breast cancer cells through the PI3K/Akt signaling pathway, thereby inhibiting breast cancer growth.
{"title":"Polyphyllin II inhibits breast cancer cell proliferation via the PI3K/Akt signaling pathway.","authors":"Weiwei Miao, Zhixiong Wang, Jianwen Gao, Yuko Ohno","doi":"10.3892/mmr.2024.13348","DOIUrl":"10.3892/mmr.2024.13348","url":null,"abstract":"<p><p>Paridis Rhizoma saponins (PRS) are significant components of Rhizoma Paridis and have inhibitory effects on various tumors, such as bladder, breast, liver and colon cancer. Polyphyllin II (PPII), one of the PRS, has an unclear effect on breast cancer. The present study aimed to explore the effect and mechanism of PPII in breast cancer. A network pharmacology approach was employed to predict the core components and breast cancer‑related targets of PRS. Moreover, a xenograft tumor model was established to determine the anti‑breast cancer effect of PPII <i>in vivo</i>. The viability of MDA‑MB‑231 cells was determined by a Cell Counting Kit‑8 assay. Apoptosis was analyzed using annexin V/PI double staining. Additionally, Transwell and scratch assays were performed to evaluate invasion and migration. The potential mechanism was predicted by Kyoto Encyclopedia of Genes and Genomes enrichment analysis and molecular docking analysis and verified by western blot analysis. The effect of PPII on aerobic glycolysis in breast cancer cells was detected by lactic acid and pyruvate kits and Western blotting of glycolytic rate‑limiting enzymes. Network pharmacology analysis revealed 26 core targets involved in breast cancer and that PPII was the core active component of PRS. The in vivo studies showed that PPII could inhibit the growth of breast cancer in mice. <i>In vitro</i> experiments confirmed that PPII induced cancer cell apoptosis and inhibited invasion and migration. Furthermore, PPII was capable of suppressing the expression of key proteins in the PI3K/Akt signaling pathway, reducing the generation of aerobic glycolytic products, and diminishing the protein expression levels of hexokinase 2 and pyruvate kinase M2. The results indicated that PPII inhibited aerobic glycolysis in breast cancer cells through the PI3K/Akt signaling pathway, thereby inhibiting breast cancer growth.</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/PMC11465422/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142372281","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.2024.13360
Zhidan Mu, Bin Li, Mingyang Chen, Chen Liang, Wei Gu, Juan Su
The aim of the present study was to investigate the role and mechanism of endoplasmic reticulum stress (ERS) in kidney injury caused by high‑fat diet (HFD). An obese mouse model was established via HFD feeding and intervention was performed by intraperitoneal injection of the ERS inhibitor salubrinal (Sal). Changes in the body and kidney weight and serum biochemical indices of the mice were determined. Hematoxylin and eosin and Masson staining were used to observe the pathological changes of renal tissues. Reverse transcription‑quantitative PCR and western blotting were used to observe the expression of ERS‑related proteins and TGF‑β/SMAD pathway‑related proteins. Immunohistochemistry was employed to explore the distribution of these proteins. Compared with those in the control group, the weight gain, lipid metabolism disorders and deterioration of renal function in the model group were greater. Malondialdehyde was elevated and superoxide dismutase was decreased in renal tissues. The mRNA and protein levels of TGF‑β1, SMAD2/3, α‑smooth muscle actin, collagen I, glucose‑regulated protein 78 and C/EBP‑homologous protein were markedly elevated, whereas SMAD7 was markedly decreased. Sal markedly inhibited the aforementioned effects. This investigation revealed a link between ERS and renal injury caused by HFD. ERS in HFD‑fed mice triggers renal fibrosis through the TGF‑β/SMAD pathway.
本研究旨在探讨内质网应激(ERS)在高脂饮食(HFD)引起的肾损伤中的作用和机制。通过喂食高脂饮食建立了肥胖小鼠模型,并通过腹腔注射ERS抑制剂salubrinal(Sal)进行干预。测定了小鼠的体重、肾脏重量和血清生化指标的变化。采用苏木精和Masson染色法观察肾组织的病理变化。采用逆转录-定量 PCR 和 Western 印迹技术观察 ERS 相关蛋白和 TGF-β/SMAD 通路相关蛋白的表达。免疫组化技术用于检测这些蛋白的分布。与对照组相比,模型组的体重增加、脂质代谢紊乱和肾功能恶化程度更严重。肾组织中丙二醛升高,超氧化物歧化酶降低。TGF-β1、SMAD2/3、α-平滑肌肌动蛋白、胶原蛋白I、葡萄糖调节蛋白78和C/EBP同源蛋白的mRNA和蛋白水平明显升高,而SMAD7则明显下降。Sal 能明显抑制上述效应。这项研究揭示了 ERS 与高纤维食物引起的肾损伤之间的联系。HFD喂养小鼠的ERS通过TGF-β/SMAD途径引发肾脏纤维化。
{"title":"Endoplasmic reticulum stress induces renal fibrosis in high‑fat diet mice via the TGF‑β/SMAD pathway.","authors":"Zhidan Mu, Bin Li, Mingyang Chen, Chen Liang, Wei Gu, Juan Su","doi":"10.3892/mmr.2024.13360","DOIUrl":"https://doi.org/10.3892/mmr.2024.13360","url":null,"abstract":"<p><p>The aim of the present study was to investigate the role and mechanism of endoplasmic reticulum stress (ERS) in kidney injury caused by high‑fat diet (HFD). An obese mouse model was established via HFD feeding and intervention was performed by intraperitoneal injection of the ERS inhibitor salubrinal (Sal). Changes in the body and kidney weight and serum biochemical indices of the mice were determined. Hematoxylin and eosin and Masson staining were used to observe the pathological changes of renal tissues. Reverse transcription‑quantitative PCR and western blotting were used to observe the expression of ERS‑related proteins and TGF‑β/SMAD pathway‑related proteins. Immunohistochemistry was employed to explore the distribution of these proteins. Compared with those in the control group, the weight gain, lipid metabolism disorders and deterioration of renal function in the model group were greater. Malondialdehyde was elevated and superoxide dismutase was decreased in renal tissues. The mRNA and protein levels of TGF‑β1, SMAD2/3, α‑smooth muscle actin, collagen I, glucose‑regulated protein 78 and C/EBP‑homologous protein were markedly elevated, whereas SMAD7 was markedly decreased. Sal markedly inhibited the aforementioned effects. This investigation revealed a link between ERS and renal injury caused by HFD. ERS in HFD‑fed mice triggers renal fibrosis through the TGF‑β/SMAD 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":"142470264","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}
Addressing the repair and regeneration of large bone defects poses significant challenges in bone tissue engineering. Despite the abundant evidence demonstrating the positive role of MSCs in osteogenesis, their limited osteogenic differentiation ability still needs to be improved. The present study used lipopolysaccharide (LPS) to enhance the osteogenic properties of ecto‑mesenchymal stem cells (EMSCs). Human nasal respiratory mucosa‑derived EMSCs were cultured on plates and stimulated with LPS for 5 days prior to undergoing osteogenic differentiation. The findings revealed that LPS effectively stimulated the osteogenic differentiation capacity of EMSCs, as evidenced by heightened alkaline phosphatase activity, elevated expression levels of osteogenic‑related proteins and enhanced mineralization of EMSCs. The present study also demonstrated that the augmentation occurred due to increased IL‑10 levels, although it was not solely attributable to this factor. Together, the findings illustrated that the LPS‑mediated adaptation of EMSCs is an active process driving osteogenic differentiation and could be a novel strategy for bone regeneration.
{"title":"LPS‑mediated adaptation accelerates ecto‑MSCs differentiation into osteoblasts.","authors":"Demin Lv, Bingxia Li, Zhen Liu, Qing Zhang, Sucheng Cao, Yanlong Xu, Zheng Zhang","doi":"10.3892/mmr.2024.13365","DOIUrl":"https://doi.org/10.3892/mmr.2024.13365","url":null,"abstract":"<p><p>Addressing the repair and regeneration of large bone defects poses significant challenges in bone tissue engineering. Despite the abundant evidence demonstrating the positive role of MSCs in osteogenesis, their limited osteogenic differentiation ability still needs to be improved. The present study used lipopolysaccharide (LPS) to enhance the osteogenic properties of ecto‑mesenchymal stem cells (EMSCs). Human nasal respiratory mucosa‑derived EMSCs were cultured on plates and stimulated with LPS for 5 days prior to undergoing osteogenic differentiation. The findings revealed that LPS effectively stimulated the osteogenic differentiation capacity of EMSCs, as evidenced by heightened alkaline phosphatase activity, elevated expression levels of osteogenic‑related proteins and enhanced mineralization of EMSCs. The present study also demonstrated that the augmentation occurred due to increased IL‑10 levels, although it was not solely attributable to this factor. Together, the findings illustrated that the LPS‑mediated adaptation of EMSCs is an active process driving osteogenic differentiation and could be a novel strategy for bone regeneration.</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":"142470266","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.2024.13357
Xiaoqing Jia, Jingyi Cheng, Zhenzhou Shen, Zhimin Shao, Guangyu Liu
Following the publication of the above article, the authors drew to the Editor's attention that they had inadvertently used the same immunohistochemical image to show the experiments depicting the zoledronic acid‑treated MCF‑7/HIF‑1α xenograft (the 'ZOL/MCF‑7/hif' panel) and the fulvestrant‑treated MCF‑7/vector xenograft (the 'FUL/MCF‑7/cdh' panel) in Fig. 3A on p. 5474. Subsequently, upon performing an independent review of the data in this paper, the Editorial Office pointed out to the authors that the same colony‑formation assay image had been included in Fig. 1C to show the 'MCF‑7/cdh‑ZOL' and 'MCF‑7/cdh‑FUL' experiments. The authors re‑examined their original data, and realized that inadvertent errors were made during the compilation of this pair of figures. The corrected versions of Figs. 1 and 3 are shown on the next two pages, now featuring the correct data for the 'MCF‑7/cdh‑ZOL' experiment in Fig. 1C and the 'ZOL/MCF‑7/hif' experiment in Fig. 3A. All the authors agree with the publication of this corrigendum, and are grateful to the Editor of Molecular Medicine Reports for granting them the opportunity to publish this. Furthermore, they regret that these errors were introduced into the paper, even though they did not substantially alter any of the major conclusions reported in the paper, and apologize to the readership for any inconvenience caused. [Molecular Medicine Reports 17: 5470‑5476, 2018; DOI: 10.3892/mmr.2018.8514].
{"title":"[Corrigendum] Zoledronic acid sensitizes breast cancer cells to fulvestrant via ERK/HIF‑1 pathway inhibition <i>in vivo</i>.","authors":"Xiaoqing Jia, Jingyi Cheng, Zhenzhou Shen, Zhimin Shao, Guangyu Liu","doi":"10.3892/mmr.2024.13357","DOIUrl":"https://doi.org/10.3892/mmr.2024.13357","url":null,"abstract":"<p><p>Following the publication of the above article, the authors drew to the Editor's attention that they had inadvertently used the same immunohistochemical image to show the experiments depicting the zoledronic acid‑treated MCF‑7/HIF‑1α xenograft (the 'ZOL/MCF‑7/hif' panel) and the fulvestrant‑treated MCF‑7/vector xenograft (the 'FUL/MCF‑7/cdh' panel) in Fig. 3A on p. 5474. Subsequently, upon performing an independent review of the data in this paper, the Editorial Office pointed out to the authors that the same colony‑formation assay image had been included in Fig. 1C to show the 'MCF‑7/cdh‑ZOL' and 'MCF‑7/cdh‑FUL' experiments. The authors re‑examined their original data, and realized that inadvertent errors were made during the compilation of this pair of figures. The corrected versions of Figs. 1 and 3 are shown on the next two pages, now featuring the correct data for the 'MCF‑7/cdh‑ZOL' experiment in Fig. 1C and the 'ZOL/MCF‑7/hif' experiment in Fig. 3A. All the authors agree with the publication of this corrigendum, and are grateful to the Editor of <i>Molecular Medicine Reports</i> for granting them the opportunity to publish this. Furthermore, they regret that these errors were introduced into the paper, even though they did not substantially alter any of the major conclusions reported in the paper, and apologize to the readership for any inconvenience caused. [Molecular Medicine Reports 17: 5470‑5476, 2018; DOI: 10.3892/mmr.2018.8514].</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":"142400775","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.2024.13346
Zhongbao Zhang, Jiajing Cheng, Yi Wu, Jin Qiu, Yi Sun, Xiaowen Tong
Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that the cell apoptotic data shown in Fig. 3C and the Hoeschst 33342‑stained images in Fig. 3D on p. 2468, and certain of the scratch‑wound assay data shown in Fig. 5E on p. 2470 were strikingly similar to data appearing in different form in other articles written by different authors at different research institutes that had either already been published elsewhere prior to the submission of this paper to Molecular Medicine Reports, or were submitted for publication at around the same time. Owing to the fact that some of the abovementioned data had already apparently been published previously, the Editor of Molecular Medicine Reports 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 14: 2465‑2472, 2016; DOI: 10.3892/mmr.2016.5572].
该论文发表后,一位相关读者提请编辑注意,第 2468 页图 3C 所示的细胞凋亡数据和图 3D 所示的 Hoeschst 33342 染色图像,以及第 2470 页图 5E 所示的某些划痕试验数据,与不同研究机构不同作者撰写的其他文章中以不同形式出现的数据惊人地相似。由于上述部分数据显然已在此前发表过,《分子医学报告》编辑决定从期刊上撤回这篇论文。编辑部要求作者就上述问题做出解释,但未收到回复。对于给读者带来的不便,编辑深表歉意。[分子医学报告 14: 2465-2472, 2016; DOI: 10.3892/mmr.2016.5572]。
{"title":"[Retracted] LncRNA HOTAIR controls the expression of Rab22a by sponging miR‑373 in ovarian cancer.","authors":"Zhongbao Zhang, Jiajing Cheng, Yi Wu, Jin Qiu, Yi Sun, Xiaowen Tong","doi":"10.3892/mmr.2024.13346","DOIUrl":"10.3892/mmr.2024.13346","url":null,"abstract":"<p><p>Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that the cell apoptotic data shown in Fig. 3C and the Hoeschst 33342‑stained images in Fig. 3D on p. 2468, and certain of the scratch‑wound assay data shown in Fig. 5E on p. 2470 were strikingly similar to data appearing in different form in other articles written by different authors at different research institutes that had either already been published elsewhere prior to the submission of this paper to <i>Molecular Medicine Reports</i>, or were submitted for publication at around the same time. Owing to the fact that some of the abovementioned data had already apparently been published previously, the Editor of <i>Molecular Medicine Reports</i> 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 14: 2465‑2472, 2016; DOI: 10.3892/mmr.2016.5572].</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/PMC11462393/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142372277","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: 2024-10-04DOI: 10.3892/mmr.2024.13350
Ping Zhao, Kui Zhu, Cuihua Xie, Sinan Liu, Xiang Chen
Transfer RNA‑derived small RNAs (tsRNAs) are novel non‑coding RNAs that are associated with the pathogenesis of various diseases. However, their association with lung adenocarcinoma (LUAD) has not been studied comprehensively. Therefore, the present study aimed to explore the diagnostic value of a tsRNA, hsa_tsr011468, in LUAD. The OncotRF database was used to screen tsRNAs and reverse transcription‑quantitative PCR (RT‑qPCR) was performed to detect the expression levels of hsa_tsr011468 in various samples. Subsequently, the diagnostic and prognostic values of hsa_tsr011468 for LUAD were determined via receiver operating characteristic (ROC) curve and survival curve analyses, and by assessing clinicopathological parameters. In addition, both nuclear and cytoplasmic RNA were extracted to assess the location of hsa_tsr011468. The OncotRF database identified high expression of hsa_tsr011468 in LUAD. In addition, the results of RT‑qPCR showed that the relative expression levels of hsa_tsr011468 in the serum and tissues of patients with LUAD were higher than those in normal controls. Furthermore, its expression was lower in postoperative serum samples than in preoperative serum samples from patients with LUAD. ROC and survival curves indicated that hsa_tsr011468 had good diagnostic and prognostic value. Furthermore, the clinicopathological analysis revealed that hsa_tsr011468 was associated with tumor size. In addition, hsa_tsr011468 was mainly localized in the cytoplasm of LUAD cells. The present study indicated that hsa_tsr011468 has good diagnostic value and, therefore, could be employed as a serum marker for LUAD.
{"title":"Role and clinical value of serum hsa_tsr011468 in lung adenocarcinoma.","authors":"Ping Zhao, Kui Zhu, Cuihua Xie, Sinan Liu, Xiang Chen","doi":"10.3892/mmr.2024.13350","DOIUrl":"10.3892/mmr.2024.13350","url":null,"abstract":"<p><p>Transfer RNA‑derived small RNAs (tsRNAs) are novel non‑coding RNAs that are associated with the pathogenesis of various diseases. However, their association with lung adenocarcinoma (LUAD) has not been studied comprehensively. Therefore, the present study aimed to explore the diagnostic value of a tsRNA, hsa_tsr011468, in LUAD. The OncotRF database was used to screen tsRNAs and reverse transcription‑quantitative PCR (RT‑qPCR) was performed to detect the expression levels of hsa_tsr011468 in various samples. Subsequently, the diagnostic and prognostic values of hsa_tsr011468 for LUAD were determined via receiver operating characteristic (ROC) curve and survival curve analyses, and by assessing clinicopathological parameters. In addition, both nuclear and cytoplasmic RNA were extracted to assess the location of hsa_tsr011468. The OncotRF database identified high expression of hsa_tsr011468 in LUAD. In addition, the results of RT‑qPCR showed that the relative expression levels of hsa_tsr011468 in the serum and tissues of patients with LUAD were higher than those in normal controls. Furthermore, its expression was lower in postoperative serum samples than in preoperative serum samples from patients with LUAD. ROC and survival curves indicated that hsa_tsr011468 had good diagnostic and prognostic value. Furthermore, the clinicopathological analysis revealed that hsa_tsr011468 was associated with tumor size. In addition, hsa_tsr011468 was mainly localized in the cytoplasm of LUAD cells. The present study indicated that hsa_tsr011468 has good diagnostic value and, therefore, could be employed as a serum marker for LUAD.</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/PMC11485271/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142372282","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}