ACS Pharmacology and Translational Science最新文献

{"title":"Gastroprotective Effect of Linagliptin on Indomethacin-Induced Gastric Ulceration in Mice: Crosstalk Between Oxidative Stress and Inflammasome Pathways.","authors":"Maha E Wally, Mohamed H Aly","doi":"10.1021/acsptsci.4c00695","DOIUrl":"10.1021/acsptsci.4c00695","url":null,"abstract":"<p><p>The clinical efficacy of indomethacin, a nonsteroidal anti-inflammatory drug, is hindered by its high ulcerogenic potential. Linagliptin, a dipeptidyl peptidase-4 inhibitor, has demonstrated anti-inflammatory properties through NLRP3 inflammasome modulation; however, its possible antiulcerogenic effect remains unclear. This study aimed to examine the potential prophylactic effect of linagliptin against indomethacin-induced gastric ulcers with a focus on NLRP3 inflammasome signaling. Gastric ulcers were induced using indomethacin and compared to pretreatment with linagliptin or the standard prophylactic omeprazole. Gastric injury was confirmed by gross morphology, ulcer scoring, and histopathological assessments. Additionally, redox status markers glutathione reductase (GSH), malondialdehyde (MDA), and Nrf2/Keap-1/HO-1 were evaluated in the gastric tissue. Immunohistochemical analysis of pNF-κB, NLRP3, and Caspase-1 inflammasome parameters was also conducted. Finally, measurement of gastric levels of Gasdermin-D was performed, as well as immunohistochemical and gene expression of IL-1β. Pretreatment with linagliptin suppressed all features of mucosal damage as well as inflammatory cell infiltration. The antioxidant effect of linagliptin was evident in low MDA, high GSH gastric levels, and high immunohistochemical reactivity of gastric tissues against Nrf2 and HO-1 antibodies, as well as low gastric levels of keap1. The overly active inflammasome pathway observed in indomethacin-induced ulcerated samples was reinstated by linagliptin, as seen in the suppression of pNF-κB, NLRP3, Caspase-1, and IL-1β immunohistochemical reactivity as well as Gasdermin-D levels. Our study showed that NLRP3 inflammasome contributes to the pathogenesis of indomethacin-mediated gastric injury and that linagliptin exhibits a protective effect against indomethacin-induced gastric ulcers, possibly through activation of the Nrf2/HO-1 antioxidant pathway and inhibition of the NLRP3 inflammasome axis.</p>","PeriodicalId":36426,"journal":{"name":"ACS Pharmacology and Translational Science","volume":"8 3","pages":"808-818"},"PeriodicalIF":4.9,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11915470/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143664857","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":"Gastroprotective Effect of Linagliptin on Indomethacin-Induced Gastric Ulceration in Mice: Crosstalk Between Oxidative Stress and Inflammasome Pathways","authors":"Maha E. Wally*,&nbsp; and ,&nbsp;Mohamed H. Aly*,&nbsp;","doi":"10.1021/acsptsci.4c0069510.1021/acsptsci.4c00695","DOIUrl":"https://doi.org/10.1021/acsptsci.4c00695https://doi.org/10.1021/acsptsci.4c00695","url":null,"abstract":"<p >The clinical efficacy of indomethacin, a nonsteroidal anti-inflammatory drug, is hindered by its high ulcerogenic potential. Linagliptin, a dipeptidyl peptidase-4 inhibitor, has demonstrated anti-inflammatory properties through NLRP3 inflammasome modulation; however, its possible antiulcerogenic effect remains unclear. This study aimed to examine the potential prophylactic effect of linagliptin against indomethacin-induced gastric ulcers with a focus on NLRP3 inflammasome signaling. Gastric ulcers were induced using indomethacin and compared to pretreatment with linagliptin or the standard prophylactic omeprazole. Gastric injury was confirmed by gross morphology, ulcer scoring, and histopathological assessments. Additionally, redox status markers glutathione reductase (GSH), malondialdehyde (MDA), and Nrf2/Keap-1/HO-1 were evaluated in the gastric tissue. Immunohistochemical analysis of pNF-κB, NLRP3, and Caspase-1 inflammasome parameters was also conducted. Finally, measurement of gastric levels of Gasdermin-D was performed, as well as immunohistochemical and gene expression of IL-1β. Pretreatment with linagliptin suppressed all features of mucosal damage as well as inflammatory cell infiltration. The antioxidant effect of linagliptin was evident in low MDA, high GSH gastric levels, and high immunohistochemical reactivity of gastric tissues against Nrf2 and HO-1 antibodies, as well as low gastric levels of keap1. The overly active inflammasome pathway observed in indomethacin-induced ulcerated samples was reinstated by linagliptin, as seen in the suppression of pNF-κB, NLRP3, Caspase-1, and IL-1β immunohistochemical reactivity as well as Gasdermin-D levels. Our study showed that NLRP3 inflammasome contributes to the pathogenesis of indomethacin-mediated gastric injury and that linagliptin exhibits a protective effect against indomethacin-induced gastric ulcers, possibly through activation of the Nrf2/HO-1 antioxidant pathway and inhibition of the NLRP3 inflammasome axis.</p>","PeriodicalId":36426,"journal":{"name":"ACS Pharmacology and Translational Science","volume":"8 3","pages":"808–818 808–818"},"PeriodicalIF":4.9,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143608947","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":"Synthesis and Biological Evaluation of Metamorphine: A Morphine-Metamizole Adduct from Patient-Controlled Analgesia Pumps.","authors":"Aly Abotaleb, Aurélien F A Moumbock, Rainer Trittler, Gernot Zissel, Stefan Günther, Martin J Hug","doi":"10.1021/acsptsci.4c00546","DOIUrl":"10.1021/acsptsci.4c00546","url":null,"abstract":"<p><p>Opioids are among the most effective drugs in managing moderate to severe pain. Herein, we describe a morphine-metamizole adduct with a phenazone moiety added at position C2 of the morphinan backbone. This adduct, coined metamorphine, was first detected as a byproduct of the morphine-metamizole drug interaction in patient-controlled analgesia (PCA) pumps used for management of severe pain. In this study, metamorphine was successfully synthesized using the Mannich condensation. Qualitative high-performance liquid chromatography with ultraviolet detection (HPLC-UV) analysis was employed to confirm the identity of metamorphine, and the yield was then purified using preparative HPLC. Subsequent studies were undertaken to investigate the pharmacological properties of the newly synthesized compound. A radioligand-based binding assay demonstrated that metamorphine binds strongly to the μ-opioid receptor (<i>K_i</i> = 3.0 nM). Functional assays showed that it activates both G-protein and β-arrestin pathways, with EC₅₀ values of 0.169 and 3.06 μM, respectively. However, metamorphine did not exhibit significant activity on TNF, suggesting that it may lack analgesic, antipyretic, and anti-inflammatory effects associated with this pathway. Based on our findings, PCA pumps should be closely monitored, while therapeutic drug monitoring can be utilized to measure metamorphine serum concentration alongside with other opioids. Lead optimization of metamorphine could potentially result in new opioids with an expanded pharmacological spectrum and/or reduced side effects.</p>","PeriodicalId":36426,"journal":{"name":"ACS Pharmacology and Translational Science","volume":"8 3","pages":"718-725"},"PeriodicalIF":4.9,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11915030/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143665086","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":"Synthesis and Biological Evaluation of Metamorphine: A Morphine–Metamizole Adduct from Patient-Controlled Analgesia Pumps","authors":"Aly Abotaleb*,&nbsp;Aurélien F. A. Moumbock,&nbsp;Rainer Trittler,&nbsp;Gernot Zissel,&nbsp;Stefan Günther* and Martin J. Hug,&nbsp;","doi":"10.1021/acsptsci.4c0054610.1021/acsptsci.4c00546","DOIUrl":"https://doi.org/10.1021/acsptsci.4c00546https://doi.org/10.1021/acsptsci.4c00546","url":null,"abstract":"<p >Opioids are among the most effective drugs in managing moderate to severe pain. Herein, we describe a morphine-metamizole adduct with a phenazone moiety added at position C2 of the morphinan backbone. This adduct, coined metamorphine, was first detected as a byproduct of the morphine-metamizole drug interaction in patient-controlled analgesia (PCA) pumps used for management of severe pain. In this study, metamorphine was successfully synthesized using the Mannich condensation. Qualitative high-performance liquid chromatography with ultraviolet detection (HPLC-UV) analysis was employed to confirm the identity of metamorphine, and the yield was then purified using preparative HPLC. Subsequent studies were undertaken to investigate the pharmacological properties of the newly synthesized compound. A radioligand-based binding assay demonstrated that metamorphine binds strongly to the μ-opioid receptor (<i>K_i</i> = 3.0 nM). Functional assays showed that it activates both G-protein and β-arrestin pathways, with EC₅₀ values of 0.169 and 3.06 μM, respectively. However, metamorphine did not exhibit significant activity on TNF, suggesting that it may lack analgesic, antipyretic, and anti-inflammatory effects associated with this pathway. Based on our findings, PCA pumps should be closely monitored, while therapeutic drug monitoring can be utilized to measure metamorphine serum concentration alongside with other opioids. Lead optimization of metamorphine could potentially result in new opioids with an expanded pharmacological spectrum and/or reduced side effects.</p>","PeriodicalId":36426,"journal":{"name":"ACS Pharmacology and Translational Science","volume":"8 3","pages":"718–725 718–725"},"PeriodicalIF":4.9,"publicationDate":"2025-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acsptsci.4c00546","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143609055","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":"Oxidative Stress-Responsive 1 Kinase Catalytic Activity Promotes Triple Negative Breast Cancer Oncogenic Potential.","authors":"Azeza M Fdel, Loren Waters, Ira Sharma, Samuel Jones, Julia Gee, John R Atack, Sourav Banerjee, Youcef Mehellou","doi":"10.1021/acsptsci.4c00603","DOIUrl":"10.1021/acsptsci.4c00603","url":null,"abstract":"<p><p>The protein kinase OSR1 has been highlighted as a biomarker for a poor prognosis in breast cancer (BC) patients. To further decipher the mechanism underpinning this, we studied the expression, phosphorylation status, and catalytic activity of OSR1 across a series of BC cell lines. OSR1 was found to be expressed across the various luminal and triple negative BC (TNBC) cell lines studied, although it was only constitutively active in the highly migratory TNBC cell line MDA-MB-231. Although this cell line carries p53 mutations, our data indicated that OSR1 constitutive kinase activity of the OSR1 in MDA-MB-231 was independent of p53. Interestingly, the inhibition of OSR1 had no significant impact on MDA-MB-231 cell viability, but it was found to contribute to its substantial cell migration and invasion, as this was significantly attenuated by the WNK/OSR1 inhibitor WNK463. Analogously, the overexpression of constitutively active OSR1 in the poorly migrating BC cell line MCF7 enhanced its cell mobility. Collectively, our results indicate that the pharmacological inhibition of OSR1 could be a promising novel strategy for preventing the oncogenic potential of TNBC.</p>","PeriodicalId":36426,"journal":{"name":"ACS Pharmacology and Translational Science","volume":"8 3","pages":"726-735"},"PeriodicalIF":4.9,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11915029/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143664930","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":"Safe-by-Design Strategies for Intranasal Drug Delivery Systems: Machine and Deep Learning Solutions to Differentiate Epithelial Tissues via Attenuated Total Reflection Fourier Transform Infrared Spectroscopy.","authors":"Romain Topalian, Leo Kavallaris, Frank Rosenau, Chrystelle Mavoungou","doi":"10.1021/acsptsci.4c00643","DOIUrl":"10.1021/acsptsci.4c00643","url":null,"abstract":"<p><p>The development of nasal drug delivery systems requires advanced analytical techniques and tools that allow for distinguishing between the nose-to-brain epithelial tissues with better precision, where traditional bioanalytical methods frequently fail. In this study, attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy is coupled to machine learning (ML) and deep learning (DL) techniques to discriminate effectively between epithelial tissues. The primary goal of this work was to develop Safe-by-Design models for intranasal drug delivery using ex vivo pig tissues experiment, which were analyzed by way of ML modeling. We compiled an ATR-FTIR spectral data set from olfactory epithelium (OE), respiratory epithelium (RE), and tracheal tissues. The data set was used to train and test different ML algorithms. Accuracy, sensitivity, specificity, and F1 score metrics were used to evaluate optimized model performance and their abilities to identify specific spectral signatures relevant to each tissue type. The used feedforward neural network (FNN) has shown 0.99 accuracy, indicating that it had performed a discrimination with a high level of trueness estimates, without overfitting, unlike the built support vector machine (SVM) model. Important spectral features detailing the assignment and site of two-dimensional (2D) protein structures per tissue type were determined by the SHapley Additive exPlanations (SHAP) value analysis of the FNN model. Furthermore, a denoising autoencoder was built to improve spectral quality by reducing noise, as confirmed by higher Pearson correlation coefficients for denoised spectra. The combination of spectroscopic analysis with ML modeling offers a promising strategy called, Safe-by-Design, as a monitoring strategy for intranasal drug delivery systems, also for designing the analysis of tissue for diagnosis purposes.</p>","PeriodicalId":36426,"journal":{"name":"ACS Pharmacology and Translational Science","volume":"8 3","pages":"762-773"},"PeriodicalIF":4.9,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11915033/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143665072","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":"Safe-by-Design Strategies for Intranasal Drug Delivery Systems: Machine and Deep Learning Solutions to Differentiate Epithelial Tissues via Attenuated Total Reflection Fourier Transform Infrared Spectroscopy","authors":"Romain Topalian,&nbsp;Leo Kavallaris,&nbsp;Frank Rosenau and Chrystelle Mavoungou*,&nbsp;","doi":"10.1021/acsptsci.4c0064310.1021/acsptsci.4c00643","DOIUrl":"https://doi.org/10.1021/acsptsci.4c00643https://doi.org/10.1021/acsptsci.4c00643","url":null,"abstract":"<p >The development of nasal drug delivery systems requires advanced analytical techniques and tools that allow for distinguishing between the nose-to-brain epithelial tissues with better precision, where traditional bioanalytical methods frequently fail. In this study, attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy is coupled to machine learning (ML) and deep learning (DL) techniques to discriminate effectively between epithelial tissues. The primary goal of this work was to develop Safe-by-Design models for intranasal drug delivery using ex vivo pig tissues experiment, which were analyzed by way of ML modeling. We compiled an ATR-FTIR spectral data set from olfactory epithelium (OE), respiratory epithelium (RE), and tracheal tissues. The data set was used to train and test different ML algorithms. Accuracy, sensitivity, specificity, and F1 score metrics were used to evaluate optimized model performance and their abilities to identify specific spectral signatures relevant to each tissue type. The used feedforward neural network (FNN) has shown 0.99 accuracy, indicating that it had performed a discrimination with a high level of trueness estimates, without overfitting, unlike the built support vector machine (SVM) model. Important spectral features detailing the assignment and site of two-dimensional (2D) protein structures per tissue type were determined by the SHapley Additive exPlanations (SHAP) value analysis of the FNN model. Furthermore, a denoising autoencoder was built to improve spectral quality by reducing noise, as confirmed by higher Pearson correlation coefficients for denoised spectra. The combination of spectroscopic analysis with ML modeling offers a promising strategy called, Safe-by-Design, as a monitoring strategy for intranasal drug delivery systems, also for designing the analysis of tissue for diagnosis purposes.</p>","PeriodicalId":36426,"journal":{"name":"ACS Pharmacology and Translational Science","volume":"8 3","pages":"762–773 762–773"},"PeriodicalIF":4.9,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acsptsci.4c00643","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143608955","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":"Oxidative Stress-Responsive 1 Kinase Catalytic Activity Promotes Triple Negative Breast Cancer Oncogenic Potential","authors":"Azeza M. Fdel,&nbsp;Loren Waters,&nbsp;Ira Sharma,&nbsp;Samuel Jones,&nbsp;Julia Gee,&nbsp;John R. Atack,&nbsp;Sourav Banerjee* and Youcef Mehellou*,&nbsp;","doi":"10.1021/acsptsci.4c0060310.1021/acsptsci.4c00603","DOIUrl":"https://doi.org/10.1021/acsptsci.4c00603https://doi.org/10.1021/acsptsci.4c00603","url":null,"abstract":"<p >The protein kinase OSR1 has been highlighted as a biomarker for a poor prognosis in breast cancer (BC) patients. To further decipher the mechanism underpinning this, we studied the expression, phosphorylation status, and catalytic activity of OSR1 across a series of BC cell lines. OSR1 was found to be expressed across the various luminal and triple negative BC (TNBC) cell lines studied, although it was only constitutively active in the highly migratory TNBC cell line MDA-MB-231. Although this cell line carries p53 mutations, our data indicated that OSR1 constitutive kinase activity of the OSR1 in MDA-MB-231 was independent of p53. Interestingly, the inhibition of OSR1 had no significant impact on MDA-MB-231 cell viability, but it was found to contribute to its substantial cell migration and invasion, as this was significantly attenuated by the WNK/OSR1 inhibitor WNK463. Analogously, the overexpression of constitutively active OSR1 in the poorly migrating BC cell line MCF7 enhanced its cell mobility. Collectively, our results indicate that the pharmacological inhibition of OSR1 could be a promising novel strategy for preventing the oncogenic potential of TNBC.</p>","PeriodicalId":36426,"journal":{"name":"ACS Pharmacology and Translational Science","volume":"8 3","pages":"726–735 726–735"},"PeriodicalIF":4.9,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acsptsci.4c00603","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143608957","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":"Development of a Fluorescence Polarization Assay for the SARS-CoV-2 Papain-like Protease.","authors":"Kan Li, Prakash Jadhav, Yu Wen, Haozhou Tan, Jun Wang","doi":"10.1021/acsptsci.4c00642","DOIUrl":"10.1021/acsptsci.4c00642","url":null,"abstract":"<p><p>The COVID-19 pandemic has caused significant losses to the global community. Although effective vaccination and antiviral therapeutics provide primary defense, SARS-CoV-2 remains a public health threat, given the emerging resistant variants. The SARS-CoV-2 papain-like protease (PL^pro) is essential for viral replication and is a promising drug target. We recently designed a series of biarylphenyl PL^pro inhibitors with a representative lead <b>Jun12682</b> showing potent antiviral efficacy in a SARS-CoV-2 infection mouse model. In this study, we designed a fluorescein-labeled biarylphenyl probe <b>Jun12781</b> and used it to optimize a fluorescence polarization (FP) assay. The FP assay is suitable for high-throughput screening with a <i>Z</i>' factor of 0.69. In addition, we found a positive correlation between the FP binding affinity and the enzymatic inhibitory potency of PL^pro inhibitors, suggesting that the FP assay is valid in characterizing the binding affinity of PL^pro inhibitors.</p>","PeriodicalId":36426,"journal":{"name":"ACS Pharmacology and Translational Science","volume":"8 3","pages":"774-784"},"PeriodicalIF":4.9,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11915184/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143664905","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":"Exploring End-of-Life Experiences and Consciousness through the Lens of Psychedelics","authors":"Hongyuan Li,&nbsp; and ,&nbsp;Xiaohui Wang*,&nbsp;","doi":"10.1021/acsptsci.5c0011810.1021/acsptsci.5c00118","DOIUrl":"https://doi.org/10.1021/acsptsci.5c00118https://doi.org/10.1021/acsptsci.5c00118","url":null,"abstract":"<p >Exploring dying through the lens of psychedelic experiences offers transformative perspectives on the end-of-life process, potentially alleviating existential distress and enriching the quality of life for those nearing death. Their potential in palliative care, therapy, and spiritual exploration is increasingly recognized, promising to revolutionize end-of-life understanding and care.</p>","PeriodicalId":36426,"journal":{"name":"ACS Pharmacology and Translational Science","volume":"8 3","pages":"907–909 907–909"},"PeriodicalIF":4.9,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143608970","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}