Altered energy metabolism is an emerging hallmark of cancer and plays a pivotal in cell survival, proliferation, and biosynthesis. In a rapidly proliferating cancer, energy metabolism acts in synergism with epithelial-to-mesenchymal transition (EMT), enabling cancer stemness, dissemination, and metastasis. In this study, an interconnected functional network governing energy metabolism and EMT signaling pathways was targeted through the concurrent inhibition of IR, ITGB1, and CD36 activity. A novel multicomponent MD simulation approach was employed to portray the simultaneous inhibition of IR, ITGB1, and CD36 by a 2:1 combination of Pimozide and Ponatinib. Further, in-vitro studies revealed the synergistic anticancer efficacy of drugs against monolayer as well as tumor spheroids of breast cancer cell lines (MCF-7 and MDA-MB-231). In addition, the combination therapy exerted approximately 40% of the apoptotic population and more than 1.5- to 3-fold reduction in the expression of ITGB1, IR, p-IR, IRS-1, and p-AKT in MCF-7 and MDA-MB-231 cell lines. Moreover, the reduction in fatty acid uptake, lipid droplet accumulation, cancer stemness, and migration properties were also observed. Thus, targeting IR, ITGB1, and CD36 in the interconnected network with the combination of Pimozide and Ponatinib represents a promising therapeutic approach for breast cancer.
{"title":"Concurrent inhibition of IR, ITGB1, and CD36 perturbated the interconnected network of energy metabolism and epithelial-to-mesenchymal transition in breast cancer cells","authors":"Thirukumaran Kandasamy, Shilpi Sarkar, Plaboni Sen, Dheepika Venkatesh, Siddhartha Sankar Ghosh","doi":"10.1002/jcb.30574","DOIUrl":"10.1002/jcb.30574","url":null,"abstract":"<p>Altered energy metabolism is an emerging hallmark of cancer and plays a pivotal in cell survival, proliferation, and biosynthesis. In a rapidly proliferating cancer, energy metabolism acts in synergism with epithelial-to-mesenchymal transition (EMT), enabling cancer stemness, dissemination, and metastasis. In this study, an interconnected functional network governing energy metabolism and EMT signaling pathways was targeted through the concurrent inhibition of IR, ITGB1, and CD36 activity. A novel multicomponent MD simulation approach was employed to portray the simultaneous inhibition of IR, ITGB1, and CD36 by a 2:1 combination of Pimozide and Ponatinib. Further, in-vitro studies revealed the synergistic anticancer efficacy of drugs against monolayer as well as tumor spheroids of breast cancer cell lines (MCF-7 and MDA-MB-231). In addition, the combination therapy exerted approximately 40% of the apoptotic population and more than 1.5- to 3-fold reduction in the expression of ITGB1, IR, p-IR, IRS-1, and p-AKT in MCF-7 and MDA-MB-231 cell lines. Moreover, the reduction in fatty acid uptake, lipid droplet accumulation, cancer stemness, and migration properties were also observed. Thus, targeting IR, ITGB1, and CD36 in the interconnected network with the combination of Pimozide and Ponatinib represents a promising therapeutic approach for breast cancer.</p>","PeriodicalId":15219,"journal":{"name":"Journal of cellular biochemistry","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140862478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
P. G. Roopashree, Shilpa S. Shetty, Vijith Vittal Shetty, P. C. Suhasini, Kumari N. Suchetha
Medium-chain fatty acids (MCFAs) have 6–12 carbon atoms and are instantly absorbed into the bloodstream before traveling to the portal vein and the liver, where they are immediately used for energy and may have antitumor effects. Its role in breast cancer is poorly understood. To investigate the apoptosis-inducing effect of MCFAs in breast cancer cells, cell viability assay, colony formation assay, cell migration assay, cell invasion assay, nuclear morphology, cell cycle assay, intracellular reactive oxygen species (ROS), matrix metalloproteinase (MMP), apoptosis, RT-qPCR analysis, and Western blot analysis were performed. In the present study, MCFA treatments reduced proliferative capability, increased ROS level, increased the depletion of MMP, induced G0/G1 and S phase cell cycle arrest, and late apoptosis of breast cancer cells in an effective concentration. Besides, MCFA treatment contributed to the upregulation of proapoptotic protein (BAK) and caspase-3, and the downregulation of antiapoptotic protein (Bcl-2). Mechanistically, phosphorylation levels of EGFR, Akt, and mTOR were significantly reduced in breast cancer cells treated with MCFAs. However, no significant changes in apoptosis and signaling-related proteins were observed in lauric acid-treated ER-positive cancer cells. Our findings suggested that MCFAs suppressed breast cancer cell proliferation by modulating the PI3K/Akt/mTOR signaling pathway. MCFAs may be a promising therapeutic drug for treating breast cancer.
{"title":"Inhibitory effects of medium-chain fatty acids on the proliferation of human breast cancer cells via suppression of Akt/mTOR pathway and modulating the Bcl-2 family protein","authors":"P. G. Roopashree, Shilpa S. Shetty, Vijith Vittal Shetty, P. C. Suhasini, Kumari N. Suchetha","doi":"10.1002/jcb.30571","DOIUrl":"10.1002/jcb.30571","url":null,"abstract":"<p>Medium-chain fatty acids (MCFAs) have 6–12 carbon atoms and are instantly absorbed into the bloodstream before traveling to the portal vein and the liver, where they are immediately used for energy and may have antitumor effects. Its role in breast cancer is poorly understood. To investigate the apoptosis-inducing effect of MCFAs in breast cancer cells, cell viability assay, colony formation assay, cell migration assay, cell invasion assay, nuclear morphology, cell cycle assay, intracellular reactive oxygen species (ROS), matrix metalloproteinase (MMP), apoptosis, RT-qPCR analysis, and Western blot analysis were performed. In the present study, MCFA treatments reduced proliferative capability, increased ROS level, increased the depletion of MMP, induced G0/G1 and S phase cell cycle arrest, and late apoptosis of breast cancer cells in an effective concentration. Besides, MCFA treatment contributed to the upregulation of proapoptotic protein (BAK) and caspase-3, and the downregulation of antiapoptotic protein (Bcl-2). Mechanistically, phosphorylation levels of EGFR, Akt, and mTOR were significantly reduced in breast cancer cells treated with MCFAs. However, no significant changes in apoptosis and signaling-related proteins were observed in lauric acid-treated ER-positive cancer cells. Our findings suggested that MCFAs suppressed breast cancer cell proliferation by modulating the PI3K/Akt/mTOR signaling pathway. MCFAs may be a promising therapeutic drug for treating breast cancer.</p>","PeriodicalId":15219,"journal":{"name":"Journal of cellular biochemistry","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140652675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tilbe Özar, Aadil Javed, Gülseren Özduman, Kemal S. Korkmaz
Hematological and neurological expressed 1 (HN1), encoding a small protein, has been recently explored in different cancers owing to its higher expression in tumor samples as compared to adjacent normal. It was discovered and subsequently named because of its higher expression in hematological and neurological tissues in developing mice. Following discovery, it was considered a neuronal regeneration or dedifferentiation‐related gene. However, since then, it has not been characterized in neuroblastoma or differentiated neurons. SH‐SY5Y cell line presents a unique model of neuroblastoma often utilized in neurobiology research. In this study, first, we employed bioinformatics analysis along with in vitro evaluation using normal and retinoic acid (RA)‐differentiated SH‐SY5Y cells to determine the responses of HN1 and its function. The analysis revealed that HN1 expression is higher in neuroblastoma and lower in differentiated neurons and Parkinson's disease as compared to appropriate controls. Since HN1 coexpression network in neuroblastoma is found to be enriched in cell‐cycle‐related pathways, we have shown that HN1 expression increases in S‐phase and remains lower in the rest of the cell cycle phases. Moreover, HN1 expression is also correlated with the microtubule stability in SH‐SY5Y cells, which was investigated with nocodazole and taxol treatments. HN1 overexpression increased the ratio of S‐type cells (undifferentiated), indicating that it acts as a dedifferentiating factor in neuroblastoma cells. Moreover, cell cycle dynamics also changed upon HN1 overexpression with alternating effects on SH‐SY5Y and RA‐differentiated (N‐type) cells. Therefore, HN1 is a potential cell cycle regulatory element in the development of neuroblastoma or dedifferentiation of neurons, which requires further studies to decipher its mechanistic role.
{"title":"HN1 is a novel dedifferentiation factor involved in regulating the cell cycle and microtubules in SH‐SY5Y neuroblastoma cells","authors":"Tilbe Özar, Aadil Javed, Gülseren Özduman, Kemal S. Korkmaz","doi":"10.1002/jcb.30569","DOIUrl":"https://doi.org/10.1002/jcb.30569","url":null,"abstract":"<jats:italic>Hematological and neurological expressed 1</jats:italic> (<jats:italic>HN1</jats:italic>), encoding a small protein, has been recently explored in different cancers owing to its higher expression in tumor samples as compared to adjacent normal. It was discovered and subsequently named because of its higher expression in hematological and neurological tissues in developing mice. Following discovery, it was considered a neuronal regeneration or dedifferentiation‐related gene. However, since then, it has not been characterized in neuroblastoma or differentiated neurons. SH‐SY5Y cell line presents a unique model of neuroblastoma often utilized in neurobiology research. In this study, first, we employed bioinformatics analysis along with in vitro evaluation using normal and retinoic acid (RA)‐differentiated SH‐SY5Y cells to determine the responses of HN1 and its function. The analysis revealed that <jats:italic>HN1</jats:italic> expression is higher in neuroblastoma and lower in differentiated neurons and Parkinson's disease as compared to appropriate controls. Since HN1 coexpression network in neuroblastoma is found to be enriched in cell‐cycle‐related pathways, we have shown that HN1 expression increases in S‐phase and remains lower in the rest of the cell cycle phases. Moreover, HN1 expression is also correlated with the microtubule stability in SH‐SY5Y cells, which was investigated with nocodazole and taxol treatments. <jats:italic>HN1</jats:italic> overexpression increased the ratio of S‐type cells (undifferentiated), indicating that it acts as a dedifferentiating factor in neuroblastoma cells. Moreover, cell cycle dynamics also changed upon <jats:italic>HN1</jats:italic> overexpression with alternating effects on SH‐SY5Y and RA‐differentiated (N‐type) cells. Therefore, <jats:italic>HN1</jats:italic> is a potential cell cycle regulatory element in the development of neuroblastoma or dedifferentiation of neurons, which requires further studies to decipher its mechanistic role.","PeriodicalId":15219,"journal":{"name":"Journal of cellular biochemistry","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140612606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alex M. Woodworth, Kristine Hardy, Phillippa C. Taberlay, Joanne L. Dickinson, Adele F. Holloway
Runt-related transcription factor 1 (RUNX1) plays an important role in normal haematopoietic cell development and function, and its function is frequently disrupted in leukaemia. RUNX1 is widely recognised as a sequence-specific DNA binding factor that recognises the motif 5′-TG(T/C)GGT-3′ in promoter and enhancer regions of its target genes. Moreover, RUNX1 fusion proteins, such as RUNX1-ETO formed by the t(8;21) translocation, retain the ability to recognise and bind to this sequence to elicit atypical gene regulatory effects on bona fide RUNX1 targets. However, our analysis of publicly available RUNX1 chromatin immunoprecipitation sequencing (ChIP-Seq) data has provided evidence challenging this dogma, revealing that this motif-specific model of RUNX1 recruitment and function is incomplete. Our analyses revealed that the majority of RUNX1 genomic localisation occurs outside of promoters, that 20% of RUNX1 binding sites lack consensus RUNX motifs, and that binding in the absence of a cognate binding site is more common in promoter regions compared to distal sites. Reporter assays demonstrate that RUNX1 can drive promoter activity in the absence of a recognised DNA binding motif, in contrast to RUNX1-ETO. RUNX1-ETO supresses activity when it is recruited to promoters containing a sequence specific motif, while interestingly, it binds but does not repress promoters devoid of a RUNX1 recognition site. These data suggest that RUNX1 regulation of target genes occurs through multiple mechanisms depending on genomic location, the type of regulatory element and mode of recruitment.
{"title":"RUNX1 regulates promoter activity in the absence of cognate DNA binding motifs","authors":"Alex M. Woodworth, Kristine Hardy, Phillippa C. Taberlay, Joanne L. Dickinson, Adele F. Holloway","doi":"10.1002/jcb.30570","DOIUrl":"10.1002/jcb.30570","url":null,"abstract":"<p>Runt-related transcription factor 1 (RUNX1) plays an important role in normal haematopoietic cell development and function, and its function is frequently disrupted in leukaemia. RUNX1 is widely recognised as a sequence-specific DNA binding factor that recognises the motif 5′-TG(T/C)GGT-3′ in promoter and enhancer regions of its target genes. Moreover, RUNX1 fusion proteins, such as RUNX1-ETO formed by the <i>t</i>(8;21) translocation, retain the ability to recognise and bind to this sequence to elicit atypical gene regulatory effects on bona fide RUNX1 targets. However, our analysis of publicly available RUNX1 chromatin immunoprecipitation sequencing (ChIP-Seq) data has provided evidence challenging this dogma, revealing that this motif-specific model of RUNX1 recruitment and function is incomplete. Our analyses revealed that the majority of RUNX1 genomic localisation occurs outside of promoters, that 20% of RUNX1 binding sites lack consensus RUNX motifs, and that binding in the absence of a cognate binding site is more common in promoter regions compared to distal sites. Reporter assays demonstrate that RUNX1 can drive promoter activity in the absence of a recognised DNA binding motif, in contrast to RUNX1-ETO. RUNX1-ETO supresses activity when it is recruited to promoters containing a sequence specific motif, while interestingly, it binds but does not repress promoters devoid of a RUNX1 recognition site. These data suggest that RUNX1 regulation of target genes occurs through multiple mechanisms depending on genomic location, the type of regulatory element and mode of recruitment.</p>","PeriodicalId":15219,"journal":{"name":"Journal of cellular biochemistry","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcb.30570","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140588075","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
This study aimed to explore the effects of peroxisome proliferator-activated receptor γ (PPARγ) inhibition on fracture healing of nonunion and the underlying mechanisms. Bone marrow mesenchymal stem cells (BMSCs) were treated with PPARγ antagonist GW9662 (5 μM, 10 μM). Alkaline phosphatase (ALP) staining and Alizarin Red S was used to assess early stage of osteogenesis and osteogenic differentiation. GW9662 (1 mg/kg/day) were administered intraperitoneally into the rats with bone fracture. Bone healing processes in the rat femur fracture model were recorded and assessed by radiographic methods on Weeks 8, 14, and 20 postoperation. Osteogenesis and angiogenesis at the fracture sites were evaluated by radiographic and histological methods on postoperative Week 20. GW9662 treatment increased ALP activity and Alp mRNA expression in rat BMSCs. Moreover, GW9662 administration increased matrix mineralization and mRNA and protein levels of Bmp2 and Runx2 in the BMSCs. In addition, GW9662 treatment improved radiographic score in the fracture rats and increased osteogenesis-related proteins, including type I collagen, osteopontin, and osteoglycin, in the bone tissues of the fracture sites. In conclusion, PPARγ inhibition promotes osteogenic differentiation of rat BMSCs, as well as improves the fracture healing of rats through Bmp2/Runx2 signaling pathway in the rat model of bone fracture.
{"title":"PPARγ inhibition promotes osteogenic differentiation of bone marrow mesenchymal stem cells and fracture healing","authors":"Guohui Yang, Kexi Liu, Shengli Ma, Peiyi Qi","doi":"10.1002/jcb.30568","DOIUrl":"10.1002/jcb.30568","url":null,"abstract":"<p>This study aimed to explore the effects of peroxisome proliferator-activated receptor γ (PPARγ) inhibition on fracture healing of nonunion and the underlying mechanisms. Bone marrow mesenchymal stem cells (BMSCs) were treated with PPARγ antagonist GW9662 (5 μM, 10 μM). Alkaline phosphatase (ALP) staining and Alizarin Red S was used to assess early stage of osteogenesis and osteogenic differentiation. GW9662 (1 mg/kg/day) were administered intraperitoneally into the rats with bone fracture. Bone healing processes in the rat femur fracture model were recorded and assessed by radiographic methods on Weeks 8, 14, and 20 postoperation. Osteogenesis and angiogenesis at the fracture sites were evaluated by radiographic and histological methods on postoperative Week 20. GW9662 treatment increased ALP activity and <i>Alp</i> mRNA expression in rat BMSCs. Moreover, GW9662 administration increased matrix mineralization and mRNA and protein levels of Bmp2 and Runx2 in the BMSCs. In addition, GW9662 treatment improved radiographic score in the fracture rats and increased osteogenesis-related proteins, including type I collagen, osteopontin, and osteoglycin, in the bone tissues of the fracture sites. In conclusion, PPARγ inhibition promotes osteogenic differentiation of rat BMSCs, as well as improves the fracture healing of rats through Bmp2/Runx2 signaling pathway in the rat model of bone fracture.</p>","PeriodicalId":15219,"journal":{"name":"Journal of cellular biochemistry","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140588196","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Retraction: “H19 suppresses the growth of hepatoblastoma cells by promoting their apoptosis via the signaling pathways of miR‐675/FADD and miR‐138/PTK2” by Lili Ge, Xianwei Zhang, Shengnan Hu, Yinsen Song, Jinghui Kong, Bo Zhang, Xiaoang Yang, J Cell Biochem 2019, 120: 5218‐5231. The above article, published online on 26 October 2018 in Wiley Online Library (https://doi.org/10.1002/jcb.27797) has been retracted by agreement between the authors, the journal's Editor in Chief, Christian Behl, and Wiley Periodicals LLC.The decision to retract the article was made following a request for retraction from the authors. An initial assessment uncovered the duplication of image elements between Figure 2A and 2C.The editors believe that these findings compromise the interpretation of the data and results presented.
{"title":"Retraction: “H19 suppresses the growth of hepatoblastoma cells by promoting their apoptosis via the signaling pathways of miR‐675/FADD and miR‐138/PTK2”","authors":"","doi":"10.1002/jcb.30549","DOIUrl":"https://doi.org/10.1002/jcb.30549","url":null,"abstract":"Retraction: “H19 suppresses the growth of hepatoblastoma cells by promoting their apoptosis via the signaling pathways of miR‐675/FADD and miR‐138/PTK2” by Lili Ge, Xianwei Zhang, Shengnan Hu, Yinsen Song, Jinghui Kong, Bo Zhang, Xiaoang Yang, J Cell Biochem 2019, 120: 5218‐5231. The above article, published online on 26 October 2018 in Wiley Online Library (<jats:ext-link xmlns:xlink=\"http://www.w3.org/1999/xlink\" xlink:href=\"https://doi.org/10.1002/jcb.27797\">https://doi.org/10.1002/jcb.27797</jats:ext-link>) has been retracted by agreement between the authors, the journal's Editor in Chief, Christian Behl, and Wiley Periodicals LLC.The decision to retract the article was made following a request for retraction from the authors. An initial assessment uncovered the duplication of image elements between Figure 2A and 2C.The editors believe that these findings compromise the interpretation of the data and results presented.","PeriodicalId":15219,"journal":{"name":"Journal of cellular biochemistry","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140588195","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
High glucose (HG)-induced endothelial cell (EC) and smooth muscle cell (SMC) dysfunction is critical in diabetes-associated atherosclerosis. However, the roles of heme oxygenase-1 (HO-1), a stress-response protein, in hemodynamic force-generated shear stress and HG-induced metabolic stress remain unclear. This investigation examined the cellular effects and mechanisms of HO-1 under physiologically high shear stress (HSS) in HG-treated ECs and adjacent SMCs. We found that exposure of human aortic ECs to HSS significantly increased HO-1 expression; however, this upregulation appeared to be independent of adenosine monophosphate-activated protein kinase, a regulator of HO-1. Furthermore, HSS inhibited the expression of HG-induced intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and reactive oxygen species (ROS) production in ECs. In an EC/SMC co-culture, compared with static conditions, subjecting ECs close to SMCs to HSS and HG significantly suppressed SMC proliferation while increasing the expression of physiological contractile phenotype markers, such as α-smooth muscle actin and serum response factor. Moreover, HSS and HG decreased the expression of vimentin, an atherogenic synthetic phenotypic marker, in SMCs. Transfecting ECs with HO-1-specific small interfering (si)RNA reversed HSS inhibition on HG-induced inflammation and ROS production in ECs. Similarly, reversed HSS inhibition on HG-induced proliferation and synthetic phenotype formation were observed in co-cultured SMCs. Our findings provide insights into the mechanisms underlying EC-SMC interplay during HG-induced metabolic stress. Strategies to promote HSS in the vessel wall, such as continuous exercise, or the development of HO-1 analogs and mimics of the HSS effect, could provide an effective approach for preventing and treating diabetes-related atherosclerotic vascular complications.
{"title":"Activation of heme oxygenase-1 by laminar shear stress ameliorates high glucose-induced endothelial cell and smooth muscle cell dysfunction","authors":"Hung-Che Chien, Yu-Lin Wang, Yun-Chin Tu, Pi-Fen Tsui, Min-Chien Tsai","doi":"10.1002/jcb.30563","DOIUrl":"10.1002/jcb.30563","url":null,"abstract":"<p>High glucose (HG)-induced endothelial cell (EC) and smooth muscle cell (SMC) dysfunction is critical in diabetes-associated atherosclerosis. However, the roles of heme oxygenase-1 (HO-1), a stress-response protein, in hemodynamic force-generated shear stress and HG-induced metabolic stress remain unclear. This investigation examined the cellular effects and mechanisms of HO-1 under physiologically high shear stress (HSS) in HG-treated ECs and adjacent SMCs. We found that exposure of human aortic ECs to HSS significantly increased HO-1 expression; however, this upregulation appeared to be independent of adenosine monophosphate-activated protein kinase, a regulator of HO-1. Furthermore, HSS inhibited the expression of HG-induced intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and reactive oxygen species (ROS) production in ECs. In an EC/SMC co-culture, compared with static conditions, subjecting ECs close to SMCs to HSS and HG significantly suppressed SMC proliferation while increasing the expression of physiological contractile phenotype markers, such as α-smooth muscle actin and serum response factor. Moreover, HSS and HG decreased the expression of vimentin, an atherogenic synthetic phenotypic marker, in SMCs. Transfecting ECs with HO-1-specific small interfering (si)RNA reversed HSS inhibition on HG-induced inflammation and ROS production in ECs. Similarly, reversed HSS inhibition on HG-induced proliferation and synthetic phenotype formation were observed in co-cultured SMCs. Our findings provide insights into the mechanisms underlying EC-SMC interplay during HG-induced metabolic stress. Strategies to promote HSS in the vessel wall, such as continuous exercise, or the development of HO-1 analogs and mimics of the HSS effect, could provide an effective approach for preventing and treating diabetes-related atherosclerotic vascular complications.</p>","PeriodicalId":15219,"journal":{"name":"Journal of cellular biochemistry","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140588082","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Retraction: “Downregulation of long noncoding RNA SNHG1 inhibits cell proliferation, metastasis, and invasion by suppressing the Notch‐1 signaling pathway in pancreatic cancer” by Long Cui, Yadong Dong, Xiaochuan Wang, Xin Zhao, Chenchen Kong, Yangsui Liu, Xinchun Jiang, Xinhui Zhang, J Cell Biochem 2019, 120: 6106‐6112. The above article, published online on 5 December 2018 in Wiley Online Library (https://onlinelibrary.wiley.com/doi/10.1002/jcb.27897) has been retracted by agreement between the authors, the journal's Editor in Chief, Christian Behl, and Wiley Periodicals LLC.The retraction has been agreed upon authors’ request due to concerns related to the data presented in the article. The authors admitted several mistakes during figure compilation resulting in flaws and inconsistencies between results presented and experimental methods described. Thus, the conclusions of this article are considered invalid.
撤稿:"Downregulation of long noncoding RNA SNHG1 inhibits cell proliferation, metastasis, and invasion by suppressing the Notch-1 signaling pathway in pancreatic cancer" by Long Cui, Yadong Dong, Xiaochuan Wang, Xin Zhao, Chenchen Kong, Yangsui Liu, Xinchun Jiang, Xinhui Zhang, J Cell Biochem 2019, 120: 6106-6112.上述文章于2018年12月5日在线发表于《Wiley Online Library》(https://onlinelibrary.wiley.com/doi/10.1002/jcb.27897),经作者、该杂志主编Christian Behl和Wiley Periodicals LLC三方协商,已同意撤回该文章。由于对文章中数据的担忧,经作者请求,已同意撤回该文章。作者承认在图表编辑过程中出现了一些错误,导致所提供的结果与所描述的实验方法之间存在缺陷和不一致。因此,这篇文章的结论被认为是无效的。
{"title":"Retraction: “Downregulation of long noncoding RNA SNHG1 inhibits cell proliferation, metastasis, and invasion by suppressing the Notch‐1 signaling pathway in pancreatic cancer”","authors":"","doi":"10.1002/jcb.30550","DOIUrl":"https://doi.org/10.1002/jcb.30550","url":null,"abstract":"Retraction: “Downregulation of long noncoding RNA SNHG1 inhibits cell proliferation, metastasis, and invasion by suppressing the Notch‐1 signaling pathway in pancreatic cancer” by Long Cui, Yadong Dong, Xiaochuan Wang, Xin Zhao, Chenchen Kong, Yangsui Liu, Xinchun Jiang, Xinhui Zhang, <jats:italic>J Cell Biochem</jats:italic> 2019, 120: 6106‐6112. The above article, published online on 5 December 2018 in Wiley Online Library (<jats:ext-link xmlns:xlink=\"http://www.w3.org/1999/xlink\" xlink:href=\"https://onlinelibrary.wiley.com/doi/10.1002/jcb.27897\">https://onlinelibrary.wiley.com/doi/10.1002/jcb.27897</jats:ext-link>) has been retracted by agreement between the authors, the journal's Editor in Chief, Christian Behl, and Wiley Periodicals LLC.The retraction has been agreed upon authors’ request due to concerns related to the data presented in the article. The authors admitted several mistakes during figure compilation resulting in flaws and inconsistencies between results presented and experimental methods described. Thus, the conclusions of this article are considered invalid.","PeriodicalId":15219,"journal":{"name":"Journal of cellular biochemistry","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140588204","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
(https://onlinelibrary.wiley.com/doi/10.1002/jcb.24742) has been retracted by agreement between the journal's Editor in Chief, Christian Behl, and Wiley Periodicals LLC.The retraction has been agreed following an investigation based on allegations raised by a third party. Several flaws and inconsistencies between results presented and experimental methods described were found. Thus, the editors consider the conclusions of this article to be invalid. The authors were not available for a final confirmation of the retraction.
{"title":"Retraction: ‘MicroRNA‐198 Inhibits Proliferation and Induces Apoptosis of Lung Cancer Cells Via Targeting FGFR1’","authors":"","doi":"10.1002/jcb.30547","DOIUrl":"https://doi.org/10.1002/jcb.30547","url":null,"abstract":"(<jats:ext-link xmlns:xlink=\"http://www.w3.org/1999/xlink\" xlink:href=\"https://onlinelibrary.wiley.com/doi/10.1002/jcb.24742\">https://onlinelibrary.wiley.com/doi/10.1002/jcb.24742</jats:ext-link>) has been retracted by agreement between the journal's Editor in Chief, Christian Behl, and Wiley Periodicals LLC.The retraction has been agreed following an investigation based on allegations raised by a third party. Several flaws and inconsistencies between results presented and experimental methods described were found. Thus, the editors consider the conclusions of this article to be invalid. The authors were not available for a final confirmation of the retraction.","PeriodicalId":15219,"journal":{"name":"Journal of cellular biochemistry","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140588205","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bruna I. Pilger, Alex Castro, Franciane F. Vasconcellos, Karen F. Moura, Étore De Favari Signini, Luis Felipe B. Marqueze, Edson A. Fiorenza-Neto, Mateus T. Rocha, Giulia S. Pedroso, Claudia R. Cavaglieri, Antonio G. Ferreira, Caique Figueiredo, Luciele G. Minuzzi, Guilherme H. Gatti da Silva, Gabriela S. Castro, Fábio S. Lira, Marilia Seelaender, Ricardo A. Pinho
We investigated the effects of obesity on metabolic, inflammatory, and oxidative stress parameters in the adipose tissue of patients with fatal COVID-19. Postmortem biopsies of subcutaneous adipose tissue were obtained from 25 unvaccinated inpatients who passed from COVID-19, stratified as nonobese (N-OB; body mass index [BMI], 26.5 ± 2.3 kg m−2) or obese (OB BMI 34.2 ± 5.1 kg m−2). Univariate and multivariate analyses revealed that body composition was responsible for most of the variations detected in the metabolome, with greater dispersion observed in the OB group. Fifteen metabolites were major segregation factors. Results from the OB group showed higher levels of creatinine, myo-inositol, O-acetylcholine, and succinate, and lower levels of sarcosine. The N-OB group showed lower levels of glutathione peroxidase activity, as well as higher content of IL-6 and adiponectin. We revealed significant changes in the metabolomic profile of the adipose tissue in fatal COVID-19 cases, with high adiposity playing a key role in these observed variations. These findings highlight the potential involvement of metabolic and inflammatory pathways, possibly dependent on hypoxia, shedding light on the impact of obesity on disease pathogenesis and suggesting avenues for further research and possible therapeutic targets.
{"title":"Obesity-dependent molecular alterations in fatal COVID-19: A retrospective postmortem study of metabolomic profile of adipose tissue","authors":"Bruna I. Pilger, Alex Castro, Franciane F. Vasconcellos, Karen F. Moura, Étore De Favari Signini, Luis Felipe B. Marqueze, Edson A. Fiorenza-Neto, Mateus T. Rocha, Giulia S. Pedroso, Claudia R. Cavaglieri, Antonio G. Ferreira, Caique Figueiredo, Luciele G. Minuzzi, Guilherme H. Gatti da Silva, Gabriela S. Castro, Fábio S. Lira, Marilia Seelaender, Ricardo A. Pinho","doi":"10.1002/jcb.30566","DOIUrl":"10.1002/jcb.30566","url":null,"abstract":"<p>We investigated the effects of obesity on metabolic, inflammatory, and oxidative stress parameters in the adipose tissue of patients with fatal COVID-19. Postmortem biopsies of subcutaneous adipose tissue were obtained from 25 unvaccinated inpatients who passed from COVID-19, stratified as nonobese (N-OB; body mass index [BMI], 26.5 ± 2.3 kg m<sup>−2</sup>) or obese (OB BMI 34.2 ± 5.1 kg m<sup>−2</sup>). Univariate and multivariate analyses revealed that body composition was responsible for most of the variations detected in the metabolome, with greater dispersion observed in the OB group. Fifteen metabolites were major segregation factors. Results from the OB group showed higher levels of creatinine, myo-inositol, O-acetylcholine, and succinate, and lower levels of sarcosine. The N-OB group showed lower levels of glutathione peroxidase activity, as well as higher content of IL-6 and adiponectin. We revealed significant changes in the metabolomic profile of the adipose tissue in fatal COVID-19 cases, with high adiposity playing a key role in these observed variations. These findings highlight the potential involvement of metabolic and inflammatory pathways, possibly dependent on hypoxia, shedding light on the impact of obesity on disease pathogenesis and suggesting avenues for further research and possible therapeutic targets.</p>","PeriodicalId":15219,"journal":{"name":"Journal of cellular biochemistry","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140588199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}