RETRACTION: U. K. Misra and S. V. Pizzo, “Epac1-Induced Cellular Proliferation in Prostate Cancer Cells Is Mediated by B-Raf/ERK and mTOR Signaling Cascades,” Journal of Cellular Biochemistry 108, no. 4 (2009): 998–1011, https://doi.org/10.1002/jcb.22333.
The above article, published online on 1 September 2009 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, Christian Behl; and Wiley Periodicals LLC. The retraction has been agreed due to concerns raised by third parties. Specifically, duplication of image elements has been detected between Figures 2A and 4B, between Figure 3B and 3D, and between Figures 3B and 4C. In all instances, these image elements have been used to represent different experimental conditions. An institutional review confirmed the validity of the concerns. Accordingly, the article is retracted as the editors have lost trust in the accuracy and integrity of the whole body of data and consider the conclusions of the article invalid. The authors have been informed of the decision of retraction.
引用本文：U. K. Misra和S. V. Pizzo，“epac1诱导前列腺癌细胞增殖的B-Raf/ERK和mTOR信号级联介导”，《细胞生物化学杂志》第108期。4 (2009): 998-1011, https://doi.org/10.1002/jcb.22333.The上述文章于2009年9月1日在线发表在Wiley在线图书馆（wileyonlinelibrary.com）上，经期刊主编Christian Behl；和Wiley期刊有限责任公司。由于第三方提出的担忧，已同意撤回。具体来说，在图2A和4B之间、图3B和3D之间以及图3B和4C之间发现了图像元素的重复。在所有情况下，这些图像元素被用来表示不同的实验条件。一项机构审查证实了这些担忧的有效性。因此，由于编辑对整个数据的准确性和完整性失去信任，并认为文章的结论无效，文章被撤回。作者已被告知撤稿的决定。
{"title":"RETRACTION: Epac1-Induced Cellular Proliferation in Prostate Cancer Cells Is Mediated by B-Raf/ERK and mTOR Signaling Cascades","authors":"","doi":"10.1002/jcb.70046","DOIUrl":"https://doi.org/10.1002/jcb.70046","url":null,"abstract":"<p><b>RETRACTION</b>: U. K. Misra and S. V. Pizzo, “Epac1-Induced Cellular Proliferation in Prostate Cancer Cells Is Mediated by B-Raf/ERK and mTOR Signaling Cascades,” <i>Journal of Cellular Biochemistry</i> 108, no. 4 (2009): 998–1011, https://doi.org/10.1002/jcb.22333.</p><p>The above article, published online on 1 September 2009 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, Christian Behl; and Wiley Periodicals LLC. The retraction has been agreed due to concerns raised by third parties. Specifically, duplication of image elements has been detected between Figures 2A and 4B, between Figure 3B and 3D, and between Figures 3B and 4C. In all instances, these image elements have been used to represent different experimental conditions. An institutional review confirmed the validity of the concerns. Accordingly, the article is retracted as the editors have lost trust in the accuracy and integrity of the whole body of data and consider the conclusions of the article invalid. The authors have been informed of the decision of retraction.</p>","PeriodicalId":15219,"journal":{"name":"Journal of cellular biochemistry","volume":"126 7","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcb.70046","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144624739","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}
RETRACTION: U. K. Misra, and S. V. Pizzo, “Activation of Akt/PDK Signaling in Macrophages Upon Binding of Receptor-Recognized Forms of α2-Macroglobulin to Its Cellular Receptor: Effect of Silencing the CREB Gene,” Journal of Cellular Biochemistry 93, no. 5 (2004): 1020–1032, https://doi.org/10.1002/jcb.20233.
The above article, published online on 9 September 2004 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, Christian Behl; and Wiley Periodicals LLC. The retraction has been agreed due to concerns raised by third parties. Specifically, duplication of image elements has been detected between Figures 2A and 5A, within Figure 3 and between Figures 3 and 4B, and between Figures 4A and 6. In all instances, these image elements have been used to represent different experimental conditions. An institutional review confirmed the validity of the concerns. Accordingly, the article is retracted as the editors have lost trust in the accuracy and integrity of the whole body of data and consider the conclusions of the article invalid. The authors have been informed of the decision of retraction.
{"title":"RETRACTION: Activation of Akt/PDK Signaling in Macrophages Upon Binding of Receptor-Recognized Forms of α2-Macroglobulin to Its Cellular Receptor: Effect of Silencing the CREB Gene","authors":"","doi":"10.1002/jcb.70044","DOIUrl":"https://doi.org/10.1002/jcb.70044","url":null,"abstract":"<p><b>RETRACTION</b>: U. K. Misra, and S. V. Pizzo, “Activation of Akt/PDK Signaling in Macrophages Upon Binding of Receptor-Recognized Forms of α2-Macroglobulin to Its Cellular Receptor: Effect of Silencing the CREB Gene,” <i>Journal of Cellular Biochemistry</i> 93, no. 5 (2004): 1020–1032, https://doi.org/10.1002/jcb.20233.</p><p>The above article, published online on 9 September 2004 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, Christian Behl; and Wiley Periodicals LLC. The retraction has been agreed due to concerns raised by third parties. Specifically, duplication of image elements has been detected between Figures 2A and 5A, within Figure 3 and between Figures 3 and 4B, and between Figures 4A and 6. In all instances, these image elements have been used to represent different experimental conditions. An institutional review confirmed the validity of the concerns. Accordingly, the article is retracted as the editors have lost trust in the accuracy and integrity of the whole body of data and consider the conclusions of the article invalid. The authors have been informed of the decision of retraction.</p>","PeriodicalId":15219,"journal":{"name":"Journal of cellular biochemistry","volume":"126 7","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcb.70044","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144624740","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}
RETRACTION: U. K. Misra and S. V. Pizzo, “Upregulation of mTORC2 Activation by the Selective Agonist of EPAC, 8-CPT-2Me-cAMP, in Prostate Cancer Cells: Assembly of a Multiprotein Signaling Complex,” Journal of Cellular Biochemistry 113, no. 5 (2011): 1488–1500, https://doi.org/10.1002/jcb.24018.
The above article, published online on 15 December 2011 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, Christian Behl; and Wiley Periodicals LLC. The retraction has been agreed due to concerns raised by third parties. Specifically, duplication of image elements has been detected between Figures 4C and 7B, between Figure 7A and 7B, and within Figure 6C. An institutional review confirmed the validity of the concerns. Accordingly, the article is retracted as the editors have lost trust in the accuracy and integrity of the whole body of data and consider the conclusions of the article invalid. The authors have been informed of the decision of retraction.
撤回：U. K. Misra和S. V. Pizzo，“选择性激动剂EPAC， 8-CPT-2Me-cAMP在前列腺癌细胞中mTORC2激活的上调：多蛋白信号复合物的组装”，细胞生物化学杂志，第113期。5 (2011): 1488-1500, https://doi.org/10.1002/jcb.24018.The上述文章于2011年12月15日在线发表在Wiley online Library （wileyonlinelibrary.com）上，经主编Christian Behl；和Wiley期刊有限责任公司。由于第三方提出的担忧，已同意撤回。具体来说，在图4C和图7B之间、图7A和图7B之间以及图6C内部都发现了重复的图像元素。一项机构审查证实了这些担忧的有效性。因此，由于编辑对整个数据的准确性和完整性失去信任，并认为文章的结论无效，文章被撤回。作者已被告知撤稿的决定。
{"title":"RETRACTION: Upregulation of mTORC2 Activation by the Selective Agonist of EPAC, 8-CPT-2Me-cAMP, in Prostate Cancer Cells: Assembly of a Multiprotein Signaling Complex","authors":"","doi":"10.1002/jcb.70048","DOIUrl":"https://doi.org/10.1002/jcb.70048","url":null,"abstract":"<p><b>RETRACTION:</b> U. K. Misra and S. V. Pizzo, “Upregulation of mTORC2 Activation by the Selective Agonist of EPAC, 8-CPT-2Me-cAMP, in Prostate Cancer Cells: Assembly of a Multiprotein Signaling Complex,” <i>Journal of Cellular Biochemistry</i> 113, no. 5 (2011): 1488–1500, https://doi.org/10.1002/jcb.24018.</p><p>The above article, published online on 15 December 2011 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, Christian Behl; and Wiley Periodicals LLC. The retraction has been agreed due to concerns raised by third parties. Specifically, duplication of image elements has been detected between Figures 4C and 7B, between Figure 7A and 7B, and within Figure 6C. An institutional review confirmed the validity of the concerns. Accordingly, the article is retracted as the editors have lost trust in the accuracy and integrity of the whole body of data and consider the conclusions of the article invalid. The authors have been informed of the decision of retraction.</p>","PeriodicalId":15219,"journal":{"name":"Journal of cellular biochemistry","volume":"126 7","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcb.70048","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144624741","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}
RETRACTION: U. K. Misra, Y. M. Mowery, G. Gawdi, and S. V. Pizzo, “Loss of Cell Surface TFII-I Promotes Apoptosis in Prostate Cancer Cells Stimulated With Activated α2-Macroglobulin*,” Journal of Cellular Biochemistry 112, no. 6 (2011): 1685–1695, https://doi.org/10.1002/jcb.23083
The above article, published online on 24 February 2011 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, Christian Behl; and Wiley Periodicals LLC. The retraction has been agreed due to concerns raised by third parties. Specifically, duplication of image elements has been detected between Figures 1A and 3, and within Figure 3. In all instances, these image elements have been used to represent different experimental conditions. An institutional review confirmed the validity of the concerns. Accordingly, the article is retracted as the editors have lost trust in the accuracy and integrity of the whole body of data and consider the conclusions of the article invalid. The authors have been informed of the decision of retraction.
{"title":"RETRACTION: Loss of Cell Surface TFII-I Promotes Apoptosis in Prostate Cancer Cells Stimulated With Activated α2-Macroglobulin*","authors":"","doi":"10.1002/jcb.70047","DOIUrl":"https://doi.org/10.1002/jcb.70047","url":null,"abstract":"<p><b>RETRACTION:</b> U. K. Misra, Y. M. Mowery, G. Gawdi, and S. V. Pizzo, “Loss of Cell Surface TFII-I Promotes Apoptosis in Prostate Cancer Cells Stimulated With Activated α2-Macroglobulin*,” <i>Journal of Cellular Biochemistry</i> 112, no. 6 (2011): 1685–1695, https://doi.org/10.1002/jcb.23083</p><p>The above article, published online on 24 February 2011 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, Christian Behl; and Wiley Periodicals LLC. The retraction has been agreed due to concerns raised by third parties. Specifically, duplication of image elements has been detected between Figures 1A and 3, and within Figure 3. In all instances, these image elements have been used to represent different experimental conditions. An institutional review confirmed the validity of the concerns. Accordingly, the article is retracted as the editors have lost trust in the accuracy and integrity of the whole body of data and consider the conclusions of the article invalid. The authors have been informed of the decision of retraction.</p>","PeriodicalId":15219,"journal":{"name":"Journal of cellular biochemistry","volume":"126 7","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcb.70047","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144624742","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}
H. Li, W. Gong, W. Sun, Y. Yao, and Y. Han, “Role of VPS39, a Key Tethering Protein for Endolysosomal Trafficking and Mitochondria-Lysosome Crosstalk, in Health and Disease,” Journal of Cellular Biochemistry 125, no. 11 (2024): e30396, https://doi.org/10.1002/jcb.30396.
In the article, there is an error in the citation numbering starting from the second paragraph of Section 4.1. The reference numbers in the text do not match the final reference list, and similar discrepancies occur in Table 2.
We apologize for this error.
Correction to “Role of VPS39, A Key Tethering Protein for Endolysosomal Trafficking And Mitochondria–Lysosome Crosstalk, in Health and Disease”
The reference numbers in Table 2 have also been corrected in the same way as the text. Each reference number has been increased by 2 to match the correct reference numbers, as follows:
“88” has been changed to “90”; “89” has been changed to “91”; “90” has been changed to “92”; “91” has been changed to “93”; “92” has been changed to “94”; “93” has been changed to “95”; “94” has been changed to “96”; “95” has been changed to “97”; “96” and “97” have been changed to “98” and “99”; “98” has been changed to “100”; “99” has been changed to “101”; “100” and “101” have been changed to “102” and “103”; “102” has been changed to “104”; “102-104” has been changed to “104–106”; “105” has been changed to “107”; “106” has been changed to “108.”
{"title":"Correction to “Role of VPS39, a Key Tethering Protein for Endolysosomal Trafficking and Mitochondria–Lysosome Crosstalk, in Health and Disease”","authors":"","doi":"10.1002/jcb.70041","DOIUrl":"10.1002/jcb.70041","url":null,"abstract":"<p>H. Li, W. Gong, W. Sun, Y. Yao, and Y. Han, “Role of VPS39, a Key Tethering Protein for Endolysosomal Trafficking and Mitochondria-Lysosome Crosstalk, in Health and Disease,” <i>Journal of Cellular Biochemistry</i> 125, no. 11 (2024): e30396, https://doi.org/10.1002/jcb.30396.</p><p>In the article, there is an error in the citation numbering starting from the second paragraph of Section 4.1. The reference numbers in the text do not match the final reference list, and similar discrepancies occur in Table 2.</p><p>We apologize for this error.</p><p>Correction to “Role of VPS39, A Key Tethering Protein for Endolysosomal Trafficking And Mitochondria–Lysosome Crosstalk, in Health and Disease”</p><p>The reference numbers in Table 2 have also been corrected in the same way as the text. Each reference number has been increased by 2 to match the correct reference numbers, as follows:</p><p>“88” has been changed to “90”; “89” has been changed to “91”; “90” has been changed to “92”; “91” has been changed to “93”; “92” has been changed to “94”; “93” has been changed to “95”; “94” has been changed to “96”; “95” has been changed to “97”; “96” and “97” have been changed to “98” and “99”; “98” has been changed to “100”; “99” has been changed to “101”; “100” and “101” have been changed to “102” and “103”; “102” has been changed to “104”; “102-104” has been changed to “104–106”; “105” has been changed to “107”; “106” has been changed to “108.”</p>","PeriodicalId":15219,"journal":{"name":"Journal of cellular biochemistry","volume":"126 7","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcb.70041","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144567483","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}
Beta-hydroxybutyrate (BHB), a key ketone body produced during fatty acid metabolism, plays critical roles in various physiological and pathological conditions. Synthesized in the liver through ketogenesis, BHB serves as an essential energy substrate during glucose deprivation, supporting survival by efficiently utilizing fat reserves. It crosses the blood-brain barrier, providing energy for neuronal function, enhancing cognitive processes such as learning and memory, and offering neuroprotection by modulating synaptic plasticity and neurotransmitter levels. BHB's impact extends to cellular pathways, including autophagy, mitochondrial biogenesis, and epigenetic regulation. By modulating autophagy, BHB ensures mitochondrial integrity and function through intricate molecular pathways involving AMPK, mTOR, PINK1/Parkin, and others. This regulation plays vital roles in neurodegenerative diseases, metabolic disorders, cancer, and cardiovascular diseases, reducing oxidative stress and preventing cellular dysfunction. Epigenetically, BHB acts as an endogenous histone deacetylase inhibitor, inducing beneficial histone modifications that enhance cellular resilience and stress responses. This epigenetic influence is crucial in conditions like diabetes and cancer, aiding insulin secretion, protecting pancreatic beta cells, and impacting cancer cell gene expression and survival. Furthermore, BHB's therapeutic potential is evident in its ability to improve mitochondrial function across various tissues, including neurons, muscle, and liver. By enhancing mitochondrial respiration, reducing oxidative stress, and altering metabolic pathways, BHB mitigates conditions such as ICU-acquired weakness, nonalcoholic fatty liver disease, and cardiovascular diseases. BHB's modulation of autophagy and epigenetic regulation underscores its comprehensive role in cellular homeostasis and health across multiple physiological contexts, providing a foundation for future therapeutic strategies.
{"title":"The Multifaceted Influence of Beta-Hydroxybutyrate on Autophagy, Mitochondrial Metabolism, and Epigenetic Regulation","authors":"Sajad Ehtiati, Behzad Hatami, Seyyed Hossein Khatami, Kiarash Tajernarenj, Saeed Abdi, Majid Sirati-Sabet, Seyyed Amir Hossein Ghazizadeh Hashemi, Reyhane Ahmadzade, Nastran Hamed, Marziyeh Goudarzi, Fatemeh Namvarjah, Melika Hajimohammadebrahim-Ketabforoush, Abbas Tafakhori, Vajiheh Aghamollaii, Saeed Karima","doi":"10.1002/jcb.70050","DOIUrl":"https://doi.org/10.1002/jcb.70050","url":null,"abstract":"<div>\u0000 \u0000 <p>Beta-hydroxybutyrate (BHB), a key ketone body produced during fatty acid metabolism, plays critical roles in various physiological and pathological conditions. Synthesized in the liver through ketogenesis, BHB serves as an essential energy substrate during glucose deprivation, supporting survival by efficiently utilizing fat reserves. It crosses the blood-brain barrier, providing energy for neuronal function, enhancing cognitive processes such as learning and memory, and offering neuroprotection by modulating synaptic plasticity and neurotransmitter levels. BHB's impact extends to cellular pathways, including autophagy, mitochondrial biogenesis, and epigenetic regulation. By modulating autophagy, BHB ensures mitochondrial integrity and function through intricate molecular pathways involving AMPK, mTOR, PINK1/Parkin, and others. This regulation plays vital roles in neurodegenerative diseases, metabolic disorders, cancer, and cardiovascular diseases, reducing oxidative stress and preventing cellular dysfunction. Epigenetically, BHB acts as an endogenous histone deacetylase inhibitor, inducing beneficial histone modifications that enhance cellular resilience and stress responses. This epigenetic influence is crucial in conditions like diabetes and cancer, aiding insulin secretion, protecting pancreatic beta cells, and impacting cancer cell gene expression and survival. Furthermore, BHB's therapeutic potential is evident in its ability to improve mitochondrial function across various tissues, including neurons, muscle, and liver. By enhancing mitochondrial respiration, reducing oxidative stress, and altering metabolic pathways, BHB mitigates conditions such as ICU-acquired weakness, nonalcoholic fatty liver disease, and cardiovascular diseases. BHB's modulation of autophagy and epigenetic regulation underscores its comprehensive role in cellular homeostasis and health across multiple physiological contexts, providing a foundation for future therapeutic strategies.</p>\u0000 </div>","PeriodicalId":15219,"journal":{"name":"Journal of cellular biochemistry","volume":"126 6","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144514958","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}
Pooja Anantha, Xiangdong Wu, Salaheldeen Elsaid, Piyush Raj, Junkai Hu, Ishan Barman, Sui Seng Tee
The thermogenic capacity of brown adipose tissue (BAT) has garnered much attention for its potential to regulate systemic energy balance. BAT depot size and function need to be tightly regulated to prevent loss of metabolic homeostasis due to energy dissipation via non-shivering thermogenesis. While adipocyte-intrinsic mechanisms controlling thermogenesis are critical, an increasing appreciation for the role of the BAT microenvironment is emerging. For example, changes in circulating hexoses due to dietary intake have shown to impact BAT function. Here, we show that murine BAT preadipocytes metabolism is impacted when fructose is used as the sole carbon source. Similarly, differentiation medium containing only fructose yield mature adipocytes with fewer lipid droplets, with a concomitant decrease in adipogenic genes. These deficiencies are also observed in human BAT preadipocytes, where cutting-edge optical imaging modalities show a decrease in total cell mass and lipid mass in fructose-only medium. Taken together, the metabolic microenvironment significantly impacts BAT growth and function, with implications for the role of diets potentially mitigating the efficacy of BAT-targeted therapies.
{"title":"Sweet Science: Exploring the Impact of Fructose and Glucose on Brown Adipocyte Differentiation Using Optical Diffraction Tomography","authors":"Pooja Anantha, Xiangdong Wu, Salaheldeen Elsaid, Piyush Raj, Junkai Hu, Ishan Barman, Sui Seng Tee","doi":"10.1002/jcb.70052","DOIUrl":"https://doi.org/10.1002/jcb.70052","url":null,"abstract":"<p>The thermogenic capacity of brown adipose tissue (BAT) has garnered much attention for its potential to regulate systemic energy balance. BAT depot size and function need to be tightly regulated to prevent loss of metabolic homeostasis due to energy dissipation via non-shivering thermogenesis. While adipocyte-intrinsic mechanisms controlling thermogenesis are critical, an increasing appreciation for the role of the BAT microenvironment is emerging. For example, changes in circulating hexoses due to dietary intake have shown to impact BAT function. Here, we show that murine BAT preadipocytes metabolism is impacted when fructose is used as the sole carbon source. Similarly, differentiation medium containing only fructose yield mature adipocytes with fewer lipid droplets, with a concomitant decrease in adipogenic genes. These deficiencies are also observed in human BAT preadipocytes, where cutting-edge optical imaging modalities show a decrease in total cell mass and lipid mass in fructose-only medium. Taken together, the metabolic microenvironment significantly impacts BAT growth and function, with implications for the role of diets potentially mitigating the efficacy of BAT-targeted therapies.</p>","PeriodicalId":15219,"journal":{"name":"Journal of cellular biochemistry","volume":"126 6","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcb.70052","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144514954","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}
Anupama Binoy, Ratul Bhowmik, Preena S. Parvathy, C. Gopi Mohan
Generating new and efficient drugs through machine learning-assisted quantitative structure–activity relationships (ML-QSAR) has become a promising strategy for addressing multidrug-resistant gram-negative bacterial infections. We developed robust ML-QSAR models using Genetic Function Approximation (GFA), Support Vector Machine (SVM), and Artificial Neural Network (ANN) methods to predict the activity of experimentally known quinoline-based MsbA inhibitors, aiming to create more effective antibacterial drugs. The ML models were built using eight significant molecular descriptors: B09[N-Cl], CATS3D_04_AA, F06[N-O], G2i, molecular weight (MW), Mor04p, VE1sign_B(s), and VE1sign_Dz(i), along with 279 molecular fingerprints to predict the MsbA inhibition activity of quinoline-based compounds. The molecular descriptor-based SVM model achieved an R² of 0.9891 and a q² cross-validation correlation of 0.9388. In contrast, the molecular fingerprint-based SVM model had an R² of 0.9981 and a q² cross-validation correlation of 0.7584, making it the best-performing model. The robustness of these developed models was further validated through various internal, external, and applicability domain analyses. The most active compounds identified in this data set, compounds 31 and 40, were subsequently used to generate 62 new quinoline-based compounds. Additionally, three modelled quinoline-based inhibitors, M28, N7, and N23, demonstrated excellent bioactivity, binding affinity, and pharmacokinetic profiles. To support further research, the fingerprint-based ML-QSAR model is available as a web application, MsbA-Pred (https://msba-mohan-amrita.streamlit.app/), which allows users to predict MsbA inhibitory activity from any device.
通过机器学习辅助的定量构效关系（ML-QSAR）生成新的高效药物已成为解决多重耐药革兰氏阴性细菌感染的一种有前途的策略。我们利用遗传函数逼近（GFA）、支持向量机（SVM）和人工神经网络（ANN）方法建立了鲁棒的ML-QSAR模型，以预测实验中已知的喹啉类MsbA抑制剂的活性，旨在开发更有效的抗菌药物。利用B09[N-Cl]、CATS3D_04_AA、F06[N-O]、G2i、分子量（MW）、Mor04p、VE1sign_B(s)、VE1sign_Dz(i)等8个重要分子描述符和279个分子指纹图谱建立ML模型，预测喹啉类化合物对MsbA的抑制活性。基于分子描述符的SVM模型的交叉验证相关系数R²为0.9891，q²为0.9388。相比之下，基于分子指纹的SVM模型的R²为0.9981，q²交叉验证相关系数为0.7584，是表现最好的模型。通过各种内部、外部和适用性领域分析，进一步验证了这些开发模型的鲁棒性。在该数据集中发现的活性最高的化合物，化合物31和40，随后被用来生成62个新的喹啉类化合物。此外，三种基于喹啉的模拟抑制剂M28、N7和N23表现出优异的生物活性、结合亲和力和药代动力学特征。为了支持进一步的研究，基于指纹的ML-QSAR模型可作为web应用程序MsbA- pred （https://msba-mohan-amrita.streamlit.app/）提供，该应用程序允许用户从任何设备预测MsbA抑制活性。
{"title":"Machine Learning Models and Structure-Based Antibacterial Drug Discovery of the Key ABC Transporter Maltose-Binding Protein A","authors":"Anupama Binoy, Ratul Bhowmik, Preena S. Parvathy, C. Gopi Mohan","doi":"10.1002/jcb.70049","DOIUrl":"https://doi.org/10.1002/jcb.70049","url":null,"abstract":"<div>\u0000 \u0000 <p>Generating new and efficient drugs through machine learning-assisted quantitative structure–activity relationships (ML-QSAR) has become a promising strategy for addressing multidrug-resistant gram-negative bacterial infections. We developed robust ML-QSAR models using Genetic Function Approximation (GFA), Support Vector Machine (SVM), and Artificial Neural Network (ANN) methods to predict the activity of experimentally known quinoline-based MsbA inhibitors, aiming to create more effective antibacterial drugs. The ML models were built using eight significant molecular descriptors: B09[N-Cl], CATS3D_04_AA, F06[N-O], G2i, molecular weight (MW), Mor04p, VE1sign_B(s), and VE1sign_Dz(i), along with 279 molecular fingerprints to predict the MsbA inhibition activity of quinoline-based compounds. The molecular descriptor-based SVM model achieved an R² of 0.9891 and a q² cross-validation correlation of 0.9388. In contrast, the molecular fingerprint-based SVM model had an R² of 0.9981 and a q² cross-validation correlation of 0.7584, making it the best-performing model. The robustness of these developed models was further validated through various internal, external, and applicability domain analyses. The most active compounds identified in this data set, compounds 31 and 40, were subsequently used to generate 62 new quinoline-based compounds. Additionally, three modelled quinoline-based inhibitors, M28, N7, and N23, demonstrated excellent bioactivity, binding affinity, and pharmacokinetic profiles. To support further research, the fingerprint-based ML-QSAR model is available as a web application, MsbA-Pred (https://msba-mohan-amrita.streamlit.app/), which allows users to predict MsbA inhibitory activity from any device.</p>\u0000 </div>","PeriodicalId":15219,"journal":{"name":"Journal of cellular biochemistry","volume":"126 6","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144514959","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}
Erandi Velázquez-Miranda, Ana Patricia Juárez-Mercado, Esperanza Mata-Martínez, María Guadalupe Ramírez-Ledesma, Adriana González-Gallardo, María Eugenia Ramos-Aguilar, Olivia Vázquez-Martínez, Mauricio Díaz-Muñoz, Francisco G. Vázquez-Cuevas
DNA damage is one of the key processes that underlie hepatic fibrosis, and its progression could lead to the development of neoplastic events and ultimately hepatocarcinoma. Tissue injury, including DNA damage, can involve the activation of purinergic signaling. It has been shown that P2Y2 receptor signaling is exacerbated during hepatic fibrosis. Little is known, however, about the roles played by P2Y2 receptor in the processes involved in fibrosis. In this study, we used CCl4 treatment to induce a reversible hepatic fibrosis, and by using a microarray assay we observed an upregulation of transcripts related to the DNA damage repair of double strand breaks (DNA-dr-dsb) after P2Y2 receptor stimulation in primary cultures of hepatocytes from fibrotic mice. The transcriptional data were confirmed demonstrating an UTP-promoted reduction in the number of γH2AX+ positive cells in etoposide-treated fibrotic primary hepatocytes. Furthermore, HIF-1α, a known transcription factor that drives P2Y2 receptor expression, showed a significant increase upon CCl4 treatment, especially within the perivascular zones. Chemical activation of HIF-1α by CoCl2 in fibrotic hepatocytes promoted a partial protection against increased levels of γH2AX induced by etoposide, as well as an evident enhancement in the intracellular calcium response induced by UTP in fibrotic hepatocytes, suggesting a regulatory role of this transcriptional factor on the effect of P2Y2 receptor on DNA-dr-dbs response. This regulation was also investigated pharmacologically by activating or blocking the signaling from either P2Y2 receptor or HIF-1α. Our work, in summary, shows a novel relationship between P2Y2 receptor-dependent purinergic signaling and DNA-dr-dbs in hepatic fibrosis.
{"title":"Purinergic Receptor P2Y2 Activity Prevents DNA Damage in CCl4-Induced Hepatic Fibrosis","authors":"Erandi Velázquez-Miranda, Ana Patricia Juárez-Mercado, Esperanza Mata-Martínez, María Guadalupe Ramírez-Ledesma, Adriana González-Gallardo, María Eugenia Ramos-Aguilar, Olivia Vázquez-Martínez, Mauricio Díaz-Muñoz, Francisco G. Vázquez-Cuevas","doi":"10.1002/jcb.70042","DOIUrl":"https://doi.org/10.1002/jcb.70042","url":null,"abstract":"<p>DNA damage is one of the key processes that underlie hepatic fibrosis, and its progression could lead to the development of neoplastic events and ultimately hepatocarcinoma. Tissue injury, including DNA damage, can involve the activation of purinergic signaling. It has been shown that P2Y2 receptor signaling is exacerbated during hepatic fibrosis. Little is known, however, about the roles played by P2Y2 receptor in the processes involved in fibrosis. In this study, we used CCl<sub>4</sub> treatment to induce a reversible hepatic fibrosis, and by using a microarray assay we observed an upregulation of transcripts related to the DNA damage repair of double strand breaks (DNA-dr-dsb) after P2Y2 receptor stimulation in primary cultures of hepatocytes from fibrotic mice. The transcriptional data were confirmed demonstrating an UTP-promoted reduction in the number of γH2AX+ positive cells in etoposide-treated fibrotic primary hepatocytes. Furthermore, HIF-1α, a known transcription factor that drives P2Y2 receptor expression, showed a significant increase upon CCl<sub>4</sub> treatment, especially within the perivascular zones. Chemical activation of HIF-1α by CoCl<sub>2</sub> in fibrotic hepatocytes promoted a partial protection against increased levels of γH2AX induced by etoposide, as well as an evident enhancement in the intracellular calcium response induced by UTP in fibrotic hepatocytes, suggesting a regulatory role of this transcriptional factor on the effect of P2Y2 receptor on DNA-dr-dbs response. This regulation was also investigated pharmacologically by activating or blocking the signaling from either P2Y2 receptor or HIF-1α. Our work, in summary, shows a novel relationship between P2Y2 receptor-dependent purinergic signaling and DNA-dr-dbs in hepatic fibrosis.</p>","PeriodicalId":15219,"journal":{"name":"Journal of cellular biochemistry","volume":"126 6","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcb.70042","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144255809","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}
Irina L. Tourkova, Deborah J. Nelson, Paul H. Schlesinger, Harry C. Blair
Bone formation and resorption are mediated by an epithelial-like cell layer on bone. Formation or resorption requires active transport that depends on aerobic glycolysis, ATP, and acid transport. Metabolic activity of bone cells during matrix formation or removal is so high that the cells autolyze rapidly after cell death. Mineralization of bone matrix uses import of phosphate by sodium-phosphate cotransport, supported by the Na+/K+ ATPase. Glucose is the main energy source; ATP is exported to generate phosphate for hydroxyapatite in the bone matrix. Mechanism of export is not established, but phosphate is generated at least in part via phosphatase/pyrophosphatase activity including the tissue nonspecific alkaline phosphatase (TNAP) and ectonucleotide pyrophosphatase/phosphodiesterase 2 (ENPP2). Ca2+ is imported by paracellular transport. Protons, generated in producing hydroxyapatite, are exported by apical H+/Cl− exchangers ClC3 and ClC5, and basolateral Na+/H+ exchange. In bone resorption, ATP-dependent acid transport, the reverse of acid transport in bone formation, is essential. This uses the vacuolar-type H+ATPase linked to Cl− transport via a ClC family H+/Cl− exchanger, ClC7, and a Cl− channel. Other transporters contributing include carbonic anhydrase and chloride-bicarbonate exchange to replace H+ equivalents exported for bone resorption.
New and Noteworthy
This focused short review considers the relationship of oxidative phosphorylation to acid transport in bone formation and resorption, processes with very high metabolic activity for storage or removal of phosphate, calcium and acid equivalents.
{"title":"Energy-Dependent Phosphate and Acid Transport for Bone Formation and Resorption","authors":"Irina L. Tourkova, Deborah J. Nelson, Paul H. Schlesinger, Harry C. Blair","doi":"10.1002/jcb.70039","DOIUrl":"https://doi.org/10.1002/jcb.70039","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 <p>Bone formation and resorption are mediated by an epithelial-like cell layer on bone. Formation or resorption requires active transport that depends on aerobic glycolysis, ATP, and acid transport. Metabolic activity of bone cells during matrix formation or removal is so high that the cells autolyze rapidly after cell death. Mineralization of bone matrix uses import of phosphate by sodium-phosphate cotransport, supported by the Na<sup>+</sup>/K<sup>+</sup> ATPase. Glucose is the main energy source; ATP is exported to generate phosphate for hydroxyapatite in the bone matrix. Mechanism of export is not established, but phosphate is generated at least in part via phosphatase/pyrophosphatase activity including the tissue nonspecific alkaline phosphatase (TNAP) and ectonucleotide pyrophosphatase/phosphodiesterase 2 (ENPP2). Ca<sup>2+</sup> is imported by paracellular transport. Protons, generated in producing hydroxyapatite, are exported by apical H<sup>+</sup>/Cl<sup>−</sup> exchangers ClC3 and ClC5, and basolateral Na<sup>+</sup>/H<sup>+</sup> exchange. In bone resorption, ATP-dependent acid transport, the reverse of acid transport in bone formation, is essential. This uses the vacuolar-type H<sup>+</sup>ATPase linked to Cl<sup>−</sup> transport via a ClC family H<sup>+</sup>/Cl<sup>−</sup> exchanger, ClC7, and a Cl<sup>−</sup> channel. Other transporters contributing include carbonic anhydrase and chloride-bicarbonate exchange to replace H<sup>+</sup> equivalents exported for bone resorption.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> New and Noteworthy</h3>\u0000 \u0000 <p>This focused short review considers the relationship of oxidative phosphorylation to acid transport in bone formation and resorption, processes with very high metabolic activity for storage or removal of phosphate, calcium and acid equivalents.</p>\u0000 </section>\u0000 </div>","PeriodicalId":15219,"journal":{"name":"Journal of cellular biochemistry","volume":"126 5","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcb.70039","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144171947","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}
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