PHARMACOLOGY & THERAPEUTICS药理学与治疗学
PHARMACOLOGY & THERAPEUTICS(英文缩写 PHARMACOL THERAPEUT),ISSN 0163-7258,eISSN 1879-016X,中文译名:药理学与治疗学 是一本学术期刊。本页汇总该期刊的最新影响因子、分区信息以及最新收录于 PubMed 的文献,帮助您快速了解期刊全貌。
发文量统计区间：2025-11-01 至 2026-10-31，按本站收录文献的发表日期统计。
期刊介绍
历年影响因子趋势
| JCR 数据年份 | 影响因子 | JCR 分区 |
|---|---|---|
| 2021 | 13.400 | Q1 |
| 2022 | 13.500 | Q1 |
| 2023 | 12.000 | Q1 |
| 2024 | 12.500 | Q1 |
| 2025 | 13.500 | Q1 |
PHARMACOLOGY & THERAPEUTICS 最新收录文献
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1. Drug resistance in cancer: Emerging mechanisms, translational barriers, and pharmacological strategies.
1. 癌症耐药性：新兴机制、转化障碍与药理学策略PMID:日期:2026-09-16Multidrug resistance (MDR) remains a major challenge in cancer treatment. MDR has been explained by single-gene mechanisms, such as overexpression of ATP-binding cassette (ABC) transporters, drug-target mutations, activation of bypass signaling pathways, and increased DNA repair. However, these mechanisms alone are insufficient to explain the heterogeneity, reversibility, temporal evolution, and environmental dependence of drug resistance observed in clinical settings. Increasing evidence suggests that MDR is better viewed as a complex and evolving biological phenomenon rather than the result of isolated molecular events. This shift in perspective presents both challenges and opportunities for drug development. Future strategies will therefore require dynamic and mechanism-informed approaches that integrate rational drug combinations with sequential, intermittent, or adaptive treatment according to the evolving resistance state. In this review, we propose a conceptual shift from conventional MDR models toward systemic adaptive resistance. We review classical drug resistance, including drug uptake/efflux, compensatory pathway activation, and apoptosis evasion. We explore non-genetic drug resistance, such as drug-tolerant persisters (DTPs), epithelial-mesenchymal transition (EMT), cancer stem cell (CSC) plasticity, and related factors. Then, we discuss the interaction between these mechanisms, and how their coordinated effects contribute to tumor persistence and the evolution of MDR. Finally, we evaluate barriers in translational medicine and emerging pharmacological strategies, including longitudinal molecular monitoring and artificial intelligence (AI) -assisted drug resistance prediction.
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2. Neuroregulation as a modulatory force in immune checkpoint inhibitor resistance: mechanistic neuro-immune crosstalk informing biomarker-led diagnosis and targetable therapeutic sensitization.
2. 神经调控作为免疫检查点抑制剂耐药中的调节力量：机制性神经-免疫串扰为生物标志物导向的诊断和可靶向的治疗增敏提供信息PMID:日期:2026-09-12Immune checkpoint inhibitor (ICI) resistance remains a major challenge. This review discusses emerging evidence that neuroregulation constitutes an underrecognized regulatory layer in ICI resistance and summarizes its mechanistic, biomarker, and therapeutic implications. Mechanistically, neural components can modulate antitumor immunity through signaling, structural, spatial, and metabolic routes. Neural signaling may contribute to T-cell dysfunction by stabilizing exhausted phenotypes, increasing the expression of inhibitory receptors, and suppressing effector cytokine production. Neuroglial cells and neuropeptides further exacerbate immunosuppression through the induction of regulatory T cells and the reprogramming of myeloid cells. Beyond causing functional impairment, neuroregulation alters the spatial distribution of immune cells by inhibiting chemokine networks essential for the recruitment of dendritic cells and cytotoxic T cells, thereby promoting immune-excluded and immune-cold tumor states. Neural injury creates perineural immunosuppressive niches enriched in immunoregulatory tumor-associated macrophage states and regulatory T cells, which can extend into the broader tumor microenvironment and restrict CD8 T-cell infiltration and function. Neural inputs also reshape the metabolism of tumor and immune cells, establishing neuro-metabolic-immune circuits that limit effector cell fitness and reinforce ICI resistance. Therapeutically, pharmacological targeting of neural pathways, along with emerging bioelectronic and ex vivo neuro-immune strategies, may enhance the efficacy of ICIs across various tumor models. Neural abundance and injury signatures also emerge as potentially clinically relevant biomarkers that complement immune-centric predictors of response. Overall, neuroregulation provides a biologically coherent and potentially targetable framework for understanding and overcoming ICI resistance.
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3. Galectin-3 and its inhibitors: Overview and perspectives.
3. 半乳糖凝集素-3及其抑制剂：概述与展望PMID:日期:2026-09-12Galectin-3, a β-galactoside-binding lectin, is a driver and regulator of inflammation and fibrosis, and its levels are elevated in some heart and lung diseases. It also serves as a biomarker for the risk and severity of some forms of heart failure and, potentially, for various other pathological conditions. These observations make galectin-3 a promising potential therapeutic target. Both genetic and pharmacological inhibition of galectin-3 have been shown to ameliorate renal dysfunction and exert protective effects against liver fibrosis in animal models. Several galectin-3 inhibitors have been developed for therapeutic application in various pathological conditions. This review examines the progress of the development of 161 galectin-3 inhibitors, including monosaccharides, oligosaccharides, natural polysaccharides and their derivatives, carbohydrate polymers, antibody-drug conjugates, and non-carbohydrate compounds. Structure-activity relationships are emerging for these inhibitors, and the atypical binding pockets of galectin-3 have informed the development of a pharmacophore model that is expected to guide the design and discovery of potent, selective inhibitors for treatment of cancer, inflammation, and fibrosis.
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4. B-cell precursor acute lymphoblastic leukaemia: origins, classification, and therapeutic advances.
PMID:日期:2026-09-10B-cell precursor acute lymphoblastic leukaemia (BCP-ALL) is the most common form of paediatric cancer and is characterised by the clonal expansion of immature B lymphocytes. The advent of targeted therapies has transformed BCP-ALL from a largely fatal disease to one which is well managed under current protocols. Continued refinements to disease classification have facilitated the identification of novel drug targets that underscore much of this change. Despite this progress, some patients remain unclassified by current conventions, and have not profited from the era of targeted therapy. Relapsed disease likewise remains a major challenge, and although new immunotherapies have gone a long way, additional strategies are needed. Addressing these issues requires a concerted effort to identify novel drug targets. Here, we discuss the origins and classification of BCP-ALL, before outlining the therapeutic advances that have considerably improved disease outlook over the last few decades. We then outline the latest trends in disease treatment, and propose how recent discoveries may translate into new therapeutic approaches.
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5. Targeting depression: Pharmacological mechanisms and therapeutic targets.
PMID:日期:2026-09-10Depression remains a leading cause of disability worldwide with a rapidly escalating disease burden, yet current pharmacotherapies are limited by delayed onset of action, insufficient efficacy in treatment-resistant depression, and troublesome adverse effects. This review provides a systematic and critical evaluation of pharmacological mechanisms in depression and related therapeutic targets. We examine established targets spanning the neurotransmitters corresponding to serotonergic, glutamatergic, GABAergic, and dopaminergic systems, alongside emerging glial gap junctions and inflammatory perspectives. For each target, we assess the quality of evidence from preclinical studies and clinical trials, discuss corresponding antidepressant drug classes, and identify knowledge gaps. Finally, we propose future directions for antidepressant drug development, including novel target discovery, rational multi-target design, and optimization of preclinical-to-clinical translation. By providing a pharmacology-driven roadmap of druggable targets and their therapeutic mechanisms, this review aims to inform both mechanistic understanding and drug discovery efforts in depression.
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6. Apolipoprotein E in spinal cord injury: mechanisms of lipid dysregulation, neuroinflammation, and opportunities for repair.
6. 载脂蛋白E在脊髓损伤中的作用：脂质失调、神经炎症机制及修复机遇PMID:日期:2026-09-09Traumatic spinal cord injury (SCI) is a devastating condition that affects millions of people worldwide and remains without effective pharmacological therapies that substantially improve neurological recovery. A major barrier to repair is the persistent secondary neuroinflammatory response that evolves over weeks to months after injury. Although neuroinflammation represents an attractive therapeutic target, broadly acting immunosuppressive approaches have yielded limited clinical benefit, highlighting the need to identify mechanisms that drive detrimental inflammation while preserving beneficial immune functions that support repair. Emerging evidence identifies dysregulated lipid handling as one such mechanism. SCI generates a substantial lipid burden through myelin and cellular breakdown, while lipidomic and metabolomic studies reveal persistent, dynamic alterations in lipid processing, storage, and transport. The capacity of resident glia and infiltrating immune cells to manage this lipid burden has important consequences for inflammatory state and tissue repair. Apolipoprotein E (ApoE), a major regulator of lipid transport and redistribution in the central nervous system, lies at the intersection of these processes, linking lipid metabolism with neuroinflammation and recovery after SCI. Here, we critically evaluate ApoE biology and its relationship to lipid dysregulation after SCI, together with preclinical evidence targeting ApoE-associated and broader lipid-regulatory pathways, including ApoE mimetics, LXR/RXR and PPARγ signaling, and statins. We distinguish demonstrated therapeutic mechanisms from proposed ApoE-dependent effects and evaluate emerging clinical evidence for lipid-modifying interventions in SCI. Finally, we consider key barriers to translation, including injury heterogeneity, sex, age, ApoE genotype, timing and delivery method, and how lipid-directed interventions can be integrated into multimodal strategies for SCI repair. Together, current evidence identifies dysregulated lipid handling as a mechanistically important and potentially tractable component of secondary SCI pathology, while highlighting the critical studies needed to determine whether ApoE-directed and broader lipid-modifying strategies can improve neurological recovery.
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7. Cell death-induced chronic inflammation as a therapeutic target for metabolic dysfunction-associated steatohepatitis.
7. 细胞死亡诱导的慢性炎症作为代谢功能障碍相关脂肪性肝炎的治疗靶点PMID:日期:2026-09-09Metabolic dysfunction-associated steatohepatitis (MASH) is a progressive liver disease characterized by hepatic steatosis, inflammation, and fibrosis, which can ultimately lead to cirrhosis and hepatocellular carcinoma. Although recent Food and Drug Administration approvals of resmetirom and semaglutide mark a milestone in MASH therapy, no approved agents directly target hepatic inflammation or fibrosis, underscoring the urgent need for novel therapeutic strategies. Hepatocyte death is a histological hallmark that distinguishes MASH from simple steatosis, yet the mechanisms by which it drives chronic inflammation and fibrosis remain incompletely understood. We identified hepatic crown-like structures (CLSs), aggregates of macrophages surrounding dead hepatocytes, as the histological hub of this process. In steatotic livers, impaired dead cell clearance allows sustained macrophage-dead cell interactions within CLSs, where tissue-resident macrophages acquire profibrotic properties. Cholesterol accumulation in hepatocytes promotes cholesterol crystallization, triggering hepatocyte death and subsequent lysosomal cholesterol overload in CLS-constituting macrophages, thereby accelerating inflammation and fibrosis. Targeting this pathway using a liver-tropic supramolecular β-cyclodextrin polyrotaxane (βCD-PRX), which selectively delivers βCD to lysosomes via endocytosis, ameliorated macrophage lysosomal stress and hepatic fibrosis in murine MASH models without affecting body weight or steatosis. Beyond the liver, CLS-driven chronic inflammation contributes to adipose tissue dysfunction in obesity and the transition from acute kidney injury to chronic kidney disease, suggesting broad therapeutic relevance. Continued investigation of CLSs as a shared pathological microenvironment across metabolic diseases may pave the way for novel diagnostic and therapeutic modalities for MASH and related conditions.
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8. Clusterin as a therapeutic agent: Bridging the gap in brain and eye research.
8. 簇集素作为治疗剂：弥合脑与眼研究之间的鸿沟PMID:日期:2026-09-07Clusterin (CLU) is a multifunctional secreted glycoprotein that is widely expressed in human tissues and body fluids. It plays critical roles in maintaining tissue homeostasis, regulating inflammation, modulating immune responses, and promoting cellular survival in both the brain and the eye. The CLU gene undergoes alternative splicing, yielding protein isoforms with distinct, and sometimes opposing, functions within a single disease condition. While secreted CLU (sCLU) is generally associated with cytoprotection, regulation of complement activation, protein chaperoning, and resolution of inflammation, the nuclear CLU (nCLU) isoform has been implicated in cell stress responses, apoptosis, and disease progression. Understanding these isoform-specific functions is essential for interpreting the diverse and sometimes contradictory roles of CLU across disease states. In this review, we discuss endogenous CLU expression, alternative splicing, and the resulting functions of its different isoforms. In addition to its inherent physiological role, we review recent research on exogenous CLU administration in the eye and brain. We identify knowledge gaps that need to be addressed before CLU is developed as a therapeutic agent. To help with the identification of future drug targets, we also summarize common CLU mechanisms in the brain and eye. By combining and contrasting knowledge from these two interconnected organs, we identify convergent CLU-regulated pathways and therapeutic opportunities, providing a comprehensive guide to future mechanistic studies, biomarker development, and CLU-based drug discovery. Therefore, the summaries in this review make it a highly relevant reference for CLU translational research and drug discovery across multiple brain and eye disorders.
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9. Antimicrobial photodynamic therapy across ESKAPE pathogens: Efficacy, limitations, and a pathogen-adapted framework toward clinical translation.
PMID:日期:2026-09-01Multidrug-resistant (MDR) bacteria belonging to the ESKAPE group-Enterococcus spp., Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.-represent some of the most urgent threats to global health. These pathogens are major causes of healthcare-associated infections and are characterized by extensive antibiotic resistance, biofilm formation, persistence phenotypes, and multiple virulence mechanisms that limit the effectiveness of conventional antimicrobial therapies. Antimicrobial photodynamic therapy (aPDT) has emerged as a promising non-antibiotic approach based on the light activation of photosensitizers, leading to the generation of reactive oxygen species (ROS) that induce multi-target oxidative damage. This review evaluates the current evidence supporting aPDT against ESKAPE pathogens and examines the biological and therapeutic factors that influence treatment outcomes. Across ESKAPE pathogens, aPDT frequently achieved clinically relevant antibacterial effects, including reductions of ≥3 log₁₀ CFU under optimized conditions. However, treatment efficacy varied substantially according to bacterial envelope architecture, biofilm organization, and infection accessibility. Gram-positive pathogens generally exhibited higher susceptibility, whereas Gram-negative species-particularly P. aeruginosa-required strategies to overcome outer membrane barriers, biofilm-associated protection, and limited photosensitizer penetration. Beyond direct antimicrobial activity, numerous studies reported biofilm disruption, modulation of virulence-associated pathways, and enhanced susceptibility to conventional antibiotics. Collectively, these findings suggest that aPDT efficacy is determined not only by photosensitizer potency but also by pathogen-specific structural and physiological constraints. Current evidence supports aPDT as a promising adjunctive strategy against MDR ESKAPE pathogens, particularly in localized and accessible infections where effective light delivery can be achieved. The therapeutic performance of aPDT appears to follow a pathogen-dependent gradient shaped by bacterial structure, biofilm complexity, and treatment accessibility. These observations support a pathogen-adapted framework for aPDT development, in which photosensitizer selection, delivery systems, and irradiation strategies are tailored to the biological characteristics of individual pathogens. Future progress will require greater protocol standardization, improved translational models, and well-designed clinical studies to facilitate the integration of aPDT into antimicrobial practice.
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10. Prospects for treatment of cerebral ischemic stroke with Hydroxysafflower Yellow A.
10. 羟基红花黄色素A治疗脑缺血性卒中的前景PMID:日期:2026-08-31Cerebral ischemic stroke (CIS) is characterized by high morbidity, disability, and mortality, representing a major global public health challenge and imposing a substantial social and economic burden worldwide. Cerebral ischemia/reperfusion (I/R) triggers complex pathological cascades, resulting in secondary brain injury, thereby limiting the therapeutic efficacy of single-target interventions. Therefore, the development of novel neuroprotective strategies with multitarget pharmacological properties remains an important research focus. Hydroxysafflower yellow A (HSYA), the major bioactive component of safflower (Carthamus tinctorius L.), has demonstrated protective effects in multiple experimental models of CIS. Accumulating preclinical evidence indicates that HSYA mitigates ischemic brain injury through multiple pathways, including maintaining mitochondrial homeostasis, suppressing excitotoxicity and calcium overload, attenuating oxidative stress, inhibiting inflammatory responses, and promoting angiogenesis. However, current mechanistic evidence is predominantly derived from cellular and animal studies. Limited clinical investigations have explored the effects of HSYA-containing preparations or HSYA injection in ischemic stroke; however, current evidence remains insufficient to establish definitive clinical efficacy. The clinical efficacy, optimal dosing strategies, and long-term benefits of HSYA remain to be fully established. In addition, limited brain distribution and unfavorable pharmacokinetic properties represent important challenges for its further clinical translation. This review summarizes the current understanding of the pharmacological effects of HSYA during different phases of CIS. Furthermore, from the perspective of the stroke-heart syndrome, the potential therapeutic value of HSYA in brain-heart comorbidity is discussed. Collectively, this review provides a new perspective on the therapeutic potential and translational challenges of HSYA in CIS management.