Pub Date : 2026-04-01Epub Date: 2026-02-01DOI: 10.1016/j.pharmthera.2026.108991
Yumin Wang , Yan Wang , Qingzhu Gao , Yonglin Zhu , Yulin Li , Zhe-Sheng Chen , Junjing Zhang , Geng Zhang , Hongquan Wang
Therapeutic resistance remains a major challenge in cancer management. The cyclic GMP–AMP synthase (cGAS)–stimulator of interferon genes (STING) pathway senses cytosolic DNA and triggers innate immune responses. Cancer cells frequently acquire drug resistance by inhibiting cGAS-STING signaling, leading to growing interest in small-molecule agonists that reactivate this pathway to counter resistance. In this review, we summarize recent molecular and cellular findings explaining how cancer cells suppress cGAS-STING through epigenetic regulation, post-translational modifications (PTMs), and altered metabolic pathways. We also evaluate recent studies on cGAS-STING agonists aimed at restoring sensitivity to chemotherapy, immunotherapy, and targeted cancer therapies to inform new strategies to pharmacologically reactivate cGAS-STING signaling pathway to reverse existing therapeutic barriers.
{"title":"Pharmacological activation of cGAS-STING pathway to reverse cancer drug resistance","authors":"Yumin Wang , Yan Wang , Qingzhu Gao , Yonglin Zhu , Yulin Li , Zhe-Sheng Chen , Junjing Zhang , Geng Zhang , Hongquan Wang","doi":"10.1016/j.pharmthera.2026.108991","DOIUrl":"10.1016/j.pharmthera.2026.108991","url":null,"abstract":"<div><div>Therapeutic resistance remains a major challenge in cancer management. The cyclic GMP–AMP synthase (cGAS)–stimulator of interferon genes (STING) pathway senses cytosolic DNA and triggers innate immune responses. Cancer cells frequently acquire drug resistance by inhibiting cGAS-STING signaling, leading to growing interest in small-molecule agonists that reactivate this pathway to counter resistance. In this review, we summarize recent molecular and cellular findings explaining how cancer cells suppress cGAS-STING through epigenetic regulation, post-translational modifications (PTMs), and altered metabolic pathways. We also evaluate recent studies on cGAS-STING agonists aimed at restoring sensitivity to chemotherapy, immunotherapy, and targeted cancer therapies to inform new strategies to pharmacologically reactivate cGAS-STING signaling pathway to reverse existing therapeutic barriers.</div></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"280 ","pages":"Article 108991"},"PeriodicalIF":12.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146102576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Restoration of coronary blood flow is essential for myocardial salvage in acute myocardial infarction (AMI), yet substantial injury and adverse remodeling often persist after successful reperfusion. Experimental ischemia-reperfusion models have identified dynamic innate immune responses involving neutrophils, monocytes, macrophages, and inflammatory signaling pathways that shape myocardial injury and repair under controlled conditions. In this review, we critically reappraise innate immune activation associated with myocardial ischemia and reperfusion by explicitly distinguishing experimental evidence from immune signatures observed in human myocardial infarction. While experimental studies demonstrate temporally structured and modifiable immune responses following brief ischemia and reperfusion, clinical myocardial infarction is typically characterized by prolonged ischemia, in which irreversible cardiomyocyte necrosis is largely established before reperfusion. Consequently, immune responses observed after revascularization predominantly reflect downstream consequences of ischemic injury and tissue repair rather than injury newly induced by reperfusion. Recognizing this distinction provides a refined framework for interpreting immune mechanisms and for guiding the rational development of immunomodulatory strategies in ischemic heart disease.
{"title":"Innate immune responses following myocardial ischemia and reperfusion: Evidence, mechanisms, and translational challenges.","authors":"Shuya Zhang,Pengju Du,Cheng Zhang,Wei Jie,Guo-Ping Shi,Junli Guo","doi":"10.1016/j.pharmthera.2026.109026","DOIUrl":"https://doi.org/10.1016/j.pharmthera.2026.109026","url":null,"abstract":"Restoration of coronary blood flow is essential for myocardial salvage in acute myocardial infarction (AMI), yet substantial injury and adverse remodeling often persist after successful reperfusion. Experimental ischemia-reperfusion models have identified dynamic innate immune responses involving neutrophils, monocytes, macrophages, and inflammatory signaling pathways that shape myocardial injury and repair under controlled conditions. In this review, we critically reappraise innate immune activation associated with myocardial ischemia and reperfusion by explicitly distinguishing experimental evidence from immune signatures observed in human myocardial infarction. While experimental studies demonstrate temporally structured and modifiable immune responses following brief ischemia and reperfusion, clinical myocardial infarction is typically characterized by prolonged ischemia, in which irreversible cardiomyocyte necrosis is largely established before reperfusion. Consequently, immune responses observed after revascularization predominantly reflect downstream consequences of ischemic injury and tissue repair rather than injury newly induced by reperfusion. Recognizing this distinction provides a refined framework for interpreting immune mechanisms and for guiding the rational development of immunomodulatory strategies in ischemic heart disease.","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"11 1","pages":"109026"},"PeriodicalIF":13.5,"publicationDate":"2026-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147465095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Myeloid differentiation primary response 88 (MyD88), a central adaptor protein governing Toll-like receptor (TLR) and interleukin-1 receptor (IL-1R) signaling cascades, is increasingly recognized as a pivotal mediator of neuroimmune interactions and neuromodulation. Beyond its canonical immune functions, emerging evidence reveals widespread MyD88 expression throughout the nervous system, where it plays functional roles in both glial populations and neuronal networks. While previous reviews have largely focused on glial mechanisms, recent studies highlight a complex, often overlooked aspect: the dual role of neuronal MyD88 signaling in orchestrating neurodevelopment while paradoxically driving neuroinflammation and synaptic dysregulation. Given the growing interest in innate immunity's involvement in central nervous system (CNS) diseases, a timely synthesis of MyD88 biology-from molecular mechanisms to therapeutic implications-is essential to bridge the fields of immunology and neuroscience. This article provides a comprehensive review of MyD88, synthesizing contemporary insights into its multifaceted regulatory roles in neural homeostasis and pathogenesis. We place particular emphasis on its mechanistic contributions to brain injury, chronic pain, and neurodegenerative disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). Furthermore, we evaluate innovative therapeutic approaches targeting MyD88-dependent pathways, highlighting recent pharmacotherapeutic advances and their neuroprotective potential. Finally, addressing the limitations of current strategies, we advocate for a new framework focused on developing therapeutics with increased cell selectivity, thereby advancing the precision and translational potential of MyD88-targeted interventions.
{"title":"The role of MyD88 in the nervous system: Neuronal functions, implications in neurological diseases, and therapeutic potential.","authors":"Hai-Li Pan,Jia-Yi Ge,Zi-Ang Zhang,Jia-Huan Xu,Jia-Ni Wu,Yi Ju,Xi-Yu Zhang,Zuo-Jie Jiang,Yong Chen,Yun-Zhao Xu,Xing-Jun Liu","doi":"10.1016/j.pharmthera.2026.109016","DOIUrl":"https://doi.org/10.1016/j.pharmthera.2026.109016","url":null,"abstract":"Myeloid differentiation primary response 88 (MyD88), a central adaptor protein governing Toll-like receptor (TLR) and interleukin-1 receptor (IL-1R) signaling cascades, is increasingly recognized as a pivotal mediator of neuroimmune interactions and neuromodulation. Beyond its canonical immune functions, emerging evidence reveals widespread MyD88 expression throughout the nervous system, where it plays functional roles in both glial populations and neuronal networks. While previous reviews have largely focused on glial mechanisms, recent studies highlight a complex, often overlooked aspect: the dual role of neuronal MyD88 signaling in orchestrating neurodevelopment while paradoxically driving neuroinflammation and synaptic dysregulation. Given the growing interest in innate immunity's involvement in central nervous system (CNS) diseases, a timely synthesis of MyD88 biology-from molecular mechanisms to therapeutic implications-is essential to bridge the fields of immunology and neuroscience. This article provides a comprehensive review of MyD88, synthesizing contemporary insights into its multifaceted regulatory roles in neural homeostasis and pathogenesis. We place particular emphasis on its mechanistic contributions to brain injury, chronic pain, and neurodegenerative disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). Furthermore, we evaluate innovative therapeutic approaches targeting MyD88-dependent pathways, highlighting recent pharmacotherapeutic advances and their neuroprotective potential. Finally, addressing the limitations of current strategies, we advocate for a new framework focused on developing therapeutics with increased cell selectivity, thereby advancing the precision and translational potential of MyD88-targeted interventions.","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"16 1","pages":"109016"},"PeriodicalIF":13.5,"publicationDate":"2026-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147446927","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-05DOI: 10.1016/j.pharmthera.2026.109014
Konstantin M. Nakov, M. Elise Gething, Tiana K. Kassis, Garrett J. Rutt, Brian Ho, Neha Bhandari, Taylor E. Collignon, Sabyasachi Banerjee, Anupam Bishayee
{"title":"Targeting signaling cascades by bioactive phytocompounds in osteosarcoma: A novel therapeutic approach","authors":"Konstantin M. Nakov, M. Elise Gething, Tiana K. Kassis, Garrett J. Rutt, Brian Ho, Neha Bhandari, Taylor E. Collignon, Sabyasachi Banerjee, Anupam Bishayee","doi":"10.1016/j.pharmthera.2026.109014","DOIUrl":"https://doi.org/10.1016/j.pharmthera.2026.109014","url":null,"abstract":"","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"56 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2026-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147360512","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-01Epub Date: 2026-01-19DOI: 10.1016/j.pharmthera.2026.108983
Dan Li , Ana L. Manzano-Covarrubias , Kelly B.I. Douglas , Karim Rafie , Martina Schmidt
Chronic obstructive pulmonary disease (COPD) and asthma are two major obstructive lung disorders characterized by persistent airway inflammation that leads to progressive lung function decline. Although both chronic in nature, the inflammatory profiles that characterize these diseases differ significantly: COPD is predominantly driven by neutrophilic inflammation, whereas allergic asthma, a major subtype of asthma disease, is traditionally associated with eosinophilic and T helper 2 (Th2)-mediated responses. This review explores first the mechanisms underlying chronic inflammation in COPD and asthma, emphasizing thereafter the impact of bacterial and viral infections in exacerbating inflammatory responses and accelerating lung damage. Current therapeutic approaches, including the use of corticosteroids, bronchodilators, and biologics, are evaluated, highlighting their mechanisms of actions and limitations. Finally, the review focuses on novel therapeutic targets that have emerged from recent advances in (airway) inflammation research. The roles of key signaling pathways such as those involving Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), C-X-C motif chemokine receptor 2 (CXCR2), toll-like receptors (TLRs), tumor necrosis factor (TNF) signaling, P2X purinoceptor 4 (P2X4 receptor), and the NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome in sustaining chronic inflammation are discussed. Understanding these pathways offers insights into the potential for development of more targeted and effective treatments. By offering a comprehensive overview of both established and (potential) novel approaches, this review aims to promote the identification and development of therapeutic strategies that could revolutionize the options for effective treatment of chronic inflammation in obstructive lung disorders.
{"title":"Therapeutic potential of targeting novel signaling pathways in regulating chronic inflammation in obstructive lung disorders","authors":"Dan Li , Ana L. Manzano-Covarrubias , Kelly B.I. Douglas , Karim Rafie , Martina Schmidt","doi":"10.1016/j.pharmthera.2026.108983","DOIUrl":"10.1016/j.pharmthera.2026.108983","url":null,"abstract":"<div><div>Chronic obstructive pulmonary disease (COPD) and asthma are two major obstructive lung disorders characterized by persistent airway inflammation that leads to progressive lung function decline. Although both chronic in nature, the inflammatory profiles that characterize these diseases differ significantly: COPD is predominantly driven by neutrophilic inflammation, whereas allergic asthma, a major subtype of asthma disease, is traditionally associated with eosinophilic and T helper 2 (Th2)-mediated responses. This review explores first the mechanisms underlying chronic inflammation in COPD and asthma, emphasizing thereafter the impact of bacterial and viral infections in exacerbating inflammatory responses and accelerating lung damage. Current therapeutic approaches, including the use of corticosteroids, bronchodilators, and biologics, are evaluated, highlighting their mechanisms of actions and limitations. Finally, the review focuses on novel therapeutic targets that have emerged from recent advances in (airway) inflammation research. The roles of key signaling pathways such as those involving Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), C-X-C motif chemokine receptor 2 (CXCR2), toll-like receptors (TLRs), tumor necrosis factor (TNF) signaling, P2X purinoceptor 4 (P2X4 receptor), and the NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome in sustaining chronic inflammation are discussed. Understanding these pathways offers insights into the potential for development of more targeted and effective treatments. By offering a comprehensive overview of both established and (potential) novel approaches, this review aims to promote the identification and development of therapeutic strategies that could revolutionize the options for effective treatment of chronic inflammation in obstructive lung disorders.</div></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"279 ","pages":"Article 108983"},"PeriodicalIF":12.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146000573","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-01Epub Date: 2026-01-05DOI: 10.1016/j.pharmthera.2025.108973
Ricardo Caballero, Juan Tamargo, Eva Delpón
Sodium-glucose cotransporter 2 inhibitors (SGLT2i) represent the cornerstone of therapy in patients with type 2 diabetes (T2D), heart failure (HF), or chronic kidney disease (CKD). These patients present a high risk of cardiac arrhythmias, particularly when these comorbidities coexist. In experimental models, SGLT2i exert antiarrhythmic effects and clinical studies and meta-analyses strongly suggest that they reduce new-onset and recurrences of atrial fibrillation in patients with HF or CKD irrespective of the diabetic status. Although some trials and meta-analyses suggest that SGLT2i could decrease the risk of ventricular arrhythmias and sudden cardiac arrest, the evidence is weak, and their potential remains to be confirmed. Thus, clinical evidence so far should be considered as hypothesis-generating. Although the exact mechanism underlying their antiarrhythmic effects remains uncertain and much research is needed, multiple direct cardiac and extracardiac effects may be involved. They improve cardiac electrical (via changes in ion channels and transporters; maintenance of Na+ and Ca2+ homeostasis), structural (reduce hypertrophy, fibrosis, inflammation, and epicardial fat; improve mitochondrial function and energetic metabolism), and autonomic (reduce sympathetic hyperactivity) remodelling. Indirect extracardiac effects related to an improvement in cardiovascular risk factors and haemodynamics, together with their protective renal and vascular effects, may also play a role. This narrative review summarises the experimental and clinical evidence of their antiarrhythmic effects, potential underlying mechanisms, limitations of present evidence, and gaps of knowledge that should be filled before SGLT2i can be recommended for the prevention and treatment of arrhythmias in patients for whom these drugs are indicated.
{"title":"SGLT2 inhibitors: Do they have antiarrhythmic properties?","authors":"Ricardo Caballero, Juan Tamargo, Eva Delpón","doi":"10.1016/j.pharmthera.2025.108973","DOIUrl":"10.1016/j.pharmthera.2025.108973","url":null,"abstract":"<div><div>Sodium-glucose cotransporter 2 inhibitors (SGLT2i) represent the cornerstone of therapy in patients with type 2 diabetes (T2D), heart failure (HF), or chronic kidney disease (CKD). These patients present a high risk of cardiac arrhythmias, particularly when these comorbidities coexist. In experimental models, SGLT2i exert antiarrhythmic effects and clinical studies and meta-analyses strongly suggest that they reduce new-onset and recurrences of atrial fibrillation in patients with HF or CKD irrespective of the diabetic status. Although some trials and meta-analyses suggest that SGLT2i could decrease the risk of ventricular arrhythmias and sudden cardiac arrest, the evidence is weak, and their potential remains to be confirmed. Thus, clinical evidence so far should be considered as hypothesis-generating. Although the exact mechanism underlying their antiarrhythmic effects remains uncertain and much research is needed, multiple direct cardiac and extracardiac effects may be involved. They improve cardiac electrical (via changes in ion channels and transporters; maintenance of Na<sup>+</sup> and Ca<sup>2+</sup> homeostasis), structural (reduce hypertrophy, fibrosis, inflammation, and epicardial fat; improve mitochondrial function and energetic metabolism), and autonomic (reduce sympathetic hyperactivity) remodelling. Indirect extracardiac effects related to an improvement in cardiovascular risk factors and haemodynamics, together with their protective renal and vascular effects, may also play a role. This narrative review summarises the experimental and clinical evidence of their antiarrhythmic effects, potential underlying mechanisms, limitations of present evidence, and gaps of knowledge that should be filled before SGLT2i can be recommended for the prevention and treatment of arrhythmias in patients for whom these drugs are indicated.</div></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"279 ","pages":"Article 108973"},"PeriodicalIF":12.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145902500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-01Epub Date: 2026-01-12DOI: 10.1016/j.pharmthera.2026.108982
Inês Costa , Daniel José Barbosa , Fernando Remião , Maria Emília Sousa , Renata Silva
Neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and multiple sclerosis, are characterized by the progressive breakdown and eventual loss of synapses and neurons, primarily driven by the accumulation of pathologically altered proteins within the brain and spinal cord. These diseases have complex and multifactorial etiologies, involving a broad spectrum of pathophysiological mechanisms, many of which remain incompletely understood. Nonetheless, several key pathways are consistently implicated across these conditions, including oxidative stress, mitochondrial dysfunction, neuroinflammation, and apoptosis. Given their rising prevalence and the persistent lack of effective disease-modifying therapies, the development of novel therapeutic strategies capable of targeting multiple pathophysiological processes is of critical importance for delaying or halting disease progression. In this context, marine natural compounds have emerged as promising candidates for counteracting neurodegeneration, owing to their ability to modulate key pathophysiological hallmarks of distinct neurodegenerative diseases. Derived from a wide range of marine organisms – including algae, sponges, fungi, and cyanobacteria - these bioactive molecules possess unique chemical structures and exhibit a broad spectrum of neuroprotective effects. Many have demonstrated potent antioxidant, anti-apoptotic, and mitochondrial-stabilizing activities in preclinical models. This review highlights recent advances in the discovery and characterization of marine-derived compounds with therapeutic potential in neurodegenerative diseases, contextualizing their pathologic mechanisms.
{"title":"A dive into the untapped potential of marine compounds in counteracting neurodegeneration","authors":"Inês Costa , Daniel José Barbosa , Fernando Remião , Maria Emília Sousa , Renata Silva","doi":"10.1016/j.pharmthera.2026.108982","DOIUrl":"10.1016/j.pharmthera.2026.108982","url":null,"abstract":"<div><div>Neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and multiple sclerosis, are characterized by the progressive breakdown and eventual loss of synapses and neurons, primarily driven by the accumulation of pathologically altered proteins within the brain and spinal cord. These diseases have complex and multifactorial etiologies, involving a broad spectrum of pathophysiological mechanisms, many of which remain incompletely understood. Nonetheless, several key pathways are consistently implicated across these conditions, including oxidative stress, mitochondrial dysfunction, neuroinflammation, and apoptosis. Given their rising prevalence and the persistent lack of effective disease-modifying therapies, the development of novel therapeutic strategies capable of targeting multiple pathophysiological processes is of critical importance for delaying or halting disease progression. In this context, marine natural compounds have emerged as promising candidates for counteracting neurodegeneration, owing to their ability to modulate key pathophysiological hallmarks of distinct neurodegenerative diseases. Derived from a wide range of marine organisms – including algae, sponges, fungi, and cyanobacteria - these bioactive molecules possess unique chemical structures and exhibit a broad spectrum of neuroprotective effects. Many have demonstrated potent antioxidant, anti-apoptotic, and mitochondrial-stabilizing activities in preclinical models. This review highlights recent advances in the discovery and characterization of marine-derived compounds with therapeutic potential in neurodegenerative diseases, contextualizing their pathologic mechanisms.</div></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"279 ","pages":"Article 108982"},"PeriodicalIF":12.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145962077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-04DOI: 10.1016/j.pharmthera.2026.108995
Alessandro Maino, Jason Leo Walsh, Leonardo Portolan, Rafail Kotronias, Pietro Ameri, Rocco Vergallo, Italo Porto, Filippo Crea, Adrian Banning, Paolo Tammaro, Giovanni Luigi De Maria
{"title":"Therapeutic interventions for coronary microvascular obstruction after acute myocardial infarction: Developments and challenges","authors":"Alessandro Maino, Jason Leo Walsh, Leonardo Portolan, Rafail Kotronias, Pietro Ameri, Rocco Vergallo, Italo Porto, Filippo Crea, Adrian Banning, Paolo Tammaro, Giovanni Luigi De Maria","doi":"10.1016/j.pharmthera.2026.108995","DOIUrl":"https://doi.org/10.1016/j.pharmthera.2026.108995","url":null,"abstract":"","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"89 1","pages":""},"PeriodicalIF":13.5,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146109914","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-12-24DOI: 10.1016/j.pharmthera.2025.108972
Hao Zhang , Yilin Wu , Rui Zhao , Xuhan Hu , Xiaoou Sun
Cardiocerebrovascular disease (CCD) is a condition related to the heart and blood vessels affecting the cardiovascular system. The disease is caused by various pathogenic factors that damage the heart and brain tissues. CCD significantly threatens human health due to the increased incidence, disability, and mortality, but effective treatment options remain lacking. As precision medicine has taken center stage in recent years, the relationship between epigenetics and CCD has been increasingly studied. N6-methyladenosine (m6A) represents a dynamic and reversible methylation occurring on the sixth nitrogen atom of RNA adenine. This modification is essential in epigenetic regulation, involving the coordinated methyltransferase action, methylated reading proteins, and demethylases. Being a prevalent internal modification in eukaryotic messenger ribonucleic acid (mRNA), m6A is indispensable in numerous bioprocesses. m6A modification has been found to govern gene expression at the epigenetic, transcriptional, and post-transcriptional levels. This alteration can affect tumor development, regulate spermatogenesis and hematopoietic stem cell differentiation, thereby serving as a biomarker for CCD diagnosis and prognosis. Accordingly, we reviewed the function, mechanism, and value of m6A modification in CCD to present a fresh perspective for early diagnosis and clinical treatment.
{"title":"N6-methyladenosine (m6A) RNA methylation: a potential clinical therapeutic target in cardiocerebrovascular diseases","authors":"Hao Zhang , Yilin Wu , Rui Zhao , Xuhan Hu , Xiaoou Sun","doi":"10.1016/j.pharmthera.2025.108972","DOIUrl":"10.1016/j.pharmthera.2025.108972","url":null,"abstract":"<div><div>Cardiocerebrovascular disease (CCD) is a condition related to the heart and blood vessels affecting the cardiovascular system. The disease is caused by various pathogenic factors that damage the heart and brain tissues. CCD significantly threatens human health due to the increased incidence, disability, and mortality, but effective treatment options remain lacking. As precision medicine has taken center stage in recent years, the relationship between epigenetics and CCD has been increasingly studied. N6-methyladenosine (m6A) represents a dynamic and reversible methylation occurring on the sixth nitrogen atom of RNA adenine. This modification is essential in epigenetic regulation, involving the coordinated methyltransferase action, methylated reading proteins, and demethylases. Being a prevalent internal modification in eukaryotic messenger ribonucleic acid (mRNA), m6A is indispensable in numerous bioprocesses. m6A modification has been found to govern gene expression at the epigenetic, transcriptional, and post-transcriptional levels. This alteration can affect tumor development, regulate spermatogenesis and hematopoietic stem cell differentiation, thereby serving as a biomarker for CCD diagnosis and prognosis. Accordingly, we reviewed the function, mechanism, and value of m6A modification in CCD to present a fresh perspective for early diagnosis and clinical treatment.</div></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"278 ","pages":"Article 108972"},"PeriodicalIF":12.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145822826","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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