ACS Pharmacology and Translational Science最新文献

{"title":"Emerging Technologies and Solutions for Chronic Wound Care and Diagnosis","authors":"Simon Matoori*,  and , Elisabeth Engel*, ","doi":"10.1021/acsptsci.5c0034910.1021/acsptsci.5c00349","DOIUrl":"https://doi.org/10.1021/acsptsci.5c00349https://doi.org/10.1021/acsptsci.5c00349","url":null,"abstract":"","PeriodicalId":36426,"journal":{"name":"ACS Pharmacology and Translational Science","volume":"8 6","pages":"1435–1437 1435–1437"},"PeriodicalIF":4.9,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144269640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"","authors":"Maximilian Meudt, Julia Baumeister, Erik M.F. Machal, Matthias J. Knape, Boris Mizaikoff, Sybille Ebert, Frank Rosenau, Michaela Blech and Fabian Higel*, ","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":36426,"journal":{"name":"ACS Pharmacology and Translational Science","volume":"8 6","pages":"XXX-XXX XXX-XXX"},"PeriodicalIF":4.9,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acsptsci.5c00185","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144354597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"","authors":"Jianing Wu, Xin Zhou, Xin Xu and Jing Xie*, ","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":36426,"journal":{"name":"ACS Pharmacology and Translational Science","volume":"8 6","pages":"XXX-XXX XXX-XXX"},"PeriodicalIF":4.9,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acsptsci.4c00706","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144354598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emerging Technologies and Solutions for Chronic Wound Care and Diagnosis.","authors":"Simon Matoori, Elisabeth Engel","doi":"10.1021/acsptsci.5c00349","DOIUrl":"10.1021/acsptsci.5c00349","url":null,"abstract":"","PeriodicalId":36426,"journal":{"name":"ACS Pharmacology and Translational Science","volume":"8 6","pages":"1435-1437"},"PeriodicalIF":4.9,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12171891/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144327072","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"","authors":"Sai Balaji Andugulapati*, Vaishnavi Kambhampati, Abhisheik Eedara, Jagadeesh Kumar Gangasani, Harish Kumar B and V.G.M. Naidu*, ","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":36426,"journal":{"name":"ACS Pharmacology and Translational Science","volume":"8 6","pages":"XXX-XXX XXX-XXX"},"PeriodicalIF":4.9,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acsptsci.5c00009","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144354596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In vivo Evaluation of Copper-61-Labeled Prostate-specific Membrane Antigen Targeting Novel Radiopharmaceutical: First Steps toward Clinical Implementation","authors":"Szilvia Bunda,&nbsp;Ibolya Kálmán-Szabó,&nbsp;Dezső Szikra,&nbsp;Anikó Fekete,&nbsp;Dániel Szücs,&nbsp;Judit Péliné Szabó,&nbsp;György Trencsényi,&nbsp;Zita Képes* and Ferenc K. Kálmán*,&nbsp;","doi":"10.1021/acsptsci.4c0068510.1021/acsptsci.4c00685","DOIUrl":"https://doi.org/10.1021/acsptsci.4c00685https://doi.org/10.1021/acsptsci.4c00685","url":null,"abstract":"<p >The introduction of radiopharmaceuticals targeting prostate-specific membrane antigen (PSMA) has revolutionized the molecular imaging of prostate cancer (PCa); however, due to the potential downsides of the commonly used labeling entities (gallium-68/fluorine-18), the role of alternative isotopes is emerging. Given the desirable physical characteristics of positron emitter copper-61 (⁶¹Cu), herein, a novel PSMA PET probe using the recently introduced KFTG chelator was developed and tested <i>in vivo</i> ([⁶¹Cu]Cu-KFTG-PSMA). Pharmacokinetics was assessed in PSMA⁺ LNCaP PCa xenografts and healthy counterparts using micro-PET imaging, biodistribution, and competition studies. The uptake of [⁶¹Cu]Cu-KFTG-PSMA in LNCaP tumor lesions showed a trend to increase from 30 to 180 min post-injection (SUVmean: 1.50 ± 0.19–2.18 ± 0.25). In comparison, healthy organs demonstrated low radioactivity and fast body clearance, yielding better contrast for later time point images. Likewise, gradually increasing tumor retention was observed <i>ex vivo</i> as well (11.4 ± 1.4, 12.6 ± 1.6, and 13.8 ± 2.1%ID/g at 30, 90, and 180 min post-injection, respectively); however, some gastrointestinal organs presented moderate early time point accumulation. Followed by pretreatment with cold PSMA, blocked LNCaP tumors showed hardly any radioactivity, which further confirmed high target specificity both <i>in vivo</i> and <i>ex vivo</i>.</p>","PeriodicalId":36426,"journal":{"name":"ACS Pharmacology and Translational Science","volume":"8 6","pages":"1580–1590 1580–1590"},"PeriodicalIF":4.9,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144269669","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>In vivo</i> Evaluation of Copper-61-Labeled Prostate-specific Membrane Antigen Targeting Novel Radiopharmaceutical: First Steps toward Clinical Implementation.","authors":"Szilvia Bunda, Ibolya Kálmán-Szabó, Dezső Szikra, Anikó Fekete, Dániel Szücs, Judit Péliné Szabó, György Trencsényi, Zita Képes, Ferenc K Kálmán","doi":"10.1021/acsptsci.4c00685","DOIUrl":"10.1021/acsptsci.4c00685","url":null,"abstract":"<p><p>The introduction of radiopharmaceuticals targeting prostate-specific membrane antigen (PSMA) has revolutionized the molecular imaging of prostate cancer (PCa); however, due to the potential downsides of the commonly used labeling entities (gallium-68/fluorine-18), the role of alternative isotopes is emerging. Given the desirable physical characteristics of positron emitter copper-61 (⁶¹Cu), herein, a novel PSMA PET probe using the recently introduced KFTG chelator was developed and tested <i>in vivo</i> ([⁶¹Cu]-Cu-KFTG-PSMA). Pharmacokinetics was assessed in PSMA⁺ LNCaP PCa xenografts and healthy counterparts using micro-PET imaging, biodistribution, and competition studies. The uptake of [⁶¹Cu]-Cu-KFTG-PSMA in LNCaP tumor lesions showed a trend to increase from 30 to 180 min post-injection (SUVmean: 1.50 ± 0.19-2.18 ± 0.25). In comparison, healthy organs demonstrated low radioactivity and fast body clearance, yielding better contrast for later time point images. Likewise, gradually increasing tumor retention was observed <i>ex vivo</i> as well (11.4 ± 1.4, 12.6 ± 1.6, and 13.8 ± 2.1%ID/g at 30, 90, and 180 min post-injection, respectively); however, some gastrointestinal organs presented moderate early time point accumulation. Followed by pretreatment with cold PSMA, blocked LNCaP tumors showed hardly any radioactivity, which further confirmed high target specificity both <i>in vivo</i> and <i>ex vivo</i>.</p>","PeriodicalId":36426,"journal":{"name":"ACS Pharmacology and Translational Science","volume":"8 6","pages":"1580-1590"},"PeriodicalIF":4.9,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12171877/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144327053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sinapic Acid-Conjugated Gadolinium Complexes as Anti-Inflammatory Theranostic Agents That Target Transforming Growth Factor β‑Activated Kinase 1 (TAK1).","authors":"Sangyun Lee, Dabin Ahn, Ahrum Baek, Bokyung Sung, Byeongwoo Yang, Minsup Kim, Ji-Ae Park, Gang Ho Lee, Eunshil Lee, Yongmin Chang","doi":"10.1021/acsptsci.5c00220","DOIUrl":"10.1021/acsptsci.5c00220","url":null,"abstract":"<p><p>Recent <i>in vitro</i> studies have reported that sinapic acid (SPA) binds to transforming growth factor-β-activated kinase 1 (TAK1), a key regulator of inflammatory pathways. However, the hydrophobic nature of SPA limits its solubility in aqueous environments, posing challenges for <i>in vivo</i> biomedical applications. Thus, we synthesized Gd-DO3A-SPA by conjugating SPA with a gadolinium-based magnetic resonance imaging (MRI) contrast agent to improve its solubility. Gd-DO3A-SPA was then evaluated as a theranostic agent capable of both diagnosing inflammatory lesions via MRI and modulating inflammation by directly targeting TAK1. The physicochemical properties of the synthesized Gd-DO3A-SPA were analyzed by using MRI. The diagnostic and therapeutic effects of Gd-DO3A-SPA on inflammation were evaluated in a mouse inflammation model. TAK1 binding was investigated using cellular thermal shift assay, drug affinity responsive target stability, and <i>in silico</i> studies. The conjugated Gd-DO3A-SPA showed superior signal enhancement in inflamed tissue compared with the extracellular MR agent, Gadobutrol. Additionally, it was found to inhibit inflammatory cytokines, such as inducible nitric oxide synthase, cyclooxygenase 2, interleukin 6, interleukin 1β, and tumor necrosis factor α, as well as the NLRP3 inflammasome, through the nuclear factor kappa-light-chain-enhancer of activated B cells and mitogen-activated protein kinase pathways. Furthermore, this study demonstrated that Gd-DO3A-SPA was internalized into cells via endocytosis and directly bound to the TAK1 protein. In conclusion, Gd-DO3A-SPA demonstrated its potential as a theranostic agent that targets TAK1 at the site of inflammation and inhibits inflammatory factors; meanwhile, inflammation can be diagnosed by using MRI.</p>","PeriodicalId":36426,"journal":{"name":"ACS Pharmacology and Translational Science","volume":"8 6","pages":"1814-1831"},"PeriodicalIF":4.9,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12171879/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144327097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sinapic Acid-Conjugated Gadolinium Complexes as Anti-Inflammatory Theranostic Agents That Target Transforming Growth Factor β-Activated Kinase 1 (TAK1)","authors":"Sangyun Lee,&nbsp;Dabin Ahn,&nbsp;Ahrum Baek,&nbsp;Bokyung Sung,&nbsp;Byeongwoo Yang,&nbsp;Minsup Kim,&nbsp;Ji-Ae Park,&nbsp;Gang Ho Lee,&nbsp;Eunshil Lee* and Yongmin Chang*,&nbsp;","doi":"10.1021/acsptsci.5c0022010.1021/acsptsci.5c00220","DOIUrl":"https://doi.org/10.1021/acsptsci.5c00220https://doi.org/10.1021/acsptsci.5c00220","url":null,"abstract":"<p >Recent <i>in vitro</i> studies have reported that sinapic acid (SPA) binds to transforming growth factor-β-activated kinase 1 (TAK1), a key regulator of inflammatory pathways. However, the hydrophobic nature of SPA limits its solubility in aqueous environments, posing challenges for <i>in vivo</i> biomedical applications. Thus, we synthesized Gd-DO3A-SPA by conjugating SPA with a gadolinium-based magnetic resonance imaging (MRI) contrast agent to improve its solubility. Gd-DO3A-SPA was then evaluated as a theranostic agent capable of both diagnosing inflammatory lesions via MRI and modulating inflammation by directly targeting TAK1. The physicochemical properties of the synthesized Gd-DO3A-SPA were analyzed by using MRI. The diagnostic and therapeutic effects of Gd-DO3A-SPA on inflammation were evaluated in a mouse inflammation model. TAK1 binding was investigated using cellular thermal shift assay, drug affinity responsive target stability, and <i>in silico</i> studies. The conjugated Gd-DO3A-SPA showed superior signal enhancement in inflamed tissue compared with the extracellular MR agent, Gadobutrol. Additionally, it was found to inhibit inflammatory cytokines, such as inducible nitric oxide synthase, cyclooxygenase 2, interleukin 6, interleukin 1β, and tumor necrosis factor α, as well as the NLRP3 inflammasome, through the nuclear factor kappa-light-chain-enhancer of activated B cells and mitogen-activated protein kinase pathways. Furthermore, this study demonstrated that Gd-DO3A-SPA was internalized into cells via endocytosis and directly bound to the TAK1 protein. In conclusion, Gd-DO3A-SPA demonstrated its potential as a theranostic agent that targets TAK1 at the site of inflammation and inhibits inflammatory factors; meanwhile, inflammation can be diagnosed by using MRI.</p>","PeriodicalId":36426,"journal":{"name":"ACS Pharmacology and Translational Science","volume":"8 6","pages":"1814–1831 1814–1831"},"PeriodicalIF":4.9,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144269773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanism-Based Pharmacokinetic/Pharmacodynamic Modeling for Iron-Regulated Hematopoietic Stem and Progenitor Cells' Commitment toward Erythroid and Megakaryocytic Lineages.","authors":"Kangna Cao, Xiaoqing Fan, Raymond S M Wong, Xiaoyu Yan","doi":"10.1021/acsptsci.5c00097","DOIUrl":"10.1021/acsptsci.5c00097","url":null,"abstract":"<p><p>Iron replenishment is a cornerstone therapy for anemia in diverse diseases. While its role in erythrocyte hemoglobinization is well-established, the broader impact of iron on other aspects of hematopoiesis, such as thrombopoiesis, remains poorly understood. In this study, we demonstrate that iron plays a regulatory role in the commitment of hematopoietic stem and progenitor cells (HSPCs) toward erythroid and megakaryocytic lineages. Using colony-forming unit assays and flow cytometry, we observed that iron increases the proportion of erythroid cells while reducing the proportion of megakaryocytic cells. Transcriptomic profiling and functional output analyses identified the MAPK/ERK pathway as a critical mediator of iron-regulated HSPCs' commitment. Corroborating <i>in vitro</i> findings, rats with iron deficiency anemia exhibited continuously elevated platelets and decreased red blood cell counts, while intravenous iron supplementation reversed these effects. This effect of iron was enhanced in combination with erythropoietin, a key cytokine in erythropoiesis. A mechanism-based pharmacokinetic/pharmacodynamic model was developed to quantify the impact of iron on the two lineages. The dynamic interplay between iron levels and the development of erythropoiesis and thrombopoiesis was accurately recapitulated in rats. The model was further extrapolated to humans and validated with clinical data. Overall, this work not only provides functional insights into the pivotal role of iron in erythropoiesis and thrombopoiesis but also holds translational implications for optimizing iron therapy in anemia and potentially other hematologic conditions where erythropoiesis and thrombopoiesis are affected.</p>","PeriodicalId":36426,"journal":{"name":"ACS Pharmacology and Translational Science","volume":"8 6","pages":"1711-1725"},"PeriodicalIF":4.9,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12171892/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144327076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}