Advances in pharmacology最新文献_第3页

Modulatory and protective effects of prolyl hydroxylase domain inhibitors in the central nervous system. 脯氨酰羟化酶结构域抑制剂对中枢神经系统的调节和保护作用。

Advances in pharmacology Pub Date : 2025-01-01 Epub Date: 2024-10-18 DOI: 10.1016/bs.apha.2024.10.006

Konstantinos Matheoudakis, John J O'Connor

{"title":"Modulatory and protective effects of prolyl hydroxylase domain inhibitors in the central nervous system.","authors":"Konstantinos Matheoudakis, John J O'Connor","doi":"10.1016/bs.apha.2024.10.006","DOIUrl":"10.1016/bs.apha.2024.10.006","url":null,"abstract":"Oxygen is essential for all mammalian species, with complex organs such as the brain requiring a large and steady supply to function. During times of low or inadequate oxygen supply (hypoxia), adaptation is required in order to continue to function. Hypoxia inducible factors (HIF) are transcription factors which are activated during hypoxia and upregulate protective genes. Normally, when oxygen levels are sufficient (normoxia) HIFs are degraded by oxygen sensing prolyl hydroxylase domain proteins (PHD), but during hypoxia PHDs no longer exert influence on HIFs allowing their activation. Given that PHDs regulate the activity of HIFs, their pharmacological inhibition through PHD inhibitors (PHDIs) is believed to be the basis of their neuroprotective benefits. This review discusses some of the potential therapeutic benefits of PHDIs in a number of neurological disorders which see hypoxia as a major pathophysiological mechanism. These include stroke, Parkinson's disease, and amyotrophic lateral sclerosis. We also explore the potential neuroprotective benefits and limitations of PHDIs in a variety of disorders in the central nervous system (CNS). Additionally, the activation of HIFs by PHDIs can have modulatory effects on CNS functions such as neurotransmission and synaptic plasticity, mechanisms critical to cognitive processes such as learning and memory.","PeriodicalId":7366,"journal":{"name":"Advances in pharmacology","volume":"102 ","pages":"211-235"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143389611","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}

引用次数: 0

Integrative computational approaches in pharmaceuticals: Driving innovation in discovery and delivery. 综合计算方法在制药：推动创新的发现和交付。

Advances in pharmacology Pub Date : 2025-01-01 Epub Date: 2025-02-17 DOI: 10.1016/bs.apha.2025.01.014

Heena R Bhojwani, Nikhil P Rajnani, Asawari Hare, Nalini S Kurup

{"title":"Integrative computational approaches in pharmaceuticals: Driving innovation in discovery and delivery.","authors":"Heena R Bhojwani, Nikhil P Rajnani, Asawari Hare, Nalini S Kurup","doi":"10.1016/bs.apha.2025.01.014","DOIUrl":"10.1016/bs.apha.2025.01.014","url":null,"abstract":"In recent years, the pharmaceutical industry has increasingly emphasized the role of lead compound identification in developing new therapeutic agents. Lead compounds show promising pharmacological activity against specific targets and are critical in drug development. Integrative computational approaches streamline this process by efficiently screening chemical libraries and designing potential drug candidates. This chapter highlights various computational techniques for lead compound discovery, including molecular modeling, cheminformatics, ligand- and structure-based drug design, molecular dynamics simulations, ADMET prediction, drug-target interaction analysis, and high-throughput screening. These methods improve drug discovery's efficiency, cost-effectiveness, and target-specific focus. Computational pharmaceutics has gained popularity due to the longer formulation development time which in turn increases the cost as well as decrease in the drug discovery production. Conventionally, formulation development relied on costly and unpredictable trial-and-error methods. However, analyzing the big data, artificial intelligence, and multi-scale modeling in computational pharmaceutics is transforming drug delivery. This chapter provides valuable insights throughout pre-formulation, formulation screening, in vivo predictions, and personalized medicine applications. Multiscale computational modeling is advancing drug delivery systems, enabling targeted treatments with multifunctional nanoparticles. Although in its early stages, this approach helps understand complex interactions between drugs, delivery systems, and patients.","PeriodicalId":7366,"journal":{"name":"Advances in pharmacology","volume":"103 ","pages":"349-373"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143770907","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}

引用次数: 0

Senotherapeutic approach to age-related endocrine diseases. 老年内分泌疾病的老年治疗方法。

Advances in pharmacology Pub Date : 2025-01-01 Epub Date: 2025-03-15 DOI: 10.1016/bs.apha.2025.02.009

Şeydanur Turgut, Gülnur Andican

{"title":"Senotherapeutic approach to age-related endocrine diseases.","authors":"Şeydanur Turgut, Gülnur Andican","doi":"10.1016/bs.apha.2025.02.009","DOIUrl":"10.1016/bs.apha.2025.02.009","url":null,"abstract":"Senescent cells progressively accumulate in the endocrine glands and their target tissue during the biological aging process. Senescence leads to hormonal imbalances contributing to various age-related endocrine diseases (AREDs). Cellular senescence, characterized by irreversible cell-cycle arrest, becomes more prevalent in advanced age, and the senescent cells release pro-inflammatory and pro-fibrotic factors, exacerbating endocrine dysregulation. Senescence-associated secretory phenotype (SASP) contributes to the pathogenesis of AREDs such as metabolic syndrome, sarcopenia, osteoporosis, and type 2 diabetes mellitus. Impaired metabolism of melatonin, cortisol, insulin, growth, and thyroid hormones are all intimately linked to age-related hormonal imbalance and dysregulated circadian rhythms. Pharmacokinetic and pharmacodynamic processes are also known to be impacted by circadian oscillations, which can also impact the toxicity and effectiveness of several therapeutic agents. Diagnosing and monitoring AREDs requires an assessment of individual circadian oscillations, inappropriate polypharmacy, and the senotherapeutic benefits of routine medications in the elderly. Hormone-oriented senotherapeutic strategies combined with anti-inflammatory SASP-related treatments may alleviate the detrimental effects of ARED symptoms. However, the complexity of senotherapy and the risk of possible adverse effects necessitate personalized treatment approaches.","PeriodicalId":7366,"journal":{"name":"Advances in pharmacology","volume":"104 ","pages":"475-514"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144726370","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}

引用次数: 0

Game changer: Navigating between challenges and hopes in geropharmacology. 游戏改变者：在老年药理学的挑战和希望之间导航。

Advances in pharmacology Pub Date : 2025-01-01 Epub Date: 2025-03-12 DOI: 10.1016/bs.apha.2025.02.007

Qian Chen, Reid Hartman, Lidia Dankiv, Emily Yan, Lindon Young, Robert Barsotti

{"title":"Game changer: Navigating between challenges and hopes in geropharmacology.","authors":"Qian Chen, Reid Hartman, Lidia Dankiv, Emily Yan, Lindon Young, Robert Barsotti","doi":"10.1016/bs.apha.2025.02.007","DOIUrl":"10.1016/bs.apha.2025.02.007","url":null,"abstract":"The aging population is expanding rapidly to reshape the social and economic structures. Aging signifies the close to the end of life and threatens health because it features unavoidable compression of body reserve and gradual suppression of organ function. Tremendous research has established twelve essential aging hallmarks that shed light on mitigation frameworks. Interestingly, aging harbors inherent heterogeneity and plasticity, reflecting its multifaceted nature. Additionally, age-related diseases, such as cardiovascular and neurodegenerative diseases, often undergo the exact mechanisms with more devastating damage and speed. Therefore, interventions to promote healthy aging improve life quality and delay the disease's prevalence to later age. Clinical studies in humans have demonstrated the potential of several interventions, including lifestyle modifications, NAD+ supplementation, gut microbiota modulation, antidiabetic drugs (e.g., metformin), rapamycin, and senolytics, to mitigate the aging process and delay the onset of age-related diseases. Remarkably, clinical trials exhibit heterogeneity by showing substantial inter-individual differences in response to the interventions. It is often attributed to basal health status, tissue senescent burden, and immunity level. Continuous research would validate these correlations and solidify the personalized approaches. Lastly, generative artificial intelligence can pave a promising avenue to revolutionize anti-aging research and tailor aging management to promote healthy aging and extend health span.","PeriodicalId":7366,"journal":{"name":"Advances in pharmacology","volume":"104 ","pages":"37-85"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144726444","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}

引用次数: 0

Isothiocyanates from cruciferous plants as geroprotectors. 十字花科植物中的异硫氰酸酯作为老年保护剂。

Advances in pharmacology Pub Date : 2025-01-01 Epub Date: 2025-02-25 DOI: 10.1016/bs.apha.2025.01.023

Tetiana R Dmytriv, Volodymyr I Lushchak

{"title":"Isothiocyanates from cruciferous plants as geroprotectors.","authors":"Tetiana R Dmytriv, Volodymyr I Lushchak","doi":"10.1016/bs.apha.2025.01.023","DOIUrl":"10.1016/bs.apha.2025.01.023","url":null,"abstract":"Isothiocyanates (ITCs) are plant secondary metabolites predominantly found in the Brassicaceae family, responsible for their characteristic pungent taste and noted for their bioactive properties. The pungency of these plants arises from mustard oils, which are generated from glucosinolates when the plant material is chewed, cut, or otherwise damaged. This chapter delves into the potential of ITCs as promising geroprotectors - agents capable of delaying aging and mitigating age-related diseases. Compounds such as sulforaphane, a well-studied ITC, exhibit remarkable antioxidant and anti-inflammatory properties, which modulate key cellular signaling pathways involved in aging. Additionally, ITCs have been shown to induce autophagy, a critical cellular process that reduces the accumulation of damaged proteins and age-related aggregates, thereby supporting cellular health. The chapter reviews the biosynthesis and bioavailability of ITCs, their role in promoting longevity, and the molecular mechanisms underlying their protective effects. It also addresses potential adverse effects and challenges associated with their application. The evidence presented underscores the potential of ITCs to contribute to healthy aging and the prevention of age-associated conditions, highlighting the need for further exploration in geriatric medicine and therapeutic development.","PeriodicalId":7366,"journal":{"name":"Advances in pharmacology","volume":"104 ","pages":"199-225"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144726446","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}

引用次数: 0

Molecular imaging for senescent cells-targeted therapeutics in aging and age-related diseases. 衰老细胞靶向治疗衰老和衰老相关疾病的分子成像。

Advances in pharmacology Pub Date : 2025-01-01 Epub Date: 2025-02-24 DOI: 10.1016/bs.apha.2025.01.020

Peili Cen

{"title":"Molecular imaging for senescent cells-targeted therapeutics in aging and age-related diseases.","authors":"Peili Cen","doi":"10.1016/bs.apha.2025.01.020","DOIUrl":"10.1016/bs.apha.2025.01.020","url":null,"abstract":"Senescent cells are attributed to aging and age-related diseases. Clearance of senescent cells can delay the aging process and treat age-related diseases. Senescent cells have typical phenotypes including permanent cell cycle arrest, metabolic changes, senescence-associated secretory phenotype, and other structural and functional changes. Senescent cells-targeted therapeutics containing senolytics and senomorphics have been widely investigated but still insufficient, and the internal processes are still unclear, leaving a large gap between preclinical and clinical usage for aging and age-related disease management. Thus, it is urgently demanded to discover many more drugs or new targets with in vivo pharmacodynamics and pharmacokinetics evaluation and monitoring, promoting clinical translation. As a revolutionizing approach, molecular imaging exhibited great potential in exploring the in vivo pathophysiological mechanisms and further promoting the diagnosis and therapies of diseases. It can realize the visualization of complex biochemical processes from living cells, tissues, and organs, to subjects. Benefiting from the numerous imaging probes designed and synthesized with specificity and sensitivity, molecular imaging can vigorously facilitate exploring underlying in vivo mechanisms of senescent cells and senotherapeutics for aging and age-related diseases. Moreover, conjugating the senolytics and senomorphics with imaging probes can realize in vivo image-guided therapy for senescent cells, reversing the dysfunction of aging and treating age-related diseases. Molecular imaging exhibits great potential in visualizing and monitoring senescent cells-targeted therapeutics for aging and age-related diseases, and can forcefully contribute to the clinical translation of gerophamocology.","PeriodicalId":7366,"journal":{"name":"Advances in pharmacology","volume":"104 ","pages":"259-287"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144726448","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}

引用次数: 0

Essential database resources for modern drug discovery. 现代药物发现的基本数据库资源。

Advances in pharmacology Pub Date : 2025-01-01 Epub Date: 2025-02-08 DOI: 10.1016/bs.apha.2025.01.002

Saloni Yadav, Sweta S Koka, Priya Jain, G N Darwhekar, Kuldeep Vinchurkar

引用次数: 0

The translational impact of bioinformatics on traditional wet lab techniques. 生物信息学对传统湿实验室技术的转化影响。

Advances in pharmacology Pub Date : 2025-01-01 Epub Date: 2025-02-26 DOI: 10.1016/bs.apha.2025.01.012

S Suveena, Akhiya Anilkumar Rekha, J R Rani, Oommen V Oommen, Reshmi Ramakrishnan

{"title":"The translational impact of bioinformatics on traditional wet lab techniques.","authors":"S Suveena, Akhiya Anilkumar Rekha, J R Rani, Oommen V Oommen, Reshmi Ramakrishnan","doi":"10.1016/bs.apha.2025.01.012","DOIUrl":"10.1016/bs.apha.2025.01.012","url":null,"abstract":"Bioinformatics has taken a pivotal place in the life sciences field. Not only does it improve, but it also fine-tunes and complements the wet lab experiments. It has been a driving force in the so-called biological sciences, converting them into hypothesis and data-driven fields. This study highlights the translational impact of bioinformatics on experimental biology and discusses its evolution and the advantages it has brought to advancing biological research. Computational analyses make labor-intensive wet lab work cost-effective by reducing the use of expensive reagents. Genome/proteome-wide studies have become feasible due to the efficiency and speed of bioinformatics tools, which can hardly be compared with wet lab experiments. Computational methods provide the scalability essential for manipulating large and complex data of biological origin. AI-integrated bioinformatics studies can unveil important biological patterns that traditional approaches may otherwise overlook. Bioinformatics contributes to hypothesis formation and experiment design, which is pivotal for modern-day multi-omics and systems biology studies. Integrating bioinformatics in the experimental procedures increases reproducibility and helps reduce human errors. Although today's AI-integrated bioinformatics predictions have significantly improved in accuracy over the years, wet lab validation is still unavoidable for confirming these predictions. Challenges persist in multi-omics data integration and analysis, AI model interpretability, and multiscale modeling. Addressing these shortcomings through the latest developments is essential for advancing our knowledge of disease mechanisms, therapeutic strategies, and precision medicine.","PeriodicalId":7366,"journal":{"name":"Advances in pharmacology","volume":"103 ","pages":"287-311"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771003","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}

引用次数: 0

Computational exploration of viral cell membrane structures for identifying novel therapeutic target. 病毒细胞膜结构的计算探索，以确定新的治疗靶点。

Advances in pharmacology Pub Date : 2025-01-01 Epub Date: 2025-02-06 DOI: 10.1016/bs.apha.2025.01.005

Kirtiman Mahata, Manti Biswas, Shrestha Sengupta, Chitra Rani, Hridoy R Bairagya

{"title":"Computational exploration of viral cell membrane structures for identifying novel therapeutic target.","authors":"Kirtiman Mahata, Manti Biswas, Shrestha Sengupta, Chitra Rani, Hridoy R Bairagya","doi":"10.1016/bs.apha.2025.01.005","DOIUrl":"10.1016/bs.apha.2025.01.005","url":null,"abstract":"The membrane proteins of viruses play a critical role, and they shield viruses and takes biochemical mechanisms like sticking to the host cell membrane, merging with them, building new viruses, and breaking free. These steps make sure the virus can infect and multiply. But the membrane proteins of Nipah, Zika, SARS-CoV-2, and Hendra virus can cause special kinds of infections. Nipah and Hendra viruses use their fusion protein to join with the host cell membrane. Their glycoprotein interacts with host receptors. The matrix protein helps to build and support the virus structure. Zika virus relies on its envelope protein to attach and fuse with host cells. Its membrane protein keeps the viral envelope stable. SARS-CoV-2 uses its spike protein to enter host cells and its envelope protein helps assemble new viruses. The membrane protein gives structural stability whereas the nucleocapsid protein interacts with the RNA genome. These viral membranes contain various kinds of lipids and proteins and they make up about 30 % of the membrane area. Yet, scientists find it hard to predict their molecular structure and different biological characters. The coarse-grained molecular dynamics simulations, enhanced sampling methods, and various structural bioinformatics investigations on viral proteins provide reliable scientific data. These investigations reveal viral membrane proteins' structural features, movement patterns, and thermodynamic properties. These computer methods are vital for drug discovery because it allows researchers to find new compounds that target viral membrane proteins to prevent their functions.","PeriodicalId":7366,"journal":{"name":"Advances in pharmacology","volume":"103 ","pages":"265-285"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771225","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}

引用次数: 0

Cellular parabioisis as a senotherapeutic approach. 细胞异种共生作为一种老年治疗方法。

Advances in pharmacology Pub Date : 2025-01-01 Epub Date: 2025-02-26 DOI: 10.1016/bs.apha.2025.01.022

Sevide Sencan, Ilhan Onaran

{"title":"Cellular parabioisis as a senotherapeutic approach.","authors":"Sevide Sencan, Ilhan Onaran","doi":"10.1016/bs.apha.2025.01.022","DOIUrl":"10.1016/bs.apha.2025.01.022","url":null,"abstract":"Beyond cell death and differentiation, cell senescence is profoundly influenced by the social nature of cells, which is intricately linked to cell communication as a fundamental aspect of biological systems shaping both individual and collective cellular behaviors. As demonstrated by cellular parabiosis, sophisticated communication plays a critical role in maintaining tissue health and delaying age-related diseases. It is now widely accepted that signaling crosstalk, through both direct cell-to-cell interactions and indirect mechanisms, drives cell heterogeneity and cell state transitions, and that increasing cell heterogeneity with age significantly contributes to the development of age-related diseases. Aging is also associated with increased stem cell heterogeneity, leading to functional decline and decreased regenerative capacity. Heterochronic parabiosis and stem cell transplantation studies have indicated that impaired regeneration observed in aging organisms can be reversed by a youthful systemic environment that restores balanced signaling and rejuvenates aged cells. Multiple reports on autologous and allogeneic transplantation have confirmed the rejuvenative potential of hematopoietic stem cell and various tissue-derived mesenchymal stem cell transplants, providing insights into the potential of integrating cellular parabiosis-like approaches into regenerative medicine to combat aging and its associated pathologies. Scientific advances in these areas are now progressing to clinical trials. In this chapter, we first summarize the current knowledge of cellular parabiosis as a complex physiological process and emphasize heterogeneity in senescent cells. Subsequently, it reviews therapeutic approaches for treating aging-induced stem cell dysfunction as innovative solutions for addressing this issue. Finally, the chapter discusses future directions and challenges for senotherapeutic applications, highlighting their potential to advance the field of regenerative medicine.","PeriodicalId":7366,"journal":{"name":"Advances in pharmacology","volume":"104 ","pages":"227-258"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144726368","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}

引用次数: 0