Pub Date : 2025-03-01Epub Date: 2024-12-20DOI: 10.3892/mmr.2024.13419
Xiang Hu, Tao Lv, Shao-Feng Yang, Xiao-Hua Zhang, Yi-Feng Miao
Following the publication of the above paper, a concerned reader drew to the attention of the Editorial Office that the 'Sham' brain image featured in Fig. 1B on p. 23 was strikingly similar to an image that was published subsequently in the journal Scientific Reports, whereas the control TUNEL assay data shown in Fig. 4A on p. 25 were similarly strikingly similar to data shown in a paper published previously in the journal Mediators of Inflammation, even though the overall experiments portrayed in the other journals were different. As the three affected articles did hold at least one author in common, we asked the authors to provide an explanation to account for the sharing of these data among these papers, but no reply was forthcoming from them; therefore, in the absence of a reply from these authors, the Editor of Molecular Medicine Reports has decided that this paper should be retracted from the Journal on account of a lack of confidence in the presented data. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 17: 21‑30, 2018; DOI: 10.3892/mmr.2017.7858].
{"title":"[Retracted] Limb remote ischemic post‑conditioning reduces injury and improves long‑term behavioral recovery in rats following subarachnoid hemorrhage: Possible involvement of the autophagic process.","authors":"Xiang Hu, Tao Lv, Shao-Feng Yang, Xiao-Hua Zhang, Yi-Feng Miao","doi":"10.3892/mmr.2024.13419","DOIUrl":"10.3892/mmr.2024.13419","url":null,"abstract":"<p><p>Following the publication of the above paper, a concerned reader drew to the attention of the Editorial Office that the 'Sham' brain image featured in Fig. 1B on p. 23 was strikingly similar to an image that was published subsequently in the journal <i>Scientific Reports</i>, whereas the control TUNEL assay data shown in Fig. 4A on p. 25 were similarly strikingly similar to data shown in a paper published previously in the journal <i>Mediators of Inflammation</i>, even though the overall experiments portrayed in the other journals were different. As the three affected articles did hold at least one author in common, we asked the authors to provide an explanation to account for the sharing of these data among these papers, but no reply was forthcoming from them; therefore, in the absence of a reply from these authors, the Editor of <i>Molecular Medicine Reports</i> has decided that this paper should be retracted from the Journal on account of a lack of confidence in the presented data. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 17: 21‑30, 2018; DOI: 10.3892/mmr.2017.7858].</p>","PeriodicalId":18818,"journal":{"name":"Molecular medicine reports","volume":"31 3","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11683449/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142864060","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}
Rotator cuff tears (RCT) can cause shoulder pain, weakness and stiffness, significantly affecting daily life. Analysis of the GSE103266 dataset revealed significant changes in the mTOR/PI3K/Akt signaling pathway and lipid metabolism‑related pathways, suggesting that fatty infiltration may affect RCT. The analysis indicated that the ubiquitin ligase NEDD4 plays a critical role in RCT. NEDD4 was found to be highly associated with the mTOR/PI3K/Akt signaling pathway. An RCT model in Sprague‑Dawley (SD) rats was established to study the role of NEDD4 in regulating the mTOR pathway and investigate its effects on fatty infiltration. SD rats were divided into NEDD4 overexpression and knockout groups. Tissue recovery, apoptosis and fat deposition were measured through histological staining, reverse transcription‑quantitative PCR and western blotting. Additionally, cell culture of fibro‑adipogenic progenitors and lentiviral transfection were conducted to investigate the effect of NEDD4 on adipocyte differentiation. NEDD4 overexpression significantly reduced lipid accumulation, whereas NEDD4 knockdown enhanced lipid accumulation. NEDD4 was found to regulate the mTOR pathway and the expression of adipogenesis‑related genes, promoting fat metabolism and inhibiting adipocyte differentiation. Histological analysis indicated that NEDD4 overexpression improved tissue recovery and reduced apoptosis. Targeting NEDD4 offers a potential therapeutic strategy to improve the clinical outcomes of patients with RCT by modulating the mTOR pathway and fat metabolism.
{"title":"NEDD4 enhances bone‑tendon healing in rotator cuff tears by reducing fatty infiltration.","authors":"Jian Li, Ying Peng, Dong Zhen, Caifen Guo, Wuxun Peng","doi":"10.3892/mmr.2024.13420","DOIUrl":"10.3892/mmr.2024.13420","url":null,"abstract":"<p><p>Rotator cuff tears (RCT) can cause shoulder pain, weakness and stiffness, significantly affecting daily life. Analysis of the GSE103266 dataset revealed significant changes in the mTOR/PI3K/Akt signaling pathway and lipid metabolism‑related pathways, suggesting that fatty infiltration may affect RCT. The analysis indicated that the ubiquitin ligase NEDD4 plays a critical role in RCT. NEDD4 was found to be highly associated with the mTOR/PI3K/Akt signaling pathway. An RCT model in Sprague‑Dawley (SD) rats was established to study the role of NEDD4 in regulating the mTOR pathway and investigate its effects on fatty infiltration. SD rats were divided into NEDD4 overexpression and knockout groups. Tissue recovery, apoptosis and fat deposition were measured through histological staining, reverse transcription‑quantitative PCR and western blotting. Additionally, cell culture of fibro‑adipogenic progenitors and lentiviral transfection were conducted to investigate the effect of NEDD4 on adipocyte differentiation. NEDD4 overexpression significantly reduced lipid accumulation, whereas NEDD4 knockdown enhanced lipid accumulation. NEDD4 was found to regulate the mTOR pathway and the expression of adipogenesis‑related genes, promoting fat metabolism and inhibiting adipocyte differentiation. Histological analysis indicated that NEDD4 overexpression improved tissue recovery and reduced apoptosis. Targeting NEDD4 offers a potential therapeutic strategy to improve the clinical outcomes of patients with RCT by modulating the mTOR pathway and fat metabolism.</p>","PeriodicalId":18818,"journal":{"name":"Molecular medicine reports","volume":"31 3","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11683452/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142864073","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 : 2025-03-01Epub Date: 2025-01-17DOI: 10.3892/mmr.2025.13436
Xiangli Yan, Siqi Quan, Roujia Guo, Zibo Li, Ming Bai, Baoying Wang, Pan Su, Erping Xu, Yucheng Li
Calycosin‑7‑O‑β‑D‑glucoside (CG), a major active ingredient of Astragali Radix, exerts neuroprotective effects against cerebral ischemia; however, whether the effects of CG are associated with mitochondrial protection remains unclear. The present study explored the role of CG in improving mitochondrial function in a HT22 cell model of oxygen‑glucose deprivation/reperfusion (OGD/R). The Cell Counting Kit‑8 assay, flow cytometry, immunofluorescence and western blotting were performed to investigate the effects of CG on mitochondrial function. The results demonstrated that mitochondrial function was restored after treatment with CG, as indicated by reduced mitochondrial reactive oxygen species levels, increased mitochondrial membrane potential and improved mitochondrial morphology. Overactivated mitophagy was revealed to be inhibited by the regulation of proteins involved in fission [phosphorylated‑dynamin‑related protein 1 (Drp1) and Drp1] and mitophagy (LC3, p62 and translocase of outer mitochondrial membrane 20), and mitochondrial biogenesis was demonstrated to be enhanced by increased levels of sirtuin 1 (SIRT1) and peroxisome proliferator‑activated receptor γ coactivator‑1α (PGC‑1α). In addition, neuronal apoptosis was ameliorated by CG, as determined by a decreased rate of apoptosis, and levels of caspase‑3 and Bcl‑2/Bax. In conclusion, the present study demonstrated that CG may alleviate OGD/R‑induced injury by upregulating SIRT1 and PGC‑1α protein expression, and reducing excessive mitochondrial fission and overactivation of mitophagy.
{"title":"Calycosin‑7‑O‑β‑D‑glucoside downregulates mitophagy by mitigating mitochondrial fission to protect HT22 cells from oxygen‑glucose deprivation/reperfusion‑induced injury.","authors":"Xiangli Yan, Siqi Quan, Roujia Guo, Zibo Li, Ming Bai, Baoying Wang, Pan Su, Erping Xu, Yucheng Li","doi":"10.3892/mmr.2025.13436","DOIUrl":"10.3892/mmr.2025.13436","url":null,"abstract":"<p><p>Calycosin‑7‑O‑β‑D‑glucoside (CG), a major active ingredient of Astragali Radix, exerts neuroprotective effects against cerebral ischemia; however, whether the effects of CG are associated with mitochondrial protection remains unclear. The present study explored the role of CG in improving mitochondrial function in a HT22 cell model of oxygen‑glucose deprivation/reperfusion (OGD/R). The Cell Counting Kit‑8 assay, flow cytometry, immunofluorescence and western blotting were performed to investigate the effects of CG on mitochondrial function. The results demonstrated that mitochondrial function was restored after treatment with CG, as indicated by reduced mitochondrial reactive oxygen species levels, increased mitochondrial membrane potential and improved mitochondrial morphology. Overactivated mitophagy was revealed to be inhibited by the regulation of proteins involved in fission [phosphorylated‑dynamin‑related protein 1 (Drp1) and Drp1] and mitophagy (LC3, p62 and translocase of outer mitochondrial membrane 20), and mitochondrial biogenesis was demonstrated to be enhanced by increased levels of sirtuin 1 (SIRT1) and peroxisome proliferator‑activated receptor γ coactivator‑1α (PGC‑1α). In addition, neuronal apoptosis was ameliorated by CG, as determined by a decreased rate of apoptosis, and levels of caspase‑3 and Bcl‑2/Bax. In conclusion, the present study demonstrated that CG may alleviate OGD/R‑induced injury by upregulating SIRT1 and PGC‑1α protein expression, and reducing excessive mitochondrial fission and overactivation of mitophagy.</p>","PeriodicalId":18818,"journal":{"name":"Molecular medicine reports","volume":"31 3","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11751592/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008524","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 : 2025-03-01Epub Date: 2025-01-31DOI: 10.3892/mmr.2025.13440
Chenzi Lyu, Seok Yong Kang, Haifeng Shao, Dongeun Kim, Hyo Won Jung
Asiasarum root and rhizome (Asarum) is commonly used as a diaphoretic. Due to its warm and pungent characteristics in traditional Chinese and Korean medicine, it is considered as having the potential to prevent disease. The present study investigated the effects of Asarum extract on the symptoms of obesity in mice, and the regulation of energy metabolism in the liver and skeletal muscle tissues. In addition, to identify the potential molecular targets and signaling pathways involved in the mechanism of action of Asarum extract in obesity, network pharmacological and molecular docking analysis was performed. In vitro studies demonstrated that Asarum extract significantly increased the expression of regulators of energy metabolism [sirtuin 1 (SIRT1), peroxisome proliferator‑activated receptor γ coactivator 1‑α (PGC1α), nuclear respiratory factor 1, AMP‑activated protein kinase (AMPK) and glucose transporter type 4 (GLUT4)] and myogenic regulatory factors (MyoD, myogenin and myosin heavy chain) in C2C12 myotubes. Furthermore, the in vivo studies demonstrated that Asarum extract could reduce increases in body weight, and the levels of blood glucose, insulin, total cholesterol, triglycerides and low‑density lipoprotein cholesterol in the sera of obese mice. Asarum extract also improved pathological changes in the liver and pancreatic tissues of obese mice, and significantly increased the ratio of brown fat mass to body weight. In addition, Asarum extract reversed the expression of energy metabolism regulators and myogenic regulatory factors in the gastrocnemius tissues of obese mice. Asarum extract also activated the expression of SIRT1, PGC1α and AMPK in the liver tissues of obese mice. These findings indicated that Asarum extract may exert anti‑obesity effects, such as body weight loss, decreases in lipid metabolite levels, and inhibition of pancreatic and liver damage. Using network pharmacological analysis, the mechanisms underlying the effects of Asarum extract on the regulation of energy metabolism were explored, particularly in skeletal muscle and liver tissues.
{"title":"Ameliorative effects of <i>Asiasarum</i> root and rhizome extract on high fat diet‑induced obesity in mice through regulation of the SIRT1/PGC1α/AMPK pathways in muscle and liver tissues.","authors":"Chenzi Lyu, Seok Yong Kang, Haifeng Shao, Dongeun Kim, Hyo Won Jung","doi":"10.3892/mmr.2025.13440","DOIUrl":"10.3892/mmr.2025.13440","url":null,"abstract":"<p><p>Asiasarum root and rhizome (<i>Asarum</i>) is commonly used as a diaphoretic. Due to its warm and pungent characteristics in traditional Chinese and Korean medicine, it is considered as having the potential to prevent disease. The present study investigated the effects of <i>Asarum</i> extract on the symptoms of obesity in mice, and the regulation of energy metabolism in the liver and skeletal muscle tissues. In addition, to identify the potential molecular targets and signaling pathways involved in the mechanism of action of <i>Asarum</i> extract in obesity, network pharmacological and molecular docking analysis was performed. <i>In vitro</i> studies demonstrated that <i>Asarum</i> extract significantly increased the expression of regulators of energy metabolism [sirtuin 1 (SIRT1), peroxisome proliferator‑activated receptor γ coactivator 1‑α (PGC1α), nuclear respiratory factor 1, AMP‑activated protein kinase (AMPK) and glucose transporter type 4 (GLUT4)] and myogenic regulatory factors (MyoD, myogenin and myosin heavy chain) in C2C12 myotubes. Furthermore, the in vivo studies demonstrated that <i>Asarum</i> extract could reduce increases in body weight, and the levels of blood glucose, insulin, total cholesterol, triglycerides and low‑density lipoprotein cholesterol in the sera of obese mice. <i>Asarum</i> extract also improved pathological changes in the liver and pancreatic tissues of obese mice, and significantly increased the ratio of brown fat mass to body weight. In addition, <i>Asarum</i> extract reversed the expression of energy metabolism regulators and myogenic regulatory factors in the gastrocnemius tissues of obese mice. <i>Asarum</i> extract also activated the expression of SIRT1, PGC1α and AMPK in the liver tissues of obese mice. These findings indicated that <i>Asarum</i> extract may exert anti‑obesity effects, such as body weight loss, decreases in lipid metabolite levels, and inhibition of pancreatic and liver damage. Using network pharmacological analysis, the mechanisms underlying the effects of <i>Asarum</i> extract on the regulation of energy metabolism were explored, particularly in skeletal muscle and liver tissues.</p>","PeriodicalId":18818,"journal":{"name":"Molecular medicine reports","volume":"31 3","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11795245/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143066513","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 : 2025-03-01Epub Date: 2025-01-31DOI: 10.3892/mmr.2025.13447
Yi Chen, Meng Li, Yanqing Wu
Small heat shock proteins (sHSPs) are common molecular chaperone proteins that function in various biological processes, and serve indispensable roles in maintaining cellular protein homeostasis and regulating the hydrolysis of unfolded proteins. HSP22 is a member of the sHSP family that is primarily expressed in the heart and skeletal muscle, as well as in various types of cancer. There have been important findings concerning the role of HSP22 in cardiovascular diseases. The aim of the present study was to provide insights into the various molecular mechanisms by which HSP22 functions in the heart, including oxidative stress, autophagy, apoptosis, the subcellular distribution of proteins and the promoting effect of proteasomes. In addition, drugs and cytokines, including geranylgeranylacetone, can exert protective effects on the heart by regulating the expression of HSP22. Based on increasingly abundant research, HSP22 may be considered a potential therapeutic target in cardiovascular diseases.
{"title":"Heat shock protein 22: A new direction for cardiovascular disease (Review).","authors":"Yi Chen, Meng Li, Yanqing Wu","doi":"10.3892/mmr.2025.13447","DOIUrl":"10.3892/mmr.2025.13447","url":null,"abstract":"<p><p>Small heat shock proteins (sHSPs) are common molecular chaperone proteins that function in various biological processes, and serve indispensable roles in maintaining cellular protein homeostasis and regulating the hydrolysis of unfolded proteins. HSP22 is a member of the sHSP family that is primarily expressed in the heart and skeletal muscle, as well as in various types of cancer. There have been important findings concerning the role of HSP22 in cardiovascular diseases. The aim of the present study was to provide insights into the various molecular mechanisms by which HSP22 functions in the heart, including oxidative stress, autophagy, apoptosis, the subcellular distribution of proteins and the promoting effect of proteasomes. In addition, drugs and cytokines, including geranylgeranylacetone, can exert protective effects on the heart by regulating the expression of HSP22. Based on increasingly abundant research, HSP22 may be considered a potential therapeutic target in cardiovascular diseases.</p>","PeriodicalId":18818,"journal":{"name":"Molecular medicine reports","volume":"31 3","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11800183/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143066767","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 : 2025-03-01Epub Date: 2025-01-24DOI: 10.3892/mmr.2025.13438
Wenlu Zhang, Chunyan Xu
Exosomes are small extracellular vesicles that are naturally released into body fluids by cells. They are rich in bioactive molecules such as proteins. Sphingosine kinase 1 (SphK1) is an important potential drug target for the treatment of cancer due to its functions to regulate cancer cell migration, growth, apoptosis and angiogenesis. Tumor exosomes abundantly surround primary tumors, exchanging and transferring information between cells and modulating cancer progression. Given the importance of exosomes, the involvement of exosomal SphK1 from colorectal cancer (CRC) cells in the migration of these cells and the activation of hepatic stellate cells was investigated. Firstly, the plasma exosomal SphK1 protein expression, tested by ELISA, was compared between patients with CRC without metastasis and those with liver metastasis. The results revealed that plasma exosomal SphK1 levels were significantly upregulated in patients with liver metastasis of CRC. Secondly, exosomes with different expression levels of SphK1, which were regulated by cell transfection, were isolated from CRC cells to evaluate their effect on the expression levels of E‑cadherin and vimentin in these cells, as assessed by western blotting. The results demonstrated that depletion of exosomal SphK1 partially reversed the exosome‑induced migration of CRC cells, and caused decreased vimentin and increased E‑cadherin levels. Thirdly, the effects of exosomes from CRC cells, with different expression levels of SphK1, on hepatic stellate cell activation were investigated, with α‑SMA, TNF‑α and TGF‑β levels assessed by western blotting in LX‑2 cells. Moreover, AKT and phosphorylated (p‑)AKT levels were also assessed by western blotting. The results revealed that exosomes activated hepatic stellate cells by upregulating p‑AKT, and depletion of exosomal SphK1 partially reversed this effect. Furthermore, the application of an AKT agonist reversed the inhibition of hepatic stellate cell activation, which was induced by the depletion of exosomal SphK1. Finally, investigation of cell viability, analyzed by CCK‑8 assay, and assessment of PCNA as a proliferation marker, analyzed by western blot, revealed that the culture supernatant of the activated hepatic stellate cells promoted the viability of CRC cells. Overall, these results demonstrated that exosomal SphK1 increased the migration of CRC cells, and activated hepatic stellate cells by regulating p‑AKT. This suggests that exosomal SphK1 may serve a key role in the migration of CRC cells and potentially the liver metastasis of CRC.
{"title":"Exosomal SphK1 from colorectal cancer cells promotes cancer cell migration and activates hepatic stellate cells.","authors":"Wenlu Zhang, Chunyan Xu","doi":"10.3892/mmr.2025.13438","DOIUrl":"10.3892/mmr.2025.13438","url":null,"abstract":"<p><p>Exosomes are small extracellular vesicles that are naturally released into body fluids by cells. They are rich in bioactive molecules such as proteins. Sphingosine kinase 1 (SphK1) is an important potential drug target for the treatment of cancer due to its functions to regulate cancer cell migration, growth, apoptosis and angiogenesis. Tumor exosomes abundantly surround primary tumors, exchanging and transferring information between cells and modulating cancer progression. Given the importance of exosomes, the involvement of exosomal SphK1 from colorectal cancer (CRC) cells in the migration of these cells and the activation of hepatic stellate cells was investigated. Firstly, the plasma exosomal SphK1 protein expression, tested by ELISA, was compared between patients with CRC without metastasis and those with liver metastasis. The results revealed that plasma exosomal SphK1 levels were significantly upregulated in patients with liver metastasis of CRC. Secondly, exosomes with different expression levels of SphK1, which were regulated by cell transfection, were isolated from CRC cells to evaluate their effect on the expression levels of E‑cadherin and vimentin in these cells, as assessed by western blotting. The results demonstrated that depletion of exosomal SphK1 partially reversed the exosome‑induced migration of CRC cells, and caused decreased vimentin and increased E‑cadherin levels. Thirdly, the effects of exosomes from CRC cells, with different expression levels of SphK1, on hepatic stellate cell activation were investigated, with α‑SMA, TNF‑α and TGF‑β levels assessed by western blotting in LX‑2 cells. Moreover, AKT and phosphorylated (p‑)AKT levels were also assessed by western blotting. The results revealed that exosomes activated hepatic stellate cells by upregulating p‑AKT, and depletion of exosomal SphK1 partially reversed this effect. Furthermore, the application of an AKT agonist reversed the inhibition of hepatic stellate cell activation, which was induced by the depletion of exosomal SphK1. Finally, investigation of cell viability, analyzed by CCK‑8 assay, and assessment of PCNA as a proliferation marker, analyzed by western blot, revealed that the culture supernatant of the activated hepatic stellate cells promoted the viability of CRC cells. Overall, these results demonstrated that exosomal SphK1 increased the migration of CRC cells, and activated hepatic stellate cells by regulating p‑AKT. This suggests that exosomal SphK1 may serve a key role in the migration of CRC cells and potentially the liver metastasis of CRC.</p>","PeriodicalId":18818,"journal":{"name":"Molecular medicine reports","volume":"31 3","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11795250/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143391268","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 : 2025-03-01Epub Date: 2025-01-10DOI: 10.3892/mmr.2025.13431
Yang Yang, Wei Yang, Jie Shen, Enci Ding
Hepatocellular carcinoma (HCC) is a common cause of cancer‑related mortality and morbidity worldwide. While iodine‑125 (125I) particle brachytherapy has been extensively used in the clinical treatment of various types of cancer, the precise mechanism underlying its effectiveness in treating HCC remains unclear. In the present study, MHCC‑97H cells were treated with 125I, after which, cell viability and proliferation were assessed using Cell Counting Kit‑8, 5‑ethynyl‑2'‑deoxyuridine and colony formation assays, cell invasion and migration were evaluated using wound healing and Transwell assays, and cell apoptosis was determined using flow cytometry. Omics data were analyzed using Kyoto Encyclopedia of Genes and Genomes, Gene Ontology and STRING analyses to observe the key genes that exhibited significant changes at the transcriptional and protein levels in MHCC‑97H cells treated with 125I particles. Finally, the expression levels of key genes (GPNMB, C4BPA, CTH, H1‑0 and MT2A) were verified through reverse transcription quantitative PCR. Following treatment with 125I, the proliferation, invasion and migration of MHCC‑97H cells were inhibited, and apoptosis was enhanced. The results of omics data analysis indicated that the biological behavior of MHCC‑97H cells treated with 125I was related to the expression levels of CTH and MT2A genes. These findings indicated that intervention with 125I radiation particles may induce changes in gene expression, potentially influencing alterations in biological characteristics. In conclusion, these insights may shed light on the underlying mechanisms of 125I radiation particle therapy in HCC and offer novel targets for HCC treatment.
肝细胞癌(HCC)是世界范围内癌症相关死亡率和发病率的常见原因。虽然碘- 125 (125I)粒子近距离放射疗法已广泛用于临床治疗各种类型的癌症,但其治疗HCC有效的确切机制尚不清楚。在本研究中,MHCC - 97H细胞经125I处理后,使用细胞计数试剂盒- 8、5 -乙基- 2' -脱氧尿苷和集落形成试验评估细胞活力和增殖,使用伤口愈合和Transwell试验评估细胞侵袭和迁移,使用流式细胞术检测细胞凋亡。使用Kyoto Encyclopedia of Genes and Genomes、Gene Ontology和STRING分析对组学数据进行分析,观察125I颗粒处理的MHCC‑97H细胞中转录和蛋白水平发生显著变化的关键基因。最后,通过反转录定量PCR验证关键基因GPNMB、C4BPA、CTH、H1‑0和MT2A的表达水平。125I处理后,MHCC - 97H细胞的增殖、侵袭和迁移均受到抑制,凋亡增强。组学数据分析结果表明,125I处理MHCC - 97H细胞的生物学行为与CTH和MT2A基因的表达水平有关。这些发现表明,125I辐射颗粒的干预可能会诱导基因表达的变化,从而可能影响生物学特性的改变。总之,这些见解可能揭示125I放射粒子治疗HCC的潜在机制,并为HCC治疗提供新的靶点。
{"title":"Integrated transcriptomics and proteomics analysis of the impact of iodine‑125 in hepatocellular carcinoma.","authors":"Yang Yang, Wei Yang, Jie Shen, Enci Ding","doi":"10.3892/mmr.2025.13431","DOIUrl":"10.3892/mmr.2025.13431","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) is a common cause of cancer‑related mortality and morbidity worldwide. While iodine‑125 (<sup>125</sup>I) particle brachytherapy has been extensively used in the clinical treatment of various types of cancer, the precise mechanism underlying its effectiveness in treating HCC remains unclear. In the present study, MHCC‑97H cells were treated with <sup>125</sup>I, after which, cell viability and proliferation were assessed using Cell Counting Kit‑8, 5‑ethynyl‑2'‑deoxyuridine and colony formation assays, cell invasion and migration were evaluated using wound healing and Transwell assays, and cell apoptosis was determined using flow cytometry. Omics data were analyzed using Kyoto Encyclopedia of Genes and Genomes, Gene Ontology and STRING analyses to observe the key genes that exhibited significant changes at the transcriptional and protein levels in MHCC‑97H cells treated with <sup>125</sup>I particles. Finally, the expression levels of key genes (GPNMB, C4BPA, CTH, H1‑0 and MT2A) were verified through reverse transcription quantitative PCR. Following treatment with <sup>125</sup>I, the proliferation, invasion and migration of MHCC‑97H cells were inhibited, and apoptosis was enhanced. The results of omics data analysis indicated that the biological behavior of MHCC‑97H cells treated with <sup>125</sup>I was related to the expression levels of CTH and MT2A genes. These findings indicated that intervention with <sup>125</sup>I radiation particles may induce changes in gene expression, potentially influencing alterations in biological characteristics. In conclusion, these insights may shed light on the underlying mechanisms of <sup>125</sup>I radiation particle therapy in HCC and offer novel targets for HCC treatment.</p>","PeriodicalId":18818,"journal":{"name":"Molecular medicine reports","volume":"31 3","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11736249/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142951893","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 : 2025-03-01Epub Date: 2025-01-31DOI: 10.3892/mmr.2025.13441
Jianan Shen, Youxiang Ding
Insulin‑like growth factor 2 mRNA binding protein 2 (IGF2BP2) is an RNA binding protein that functions as an N6‑methyladenosine reader. It regulates various biological processes in human cancers by affecting the stability and expression of target RNA transcripts, including coding RNAs and non‑coding RNAs (ncRNAs). Numerous studies have shown that IGF2BP2 expression is aberrantly increased in various types of cancer and plays multifaceted roles in the development and progression of human cancers. In the present review, the clinical importance of IGF2BP2 is summarized and its involvement in the regulation of biological processes, including proliferation, metastasis, chemoresistance, metabolism, tumor immunity, stemness and cell death, in human cancers is discussed. The chemical compounds that have been developed as IGF2BP2 inhibitors are also detailed. As ncRNAs are now important potential therapeutic agents for cancer treatment, the microRNAs that have been reported to directly target and inhibit IGF2BP2 expression in cancers are also described. In summary, by reviewing the latest literature, the present study aimed to highlight the clinical importance and physiological functions of IGF2BP2 in human cancer, with a focus on the great potential of IGF2BP2 as a target for inhibitor development. The present review may inspire new ideas for future studies on IGF2BP2, which may serve as a specific therapeutic target in cancer.
{"title":"Multifaceted roles of insulin‑like growth factor 2 mRNA binding protein 2 in human cancer (Review).","authors":"Jianan Shen, Youxiang Ding","doi":"10.3892/mmr.2025.13441","DOIUrl":"10.3892/mmr.2025.13441","url":null,"abstract":"<p><p>Insulin‑like growth factor 2 mRNA binding protein 2 (IGF2BP2) is an RNA binding protein that functions as an N<sup>6</sup>‑methyladenosine reader. It regulates various biological processes in human cancers by affecting the stability and expression of target RNA transcripts, including coding RNAs and non‑coding RNAs (ncRNAs). Numerous studies have shown that IGF2BP2 expression is aberrantly increased in various types of cancer and plays multifaceted roles in the development and progression of human cancers. In the present review, the clinical importance of IGF2BP2 is summarized and its involvement in the regulation of biological processes, including proliferation, metastasis, chemoresistance, metabolism, tumor immunity, stemness and cell death, in human cancers is discussed. The chemical compounds that have been developed as IGF2BP2 inhibitors are also detailed. As ncRNAs are now important potential therapeutic agents for cancer treatment, the microRNAs that have been reported to directly target and inhibit IGF2BP2 expression in cancers are also described. In summary, by reviewing the latest literature, the present study aimed to highlight the clinical importance and physiological functions of IGF2BP2 in human cancer, with a focus on the great potential of IGF2BP2 as a target for inhibitor development. The present review may inspire new ideas for future studies on IGF2BP2, which may serve as a specific therapeutic target in cancer.</p>","PeriodicalId":18818,"journal":{"name":"Molecular medicine reports","volume":"31 3","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11795254/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143066692","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}
Cartilage‑hair hypoplasia (CHH) is an autosomal recessive form of metaphyseal chondrodysplasia caused by RNA component of mitochondrial RNA processing endoribonuclease (RMRP) gene variants; however, its molecular etiology remains unclear. Whole‑exome sequencing was performed to detect possible pathogenic variants in a patient with a typical short stature and sparse hair. A co‑segregation analysis was also conducted and variants in the family members of the patient were confirmed by Sanger sequencing. A novel compound heterozygous variant in RMRP (NR_003051.4: n.‑21_‑2dup and n.197C>T) was identified in the affected patient. Data from 2 years and 4 months of follow‑up showed a positive effect of growth hormone (GH) therapy on height. Subsequently, two gene expression profiles associated with CHH were obtained from the EMBL‑EBI ENA and ArrayExpress databases. Differentially expressed genes between patients with CHH and healthy controls were selected using R software and were subjected to core analysis using ingenuity pathway analysis (IPA) software. IPA core analysis showed that the 'cell cycle checkpoints' was the most prominent canonical pathway, and the top enriched diseases and functions included various types of cancer, immunological diseases, development disorders and respiratory diseases. The integrative analysis displayed that RMRP can regulate the aberrant expression of downstream targets mainly via the transcription factor TP53, which results in the inhibition of 'cell cycle checkpoints'; eventually, functions associated with the CHH phenotype, such as 'growth failure or short stature' are activated. In conclusion, novel disease‑causing genetic variants of RMRP expand the genetic etiology of CHH, which must be clinically differentiated from achondroplasia. The findings of the present study provide new insights into the mechanisms underlying CHH.
{"title":"RMRP variants inhibit the cell cycle checkpoints pathway in cartilage‑hair hypoplasia.","authors":"Jian Gao, Junge Zheng, Shiguo Chen, Sheng Lin, Shan Duan","doi":"10.3892/mmr.2025.13446","DOIUrl":"10.3892/mmr.2025.13446","url":null,"abstract":"<p><p>Cartilage‑hair hypoplasia (CHH) is an autosomal recessive form of metaphyseal chondrodysplasia caused by RNA component of mitochondrial RNA processing endoribonuclease (RMRP) gene variants; however, its molecular etiology remains unclear. Whole‑exome sequencing was performed to detect possible pathogenic variants in a patient with a typical short stature and sparse hair. A co‑segregation analysis was also conducted and variants in the family members of the patient were confirmed by Sanger sequencing. A novel compound heterozygous variant in RMRP (NR_003051.4: n.‑21_‑2dup and n.197C>T) was identified in the affected patient. Data from 2 years and 4 months of follow‑up showed a positive effect of growth hormone (GH) therapy on height. Subsequently, two gene expression profiles associated with CHH were obtained from the EMBL‑EBI ENA and ArrayExpress databases. Differentially expressed genes between patients with CHH and healthy controls were selected using R software and were subjected to core analysis using ingenuity pathway analysis (IPA) software. IPA core analysis showed that the 'cell cycle checkpoints' was the most prominent canonical pathway, and the top enriched diseases and functions included various types of cancer, immunological diseases, development disorders and respiratory diseases. The integrative analysis displayed that RMRP can regulate the aberrant expression of downstream targets mainly via the transcription factor TP53, which results in the inhibition of 'cell cycle checkpoints'; eventually, functions associated with the CHH phenotype, such as 'growth failure or short stature' are activated. In conclusion, novel disease‑causing genetic variants of RMRP expand the genetic etiology of CHH, which must be clinically differentiated from achondroplasia. The findings of the present study provide new insights into the mechanisms underlying CHH.</p>","PeriodicalId":18818,"journal":{"name":"Molecular medicine reports","volume":"31 3","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11800184/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143066782","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 : 2025-02-01Epub Date: 2024-12-05DOI: 10.3892/mmr.2024.13408
Fang Yang, Huiping Qin, Chaoqun Qin, Bing Huang, Feng Gao, Yi Liao, Yanping Tang, Yanju Mo, Qianjie Yang, Changming Wang
M1 macrophages activated by cigarette smoke extract (CSE) serve a pro‑inflammatory role in chronic obstructive pulmonary disease (COPD). The expression of silent information regulator 1 (SIRT1) is decreased in the alveolar macrophages of patients with COPD. However, whether SIRT1 is involved in COPD by regulating macrophage polarization remains unknown. Rat Alveolar Macrophage NR8383 cells were exposed to CSE. Cell Counting Kit‑8 assay, western blot assay and ELISA showed that with increasing concentration of CSE, the activity of NR8383 cells and expression of SIRT1 gradually decreased, while the release of inflammatory cytokines TNFα, IL‑1β and IL‑6 increased. As shown in western blot or Immunofluorescence assays, exposure to CSE also increased expression levels of the M1 markers inducible nitric oxide synthase and CD86, whereas it downregulated expression of the M2 markers arginase 1 and CD206. In addition, CSE increased expression of TNF receptor associated factor 6 (TRAF6), NOD‑like receptor thermal protein domain associated protein 3 (NLRP3) and cleaved caspase‑1 protein in NR8383 cells. Overexpression plasmids of SIRT1 and TRAF6 significantly reversed the aforementioned changes induced by CSE. Moreover, immunoprecipitation demonstrated that TRAF6 could bind to NLRP3. The overexpression of TRAF6 notably attenuated the regulatory effects of overexpression of SIRT1 on polarization and inflammation in NR8383 cells. Conversely, overexpression of SIRT1 inhibited the TRAF6/NLRP3 signaling pathway, thereby suppressing CSE‑induced M1 polarization and release of inflammatory factors in NR8383 cells. The present study demonstrates that SIRT1 regulates CSE‑induced alveolar macrophage polarization and inflammation by inhibiting the TRAF6/NLRP3 signaling pathway.
{"title":"SIRT1 regulates cigarette smoke extract‑induced alveolar macrophage polarization and inflammation by inhibiting the TRAF6/NLRP3 signaling pathway.","authors":"Fang Yang, Huiping Qin, Chaoqun Qin, Bing Huang, Feng Gao, Yi Liao, Yanping Tang, Yanju Mo, Qianjie Yang, Changming Wang","doi":"10.3892/mmr.2024.13408","DOIUrl":"10.3892/mmr.2024.13408","url":null,"abstract":"<p><p>M1 macrophages activated by cigarette smoke extract (CSE) serve a pro‑inflammatory role in chronic obstructive pulmonary disease (COPD). The expression of silent information regulator 1 (SIRT1) is decreased in the alveolar macrophages of patients with COPD. However, whether SIRT1 is involved in COPD by regulating macrophage polarization remains unknown. Rat Alveolar Macrophage NR8383 cells were exposed to CSE. Cell Counting Kit‑8 assay, western blot assay and ELISA showed that with increasing concentration of CSE, the activity of NR8383 cells and expression of SIRT1 gradually decreased, while the release of inflammatory cytokines TNFα, IL‑1β and IL‑6 increased. As shown in western blot or Immunofluorescence assays, exposure to CSE also increased expression levels of the M1 markers inducible nitric oxide synthase and CD86, whereas it downregulated expression of the M2 markers arginase 1 and CD206. In addition, CSE increased expression of TNF receptor associated factor 6 (TRAF6), NOD‑like receptor thermal protein domain associated protein 3 (NLRP3) and cleaved caspase‑1 protein in NR8383 cells. Overexpression plasmids of SIRT1 and TRAF6 significantly reversed the aforementioned changes induced by CSE. Moreover, immunoprecipitation demonstrated that TRAF6 could bind to NLRP3. The overexpression of TRAF6 notably attenuated the regulatory effects of overexpression of SIRT1 on polarization and inflammation in NR8383 cells. Conversely, overexpression of SIRT1 inhibited the TRAF6/NLRP3 signaling pathway, thereby suppressing CSE‑induced M1 polarization and release of inflammatory factors in NR8383 cells. The present study demonstrates that SIRT1 regulates CSE‑induced alveolar macrophage polarization and inflammation by inhibiting the TRAF6/NLRP3 signaling pathway.</p>","PeriodicalId":18818,"journal":{"name":"Molecular medicine reports","volume":"31 2","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11632293/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142786233","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}