Pharmacological research最新文献_第3页

Low LDL-cholesterol drives the risk of bleeding in patients treated with aspirin: A 15-year study in a real-world large population

IF 9.1 2区医学

Pharmacological research Pub Date : 2025-03-05 DOI: 10.1016/j.phrs.2025.107688

Valentina Trimarco , Raffaele Izzo , Daniela Pacella , Fahimeh Varzideh , Maria Virginia Manzi , Paola Gallo , Giuseppe Giugliano , Roberto Piccinocchi , Giovanni Esposito , Gaetano Piccinocchi , Luca Bardi , Carmine Morisco , Francesco Rozza , Maria Lembo , Bruno Trimarco , Gaetano Santulli

{"title":"Low LDL-cholesterol drives the risk of bleeding in patients treated with aspirin: A 15-year study in a real-world large population","authors":"Valentina Trimarco , Raffaele Izzo , Daniela Pacella , Fahimeh Varzideh , Maria Virginia Manzi , Paola Gallo , Giuseppe Giugliano , Roberto Piccinocchi , Giovanni Esposito , Gaetano Piccinocchi , Luca Bardi , Carmine Morisco , Francesco Rozza , Maria Lembo , Bruno Trimarco , Gaetano Santulli","doi":"10.1016/j.phrs.2025.107688","DOIUrl":"10.1016/j.phrs.2025.107688","url":null,"abstract":"<div><div>We aimed to investigate the link between LDL cholesterol (LDL-C) levels and hemorrhage risk over an extended period, both in subjects taking aspirin and in individuals not receiving any antiplatelet agent. We calculated the predicted adjusted relative hazard of bleeding by LDL-C concentration for the whole cohort and the aspirin-treated subgroup. The study included 39,784 individuals with a mean follow-up of 14.9 years, totaling over 500,000 patient-years. Across the cohort, 3380 bleeding events were reported, with a higher incidence in patients with LDL-C < 70 mg/dL compared to those with LDL-C ≥ 70 mg/dL (9.9 % vs 8.4 %). In aspirin-treated patients, multivariable analysis revealed that hemorrhagic events were significantly associated with aging, male sex, body mass index, hypertension, and LDL-C < 70 mg/dL. These patients had a significantly lower event-free survival probability if their LDL-C was < 70 mg/dL compared to ≥ 70 mg/dL. Low LDL-C values were a significant risk factor (HR >1) while higher LDL-C values were protective (HR <1). A stepwise increase of 10 mg/dL in LDL-C from < 30 to ≥ 200 mg/dL was associated with a decreasing trend for bleeding events in both the entire cohort and the aspirin-treated subgroup. This is the first report specifically addressing the relationship between LDL-C levels and bleeding risk in a population receiving low-intensity antithrombotic therapy. Our data demonstrate that in patients taking aspirin, LDL-C levels below 70 mg/dL significantly increase the risk of bleeding, with major implications for long-term cardiovascular risk management.</div></div>","PeriodicalId":19918,"journal":{"name":"Pharmacological research","volume":"215 ","pages":"Article 107688"},"PeriodicalIF":9.1,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143586621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Phytosterols and phytostanols in context: From physiology and pathophysiology to food supplementation and clinical practice

IF 9.1 2区医学

Pharmacological research Pub Date : 2025-03-04 DOI: 10.1016/j.phrs.2025.107681

Massimiliano Ruscica , Wann Jia Loh , Cesare R. Sirtori , Gerald F. Watts

{"title":"Phytosterols and phytostanols in context: From physiology and pathophysiology to food supplementation and clinical practice","authors":"Massimiliano Ruscica , Wann Jia Loh , Cesare R. Sirtori , Gerald F. Watts","doi":"10.1016/j.phrs.2025.107681","DOIUrl":"10.1016/j.phrs.2025.107681","url":null,"abstract":"<div><div>Phytosterols and phytostanols are two classes of sterol derivatives naturally synthesised in plants, but not in humans. Structurally, phytosterols and phytostanols have a sterane ring in common, but phytostanols do not have a double bond between carbons 5 and 6. The therapeutic potential of phytosterols and phytostanols supplementation in cholesterol reduction is the main reason for its wide usage in an expansive food matrix, including milk, yoghurt, margarine, mayonnaise, chocolate, tartare, chips, esterification with omega-3, and recently, as a successful nutraceutical among athletes is its fortification with whey protein. The heterogeneous effect of phytosterols and phytostanols in cholesterol lowering appears to be related to whether the individuals’ inherent physiologic tendencies to “hyper-synthesise” cholesterol in the liver or “hyperabsorb” cholesterol via the small intestine. Individuals who are ‘hypersynthesizers” of cholesterol tend to have a good reduction in plasma low-density lipoprotein cholesterol (LDLc) in response to statin therapy. Conversely, “hyper-absorbers” of cholesterol show a greater LDLc lowering in response to phytosterols or phytostanols. The ratios of cholestanol to cholesterol and lathosterol to cholesterol are good biomarkers of intestinal absorption of cholesterol and hepatic cholesterol synthesis. Animal data and human observational data suggest that phytosterols and phytostanols may have anti-atherosclerotic activities, e.g. reduction of the formation of nitric oxide, antagonism to the formation of LDL aggregates and plaque formation. The absence of cardiovascular outcome trials using phytosterol or phytostanol supplementation, makes it difficult to confirm a wider use in clinical practice, especially with the rapidly expanding list of effective and safe lipid-lowering medications.</div></div>","PeriodicalId":19918,"journal":{"name":"Pharmacological research","volume":"214 ","pages":"Article 107681"},"PeriodicalIF":9.1,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143573639","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Antagonising Yin Yang 1 ameliorates the symptoms of lupus nephritis via modulating T lymphocyte signaling-correspondence

IF 9.1 2区医学

Pharmacological research Pub Date : 2025-03-04 DOI: 10.1016/j.phrs.2025.107680

Szu-Yu Huang, An-An Ku, Wen-Chun Lo, Su-Boon Yong, Chin-Yuan Yii

引用次数: 0

Targeting EVA1B in breast cancer: New avenues for precision oncology

IF 9.1 2区医学

Pharmacological research Pub Date : 2025-03-04 DOI: 10.1016/j.phrs.2025.107684

Jui-Hu Hsiao, Chen-Yueh Wen, Su-Boon Yong, Chin-Yuan Yii, Chia-Jung Li

引用次数: 0

Toward an immunology-based classification of pain disorders?

IF 9.1 2区医学

Pharmacological research Pub Date : 2025-03-01 DOI: 10.1016/j.phrs.2025.107631

A.H.C. Rosenström, M.F. Bjurström

引用次数: 0

Correspondence: Improved glycemic and weight control with Dulaglutide addition in SGLT2 inhibitor treated obese type 2 diabetic patients at high cardiovascular risk in a real-world setting. The AWARE-2 study

IF 9.1 2区医学

Pharmacological research Pub Date : 2025-03-01 DOI: 10.1016/j.phrs.2025.107639

Chang-Yuan Hsu, Che-Wei Chang, Su-Boon Yong, Chin-Yuan Yii

引用次数: 0

Corrigendum to “Ectopic expression of NKG7 enhances CAR-T function and improves the therapeutic efficacy in liquid and solid tumors” [Pharmacol. Res. 210 (2024) 107506] 更正："异位表达 NKG7 可增强 CAR-T 功能并提高液体和固体肿瘤的疗效" [Pharmacol. Res. 210 (2024) 107506]。

IF 9.1 2区医学

Pharmacological research Pub Date : 2025-03-01 DOI: 10.1016/j.phrs.2025.107669

Yuxin Chen , Meng Wang , Shuxin Huang , Lulu Han , Ying Cai , Xiaodi Xu , Shuwen Sun , Zhaokai Chen , Junze Chen , Jiatian Yu , Hongwei Du , Huizhong Li , Junnian Zheng , Bo Ma , Gang Wang

引用次数: 0

Reply to the letter comment of Su Boon Yong MD, PhD and colleagues to: Improved glycemic and weight control with Dulaglutide addition in SGLT2 inhibitor treated obese type 2 diabetic patients at high cardiovascular risk in a real-world setting. The AWARE− 2 study

IF 9.1 2区医学

Pharmacological research Pub Date : 2025-03-01 DOI: 10.1016/j.phrs.2025.107640

Cesare Berra, Roberto Manfrini, Francesco Bifari, Elisa Cipponeri, Renata Ghelardi, Lucia Centofanti, Umberto Mortola, Elena Lunati, Loredana Bucciarelli, Vincenzo Cimino, Franco Folli

引用次数: 0

A theranostic photosensitizer-conjugated albumin co-loading with resiquimod for cancer-targeted imaging and robust photo-immunotherapy: Critical considerations from bench to bedside

IF 9.1 2区医学

Pharmacological research Pub Date : 2025-02-26 DOI: 10.1016/j.phrs.2025.107673

Peng Sheng, Shi Zhou

引用次数: 0

USP19 deficiency enhances T-cell-mediated antitumor immunity by promoting PD-L1 degradation in colorectal cancer

IF 9.1 2区医学

Pharmacological research Pub Date : 2025-02-26 DOI: 10.1016/j.phrs.2025.107668

Feng Shi , Guang-Jing Li , Yi Liu , Hai-Meng Zhou , Yue Zhang , Si-Yi Wei , Bo-Jun Zan , Meng Gao , Fei-Shan Chen , Bo-Xin Li , Bai-Qi Wang , Ming-You Dong , Run-Lei Du , Xiao-Dong Zhang

{"title":"USP19 deficiency enhances T-cell-mediated antitumor immunity by promoting PD-L1 degradation in colorectal cancer","authors":"Feng Shi , Guang-Jing Li , Yi Liu , Hai-Meng Zhou , Yue Zhang , Si-Yi Wei , Bo-Jun Zan , Meng Gao , Fei-Shan Chen , Bo-Xin Li , Bai-Qi Wang , Ming-You Dong , Run-Lei Du , Xiao-Dong Zhang","doi":"10.1016/j.phrs.2025.107668","DOIUrl":"10.1016/j.phrs.2025.107668","url":null,"abstract":"<div><div>Colorectal cancer (CRC) is characterized by a highly immunosuppressive tumor microenvironment, which limits the effectiveness of current immunotherapies. Identifying strategies to overcome this resistance is critical for improving treatment outcomes. In this study, we discovered that USP19 plays a pivotal role in regulating T-cell-mediated antitumor immunity through a CRISPR/Cas9 sgRNA library screen and co-culture assays with activated T cells. We demonstrated that USP19 deficiency significantly enhances the susceptibility to T cell-mediated cytotoxicity in CRC cells, organoids, and mouse models. Transcriptomic sequencing (RNA-seq) revealed activation of the PD-1 pathway in tumor with USP19-deficiency cells. Mechanistic investigations revealed that USP19 directly stabilizes PD-L1 by binding to its intracellular domain and preventing its degradation via K48-linked ubiquitination and proteasomal pathways. Clinically, USP19 expression was found to be significantly elevated in CRC tissues and was positively associated with PD-L1 levels, advanced tumor grade, poor differentiation, and TP53 mutations, highlighting its potential as a biomarker for aggressive CRC. Importantly, in vivo experiments demonstrated that targeting USP19, in combination with αPD-L1 therapy, synergistically suppressed CRC progression. This combination not only reduced PD-L1 levels but also enhanced CD8<sup>+</sup> T-cell activation and GzmB infiltration, resulting in robust antitumor effects. These findings establish USP19 as a key driver of immune evasion in CRC and suggest that targeting USP19 could enhance the efficacy of immunotherapy, providing a promising new avenue for CRC treatment.</div></div>","PeriodicalId":19918,"journal":{"name":"Pharmacological research","volume":"214 ","pages":"Article 107668"},"PeriodicalIF":9.1,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143512745","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0