|
1
|
Tiwari RK, Rawat SG, Rai S, Kumar A. Stress regulatory hormones and cancer: the contribution of epinephrine and cancer therapeutic value of beta blockers. Endocrine 2025; 88:359-386. [PMID: 39869294 DOI: 10.1007/s12020-025-04161-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/10/2024] [Accepted: 01/08/2025] [Indexed: 01/28/2025]
Abstract
The word "cancer" evokes myriad emotions, ranging from fear and despair to hope and determination. Cancer is aptly defined as a complex and multifaceted group of diseases that has unapologetically led to the loss of countless lives and affected innumerable families across the globe. The battle with cancer is not only a physical battle, but also an emotional, as well as a psychological skirmish for patients and for their loved ones. Cancer has been a part of our history, stories, and lives for centuries and has challenged the ingenuity of health and medical science, and the resilience of the human spirit. From the early days of surgery and radiation therapy to cutting-edge developments in chemotherapeutic agents, immunotherapy, and targeted treatments, the medical field continues to make significant headway in the fight against cancer. However, even after all these advancements, cancer is still among the leading cause of death globally. This urges us to understand the central hallmarks of neoplastic cells to identify novel molecular targets for the development of promising therapeutic approaches. Growing research suggests that stress mediators, including epinephrine, play a critical role in the development and progression of cancer by inducing neoplastic features through activating adrenergic receptors, particularly β-adrenoreceptors. Further, our experimental data has also shown that epinephrine mediates the growth of T-cell lymphoma by inducing proliferation, glycolysis, and apoptosis evasion via altering the expression levels of key regulators of these vital cellular processes. The beauty of receptor-based therapy lies in its precision and higher therapeutic value. Interestingly, the enhanced expression of β-adrenergic receptors (ADRBs), namely ADRB2 (β2-adrenoreceptor) and ADRB3 (β3-adrenoreceptor) has been noted in many cancers, such as breast, colon, gastric, pancreatic, and prostate and has been reported to play a pivotal role in facilitating cancer growth mainly by promoting proliferation, evasion of apoptosis, angiogenesis, invasion and metastasis, and chemoresistance. The present review article is an attempt to summarize the available findings which indicate a distinct relationship between stress hormones and cancer, with a special emphasis on epinephrine, considered as a key stress regulatory molecule. This article also discusses the possibility of using beta-blockers for cancer therapy.
Collapse
Affiliation(s)
- Rajan Kumar Tiwari
- Department of Zoology, Institute of Science, Banaras Hindu University, Varanasi, Uttar Pradesh, India
- School of Medicine and Health Sciences, The George Washington University, Washington DC, USA
| | - Shiv Govind Rawat
- Department of Zoology, Institute of Science, Banaras Hindu University, Varanasi, Uttar Pradesh, India
- MD Anderson Cancer Center, The University of Texas, Texas, USA
| | - Siddharth Rai
- Department of Zoology, Institute of Science, Banaras Hindu University, Varanasi, Uttar Pradesh, India
| | - Ajay Kumar
- Department of Zoology, Institute of Science, Banaras Hindu University, Varanasi, Uttar Pradesh, India.
| |
Collapse
|
|
2
|
Huang Y, Rao Z, Tan W, Zhou Y, Hu S. Green Synthesis and Chemical Characterization of Silver Nanoparticles by Tribulus terrestris for the Treatment of Myocardial Infarction. Biol Trace Elem Res 2025; 203:1961-1971. [PMID: 39134771 DOI: 10.1007/s12011-024-04336-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2024] [Accepted: 08/02/2024] [Indexed: 03/20/2025]
Abstract
Silver nanoparticles (AgNPs) are commonly utilized in the medical sector, particularly in cardiovascular applications. Nevertheless, there is a studies scarcity examining the impact of AgNPs on myocardial infarction protection. A green formulation of AgNPs was documented in the research. Different spectroscopic methods were utilized to examine the AgNPs, and their potential for treating myocardial infarction was explored. The NPs exhibited a spherical morphology upon formation. Isoproterenol (85 mg/kg) was administered to induce myocardial infarction in mice. The mice were categorized into four distinct groups (n = 15): (1) untreated; (2) normal; (3,4) AgNPs + isoproterenol at various doses (5 and 50 µg/kg). The activation of PPAR-Υ/NF-κB and subsequent cytokine release induced by lipopolysaccharide were quantified using real-time PCR and western blot techniques. Subsequent to the administration of AgNPs at different doses, the evaluation of cardiac function was conducted through biochemical, histochemical, and electrocardiogram (ECG) analysis. AgNPs significantly inhibit the levels of myocardial injury markers, reduce the incidence of mortality, and improve the condition of ventricular wall infarction. In addition, the administration of AgNPs effectively prevents the characteristic ST segment depression when compared to animals with myocardial infarction. The positive effects of AgNPs could potentially be attributed to the restoration of normal gene expression in PPAR-Υ/NF-κB/ΙκB-α/ΙΚΚα/β and PPAR-Υ phosphorylation pathways. Additionally, the application of AgNPs led to a reduction in the levels of pro-inflammatory cytokines in the hearts of mice suffering from myocardial infarction. The expression suppression of inflammation cytokines and cell death was significantly reduced by AgNPs. Recent findings suggest that AgNPs possess cardioprotective properties on isoproterenol-induced myocardial infarction, possibly by the inhibition of NF-κB signaling and activation of PPAR-γ. To summarize, the present study introduces a contemporary therapeutic approach for treating myocardial infarction in clinical settings.
Collapse
Affiliation(s)
- Yuexia Huang
- Department of Respiration, Research Center for Clinical Medicine, Wuhan Fourth Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430033, China
| | - Zhongxian Rao
- Neurosurgery, Wuhan University of Science and Technology Affiliated Geriatric Hospital, Wuhan, 430065, Hubei, China
| | - Wei Tan
- General Medicine, Wuhan University of Science and Technology Affiliated Geriatric Hospital, Wuhan, Wuhan, 430065, Hubei, China
| | - You Zhou
- General Medicine, Wuhan University of Science and Technology Affiliated Geriatric Hospital, Wuhan, Wuhan, 430065, Hubei, China
| | - Shanshan Hu
- General Medicine, Wuhan University of Science and Technology Affiliated Geriatric Hospital, Wuhan, Wuhan, 430065, Hubei, China.
| |
Collapse
|
|
3
|
Lorente JS, Sokolov AV, Ferguson G, Schiöth HB, Hauser AS, Gloriam DE. GPCR drug discovery: new agents, targets and indications. Nat Rev Drug Discov 2025:10.1038/s41573-025-01139-y. [PMID: 40033110 DOI: 10.1038/s41573-025-01139-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/13/2025] [Indexed: 03/05/2025]
Abstract
G protein-coupled receptors (GPCRs) form one of the largest drug target families, reflecting their involvement in numerous pathophysiological processes. In this Review, we analyse drug discovery trends for the GPCR superfamily, covering compounds, targets and indications that have reached regulatory approval or that are being investigated in clinical trials. We find that there are 516 approved drugs targeting GPCRs, making up 36% of all approved drugs. These drugs act on 121 GPCR targets, one-third of all non-sensory GPCRs. Furthermore, 337 agents targeting 133 GPCRs, including 30 novel targets, are being investigated in clinical trials. Notably, 165 of these agents are approved drugs being tested for additional indications and novel agents are increasingly allosteric modulators and biologics. Remarkably, diabetes and obesity drugs targeting GPCRs had sales of nearly US $30 billion in 2023 and the numbers of clinical trials for GPCR modulators in the metabolic diseases, oncology and immunology areas are increasing strongly. Finally, we highlight the potential of untapped target-disease associations and pathway-biased signalling. Overall, this Review provides an up-to-date reference for the drugged and potentially druggable GPCRome to inform future GPCR drug discovery and development.
Collapse
Affiliation(s)
- Javier Sánchez Lorente
- Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Aleksandr V Sokolov
- Department of Surgical Sciences, Functional Pharmacology and Neuroscience, University of Uppsala, Uppsala, Sweden
| | - Gavin Ferguson
- Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
- ALPX S.A.S., Grenoble, France
| | - Helgi B Schiöth
- Department of Surgical Sciences, Functional Pharmacology and Neuroscience, University of Uppsala, Uppsala, Sweden
- Laboratory of Pharmaceutical Pharmacology, Latvian Institute of Organic Synthesis, Riga, Latvia
| | - Alexander S Hauser
- Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - David E Gloriam
- Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
| |
Collapse
|
|
4
|
Fu M, Lv M, Guo J, Mei A, Qian H, Yang H, Wu W, Liu Z, Zhong J, Wei Y, Min X, Wu H, Chen J. The clinical significance of T-cell regulation in hypertension treatment. Front Immunol 2025; 16:1550206. [PMID: 40079010 PMCID: PMC11897580 DOI: 10.3389/fimmu.2025.1550206] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2025] [Accepted: 02/10/2025] [Indexed: 03/14/2025] Open
Abstract
Hypertension, a globally prevalent condition, is closely associated with T cell-mediated inflammatory responses. Studies have shown that T cells, by secreting pro-inflammatory cytokines such as interferon-gamma (IFN-γ), Interleukin-17 (IL-17), and Tumor necrosis factor-alpha (TNF-α), directly lead to vascular dysfunction and elevated blood pressure. The activation of Th1 and Th17 cell subsets, along with the dysfunction of regulatory T cells (Tregs), is a critical mechanism in the onset and progression of hypertension. This review explores the role of T cells in the pathophysiology of hypertension and discusses potential therapeutic strategies targeting T cell regulation, such as immunotherapy and gene-editing technologies. These emerging treatments hold promise for providing personalized therapeutic options for hypertensive patients, reducing inflammatory complications, and improving treatment outcomes.
Collapse
Affiliation(s)
- Miaoxin Fu
- Sinopharm Dongfeng General Hospital (Hubei Clinical Research Center of Hypertension), Hubei Key Laboratory of Wudang Local Chinese Medicine Research, Hubei University of Medicine, Shiyan, Hubei, China
| | - Mingzhu Lv
- Sinopharm Dongfeng General Hospital (Hubei Clinical Research Center of Hypertension), Hubei Key Laboratory of Wudang Local Chinese Medicine Research, Hubei University of Medicine, Shiyan, Hubei, China
| | - Jinyue Guo
- Sinopharm Dongfeng General Hospital (Hubei Clinical Research Center of Hypertension), Hubei Key Laboratory of Wudang Local Chinese Medicine Research, Hubei University of Medicine, Shiyan, Hubei, China
| | - Aihua Mei
- Sinopharm Dongfeng General Hospital (Hubei Clinical Research Center of Hypertension), Hubei Key Laboratory of Wudang Local Chinese Medicine Research, Hubei University of Medicine, Shiyan, Hubei, China
| | - Hang Qian
- Sinopharm Dongfeng General Hospital (Hubei Clinical Research Center of Hypertension), Hubei Key Laboratory of Wudang Local Chinese Medicine Research, Hubei University of Medicine, Shiyan, Hubei, China
| | - Handong Yang
- Sinopharm Dongfeng General Hospital (Hubei Clinical Research Center of Hypertension), Hubei Key Laboratory of Wudang Local Chinese Medicine Research, Hubei University of Medicine, Shiyan, Hubei, China
| | - Wenwen Wu
- Shiyan Key Laboratory of Virology, Hubei University of Medicine, Shiyan, China
- School of Public Health, Hubei University of Medicine, Shiyan, Hubei, China
| | - Zhixin Liu
- Shiyan Key Laboratory of Virology, Hubei University of Medicine, Shiyan, China
| | - Jixin Zhong
- Department of Rheumatology and Immunology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Ying Wei
- Sinopharm Dongfeng General Hospital (Hubei Clinical Research Center of Hypertension), Hubei Key Laboratory of Wudang Local Chinese Medicine Research, Hubei University of Medicine, Shiyan, Hubei, China
| | - Xinwen Min
- Sinopharm Dongfeng General Hospital (Hubei Clinical Research Center of Hypertension), Hubei Key Laboratory of Wudang Local Chinese Medicine Research, Hubei University of Medicine, Shiyan, Hubei, China
| | - Haiyan Wu
- Sinopharm Dongfeng General Hospital (Hubei Clinical Research Center of Hypertension), Hubei Key Laboratory of Wudang Local Chinese Medicine Research, Hubei University of Medicine, Shiyan, Hubei, China
| | - Jun Chen
- Sinopharm Dongfeng General Hospital (Hubei Clinical Research Center of Hypertension), Hubei Key Laboratory of Wudang Local Chinese Medicine Research, Hubei University of Medicine, Shiyan, Hubei, China
- Shiyan Key Laboratory of Virology, Hubei University of Medicine, Shiyan, China
| |
Collapse
|
|
5
|
Li H, Zhu Y. The chemical composition analysis of Yixin Tongmai Granules using UHPLC-MS/MS and exploration of its potential mechanism in treatment of coronary artery disease based on network pharmacology and molecular docking. Medicine (Baltimore) 2025; 104:e41620. [PMID: 39993113 PMCID: PMC11856895 DOI: 10.1097/md.0000000000041620] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/01/2024] [Revised: 01/31/2025] [Accepted: 02/03/2025] [Indexed: 02/26/2025] Open
Abstract
Yixin Tongmai Granules (YTG) is a popular Chinese herbal granules for the treatment of coronary artery disease (CAD), but its molecular pharmacological mechanism is still unclear. This article explores the mechanism of CAD treatment from the perspective of network pharmacology. We analyzed the chemical composition of YTG using UHPLC-MS/MS and identified 131 ingredients. The relative drug content of 33 ingredients exceeded 0.5%. These ingredients were further screened using the SwissADME platform with ADME criteria. Using the HIT database and SwissTargetPrediction platform, high probability targets for these ingredients were generated. Using Venn Diagram, 96 effective targets associated with CAD were identified, involving 14 core ingredients. This study imported these effective targets into the STRING platform and obtained the core targets through network topology analysis: TP53, STAT3, transcription factor Jun, MAPK3, MAPK1, AKT1, SRC, MYC, BCL2, transcription factor p65, TNF, and ESR2. Then enrichment analysis with Metascape platform indicated that, in the system network of YTG in anti-CAD, the principal pathways are "Lipid and Atherosclerosis", "Pathways in cancer", and "AGE-RAGE signaling pathway in diabetic complications." Next, the affinities between the core ingredients and their associated core targets were examined individually through molecular docking. Finally, based on deep mining of PubMed literature, this study investigated the relationship between each core target and CAD, the relationship between each core target and its associated core ingredients, and inferred the main pharmacological ingredients of YTG, namely Tanshinone IIA, Cryptotanshinone, Caffeic acid, Denshensu, Ononin, and Formononetin.
Collapse
Affiliation(s)
- Hongbin Li
- Medical School, Xianyang Polytechnic Institute, Xixian New Area, Xi'an, Shaanxi, P.R. China
| | - Yuye Zhu
- Medical School, Xianyang Polytechnic Institute, Xixian New Area, Xi'an, Shaanxi, P.R. China
| |
Collapse
|
|
6
|
Wang JF, Wang MC, Jiang LL, Lin NM. The neuroscience in breast cancer: Current insights and clinical opportunities. Heliyon 2025; 11:e42293. [PMID: 39975839 PMCID: PMC11835589 DOI: 10.1016/j.heliyon.2025.e42293] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2024] [Revised: 01/25/2025] [Accepted: 01/25/2025] [Indexed: 02/21/2025] Open
Abstract
The involvement of nerves in the development of breast cancer has emerged as a significant factor. Interaction between the nervous system and breast cancer can influence tumor initiation, growth, invasion, metastasis, reverse resistance to drugs, promote inflammation in tumors, and impair the immune system's ability to combat cancer. This review examined the intricate relationship linking the nervous system with breast cancer, emphasizing both central and peripheral aspects of the nervous system. Moreover, we reviewed neural cell factors and their impact on breast cancer progression, alongside the interactions between nerves and immunology, microbiota in breast cancer. Furthermore, the study discussed the potential of nerves as biomarkers for diagnosing and prognosticating breast cancer, and evaluated prospects for improving chemotherapy and immunotherapy therapeutic outcomes in breast cancer treatment. We hope to provide a deeper understanding of the neurobiological underpinnings of breast cancer and pave the way for the discovery of innovative therapeutic targets and prognostic markers.
Collapse
Affiliation(s)
- Jia-feng Wang
- Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province, Affiliated Hangzhou First People's Hospital, School of Medicine, Westlake University, Hangzhou, 310006, China
| | - Meng-chuan Wang
- Affiliated Cixi Hospital, Wenzhou Medical University, Ningbo, 315300, China
| | - Lei-lei Jiang
- The First Affiliated Hospital of Anhui University of Chinese Medicine,Hefei, 230031, China
| | - Neng-ming Lin
- Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province, Affiliated Hangzhou First People's Hospital, School of Medicine, Westlake University, Hangzhou, 310006, China
- Westlake Laboratory of Life Sciences and Biomedicine of Zhejiang Province, Hangzhou, 310024, China
| |
Collapse
|
|
7
|
Chen W, Qian H, Sun Q, Zhang S, Zhu L, Wu Y, Qian Y, Wang B, Li W. Efficacy and safety assessment of propranolol tablets vs. oral solution for infantile hemangioma: a retrospective study in China. Front Pediatr 2025; 13:1542348. [PMID: 39967746 PMCID: PMC11832506 DOI: 10.3389/fped.2025.1542348] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2024] [Accepted: 01/20/2025] [Indexed: 02/20/2025] Open
Abstract
Background Propranolol for infantile hemangiomas (IHs) is effective and relatively safe. However, propranolol has different formulations and there is no consensus on the optimal formulation for IHs. The propranolol oral solution was not used in China until 2022. Objective To evaluate the efficacy and safety of propranolol tablets and an oral solution in infants with high-risk IH. Methods A retrospective cohort study was conducted involving 234 consecutive patients with a clinical diagnosis of high-risk IH who were treated with propranolol between August 2018 and February 2023 (propranolol tablets, 168 patients; propranolol oral solution, 66 patients). All patients were assessed in the hospital at the initiation of treatment and in the outpatient setting during treatment. The Hemangioma Activity and Severity Index was used to monitor the clinical activity of the hemangioma after propranolol treatment. Results Based on the Hemangioma Activity and Severity Index, 66.52% and 69.15% improvement occurred in the propranolol tablet and oral solution groups, respectively. 23.21% of patients in the propranolol tablet group and 42.42% in the oral solution group achieved >75% score improvement (X 2 = 8.557; P = 0.003). Adverse reactions occurred in 34 (20.24%) and 11 patients (16.67%) in the propranolol tablet and oral solution groups, respectively. The most common adverse reaction in the propranolol tablet group was liver function abnormalities due to mild elevation of liver enzymes (X 2 = 4.09; P = 0.045). Conclusion Both propranolol tablets and oral solution had positive efficacy in patients with high-risk IHs, but more patients in the propranolol oral solution group achieve >75% score improvement compared to the propranolol tablet group. No life-threatening adverse reactions occurred in either group but liver function abnormalities were more likely to occur in patients treated with propranolol tablets.
Collapse
Affiliation(s)
| | | | | | | | | | | | | | | | - Wei Li
- Department of Dermatology, Children's Hospital of Soochow University, Suzhou, China
| |
Collapse
|
|
8
|
Porada M, Bułdak Ł. From Pathophysiology to Practice: Evolving Pharmacological Therapies, Clinical Complications, and Pharmacogenetic Considerations in Portal Hypertension. Metabolites 2025; 15:72. [PMID: 39997697 PMCID: PMC11857179 DOI: 10.3390/metabo15020072] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2024] [Revised: 01/07/2025] [Accepted: 01/18/2025] [Indexed: 02/26/2025] Open
Abstract
Background: Portal hypertension is a major complication of chronic liver diseases, leading to serious issues such as esophageal variceal bleeding. The increase in portal vein pressure is driven by both an organic component and a functional component, including tonic contraction of hepatic stellate cells. These processes result in a pathological rise in intrahepatic vascular resistance, stemming from partial impairment of hepatic microcirculation, which is further exacerbated by abnormalities in extrahepatic vessels, including increased portal blood flow. Objectives: This review aims to provide a comprehensive overview of the evolving pharmacological therapies for portal hypertension, with consideration and discussion of pathophysiological mechanisms, clinical complications, and pharmacogenetic considerations, highlighting potential directions for future research. Methods: A review of recent literature was performed to evaluate current knowledge and potential therapeutic strategies in portal hypertension. Results: For over 35 years, non-selective beta-blockers have been the cornerstone therapy for portal hypertension by reducing portal vein inflow as an extrahepatic target, effectively preventing decompensation and variceal hemorrhages. However, since not all patients exhibit an adequate response to non-selective beta-blockers (NSBBs), and some may not tolerate NSBBs, alternative or adjunctive therapies that enhance the effects of NSBBs on portal pressure are being investigated in preclinical and early clinical studies. Conclusions: A better understanding of pharmacogenetic factors and pathophysiological mechanisms could lead to more individualized and effective treatments for portal hypertension. These insights highlight potential directions for future research.
Collapse
Affiliation(s)
- Michał Porada
- Students’ Scientific Society, Department of Internal Medicine and Clinical Pharmacology, Medical University of Silesia, Medyków 18, 40-752 Katowice, Poland;
| | - Łukasz Bułdak
- Department of Internal Medicine and Clinical Pharmacology, Medical University of Silesia, Medyków 18, 40-752 Katowice, Poland
| |
Collapse
|
|
9
|
Treciokiene I, Forslund T, Kahan T, Taxis K, Wettermark B. Have People Treated With Antihypertensives Been Diagnosed With Hypertension? A Cross-Sectional Study in Stockholm, Sweden. Pharmacoepidemiol Drug Saf 2025; 34:e70075. [PMID: 39777806 PMCID: PMC11706671 DOI: 10.1002/pds.70075] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2024] [Revised: 11/25/2024] [Accepted: 12/05/2024] [Indexed: 01/11/2025]
Abstract
PURPOSE Studies on antihypertensive treatment are important, as hypertension remains the major risk factor for cardiovascular morbidity and premature death. However, antihypertensive medicines are also used for other conditions, and the use of these medicines as a proxy for a diagnosis of hypertension might lead to misclassification in pharmacoepidemiological studies. This study aimed to investigate to what extent people dispensed antihypertensive medicines have been diagnosed with hypertension. METHODS Cross-sectional study with data covering all healthcare and all dispensed prescriptions of antihypertensive medicines 2019 and diagnoses recorded 2015-2019 from the Stockholm Region, Sweden. Multinomial logistic regressions were used to assess the probability of having hypertension concerning age, sex, and antihypertensive drug class. RESULTS A total of 386 860 individuals were included, 49% men, 12% incident users, and 80% of all had a recorded diagnosis of hypertension. In 73% of incident users, only one antihypertensive drug class was dispensed, as compared to 36% of prevalent users. A total of 38% of incident users and 9% of prevalent users had none of the diagnoses selected for the study recorded in any health record during 5 years. Prevalent and older users over the age of 65 from high (50%-79%) to very high (80% and more) probability of a recorded diagnosis of hypertension. Patients on antiadrenergic agents, high-ceiling diuretics, aldosterone antagonists, or beta receptor blockers had a lower probability of having a recorded diagnosis of hypertension than patients dispensed angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, or calcium channel blockers. CONCLUSION Most patients dispensed antihypertensive medicines have a diagnosis of hypertension. However, caution is needed using data on dispensed medicines to classify incident antihypertensive users and younger patients as having a diagnosis of hypertension.
Collapse
Affiliation(s)
- Indre Treciokiene
- Pharmacy and Pharmacology Center, Faculty of Medicine, Vilnius UniversityVilniusLithuania
- Unit of PharmacoTherapy, ‐Epidemiology & ‐Economics, Groningen Research Institute of Pharmacy, Faculty of Science and Engineering, University of GroningenGroningenNetherlands
| | - Tomas Forslund
- Department of Healthcare DevelopmentStockholm Region, Public Healthcare Services CommitteeStockholmSweden
- Academic Primary Health Care CentreStockholmSweden
- Department of Neurobiology, Care Sciences and Society, Division of Family Medicine and Primary CareKarolinska InstitutetSolnaSweden
| | - Thomas Kahan
- Division of Cardiovascular Medicine, Department of Clinical SciencesDanderyd Hospital, Karolinska InstitutetStokcholmSweden
| | - Katja Taxis
- Unit of PharmacoTherapy, ‐Epidemiology & ‐Economics, Groningen Research Institute of Pharmacy, Faculty of Science and Engineering, University of GroningenGroningenNetherlands
| | - Björn Wettermark
- Pharmacy and Pharmacology Center, Faculty of Medicine, Vilnius UniversityVilniusLithuania
- Department of PharmacyUppsala UniversityUppsalaSweden
| |
Collapse
|
|
10
|
Drygała S, Radzikowski M, Maciejczyk M. β-blockers and metabolic modulation: unraveling the complex interplay with glucose metabolism, inflammation and oxidative stress. Front Pharmacol 2024; 15:1489657. [PMID: 39759452 PMCID: PMC11695285 DOI: 10.3389/fphar.2024.1489657] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2024] [Accepted: 12/04/2024] [Indexed: 01/07/2025] Open
Abstract
The growing burden of metabolic disorders manifested by hypertension, type 2 diabetes mellitus, hyperlipidemia, obesity and non-alcoholic fatty liver disease presents a significant global health challenge by contributing to cardiovascular diseases and high mortality rates. Β-blockers are among the most widely used drugs in the treatment of hypertension and acute cardiovascular events. In addition to blocking the receptor sites for catecholamines, third-generation β-blockers with associated vasodilating properties, such as carvedilol and nebivolol, provide a broad spectrum of metabolic effects, including anti-inflammatory and antioxidant properties and a favorable impact on glucose and lipid metabolism. This review aims to report the impact of β-blockers on metabolic modulation based on available literature data. We present an overview of β-blockers and their pleiotropic properties, discuss mechanisms by which these drugs affect cellular metabolism and outline the future perspectives. The influence of β-blockers on glucose metabolism, insulin sensitivity, inflammation and oxidative stress is complex and varies depending on the specific β-blocker used, patient population and underlying health conditions. Recent evidence particularly highlights the potential role of vasodilatory and nitric oxide-mediated properties of nebivolol and carvedilol in improving glycemic control, insulin sensitivity, and lipid metabolism and mitigating oxidative stress and inflammation. It suggests that these drugs may be potential therapeutic options for patients with metabolic disorders, extending beyond their primary role in cardiovascular management.
Collapse
Affiliation(s)
- Szymon Drygała
- Department of Hygiene, Epidemiology and Ergonomics, Medical University of Bialystok, Bialystok, Poland
| | - Michał Radzikowski
- Biochemistry of Civilisation Diseases’ Students’ Scientific Club at the Department of Hygiene, Epidemiology and Ergonomics, Medical University of Bialystok, Bialystok, Poland
| | - Mateusz Maciejczyk
- Department of Hygiene, Epidemiology and Ergonomics, Medical University of Bialystok, Bialystok, Poland
| |
Collapse
|
|
11
|
Parvan R, Aboumsallem JP, Meijers WC, De Boer RA, Danser AHJ. Innovative hypertension treatments: Transitioning from conventional therapies to siRNA-based solutions. Eur J Pharmacol 2024; 985:177110. [PMID: 39547406 DOI: 10.1016/j.ejphar.2024.177110] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2024] [Revised: 10/30/2024] [Accepted: 11/05/2024] [Indexed: 11/17/2024]
Abstract
Hypertension remains a critical global health issue, despite significant advancements in treatment, management and preventive approaches. Current antihypertensive drugs have limitations, such as low adherence, renin-angiotensin-aldosterone system reactivation, and drug resistance,. Ongoing preclinical and clinical studies for siRNA therapies show promising results, demonstrating significant blood pressure reductions and their potential as effective, durable treatments. This narrative review explores the potential of siRNA therapies in transforming hypertension management covering the literature until May 2024 and offering a precision medicine approach. We searched various databases, including PubMed, http://www.clinicaltrial.gov, and www.Espacenet.com, using 'hypertension' and 'siRNA' as the main keywords to retrieve relevant studies. The impact of these therapies could be profound, offering improved efficacy, reduced side effects, and enhanced patient adherence. As research continues to validate their safety and effectiveness, siRNA therapies may become integral components of hypertension management.
Collapse
Affiliation(s)
- Reza Parvan
- Cardiovascular Research Institute, Thorax Center, Department of Cardiology, Erasmus MC, Dr. Molewaterplein 40, Rotterdam, 3015, GD, the Netherlands
| | - Joseph Pierre Aboumsallem
- Cardiovascular Research Institute, Thorax Center, Department of Cardiology, Erasmus MC, Dr. Molewaterplein 40, Rotterdam, 3015, GD, the Netherlands.
| | - Wouter C Meijers
- Cardiovascular Research Institute, Thorax Center, Department of Cardiology, Erasmus MC, Dr. Molewaterplein 40, Rotterdam, 3015, GD, the Netherlands
| | - Rudolf A De Boer
- Cardiovascular Research Institute, Thorax Center, Department of Cardiology, Erasmus MC, Dr. Molewaterplein 40, Rotterdam, 3015, GD, the Netherlands
| | - A H Jan Danser
- Department of Internal Medicine, Erasmus MC, Dr. Molewaterplein 40, Rotterdam, 3015, GD, the Netherlands
| |
Collapse
|
|
12
|
Romero-Vera L, Ulloa-Díaz D, Araya-Sierralta S, Guede-Rojas F, Andrades-Ramírez O, Carvajal-Parodi C, Muñoz-Bustos G, Matamala-Aguilera M, Martínez-García D. Effects of High-Intensity Interval Training on Blood Pressure Levels in Hypertensive Patients: A Systematic Review and Meta-Analysis of Randomized Clinical Trials. Life (Basel) 2024; 14:1661. [PMID: 39768368 PMCID: PMC11728122 DOI: 10.3390/life14121661] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2024] [Revised: 12/10/2024] [Accepted: 12/12/2024] [Indexed: 01/16/2025] Open
Abstract
OBJECTIVE This systematic review and meta-analysis aimed to (I) evaluate the evidence on the effects of high-intensity interval training (HIIT) on systolic blood pressure (SBP) and diastolic blood pressure (DBP) in hypertensive patients; (II) determine whether HIIT impacts SBP and DBP differently; and (III) assess the clinical relevance of these effects. METHODS A comprehensive search was conducted across multiple electronic databases, resulting in the inclusion of seven randomized clinical trials in the meta-analysis. The outcomes were analyzed using random-effects models to compute mean differences (MD) and standardized mean differences (SMD) for SBP and DBP. RESULTS A small reduction in SBP was observed with HIIT interventions (MD -3.00; 95% CI -4.61 to -1.39; p < 0.0001; SMD -0.28; 95% CI -0.42 to -0.13; p = 0.0003). However, no statistically significant reductions were detected for DBP (MD -0.70; 95% CI -1.80 to 0.39; p = 0.21; SMD -0.07; 95% CI -0.22 to 0.08; p = 0.35). Despite demonstrating statistical significance for SBP, the effects did not reach clinical relevance. CONCLUSIONS HIIT interventions yield small reductions in SBP, with minimal impact on DBP. These findings suggest limited clinical relevance in the management of hypertension. Further randomized controlled trials are necessary to standardize HIIT protocols, with specific emphasis on intensity control and manipulation, to better understand their potential role in hypertensive populations.
Collapse
Affiliation(s)
- Luis Romero-Vera
- Facultad de Medicina y Ciencias de la Salud, Escuela de Kinesiología, Magíster en Fisiología Clínica del Ejercicio, Universidad Mayor, Santiago 8580745, Chile;
| | - David Ulloa-Díaz
- Department of Sports Sciences and Physical Conditioning, Universidad Católica de la Santísima, Concepción 4030000, Chile
| | | | - Francisco Guede-Rojas
- Exercise and Rehabilitation Sciences Institute, School of Physical Therapy, Faculty of Rehabilitation Sciences, Universidad Andres Bello, Santiago 7591538, Chile;
| | - Oscar Andrades-Ramírez
- Facultad de Salud y Ciencias Sociales, Escuela de Ciencias de la Actividad Física, Universidad de las Américas, Concepción 4030000, Chile;
| | - Claudio Carvajal-Parodi
- Facultad de Odontología y Ciencias de la Rehabilitación, Escuela de Kinesiología, Universidad San Sebastián, Concepción 4081339, Chile;
| | - Gustavo Muñoz-Bustos
- Facultad de Salud, Escuela de Nutrición y Dietética, Universidad Santo Tomás, Iquique 1100000, Chile;
| | | | - Darío Martínez-García
- Department of Physical Education and Sport, Faculty of Sport Sciences, University of Granada, 18011 Granada, Spain;
| |
Collapse
|
|
13
|
Dong ZK, Wang YF, Li WP, Jin WL. Neurobiology of cancer: Adrenergic signaling and drug repurposing. Pharmacol Ther 2024; 264:108750. [PMID: 39527999 DOI: 10.1016/j.pharmthera.2024.108750] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2024] [Revised: 10/04/2024] [Accepted: 11/05/2024] [Indexed: 11/16/2024]
Abstract
Cancer neuroscience, as an emerging converging discipline, provides us with new perspectives on the interactions between the nervous system and cancer progression. As the sympathetic nervous system, in particular adrenergic signaling, plays an important role in the regulation of tumor activity at every hierarchical level of life, from the tumor cell to the tumor microenvironment, and to the tumor macroenvironment, it is highly desirable to dissect its effects. Considering the far-reaching implications of drug repurposing for antitumor drug development, such a large number of adrenergic receptor antagonists on the market has great potential as one of the means of antitumor therapy, either as primary or adjuvant therapy. Therefore, this review aims to summarize the impact of adrenergic signaling on cancer development and to assess the status and prospects of intervening in adrenergic signaling as a therapeutic tool against tumors.
Collapse
Affiliation(s)
- Zi-Kai Dong
- The First Clinical Medical College of Lanzhou University, Lanzhou 730000, PR China; Institute of Cancer Neuroscience, Medical Frontier Innovation Research Center, The First Hospital of Lanzhou University, The First Clinical Medical College of Lanzhou University, Lanzhou 730000, PR China
| | - Yong-Fei Wang
- The First Clinical Medical College of Lanzhou University, Lanzhou 730000, PR China; Institute of Cancer Neuroscience, Medical Frontier Innovation Research Center, The First Hospital of Lanzhou University, The First Clinical Medical College of Lanzhou University, Lanzhou 730000, PR China
| | - Wei-Ping Li
- The First Clinical Medical College of Lanzhou University, Lanzhou 730000, PR China; Department of Urology, The First Hospital of Lanzhou University, Lanzhou, Gansu 730000, PR China
| | - Wei-Lin Jin
- The First Clinical Medical College of Lanzhou University, Lanzhou 730000, PR China; Institute of Cancer Neuroscience, Medical Frontier Innovation Research Center, The First Hospital of Lanzhou University, The First Clinical Medical College of Lanzhou University, Lanzhou 730000, PR China.
| |
Collapse
|
|
14
|
Tamim YM, Nagy AA, Abdellah AM, Osman AH, Ismail AFM. Anticancer effect of propranolol on diethylnitrosamine-induced hepatocellular carcinoma rat model. Fundam Clin Pharmacol 2024; 38:742-757. [PMID: 38325396 DOI: 10.1111/fcp.12990] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2023] [Revised: 01/04/2024] [Accepted: 01/16/2024] [Indexed: 02/09/2024]
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is the most widespread type of primary liver cancer. Diethylnitrosamine (DEN), a hepatotoxic hepatocarcinogenic compound, is used to induce HCC in animal models. The non-selective β-blocker propranolol demonstrated antiproliferative activity in many cancer types. OBJECTIVE This investigation aimed to evaluate the anticancer effect of propranolol against DEN-induced HCC in rats. METHODS Thirty adult male rats were divided into the following groups: Group I (C, control), Group II (HCC); received DEN, 70 mg/kg body weight (b.wt.) once a week for 10 weeks, to induce HCC, and Group III (HCC/Prop); received DEN for 10 weeks for HCC induction, then received 20 mg/kg b.wt. propranolol, intraperitoneally for four successive weeks. RESULTS HCC was developed in rats' livers and confirmed via significant liver architecture changes, significantly elevated activity of alanine aminotransferase (ALT), aspartate aminotransferase (AST), α-fetoprotein (AFP), total- and direct-bilirubin (Bil), and a decline in albumin (ALB) level in serum. HCC group demonstrated elevated levels of malondialdehyde (MDA), nitric oxide (NO), HIF-1α, IL-8, NF-κB, PGE2, TGF-β1, VEGF, and CD8, but significant decline of GSH, and IL-10 level, with suppression of the antioxidant enzymes' activities. In addition, the gene expression of the hepatic inducible nitric oxide synthase (iNOS), and LAG-3 were up-regulated. Moreover, the protein expression of p-PKC was up-regulated, while that of PD-1 and PD-L1 were down-regulated in the liver tissues of the HCC group. However, propranolol ameliorated the investigated parameters in the HCC/Prop group. CONCLUSION Propranolol exhibited an anticancer effect and thus can be considered as a promising treatment for HCC. Blocking of PD-1/PD-L1 and LAG-3 signals participated in the anti-tumor effect of propranolol on HCC.
Collapse
Affiliation(s)
- Yomna M Tamim
- Clinical Pharmacology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Ahmed A Nagy
- Clinical Oncology and Nuclear Medicine Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Ahmed M Abdellah
- Pathophysiology Department, Grand Canyon University, Phoenix, Arizona, USA
| | - Ahmed H Osman
- Pathology Department, Faculty of Veterinary Medicine, Cairo University, Cairo, Egypt
| | - Amel F M Ismail
- Drug Radiation Research Department, Biotechnology Division, National Center for Radiation Research and Technology (NCRRT), Egyptian Atomic Energy Authority (EAEA), Cairo, Egypt
| |
Collapse
|
|
15
|
Lee J, Chun P. Real world prescription of beta-blockers in patients with asthma. Pharmacoepidemiol Drug Saf 2024; 33:e5806. [PMID: 39090769 DOI: 10.1002/pds.5806] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2023] [Revised: 03/11/2024] [Accepted: 04/20/2024] [Indexed: 08/04/2024]
Abstract
PURPOSE This study aimed to investigate the prescription of beta-blockers (β-blockers) for patients with asthma. METHODS In this retrospective cross-sectional study using the National Patient Sample (NPS) of the Health Insurance Review and Assessment Service (HIRA) of South Korea, β-blockers and asthma medications were investigated using generic name codes provided by HIRA. Concomitant administration was identified when a β-blocker and an asthma medication were co-prescribed in one billing statement or when separate β-blocker and asthma prescriptions had overlapping dates of use. RESULTS In the 1027 patients with asthma who were prescribed non-selective β-blockers (non-SBs), 3087 non-SB prescriptions were identified, of which 62.3% and 37.3% were for carvedilol and propranolol, respectively. Of the 906 patients with asthma prescribed selective β-blockers (SBs), 2942 SB prescriptions were identified, of which 48.5%, 28.3%, and 20.3% were for bisoprolol, atenolol, and nebivolol, respectively. Overall, 2149 non-SB and 2124 SB prescriptions with overlapping use dates with asthma medications were identified, which were prescribed to 726 and 657 patients, accounting for 70.7% and 72.5% of the patients receiving non-SBs and SBs, respectively. β2-agonists accounted for 39.9% of the concomitant asthma medications with overlapping dates of use with non-SBs. Co-prescribing of bronchodilators occurred at a rate of 38.7% and 45.1% for the 3087 non-SB prescriptions and 2942 SB prescriptions, respectively. CONCLUSIONS Carvedilol and propranolol accounted for half of all β-blockers prescribed to asthma patients. Prescribing β-blockers to patients with asthma requires caution to prevent exacerbation of asthma and drug interactions between β-blockers and co-prescribed asthma medications.
Collapse
Affiliation(s)
- Jihyun Lee
- College of Pharmacy and Inje Institute of Pharmaceutical Sciences and Research, Inje University, Gimhae, Republic of Korea
| | - Pusoon Chun
- College of Pharmacy and Inje Institute of Pharmaceutical Sciences and Research, Inje University, Gimhae, Republic of Korea
| |
Collapse
|
|
16
|
Versijpt J, Deligianni C, Hussain M, Amin F, Reuter U, Sanchez-Del-Rio M, Uluduz D, Boucherie D, Zeraatkar D, MaassenVanDenBrink A, Sacco S, Lampl C, Gil-Gouveia R. European Headache Federation (EHF) critical re-appraisal and meta-analysis of oral drugs in migraine prevention - part 4: propranolol. J Headache Pain 2024; 25:119. [PMID: 39044170 PMCID: PMC11267726 DOI: 10.1186/s10194-024-01826-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2024] [Accepted: 07/11/2024] [Indexed: 07/25/2024] Open
Abstract
OBJECTIVE The aim of this paper is to critically re-appraise the published trials assessing propranolol for migraine prophylaxis. METHODS We report methods and results following the Preferred Reporting Items for Systematic Reviews (PRISMA), by searching MEDLINE, EMBASE, Cochrane CENTRAL, and ClinicalTrials.gov for randomized trials of pharmacologic treatments for migraine prophylaxis. We included randomized trials that compared propranolol with placebo for migraine prophylaxis in adults. The outcomes of interest were informed by the Core outcome set for preventive intervention trials in chronic and episodic migraine (COSMIG) and include the proportion of patients who experience a 50% or more reduction in monthly migraine days, the reduction of monthly migraine days, and the number of adverse events leading to discontinuation. We assessed risk of bias by using a modified Cochrane RoB (risk of bias) 2.0 tool and the certainty of evidence by using the GRADE approach. RESULTS Our search yielded twenty trials (n = 1291 patients) eligible for data synthesis and analysis. The analysis revealed a moderate certainty evidence that propranolol leads to a reduction in monthly migraine days versus placebo (-1.27; 95% CI: -2.25 to -0.3). We found moderate certainty evidence that propranolol increases the proportion of patients who experience a 50% or more reduction in monthly migraine days, compared to placebo with a relative risk of 1.65 (95% CI 1.41 to 1.93); absolute risk difference: 179 more per 1,000 (95% CI 113 to 256). We found high certainty evidence that propranolol increases the proportion of patients who discontinue due to adverse events compared to placebo with a risk difference of 0.02 (95% CI 0.00 to 0.03); absolute risk difference: 20 more per 1,000 (95% CI 0 to 30). CONCLUSIONS The present meta-analysis shows that propranolol has a prophylactic role in migraine, with an overall acceptable tolerability profile. Combining these results with its long-standing use and its global availability at a low cost confirms its role as a first line agent in the prophylaxis of migraine.
Collapse
Affiliation(s)
- Jan Versijpt
- Department of Neurology, Vrije Universiteit Brussel (VUB), Universitair Ziekenhuis Brussel (UZ Brussel), Brussels, Belgium.
| | | | - Muizz Hussain
- Department of Anesthesia and Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Canada
| | - Faisal Amin
- Department of Neurology, Danish Headache Center, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark
| | - Uwe Reuter
- Department of Neurology, Charité Universitätsmedizin Berlin, Berlin, Germany
| | | | - Derya Uluduz
- Department of Neurology, Istanbul University Istanbul Faculty of Medicine, Istanbul, Turkey
| | - Deirdre Boucherie
- Department of Internal Medicine, Division of Vascular Medicine and Pharmacology, Erasmus MC Medical Center, Rotterdam, the Netherlands
| | - Dena Zeraatkar
- Department of Anesthesia and Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Canada
| | - Antoinette MaassenVanDenBrink
- Department of Internal Medicine, Division of Vascular Medicine and Pharmacology, Erasmus MC Medical Center, Rotterdam, the Netherlands
| | - Simona Sacco
- Department of Biotechnological and Applied Clinical Sciences, University of L´Aquila, Rome, Italy
| | - Christian Lampl
- Department of Neurology and Stroke Unit Konventhospital Barmherzige Brüder Linz, Linz, Austria
| | - Raquel Gil-Gouveia
- Neurology Department, Hospital da Luz Headache Center, Hospital da Luz Lisboa, Lisbon, Portugal
| |
Collapse
|
|
17
|
Alshehri FS, Ashour AM, Alharbi AS, Hakami AY, Alorfi NM. Understanding migraine in Saudi society: An assessment of public knowledge and attitudes: A cross-sectional study. PLoS One 2024; 19:e0304840. [PMID: 38905175 PMCID: PMC11192400 DOI: 10.1371/journal.pone.0304840] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2024] [Accepted: 05/20/2024] [Indexed: 06/23/2024] Open
Abstract
OBJECTIVE This study aims to assess the knowledge and perceptions of the public toward migraine in Saudi Arabia. METHODS This cross-sectional survey assessed the knowledge and perceptions of migraine among Saudi Arabian individuals. The study was conducted over three months in 2023 (1st of June 2023 to 31st of August 2023) using a prevalidated online questionnaire divided into four sections. RESULTS A total of 1,975 adults aged between 18 and 64 completed the web-based survey. Of these, over half were male (n = 1,268; 64.2%). The main causes of migraine identified by the participants were genetic disease (n = 540, 27.3%), followed by physical disease (n = 341, 17.3%), head trauma (n = 274, 13.9%), and psychiatric disease (n = 157, 7.9%). The main symptoms identified by the participants were photophobia (21%), followed by inability to control urine (14.1%), vomiting and nausea (13.8%), and vision loss (8.3%). The majority of the participants in this study had a good knowledge of migraines, while 49% had poor knowledge. The migraine knowledge score was significantly associated with the participants' gender (p = 0.002), age (p = 0.0001), educational level (p = 0.001), employment status (p = 0.001), monthly income (p = 0.0001), region (p = 0.0001), and history of migraine (p = 0.0001). CONCLUSION Although one-third of the participants exhibiting good knowledge, deficiencies existed in certain clinical aspects, emphasizing the need for targeted educational interventions to enhance public awareness and understanding of migraines.
Collapse
Affiliation(s)
- Fahad S. Alshehri
- Pharmacology and Toxicology Department, College of Pharmacy, Umm Al-Qura University, Makkah, Saudi Arabia
| | - Ahmed M. Ashour
- Pharmacology and Toxicology Department, College of Pharmacy, Umm Al-Qura University, Makkah, Saudi Arabia
| | - Adnan S. Alharbi
- Pharmacy Practice Department, College of Pharmacy, Umm Al-Qura University, Makkah, Saudi Arabia
| | - Alqassem Y. Hakami
- College of Medicine, King Saud bin Abdulaziz University for Health Sciences, Jeddah, Saudi Arabia
- King Abdullah International Medical Research Center, Jeddah, Saudi Arabia
| | - Nasser M. Alorfi
- Pharmacology and Toxicology Department, College of Pharmacy, Umm Al-Qura University, Makkah, Saudi Arabia
| |
Collapse
|
|
18
|
Zhang BS, Zhang XM, Ito M, Yajima S, Yoshida K, Ohno M, Nishi E, Wang H, Li SY, Kubota M, Yoshida Y, Matsutani T, Mine S, Machida T, Takemoto M, Yamagata H, Hayashi A, Yokote K, Kobayashi Y, Takizawa H, Kuroda H, Shimada H, Iwadate Y, Hiwasa T. JMJD6 Autoantibodies as a Potential Biomarker for Inflammation-Related Diseases. Int J Mol Sci 2024; 25:4935. [PMID: 38732153 PMCID: PMC11084951 DOI: 10.3390/ijms25094935] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2024] [Revised: 04/15/2024] [Accepted: 04/29/2024] [Indexed: 05/13/2024] Open
Abstract
Inflammation is closely associated with cerebrovascular diseases, cardiovascular diseases, diabetes, and cancers, and it is accompanied by the development of autoantibodies in the early stage of inflammation-related diseases. Hence, it is meaningful to discover novel antibody biomarkers targeting inflammation-related diseases. In this study, Jumonji C-domain-containing 6 (JMJD6) was identified by the serological identification of antigens through recombinant cDNA expression cloning. In particular, JMJD6 is an antigen recognized in serum IgG from patients with unstable angina pectoris (a cardiovascular disease). Then, the serum antibody levels were examined using an amplified luminescent proximity homogeneous assay-linked immunosorbent assay and a purified recombinant JMJD6 protein as an antigen. We observed elevated levels of serum anti-JMJD6 antibodies (s-JMJD6-Abs) in patients with inflammation-related diseases such as ischemic stroke, acute myocardial infarction (AMI), diabetes mellitus (DM), and cancers (including esophageal cancer, EC; gastric cancer; lung cancer; and mammary cancer), compared with the levels in healthy donors. The s-JMJD6-Ab levels were closely associated with some inflammation indicators, such as C-reactive protein and intima-media thickness (an atherosclerosis index). A better postoperative survival status of patients with EC was observed in the JMJD6-Ab-positive group than in the negative group. An immunohistochemical analysis showed that JMJD6 was highly expressed in the inflamed mucosa of esophageal tissues, esophageal carcinoma tissues, and atherosclerotic plaques. Hence, JMJD6 autoantibodies may reflect inflammation, thereby serving as a potential biomarker for diagnosing specific inflammation-related diseases, including stroke, AMI, DM, and cancers, and for prediction of the prognosis in patients with EC.
Collapse
Affiliation(s)
- Bo-Shi Zhang
- Department of Neurological Surgery, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan; (B.-S.Z.)
- Department of Biochemistry and Genetics, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan
| | - Xiao-Meng Zhang
- Department of Biochemistry and Genetics, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan
| | - Masaaki Ito
- Department of Clinical Oncology, Graduate School of Medicine, Toho University, Tokyo 143-8541, Japan (H.S.)
| | - Satoshi Yajima
- Department of Gastroenterological Surgery, Graduate School of Medicine, Toho University, Tokyo 143-8541, Japan
| | - Kimihiko Yoshida
- Department of Gastroenterological Surgery, Graduate School of Medicine, Toho University, Tokyo 143-8541, Japan
| | - Mikiko Ohno
- Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan
- Department of Pharmacology, Shiga University of Medical Science, Otsu 520-2192, Japan
| | - Eiichiro Nishi
- Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan
- Department of Pharmacology, Shiga University of Medical Science, Otsu 520-2192, Japan
| | - Hao Wang
- Department of Biochemistry and Genetics, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan
| | - Shu-Yang Li
- Department of Neurological Surgery, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan; (B.-S.Z.)
- Department of Biochemistry and Genetics, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan
| | - Masaaki Kubota
- Department of Neurological Surgery, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan; (B.-S.Z.)
- Comprehensive Stroke Center, Chiba University Hospital, Chiba 260-8677, Japan
| | - Yoichi Yoshida
- Department of Neurological Surgery, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan; (B.-S.Z.)
- Comprehensive Stroke Center, Chiba University Hospital, Chiba 260-8677, Japan
| | - Tomoo Matsutani
- Department of Neurological Surgery, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan; (B.-S.Z.)
| | - Seiichiro Mine
- Department of Neurological Surgery, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan; (B.-S.Z.)
- Department of Neurological Surgery, Chiba Prefectural Sawara Hospital, Chiba 287-0003, Japan
- Department of Neurological Surgery, Chiba Cerebral and Cardiovascular Center, Chiba 290-0512, Japan
| | - Toshio Machida
- Department of Neurological Surgery, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan; (B.-S.Z.)
- Department of Neurological Surgery, Chiba Cerebral and Cardiovascular Center, Chiba 290-0512, Japan
- Department of Neurosurgery, Eastern Chiba Medical Center, Chiba 283-8686, Japan
| | - Minoru Takemoto
- Department of Endocrinology, Hematology and Gerontology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan
- Department of Diabetes, Metabolism and Endocrinology, School of Medicine, International University of Health and Welfare, Chiba 286-8686, Japan
| | - Hiroki Yamagata
- Department of Diabetes, Metabolism and Endocrinology, School of Medicine, International University of Health and Welfare, Chiba 286-8686, Japan
| | - Aiko Hayashi
- Department of Endocrinology, Hematology and Gerontology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan
| | - Koutaro Yokote
- Department of Endocrinology, Hematology and Gerontology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan
| | - Yoshio Kobayashi
- Department of Cardiovascular Medicine, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan
| | - Hirotaka Takizawa
- Port Square Kashiwado Clinic, Kashiwado Memorial Foundation, Chiba 260-0025, Japan
| | - Hideyuki Kuroda
- Medical Project Division, Research Development Center, Fujikura Kasei Co., Saitama 340-0203, Japan
| | - Hideaki Shimada
- Department of Clinical Oncology, Graduate School of Medicine, Toho University, Tokyo 143-8541, Japan (H.S.)
- Department of Gastroenterological Surgery, Graduate School of Medicine, Toho University, Tokyo 143-8541, Japan
| | - Yasuo Iwadate
- Department of Neurological Surgery, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan; (B.-S.Z.)
| | - Takaki Hiwasa
- Department of Neurological Surgery, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan; (B.-S.Z.)
- Department of Biochemistry and Genetics, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan
- Department of Clinical Oncology, Graduate School of Medicine, Toho University, Tokyo 143-8541, Japan (H.S.)
- Comprehensive Stroke Center, Chiba University Hospital, Chiba 260-8677, Japan
| |
Collapse
|
|
19
|
Xia Y, Sun M, Huang H, Jin WL. Drug repurposing for cancer therapy. Signal Transduct Target Ther 2024; 9:92. [PMID: 38637540 PMCID: PMC11026526 DOI: 10.1038/s41392-024-01808-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2023] [Revised: 03/05/2024] [Accepted: 03/19/2024] [Indexed: 04/20/2024] Open
Abstract
Cancer, a complex and multifactorial disease, presents a significant challenge to global health. Despite significant advances in surgical, radiotherapeutic and immunological approaches, which have improved cancer treatment outcomes, drug therapy continues to serve as a key therapeutic strategy. However, the clinical efficacy of drug therapy is often constrained by drug resistance and severe toxic side effects, and thus there remains a critical need to develop novel cancer therapeutics. One promising strategy that has received widespread attention in recent years is drug repurposing: the identification of new applications for existing, clinically approved drugs. Drug repurposing possesses several inherent advantages in the context of cancer treatment since repurposed drugs are typically cost-effective, proven to be safe, and can significantly expedite the drug development process due to their already established safety profiles. In light of this, the present review offers a comprehensive overview of the various methods employed in drug repurposing, specifically focusing on the repurposing of drugs to treat cancer. We describe the antitumor properties of candidate drugs, and discuss in detail how they target both the hallmarks of cancer in tumor cells and the surrounding tumor microenvironment. In addition, we examine the innovative strategy of integrating drug repurposing with nanotechnology to enhance topical drug delivery. We also emphasize the critical role that repurposed drugs can play when used as part of a combination therapy regimen. To conclude, we outline the challenges associated with repurposing drugs and consider the future prospects of these repurposed drugs transitioning into clinical application.
Collapse
Affiliation(s)
- Ying Xia
- Center for Clinical Laboratories, The Affiliated Hospital of Guizhou Medical University, Guiyang, 550004, PR China
- The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang, 550001, PR China
- School of Clinical Laboratory Science, Guizhou Medical University, Guiyang, 550004, PR China
- Division of Gastroenterology and Hepatology, Department of Medicine and, Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA
| | - Ming Sun
- Center for Clinical Laboratories, The Affiliated Hospital of Guizhou Medical University, Guiyang, 550004, PR China
- School of Clinical Laboratory Science, Guizhou Medical University, Guiyang, 550004, PR China
| | - Hai Huang
- Center for Clinical Laboratories, The Affiliated Hospital of Guizhou Medical University, Guiyang, 550004, PR China.
- School of Clinical Laboratory Science, Guizhou Medical University, Guiyang, 550004, PR China.
| | - Wei-Lin Jin
- Institute of Cancer Neuroscience, Medical Frontier Innovation Research Center, The First Hospital of Lanzhou University, The First Clinical Medical College of Lanzhou University, Lanzhou, 730000, PR China.
| |
Collapse
|
|
20
|
Tabassum M, Chikermane SG, Johnson C, Abdulkareem NM, Wang EM, Johnson ML, Trivedi MV. Comparing the effects of various β-blockers on cardiovascular mortality in breast cancer patients. CARDIO-ONCOLOGY (LONDON, ENGLAND) 2024; 10:17. [PMID: 38532523 PMCID: PMC10964697 DOI: 10.1186/s40959-024-00217-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/08/2023] [Accepted: 03/05/2024] [Indexed: 03/28/2024]
Abstract
BACKGROUND Cardiovascular (CV) disease is a leading cause of death in breast cancer (BC) patients due to the increased age and treatments. While individual β-blockers have been investigated to manage CV complications, various β-blockers have not been compared for their effects on CV death in this population. We aimed to compare CV mortality in older BC patients taking one of the commonly used β-blockers. METHODS This retrospective cohort study was conducted using the Surveillance, Epidemiology and End Results (SEER) - Medicare data (2010-2015). Patients of age 66 years or older at BC diagnosis receiving metoprolol, atenolol, or carvedilol monotherapy were included. The competing risk regression model was used to determine the risk of CV mortality in the three β-blocker groups. The multivariable model was adjusted for demographic and clinical covariates. The adjusted hazard ratio (HR) and 95% confidence intervals (CI) were reported for the risk of CV mortality. RESULTS The study cohort included 6,540 patients of which 55% were metoprolol users, 30% were atenolol users, and 15% were carvedilol users. Metoprolol was associated with a 37% reduced risk of CV mortality (P = 0.03) compared to carvedilol after adjusting for the covariates (HR = 0.63; 95% CI 0.41-0.96). No significant difference in the risk of CV mortality between atenolol and carvedilol users was observed (HR = 0.74; 95% CI 0.44-1.22). CONCLUSIONS Our findings suggest that metoprolol is associated with a reduced risk of CV mortality in BC patients. Future studies are needed to confirm these findings and understand the mechanism of action.
Collapse
Affiliation(s)
- Mantasha Tabassum
- Department of Pharmacological and Pharmaceutical Sciences, University of Houston College of Pharmacy, 4349 Martin Luther King Blvd, 77204, Houston, TX, USA
| | - Soumya G Chikermane
- Department of Pharmaceutical Health Outcomes and Policy, University of Houston College of Pharmacy, Houston, TX, USA
| | - Camille Johnson
- Department of Pharmacy Practice and Translational Research, University of Houston College of Pharmacy, Houston, TX, USA
| | - Noor M Abdulkareem
- Department of Pharmacological and Pharmaceutical Sciences, University of Houston College of Pharmacy, 4349 Martin Luther King Blvd, 77204, Houston, TX, USA
| | - Elisabeth M Wang
- Department of Pharmacy Practice and Translational Research, University of Houston College of Pharmacy, Houston, TX, USA
| | - Michael L Johnson
- Department of Pharmaceutical Health Outcomes and Policy, University of Houston College of Pharmacy, Houston, TX, USA
| | - Meghana V Trivedi
- Department of Pharmacological and Pharmaceutical Sciences, University of Houston College of Pharmacy, 4349 Martin Luther King Blvd, 77204, Houston, TX, USA.
- Department of Pharmacy Practice and Translational Research, University of Houston College of Pharmacy, Houston, TX, USA.
| |
Collapse
|
|
21
|
Engel J, Haack B, Zolk O, Greiner T, Heinze M, Toto S, Seifert J, Bleich S, Glocker C, Grohmann R, Schneider M, Stübner S. Edema related to treatment with psychotropic drugs. J Neural Transm (Vienna) 2024; 131:253-266. [PMID: 38353811 PMCID: PMC10874320 DOI: 10.1007/s00702-024-02738-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2023] [Accepted: 01/02/2024] [Indexed: 02/18/2024]
Abstract
Edema as an adverse drug reaction is a commonly underestimated yet potentially debilitating condition. This study analyzes the incidence of severe psychotropic drug-induced edema (e.g., edema affecting the face, legs, or multiple body parts and lasting for more than 1 week, or in any case necessitating subsequent diuretic use) among psychiatric inpatients. The cases under examination are derived from an observational pharmacovigilance program conducted in German-speaking countries ("Arzneimittelsicherheit in der Psychiatrie", AMSP) from 1993 to 2016. Among the 462,661 inpatients monitored, severe edema was reported in 231 cases, resulting in an incidence of 0.05%. Edema occurred more frequently in women (80% of all cases) and older patients (mean age 51.8 years). Pregabalin had the highest incidence of severe edema, affecting 1.46‰ of patients treated with pregabalin, followed by mirtazapine (0.8‰). The majority of edema cases showed a positive response to appropriate countermeasures, such as dose reduction and drug discontinuation, and resolved by the end of the observation period. While most instances of drug-induced edema are reversible, they can have a significant impact on patient well-being and potentially result in decreased treatment adherence. It is, therefore, crucial to remain vigilant regarding risk-increasing circumstances during treatment with psychotropic drugs.
Collapse
Affiliation(s)
- Johanna Engel
- Brandenburg Medical School, University Clinic for Psychiatry and Psychotherapy, Immanuel Klinik Rüdersdorf, Seebad 82/83, 15562, Rüdersdorf bei Berlin, Germany.
| | - Beatrice Haack
- Brandenburg Medical School, University Clinic for Psychiatry and Psychotherapy, Immanuel Klinik Rüdersdorf, Seebad 82/83, 15562, Rüdersdorf bei Berlin, Germany
| | - Oliver Zolk
- Institute of Clinical Pharmacology of the Brandenburg Medical School, Immanuel Klinik Rüdersdorf, Seebad 82/83, 15562, Rüdersdorf bei Berlin, Germany
| | - Timo Greiner
- Brandenburg Medical School, University Clinic for Psychiatry and Psychotherapy, Immanuel Klinik Rüdersdorf, Seebad 82/83, 15562, Rüdersdorf bei Berlin, Germany
| | - Martin Heinze
- Brandenburg Medical School, University Clinic for Psychiatry and Psychotherapy, Immanuel Klinik Rüdersdorf, Seebad 82/83, 15562, Rüdersdorf bei Berlin, Germany
| | - Sermin Toto
- Department of Psychiatry, Social Psychiatry, and Psychotherapy, Hannover Medical School, Carl-Neuberg-Straße 1, 30625, Hannover, Germany
| | - Johanna Seifert
- Department of Psychiatry, Social Psychiatry, and Psychotherapy, Hannover Medical School, Carl-Neuberg-Straße 1, 30625, Hannover, Germany
| | - Stefan Bleich
- Department of Psychiatry, Social Psychiatry, and Psychotherapy, Hannover Medical School, Carl-Neuberg-Straße 1, 30625, Hannover, Germany
| | - Catherine Glocker
- Department of Psychiatry and Psychotherapy, Ludwig Maximilian University of Munich, Nussbaumstr. 7, 80336, Munich, Germany
| | - Renate Grohmann
- Department of Psychiatry and Psychotherapy, Ludwig Maximilian University of Munich, Nussbaumstr. 7, 80336, Munich, Germany
| | - Michael Schneider
- Brandenburg Medical School, University Clinic for Psychiatry and Psychotherapy, Immanuel Klinik Rüdersdorf, Seebad 82/83, 15562, Rüdersdorf bei Berlin, Germany
| | - Susanne Stübner
- Maßregelvollzugsleitung, Klinik für Forensische Psychiatrie, Bezirksklinikum Ansbach, Ludwig-Maximilians-Universität München, Feuchtwanger Straße 38, 91522, Ansbach, Germany
| |
Collapse
|
|
22
|
Wu J, Fang J, Yuan X, Ma L, Zheng L, Lin Q, An X, Wang Z, Ma Q. Associations of type 2 diabetes and the risk of migraine in Chinese populations. DIABETES & METABOLISM 2024; 50:101518. [PMID: 38272255 DOI: 10.1016/j.diabet.2024.101518] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/20/2023] [Revised: 12/11/2023] [Accepted: 01/07/2024] [Indexed: 01/27/2024]
Abstract
AIM We aimed to explore the relationship between type 2 diabetes mellitus (T2DM) and the incidence rate of migraine in a Chinese population, and analyze the clinical characteristics of migraine patients with T2DM. METHODS Data on the study cohort of 9873 individuals were obtained from the China Health and Retirement Longitudinal Study (CHARLS). The incidence rate of migraine from 2015 to 2018 was assessed. The Cox proportional hazards model was used to estimate hazard ratios (HRs) and their 95% confidence intervals (CIs) for the relationship between T2DM and the incidence of migraine. In addition, a cross-sectional study including 168 migraine patients was conducted in Xiamen, China. Migraine patients were grouped according to their T2DM status. Multivariable linear regression models were used to estimate βs and their 95% CIs for the relationship between migraine characteristics and T2DM. RESULTS The cumulative incidence rate of migraine from 2015 to 2018 in the T2DM group and control group was 7.26% [6.04%.8.65%] and 8.91% [8.27%.9.58%], respectively. The risk of migraine in patients with T2DM was reduced by 21% (HR 0.79 [0.65;0.95]) compared to patients with no T2DM after adjustment for confounders. The cross-sectional study showed that the presence of T2DM significantly reduced migraine frequency and relieved migraine intensity. CONCLUSION This was the first study to validate that T2DM reduced the risk of migraine in a Chinese population cohort. Patients with migraine and T2DM may experience significant relief from their headache symptoms. Carrying out relevant mechanistic research may help to identify new targets for migraine treatment and contribute to further understanding the impact of T2DM or related metabolic disorders on an individual's health.
Collapse
Affiliation(s)
- Jielong Wu
- Department of Neurology and Department of Neuroscience, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China; School of Medicine, Xiamen University, China; National Institute for Data Science in Health and Medicine, Xiamen University, China
| | - Jie Fang
- Department of Neurology and Department of Neuroscience, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China; The School of Clinical Medicine, Fujian Medical University, China; Fujian Key Laboratory of Brain Tumors Diagnosis and Precision Treatment, China; Xiamen Key Laboratory of Brain Center, China; Xiamen Medical Quality Control Center for Neurology, China; Fujian Provincial Clinical Research Center for Brain Diseases, China; Xiamen Clinical Research Center for Neurological Diseases, China
| | - Xiaodong Yuan
- Department of Gynecology of Xiamen Maternal and Child Health Care Hospital, China
| | - Lingshan Ma
- Department of Neurology and Department of Neuroscience, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China; School of Medicine, Xiamen University, China; National Institute for Data Science in Health and Medicine, Xiamen University, China
| | - Liangcheng Zheng
- Department of Neurology and Department of Neuroscience, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China; The School of Clinical Medicine, Fujian Medical University, China; Fujian Key Laboratory of Brain Tumors Diagnosis and Precision Treatment, China; Xiamen Key Laboratory of Brain Center, China; Xiamen Medical Quality Control Center for Neurology, China; Fujian Provincial Clinical Research Center for Brain Diseases, China; Xiamen Clinical Research Center for Neurological Diseases, China
| | - Qing Lin
- Department of Neurology and Department of Neuroscience, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China; The School of Clinical Medicine, Fujian Medical University, China; Fujian Key Laboratory of Brain Tumors Diagnosis and Precision Treatment, China; Xiamen Key Laboratory of Brain Center, China; Xiamen Medical Quality Control Center for Neurology, China; Fujian Provincial Clinical Research Center for Brain Diseases, China; Xiamen Clinical Research Center for Neurological Diseases, China
| | - Xingkai An
- Department of Neurology and Department of Neuroscience, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China; The School of Clinical Medicine, Fujian Medical University, China; Fujian Key Laboratory of Brain Tumors Diagnosis and Precision Treatment, China; Xiamen Key Laboratory of Brain Center, China; Xiamen Medical Quality Control Center for Neurology, China; Fujian Provincial Clinical Research Center for Brain Diseases, China; Xiamen Clinical Research Center for Neurological Diseases, China
| | - Zhanxiang Wang
- Fujian Key Laboratory of Brain Tumors Diagnosis and Precision Treatment, China; Xiamen Key Laboratory of Brain Center, China; Xiamen Medical Quality Control Center for Neurology, China; Fujian Provincial Clinical Research Center for Brain Diseases, China; Xiamen Clinical Research Center for Neurological Diseases, China; School of Medicine, Xiamen University, China; National Institute for Data Science in Health and Medicine, Xiamen University, China; Department of Neurosurgery and Department of Neuroscience, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China
| | - Qilin Ma
- Department of Neurology and Department of Neuroscience, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China; The School of Clinical Medicine, Fujian Medical University, China; Fujian Key Laboratory of Brain Tumors Diagnosis and Precision Treatment, China; Xiamen Key Laboratory of Brain Center, China; Xiamen Medical Quality Control Center for Neurology, China; Fujian Provincial Clinical Research Center for Brain Diseases, China; Xiamen Clinical Research Center for Neurological Diseases, China; School of Medicine, Xiamen University, China; National Institute for Data Science in Health and Medicine, Xiamen University, China.
| |
Collapse
|
|
23
|
Nair SG, Benny S, Jose WM, Aneesh T P. Beta-blocker adjunct therapy as a prospective anti-metastatic with cardio-oncologic regulation. Clin Exp Metastasis 2024; 41:9-24. [PMID: 38177715 DOI: 10.1007/s10585-023-10258-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2023] [Accepted: 12/12/2023] [Indexed: 01/06/2024]
Abstract
The prevailing treatment stratagem in cancer therapy still challenges the dilemma of a probable metastatic spread following an initial diagnosis. Including an anti-metastatic agent demands a significant focus to overrule the incidence of treatment failures. Adrenergic stimulation underlying the metastatic spread paved the way for beta blockers as a breakthrough in repurposing as an anti-metastatic agent. However, the current treatment approach fails to fully harness the versatile potential of the drug in inhibiting probable metastasis. The beta blockers were seen to show a myriad of grip over the pro-metastatic and prognostic parameters of the patient. Novel interventions in immune therapy, onco-hypertension, surgery-induced stress, induction of apoptosis and angiogenesis inhibition have been used as evidence to interpret our objective of discussing the potential adjuvant role of the drug in the existing anti-cancer regimens. Adding weight to the relative incidence of onco-hypertension as an unavoidable side effect from chemotherapy, the slot for an anti-hypertensive agent is necessitated, and we try to suggest beta-blockers to fill this position. However, pointing out the paucity in the clinical study, we aim to review the current status of beta blockers under this interest to state how the drug should be included as a drug of choice in every patient undergoing cancer treatment.
Collapse
Affiliation(s)
- Sachin G Nair
- Department of Pharmacy Practice, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Sciences Campus, Kochi, Kerala, 682041, India
| | - Sonu Benny
- Department of Pharmaceutical Chemistry, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Sciences Campus, Kochi, Kerala, 682041, India
| | - Wesley M Jose
- Department of Medical Oncology, Amrita Institute of Medical Sciences, Amrita Vishwa Vidyapeetham, AIMS PO, Kochi, Kerala, 682041, India.
| | - Aneesh T P
- Department of Pharmaceutical Chemistry, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Sciences Campus, Kochi, Kerala, 682041, India.
| |
Collapse
|
|
24
|
Kirkegård J, Cronin-Fenton D, Lund A, Mortensen FV. Beta-blocker use and survival after pancreatic cancer surgery: A nationwide population-based cohort study. Pharmacoepidemiol Drug Saf 2024; 33:e5726. [PMID: 37946571 DOI: 10.1002/pds.5726] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2023] [Revised: 09/25/2023] [Accepted: 10/23/2023] [Indexed: 11/12/2023]
Abstract
PURPOSE We examined the association between use of beta-blockers and survival in pancreatic cancer patients after curative-intent surgery. METHODS Using Danish healthcare registries, we conducted a population-based cohort study of all patients undergoing curative-intent surgery for pancreatic cancer in Denmark 1997-2021. We defined beta-blocker use according to exposure before surgery as current (≤90 days), recent (91-365 days), or former (366-730 days) use, requiring at least one filled prescription. Patients were followed from the date of surgery for up to 5 years. We used Cox regression to compute hazard ratios (HRs) of deaths with 95% confidence intervals (CIs), adjusting for age, sex, year of diagnosis, cardiovascular disease, diabetes, liver disease, alcohol, and smoking. We also conducted an active comparator analysis, where we used angiotensin-converting enzyme inhibitors/angiotensin-receptor blockers as comparators instead of nonusers. RESULTS We included 2592 patients, of which 16.7% were beta-blocker users. Median survival for the entire population was 24.4 months. Beta-blocker use was associated with increased mortality (adjusted HR: 1.18; 95% CI: 1.04-1.34). This was evident in current (adjusted HR: 1.19; 95% CI: 1.02-1.38) and recent (adjusted HR: 1.29; 95% CI: 1.04-1.59) but not former (adjusted HR: 0.91; 95% CI: 0.64-1.43) users. In the active comparator analysis, the association between beta-blocker exposure and mortality attenuated slightly (adjusted HR: 1.12; 95% CI: 0.93-1.35). CONCLUSIONS We observed an association between beta-blocker use and increased mortality in patients operated for pancreatic cancer. Findings are likely explained by confounding by indication.
Collapse
Affiliation(s)
- Jakob Kirkegård
- Department of Surgery, HPB Section, Aarhus University Hospital, Aarhus, Denmark
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - Deirdre Cronin-Fenton
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
- Department of Clinical Epidemiology, Aarhus University and Aarhus University Hospital, Aarhus, Denmark
| | - Andrea Lund
- Department of Surgery, HPB Section, Aarhus University Hospital, Aarhus, Denmark
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - Frank Viborg Mortensen
- Department of Surgery, HPB Section, Aarhus University Hospital, Aarhus, Denmark
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| |
Collapse
|
|
25
|
Chu H, Wang Y, Ling X, Li K, Yang X. Prophylactic treatments for vestibular migraine: a systematic review and network meta-analysis of randomized clinical trials. Front Pharmacol 2023; 14:1332973. [PMID: 38186654 PMCID: PMC10771287 DOI: 10.3389/fphar.2023.1332973] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2023] [Accepted: 12/04/2023] [Indexed: 01/09/2024] Open
Abstract
Objectives: We compared and ranked the efficacy and tolerability of multiple prophylactic treatments for vestibular migraine (VM), including β-blockers, calcium channel blockers, antiseizure medications, and antidepressants such as tricyclics and serotonin-noradrenaline reuptake inhibitors. Methods: PubMed, Web of Science, Embase, and Cochrane Center for Clinical Trials were systematically searched for relevant randomized clinical trials (RCTs) from March 2023 to May 2023. Studies on the efficacy and tolerability of prophylactic treatments for VM were included. Efficacy was measured using the average vertigo frequency per month and dizziness handicap inventory (DHI) improvement after 3-6 months of treatment. Tolerability was measured by the number of patients reporting at least one adverse event (AE). Network meta-analyses were performed according to a Bayesian framework and a random-effects model based on odds ratios or mean differences (MDs) and 95% confidence intervals (CIs). A sequence of ranking probability was calculated according to the surface under the cumulative ranking (SUCRA) curve. This network meta-analysis was previously registered with PROSPERO (CRD42023422258). Results: Five RCTs comprising 334 patients were analyzed by synthesizing the published evidence. Considering the examined prophylactic therapies, there is significant evidence that valproate acid (VPA) is superior to placebo or abortive treatment alone (MD = -4.12, 95% CI = -8.09, -0.15) in reducing the frequency of vertigo. Flunarizine (MD = 20.00, 95% CI = 10.90, 29.10), valproate acid (MD = 18.88, 95% CI = 10.42, 27.34), and venlafaxine (MD = 11.48, 95% CI = 9.84, 13.12) were significantly more effective than placebo or abortive treatment in reducing DHI. VPA most strongly reduced the frequency of vertigo according to SUCRA, but it ranked third-to-last in tolerability. Flunarizine ranked best in DHI improvement but worst in tolerability. Metoprolol ranked worst for efficacy but best for tolerability. Conclusion: VPA and flunarizine reduced the frequency of vertigo and improved DHI, but they had unfavorable tolerability. The effects of metoprolol on vertigo require further study. Given the low certainty and limited sample, additional head-to-head RCTs are warranted to further confirm efficacy. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/; Identifier CRD42023422258.
Collapse
Affiliation(s)
- Hongyuan Chu
- Department of Neurology, Peking University Aerospace School of Clinical Medicine (Aerospace Center Hospital), Beijing, China
- Department of Pediatrics, Peking University First Hospital, Beijing, China
| | - Yuru Wang
- Department of Neurology, Peking University Aerospace School of Clinical Medicine (Aerospace Center Hospital), Beijing, China
| | - Xia Ling
- Department of Neurology, Peking University First Hospital, Beijing, China
| | - Kangzhi Li
- Department of Neurology, Peking University Aerospace School of Clinical Medicine (Aerospace Center Hospital), Beijing, China
| | - Xu Yang
- Department of Neurology, Peking University Aerospace School of Clinical Medicine (Aerospace Center Hospital), Beijing, China
| |
Collapse
|
|
26
|
Oyedele GT, Adedara IA, Ikeji CN, Afolabi BA, Rocha JBT, Farombi EO. Metoprolol elicits neurobehavioral insufficiency and oxidative damage in nontarget Nauphoeta cinerea nymphs. ENVIRONMENTAL TOXICOLOGY 2023; 38:3006-3017. [PMID: 37584562 DOI: 10.1002/tox.23934] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/14/2023] [Revised: 07/24/2023] [Accepted: 08/01/2023] [Indexed: 08/17/2023]
Abstract
Metoprolol, a drug for hypertension and cardiovascular diseases, has become a contaminant of emerging concern because of its frequent detection in various environmental matrices globally. The dwindling in the biodiversity of useful insects owing to increasing presence of environmental chemicals is currently a great interest to the scientific community. In the current research, the toxicological impact of ecologically relevant concentrations of metoprolol at 0, 0.05, 0.1, 0.25, and 0.5 μg/L on Nauphoeta cinerea nymphs following exposure for 42 consecutive days was evaluated. The insects' behavior was analyzed with automated video-tracking software (ANY-maze, Stoelting Co, USA) while biochemical assays were done using the midgut, head and fat body. Metoprolol-exposed nymphs exhibited significant diminutions in the path efficiency, mobility time, distance traveled, body rotation, maximum speed and turn angle cum more episodes, and time of freezing. In addition, the heat maps and track plots confirmed the metoprolol-mediated wane in the exploratory and locomotor fitness of the insects. Compared with control, metoprolol exposure decreased acetylcholinesterase activity in insects head. Antioxidant enzymes activities and glutathione level were markedly decreased whereas indices of inflammation and oxidative injury to proteins and lipids were significantly increased in head, midgut and fat body of metoprolol-exposed insects. Taken together, metoprolol exposure induces neurobehavioral insufficiency and oxido-inflammatory injury in N. cinerea nymphs. These findings suggest the potential health effects of environmental contamination with metoprolol on ecologically and economically important nontarget insects.
Collapse
Affiliation(s)
- Gbemisola T Oyedele
- Drug Metabolism and Toxicology Research Laboratories, Department of Biochemistry, College of Medicine, University of Ibadan, Ibadan, Nigeria
| | - Isaac A Adedara
- Drug Metabolism and Toxicology Research Laboratories, Department of Biochemistry, College of Medicine, University of Ibadan, Ibadan, Nigeria
| | - Cynthia N Ikeji
- Drug Metabolism and Toxicology Research Laboratories, Department of Biochemistry, College of Medicine, University of Ibadan, Ibadan, Nigeria
| | - Blessing A Afolabi
- Department of Medical Biochemistry, College of Medicine and Health Sciences, Afe Babalola University, Ado Ekiti, Nigeria
| | - Joao B T Rocha
- Department of Biochemistry and Molecular Biology, Center for Natural and Exact Sciences (CCNE), Federal University of Santa Maria, Santa Maria, Brazil
| | - Ebenezer O Farombi
- Drug Metabolism and Toxicology Research Laboratories, Department of Biochemistry, College of Medicine, University of Ibadan, Ibadan, Nigeria
| |
Collapse
|
|
27
|
Ray S, Nair T, Sawhney J, Erwinanto, Rosman A, Reyes E, Go L, Sukonthasarn A, Ariyachaipanich A, Hung PM, Chaudhari H, Malhi HS. Role of β-blockers in the cardiovascular disease continuum: a collaborative Delphi survey-based consensus from Asia-Pacific. Curr Med Res Opin 2023; 39:1671-1683. [PMID: 37694536 DOI: 10.1080/03007995.2023.2256218] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2023] [Revised: 08/28/2023] [Accepted: 09/04/2023] [Indexed: 09/12/2023]
Abstract
OBJECTIVE This Delphi method of consensus was designed to develop scientific statements for β-blockers in the continuum of cardiovascular diseases with a special focus on the role of bisoprolol. METHODS Eleven experienced cardiologists from across the Asia-Pacific countries participated in two rounds of the survey. In the first round, experts were asked to rate agreement/disagreement with 35 statements across seven domains regarding the use of β-blockers for treating hypertension, heart failure, coronary artery diseases, co-morbidities, as well as their safety profile, usage pattern, and pharmacokinetic variability. A consensus for a statement could be reached with >70% agreement. RESULTS Except for seven statements, all attained consensus in the first round. In the second round that was conducted virtually, the experts re-appraised their ratings for the seven statements along with a critical appraisal of two additional statements that were suggested by experts in the preceding round. At the end of the second round, the final version included 36 statements (34 original statements, two statements suggested by experts, and the omission of one statement that did not attain consensus). The final version of statements in the second round was disseminated among experts for their approval followed by manuscript development. CONCLUSION Attainment of consensus for almost all statements reconfirms the clinical benefits of β-blockers, particularly β1-selective blockers for the entire spectrum of cardiovascular diseases.
Collapse
Affiliation(s)
- Saumitra Ray
- Department of Cardiology, AMRI Hospital (S), West Bengal, Kolkata, India
| | - Tiny Nair
- Department of Cardiology, PRS Hospital, Trivandrum, Kerala, India
| | - Jps Sawhney
- Department of Cardiology, Member Board of Management at Sir Ganga Ram Hospital, New Delhi, India
| | - Erwinanto
- Department of Cardiology and Vascular Medicine, Faculty of Medicine, Padjajaran University, Jawa Barat, Indonesia
| | | | - Eugene Reyes
- Section of Cardiology, Department of Internal Medicine, UP-Philippine General Hospital, Manila, Philippines
| | - Loewe Go
- Internal Medicine - Cardiology, St. Luke's Medical Center, Taguig, Philippines
| | | | - Aekarach Ariyachaipanich
- Division of Cardiovascular Medicine, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Phạm Manh Hung
- National Heart Institute, Bach Mai Hospital, Hanoi, Vietnam
| | - Harshal Chaudhari
- Merck Specialities Pvt. Ltd., India, an affiliate of Merck KGaA, Darmstadt, Germany
| | | |
Collapse
|
|
28
|
Ayenew B, Kumar P, Hussein A, Gashaw Y, Girma M, Ayalew A, Tadesse B. Heart failure drug classes and 30-day unplanned hospital readmission among patients with heart failure in Ethiopia. J Pharm Health Care Sci 2023; 9:49. [PMID: 38012803 PMCID: PMC10680257 DOI: 10.1186/s40780-023-00320-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2023] [Accepted: 11/20/2023] [Indexed: 11/29/2023] Open
Abstract
BACKGROUND Drug therapy is a crucial aspect of heart failure management and has been shown to reduce morbidity and mortality in heart failure patients. However, the comparative effects of these drug classes on readmission rates have not been well studied. Therefore, the aim of this study was to examine the association between different classes of heart failure drugs and 30-day readmission rates in patients with heart failure. METHOD A multicenter, hospital-based retrospective cohort design was employed and 572 randomly selected patients with heart failure were included. Data were entered in Epi-data version 4.6 and analyzed with STATA version 17. Kaplan-Meier and log-rank tests were used to estimate and compare survival time. A Cox proportional hazard model was utilized, employing both bi-variable and multi-variable analyses, to examine the effect of predictors on the timing of unplanned hospital readmissions. The strength of the association was assessed using an adjusted hazard ratio (aHR), and statistical significance was declared for p-values < 0.05 and a 95% confidence interval (CI). RESULTS In this study, a total of 151 (26.40%) heart failure patients were readmitted within 30 days of discharge. In the multivariate cox proportional hazards analysis being an age (> 65 year) (AHR: 2.34, 95%CI: 1.63, 3.37), rural in residency (AHR: 1.85, 95%CI: 1.07, 3.20), hospital stays > 7 Days (AHR: 3.68, 95%CI: 2.51,5.39), discharge with Diuretics (AHR: 2.37, 95%CI: 1.45, 3.86), and discharge with Beta-Blocker (AHR: 0.48, 95%CI: 0 0.34, 0.69) were identified as independent predictors of unplanned hospital readmission. CONCLUSION Elderly patients, being in rural areas, longer hospital stays, and discharges of patients on diuretics and not on beta-blockers were independent predictors of unplanned hospital readmission. Therefore, working on these factors will help to reduce the hazard of unplanned hospital readmissions, improve patient outcomes, and increase the efficiency of heart failure management.
Collapse
Affiliation(s)
- Birhanu Ayenew
- Department of Adult Health Nursing, College of Health Science, Assosa University, Assosa, Ethiopia.
| | - Prem Kumar
- Department of Adult Health Nursing, College of Medicine and Health Science, Wollo University, Dessie, Ethiopia
| | - Adem Hussein
- Department of Adult Health Nursing, College of Medicine and Health Science, Wollo University, Dessie, Ethiopia
| | - Yegoraw Gashaw
- Department of Pediatric and Child Health Nursing, College of Health Science, Assosa University, Assosa, Ethiopia
| | - Mitaw Girma
- Department of Comprehensive Health Nursing, College of Medicine & Health Sciences, Wollo University, Dessie, Ethiopia
| | - Abdulmelik Ayalew
- Department of Adult Health Nursing, College of Medicine and Health Science, Wollo University, Dessie, Ethiopia
| | - Beza Tadesse
- Department of Adult Health Nursing, College of Medicine and Health Science, Wollo University, Dessie, Ethiopia
| |
Collapse
|
|
29
|
Haddiya I, Valoti S. Current Knowledge of Beta-Blockers in Chronic Hemodialysis Patients. Int J Nephrol Renovasc Dis 2023; 16:223-230. [PMID: 37849744 PMCID: PMC10578177 DOI: 10.2147/ijnrd.s414774] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2023] [Accepted: 09/29/2023] [Indexed: 10/19/2023] Open
Abstract
Beta-blockers include a large spectrum of drugs with various specific characteristics, and a well-known cardioprotective efficacy. They are recommended in heart failure, hypertension and arrhythmia. Their use in chronic hemodialysis patients is still controversial, mainly because of the lack of specific randomized clinical trials. Large observational studies and two important clinical trials have reported almost unanimously their efficacy in chronic hemodialysis patients, which seems to be related to their levels of dialyzability and cardioselectivity. A recent meta-analysis suggested that high dialyzable beta-blockers are correlated to a reduced risk of all-cause mortality and cardiovascular complications compared with low dialyzable beta-blockers. Despite their benefits, beta-blockers may have adverse effects, such as intradialytic hypotension with low dialyzability beta-blockers or the risk of sub-therapeutic plasma concentration of high dialyzable ones during dialysis sessions. Both cases are linked to adverse cardiovascular events. A solution for both high and low dialyzable drugs could be their administration after dialysis sessions. Futhermore, the bulk of existing literature seems to favor cardioselective beta-blockers with moderate-to-high dialyzability as the ideal agents in dialysis patients, but further, larger studies are needed. This review aims to analyze beta-blockers' characteristics, indications and evidence-based role in chronic hemodialysis patients.
Collapse
Affiliation(s)
- Intissar Haddiya
- Department of Nephrology, Faculty of Medicine and Pharmacy, University Mohamed Premier, Oujda, Morocco
- Laboratory of Epidemiology, Clinical Research and Public Health, Faculty of Medicine and Pharmacy, University Mohamed Premier, Oujda, Morocco
| | - Siria Valoti
- Department of Medicine, Faculty of Medicine, Università degli Studi di Milano Statale, Milano, Italia
| |
Collapse
|
|
30
|
Martinez A, Lakkimsetti M, Maharjan S, Aslam MA, Basnyat A, Kafley S, Reddy SS, Ahmed SS, Razzaq W, Adusumilli S, Khawaja UA. Beta-Blockers and Their Current Role in Maternal and Neonatal Health: A Narrative Review of the Literature. Cureus 2023; 15:e44043. [PMID: 37746367 PMCID: PMC10517705 DOI: 10.7759/cureus.44043] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2023] [Accepted: 08/24/2023] [Indexed: 09/26/2023] Open
Abstract
Beta-blockers are a class of medications that act on beta-adrenergic receptors and are categorized as cardio-selective and non-selective. They are principally used to treat cardiovascular conditions such as hypertension and arrhythmias. Beta-blockers have also been used to treat non-cardiogenic indications in non-pregnant individuals and the pediatric population. In pregnancy, labetalol is the mainstay treatment for hypertension and other cardiovascular indications. However, contraindications to certain sub-types of beta-blockers include bradycardia, heart failure, obstructive lung diseases, and hemodynamic instability. There is conflicting evidence of the adverse effects on fetal and neonatal health due to a scarce safety and efficacy profile, and further studies are necessary to understand the pharmacokinetics of the different classes of beta-blockers in pregnancy and fetal health. Understanding the hemodynamic changes during the stages of pregnancy is important to target a more beneficial therapy for both mother and fetus as well as better neonatal outcomes. Beta-blocker use in the pediatric population is less documented in studies but does have the potential to treat various cardiogenic and non-cardiogenic conditions. Future comprehensive studies would further benefit the direction of beta-blocker treatment during pregnancy in neonates and pediatrics.
Collapse
Affiliation(s)
- Andrea Martinez
- Medical School, Universidad Autonoma de Guadalajara, Zapopan, MEX
| | | | - Sameep Maharjan
- General Practice, Patan Academy of Health Sciences, Kathmandu, NPL
| | - Muhammad Ammar Aslam
- Medical School, Sargodha Medical College, University of Health Sciences, Sargodha, PAK
| | - Anouksha Basnyat
- General Practice, Hospital for Advanced Medicine & Surgery (HAMS), Kathmandu, NPL
| | - Shashwat Kafley
- Medical School, Enam Medical College and Hospital, Dhaka, BGD
| | | | - Saima S Ahmed
- Vascular Surgery, Dow International Medical College, Karachi, PAK
| | - Waleed Razzaq
- Internal Medicine, Services Hospital Lahore, Lahore, PAK
| | | | | |
Collapse
|
|
31
|
Li J, Liao R, Zhang S, Weng H, Liu Y, Tao T, Yu F, Li G, Wu J. Promising remedies for cardiovascular disease: Natural polyphenol ellagic acid and its metabolite urolithins. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2023; 116:154867. [PMID: 37257327 DOI: 10.1016/j.phymed.2023.154867] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/27/2022] [Revised: 04/17/2023] [Accepted: 05/08/2023] [Indexed: 06/02/2023]
Abstract
BACKGROUND Cardiovascular disease (CVD) is a significant worldwide factor contributing to human fatality and morbidity. With the increase of incidence rates, it is of concern that there is a lack of current therapeutic alternatives because of multiple side effects. Ellagic acid (EA), the natural polyphenol (C14H6O8), is abundant in pomegranates, berries, and nuts. EA and its intestinal microflora metabolite, urolithins, have recently attracted much attention as a potential novel "medicine" because of their wide pharmacological properties. PURPOSE This study aimed to critically analyze available literature to summarize the beneficial effects of EA and urolithins, and highlights their druggability and therapeutic potential in various CVDs. METHODS We systematically studied research and review articles between 1984 and 2022 available on various databases to obtain the data on EA and urolithins with no language restriction. Their cardiovascular protective activities, underlying mechanism, and druggability were highlighted and discussed comprehensively. RESULTS We found that EA and urolithins may exert preventive and curative effects on CVD with negligible side effects and possibly regulate lipid metabolism imbalance, pro-inflammatory factor production, vascular smooth muscle cell proliferation, cardiomyocyte apoptosis, endothelial cell dysfunction, and Ca2+ intake and release. Potentially, this may lead to the prevention and amelioration of atherosclerosis, hypertension, myocardial infarction, cardiac fibrosis, cardiomyopathy, cardiac arrhythmias, and cardiotoxicities in vivo. Several molecules and signaling pathways are associated with their therapeutic actions, including phosphatidylinositol 3-kinase/protein kinase B, mitogen-activated protein kinase, NF-κB, nuclear factor erythroid-2 related factor 2, sirtuin1, miRNA, and extracellular signal-regulated kinase 1/2. CONCLUSION In vitro and in vivo studies shows that EA and urolithins could be used as valid candidates for early prevention and effective therapeutic strategies for various CVDs.
Collapse
Affiliation(s)
- Jingyan Li
- Cardiovascular Surgery Department, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China; Sichuan Key Medical Laboratory of New Drug Discovery and Drugability Evaluation, Luzhou Key Laboratory of Activity Screening and Drugability Evaluation for Chinese Materia Medica, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan 646000, China; Key Laboratory of Medical Electrophysiology, Ministry of Education and Medical Electrophysiological Key Laboratory of Sichuan Province, Collaborative Innovation Center for Prevention of Cardiovascular Diseases, Institute of Cardiovascular Research, Southwest Medical University, Luzhou, Sichuan, China
| | - Ruixue Liao
- Sichuan Key Medical Laboratory of New Drug Discovery and Drugability Evaluation, Luzhou Key Laboratory of Activity Screening and Drugability Evaluation for Chinese Materia Medica, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan 646000, China
| | - Shijia Zhang
- School of Pharmacy, Xuzhou Medical University, Xuzhou 221000, China
| | - Huimin Weng
- Cardiovascular Surgery Department, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China
| | - Yuanzhi Liu
- Cardiovascular Surgery Department, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China; Sichuan Key Medical Laboratory of New Drug Discovery and Drugability Evaluation, Luzhou Key Laboratory of Activity Screening and Drugability Evaluation for Chinese Materia Medica, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan 646000, China
| | - Tianyi Tao
- Key Laboratory of Medical Electrophysiology, Ministry of Education and Medical Electrophysiological Key Laboratory of Sichuan Province, Collaborative Innovation Center for Prevention of Cardiovascular Diseases, Institute of Cardiovascular Research, Southwest Medical University, Luzhou, Sichuan, China
| | - Fengxu Yu
- Cardiovascular Surgery Department, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China.
| | - Guang Li
- Key Laboratory of Medical Electrophysiology, Ministry of Education and Medical Electrophysiological Key Laboratory of Sichuan Province, Collaborative Innovation Center for Prevention of Cardiovascular Diseases, Institute of Cardiovascular Research, Southwest Medical University, Luzhou, Sichuan, China.
| | - Jianming Wu
- Sichuan Key Medical Laboratory of New Drug Discovery and Drugability Evaluation, Luzhou Key Laboratory of Activity Screening and Drugability Evaluation for Chinese Materia Medica, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan 646000, China; School of Basic Medical Sciences, Southwest Medical University, Luzhou, China.
| |
Collapse
|
|
32
|
Ferretti A, Gatto M, Velardi M, Di Nardo G, Foiadelli T, Terrin G, Cecili M, Raucci U, Valeriani M, Parisi P. Migraine, Allergy, and Histamine: Is There a Link? J Clin Med 2023; 12:3566. [PMID: 37240671 PMCID: PMC10218803 DOI: 10.3390/jcm12103566] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2023] [Revised: 05/14/2023] [Accepted: 05/17/2023] [Indexed: 05/28/2023] Open
Abstract
The relationship between migraines and allergies is controversial. Though they are epidemiologically linked, the underlying pathophysiological connection between them remains unclear. Migraines and allergic disorders have various underlying genetic and biological causes. As per the literature, these conditions are epidemiologically linked, and some common pathophysiological pathways have been hypothesized. The histaminergic system may be the clue to understanding the correlation among these diseases. As a neurotransmitter in the central nervous system with a vasodilatory effect, histamine has a well-documented influence on the allergic response and could be involved in the pathophysiology of migraines. Histamine may influence hypothalamic activity, which may play a major role in migraines or may simply influence their severity. In both cases, antihistamine drugs could prove useful. This review examines whether the histaminergic system, particularly H3 and H4 receptors, may provide a mechanistic link between the pathophysiology of migraines and allergic disorders, two common and debilitating conditions. Identifying their connection could help identify novel therapeutic strategies.
Collapse
Affiliation(s)
- Alessandro Ferretti
- Pediatrics Unit, Neuroscience, Mental Health and Sense Organs (NESMOS) Department, Faculty of Medicine and Psychology, Sapienza University of Rome, 00189 Rome, Italy
| | - Mattia Gatto
- Child Neurology and Psychiatry Unit, Systems Medicine Department, Tor Vergata University of Rome, 00133 Rome, Italy
| | - Margherita Velardi
- General and Emergency Department, Bambino Gesù Children’s Hospital, Istituto di Ricerca e Cura a Carattere Scientifico, 00165 Rome, Italy
| | - Giovanni Di Nardo
- Pediatrics Unit, Neuroscience, Mental Health and Sense Organs (NESMOS) Department, Faculty of Medicine and Psychology, Sapienza University of Rome, 00189 Rome, Italy
| | - Thomas Foiadelli
- Pediatric Clinic, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy
| | - Gianluca Terrin
- Department of Mother and Child, Gynecological and Urological Sciences, Faculty of Medicine and Dentistry, Sapienza University of Rome, 00185 Rome, Italy
| | - Manuela Cecili
- Pediatrics Unit, Neuroscience, Mental Health and Sense Organs (NESMOS) Department, Faculty of Medicine and Psychology, Sapienza University of Rome, 00189 Rome, Italy
| | - Umberto Raucci
- General and Emergency Department, Bambino Gesù Children’s Hospital, Istituto di Ricerca e Cura a Carattere Scientifico, 00165 Rome, Italy
| | - Massimiliano Valeriani
- Developmental Neurology Unit, Bambino Gesù Children’s Hospital, Istituto di Ricerca e Cura a Carattere Scientifico, 00165 Rome, Italy
| | - Pasquale Parisi
- Pediatrics Unit, Neuroscience, Mental Health and Sense Organs (NESMOS) Department, Faculty of Medicine and Psychology, Sapienza University of Rome, 00189 Rome, Italy
| |
Collapse
|
|
33
|
Farhoumand LS, Liu H, Tsimpaki T, Hendgen-Cotta UB, Rassaf T, Bechrakis NE, Fiorentzis M, Berchner-Pfannschmidt U. Blockade of ß-Adrenergic Receptors by Nebivolol Enables Tumor Control Potential for Uveal Melanoma in 3D Tumor Spheroids and 2D Cultures. Int J Mol Sci 2023; 24:ijms24065894. [PMID: 36982966 PMCID: PMC10054088 DOI: 10.3390/ijms24065894] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2023] [Revised: 03/07/2023] [Accepted: 03/17/2023] [Indexed: 03/30/2023] Open
Abstract
Uveal melanoma (UM) is the most common primary cancer of the eye in adults. A new systemic therapy is needed to reduce the high metastasis and mortality rate. As β-blockers are known to have anti-tumor effects on various cancer entities, this study focuses on investigating the effect of β1-selective blockers atenolol, celiprolol, bisoprolol, metoprolol, esmolol, betaxolol, and in particular, nebivolol on UM. The study was performed on 3D tumor spheroids as well as 2D cell cultures, testing tumor viability, morphological changes, long-term survival, and apoptosis. Flow cytometry revealed the presence of all three β-adrenoceptors with a dominance of β2-receptors on cell surfaces. Among the blockers tested, solely nebivolol concentration-dependently decreased viability and altered 3D tumor spheroid structure. Nebivolol blocked the repopulation of cells spreading from 3D tumor spheroids, indicating a tumor control potential at a concentration of ≥20 µM. Mechanistically, nebivolol induced ATP depletion and caspase-3/7 activity, indicating that mitochondria-dependent signaling is involved. D-nebivolol or nebivolol combined with the β2-antagonist ICI 118.551 displayed the highest anti-tumor effects, suggesting a contribution of both β1- and β2-receptors. Thus, the present study reveals the tumor control potential of nebivolol in UM, which may offer a perspective for co-adjuvant therapy to reduce recurrence or metastasis.
Collapse
Affiliation(s)
- Lina S Farhoumand
- Eye Research Lab, Department of Ophthalmology, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany
| | - Hongtao Liu
- Eye Research Lab, Department of Ophthalmology, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany
| | - Theodora Tsimpaki
- Eye Research Lab, Department of Ophthalmology, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany
| | - Ulrike B Hendgen-Cotta
- CardioScience Labs, Department of Cardiology and Vascular Medicine, West German Heart and Vascular Center, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany
| | - Tienush Rassaf
- CardioScience Labs, Department of Cardiology and Vascular Medicine, West German Heart and Vascular Center, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany
| | - Nikolaos E Bechrakis
- Eye Research Lab, Department of Ophthalmology, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany
| | - Miltiadis Fiorentzis
- Eye Research Lab, Department of Ophthalmology, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany
| | - Utta Berchner-Pfannschmidt
- Eye Research Lab, Department of Ophthalmology, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany
| |
Collapse
|
|
34
|
Pilipović I, Stojić-Vukanić Z, Leposavić G. Adrenoceptors as potential target for add-on immunomodulatory therapy in multiple sclerosis. Pharmacol Ther 2023; 243:108358. [PMID: 36804434 DOI: 10.1016/j.pharmthera.2023.108358] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2022] [Revised: 02/03/2023] [Accepted: 02/13/2023] [Indexed: 02/17/2023]
Abstract
This review summarizes recent findings related to the role of the sympathetic nervous system (SNS) in pathogenesis of multiple sclerosis (MS) and its commonly used experimental model - experimental autoimmune encephalomyelitis (EAE). They indicate that noradrenaline, the key end-point mediator of the SNS, acting through β-adrenoceptor, has a contributory role in the early stages of MS/EAE development. This stage is characterized by the SNS hyperactivity (increased release of noradrenaline) reflecting the net effect of different factors, such as the disease-associated inflammation, stress, vitamin D hypovitaminosis, Epstein-Barr virus infection and dysbiosis. Thus, the administration of propranolol, a non-selective β-adrenoceptor blocker, readily crossing the blood-brain barrier, to experimental rats before the autoimmune challenge and in the early (preclinical/prodromal) phase of the disease mitigates EAE severity. This phenomenon has been ascribed to the alleviation of neuroinflammation (due to attenuation of primarily microglial activation/proinflammatory functions) and the diminution of the magnitude of the primary CD4+ T-cell autoimmune response (the effect associated with impaired autoantigen uptake by antigen presenting cells and their migration into draining lymph nodes). The former is partly related to breaking of the catecholamine-dependent self-amplifying microglial feed-forward loop and the positive feedback loop between microglia and the SNS, leading to down-regulation of the SNS hyperactivity and its enhancing influence on microglial activation/proinflammatory functions and the magnitude of autoimmune response. The effects of propranolol are shown to be more prominent in male EAE animals, the phenomenon important as males (like men) are likely to develop clinically more severe disease. Thus, these findings could serve as a firm scientific background for formulation of a new sex-specific immune-intervention strategy for the early phases of MS (characterized by the SNS hyperactivity) exploiting anti-(neuro)inflammatory and immunomodulatory properties of propranolol and other relatively cheap and safe adrenergic drugs with similar therapeutic profile.
Collapse
Affiliation(s)
- Ivan Pilipović
- Institute of Virology, Vaccines and Sera "Torlak", Belgrade, Serbia
| | - Zorica Stojić-Vukanić
- University of Belgrade-Faculty of Pharmacy, Department of Microbiology and Immunology, Belgrade, Serbia
| | - Gordana Leposavić
- University of Belgrade-Faculty of Pharmacy, Department of Pathobiology, Belgrade, Serbia.
| |
Collapse
|
|
35
|
Yan X, Liu P, Li D, Hu R, Tao M, Zhu S, Wu W, Yang M, Qu X. Novel evidence for the prognostic impact of β-blockers in solid cancer patients receiving immune checkpoint inhibitors. Int Immunopharmacol 2022; 113:109383. [DOI: 10.1016/j.intimp.2022.109383] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2022] [Revised: 09/12/2022] [Accepted: 10/19/2022] [Indexed: 11/05/2022]
|
|
36
|
The Central Nervous Mechanism of Stress-Promoting Cancer Progression. Int J Mol Sci 2022; 23:ijms232012653. [PMID: 36293510 PMCID: PMC9604265 DOI: 10.3390/ijms232012653] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2022] [Revised: 10/16/2022] [Accepted: 10/17/2022] [Indexed: 11/07/2022] Open
Abstract
Evidence shows that stress can promote the occurrence and development of tumors. In recent years, many studies have shown that stress-related hormones or peripheral neurotransmitters can promote the proliferation, survival, and angiogenesis of tumor cells and impair the body’s immune response, causing tumor cells to escape the “surveillance” of the immune system. However, the perception of stress occurs in the central nervous system (CNS) and the role of the central nervous system in tumor progression is still unclear, as are the underlying mechanisms. This review summarizes what is known of stress-related CNS-network activation during the stress response and the influence of the CNS on tumors and discusses available adjuvant treatment methods for cancer patients with negative emotional states, such as anxiety and depression.
Collapse
|
|
37
|
Romigi A. Deprescribing antihypertensive drugs after starting OSA primary therapy: “first do no net harm?”. Sleep 2022; 45:6634036. [DOI: 10.1093/sleep/zsac138] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Affiliation(s)
- Andrea Romigi
- Sleep Medicine Center IRCCS Neuromed , Pozzilli (IS) , Italy
| |
Collapse
|
|
38
|
Kidoguchi S, Sugano N, Yokoo T, Kaneko H, Akazawa H, Mukai M, Node K, Yano Y, Nishiyama A. Antihypertensive Drugs and Cancer Risk. Am J Hypertens 2022; 35:767-783. [PMID: 35595533 DOI: 10.1093/ajh/hpac066] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2022] [Revised: 03/24/2022] [Accepted: 05/18/2022] [Indexed: 02/07/2023] Open
Abstract
Hypertension is the most prevalent comorbidity in cancer patients. Consequently, many cancer patients are prescribed antihypertensive drugs before cancer diagnosis or during cancer treatment. However, whether antihypertensive drugs affect the incidence, treatment efficacy, or prognosis of cancer remains unanswered. For instance, renin-angiotensin and β-adrenergic signaling may be involved not only in blood pressure elevation but also in cell proliferation, angiogenesis, and tissue invasion. Therefore, the inhibition of these pathways may have beneficial effects on cancer prevention or treatment. In this article, we reviewed several studies regarding antihypertensive drugs and cancer. In particular, we focused on the results of clinical trials to evaluate whether the use of antihypertensive drugs affects future cancer risk and prognosis. Unfortunately, the results are somewhat inconsistent, and evidence demonstrating the effect of antihypertensive drugs remains limited. We indicate that the heterogeneity in the study designs makes it difficult to clarify the causal relationship between antihypertensive drugs and cancer. We also propose that additional experimental studies, including research with induced pluripotent cells derived from cancer patients, single-cell analyses of cancer cell clusters, and clinical studies using artificial intelligence electronic health record systems, might be helpful to reveal the precise association between antihypertensive drugs and cancer risk.
Collapse
Affiliation(s)
- Satoshi Kidoguchi
- Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan.,Department of Pharmacology, Faculty of Medicine, Kagawa University, Kagawa, Japan
| | - Naoki Sugano
- Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
| | - Takashi Yokoo
- Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
| | - Hidehiro Kaneko
- Department of Cardiovascular Medicine, The University of Tokyo, Tokyo, Japan.,Department of Advanced Cardiology, The University of Tokyo, Tokyo, Japan
| | - Hiroshi Akazawa
- Department of Cardiovascular Medicine, The University of Tokyo, Tokyo, Japan
| | - Mikio Mukai
- Osaka Prefectural Hospital Organization, Osaka International Cancer Institute, Department of Medical Check-up, Osaka, Japan
| | - Koichi Node
- Department of Cardiovascular Medicine, Saga University, Saga, Japan
| | - Yuichiro Yano
- Department of Advanced Epidemiology, NCD Epidemiology Research Center, Shiga University of Medical Science, Shiga, Japan
| | - Akira Nishiyama
- Department of Pharmacology, Faculty of Medicine, Kagawa University, Kagawa, Japan
| | | |
Collapse
|
|
39
|
Silverio A, Parodi G, Scudiero F, Bossone E, Di Maio M, Vriz O, Bellino M, Zito C, Provenza G, Radano I, Baldi C, D'Andrea A, Novo G, Mauro C, Rigo F, Innelli P, Salerno-Uriarte J, Cameli M, Vecchione C, Antonini Canterin F, Galasso G, Citro R. Beta-blockers are associated with better long-term survival in patients with Takotsubo syndrome. Heart 2022; 108:1369-1376. [PMID: 35361673 DOI: 10.1136/heartjnl-2021-320543] [Citation(s) in RCA: 29] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/04/2021] [Accepted: 03/07/2022] [Indexed: 12/11/2022] Open
Abstract
OBJECTIVE The advantage of beta-blockers has been postulated in patients with Takotsubo syndrome (TTS) given the pathophysiological role of catecholamines. We hypothesised that beta-blocker treatment after discharge may improve the long-term clinical outcome in this patient population. METHODS This was an observational, multicentre study including consecutive patients with TTS diagnosis prospectively enrolled in the Takotsubo Italian Network (TIN) register from January 2007 to December 2018. TTS was diagnosed according to the TIN, Heart Failure Association and InterTAK Diagnostic Criteria. The primary study outcome was the occurrence of all-cause death at the longest available follow-up; secondary outcomes were TTS recurrence, cardiac and non-cardiac death. RESULTS The study population included 825 patients (median age: 72.0 (63.0-78.0) years; 91.9 % female): 488 (59.2%) were discharged on beta-blockers and 337 (40.8%) without beta-blockers. The median follow-up was 24.0 months. The adjusted Cox regression analysis showed a significantly lower risk for all-cause death (adjusted HR: 0.563; 95% CI: 0.356 to 0.889) and non-cardiac death (adjusted HR: 0.525; 95% CI: 0.309 to 0.893) in patients receiving versus those not receiving beta-blockers, but no significant differences in terms of TTS recurrence (adjusted HR: 0.607; 95% CI: 0.311 to 1.187) and cardiac death (adjusted HR: 0.699; 95% CI: 0.284 to 1.722). The positive survival effect of beta-blockers was higher in patients with hypertension than in those without (pinteraction=0.014), and in patients who developed cardiogenic shock during the acute phase than in those who did not (pinteraction=0.047). CONCLUSIONS In this real-world register population, beta-blockers were associated with a significantly higher long-term survival, particularly in patients with hypertension and in those who developed cardiogenic shock during the acute phase.
Collapse
Affiliation(s)
- Angelo Silverio
- Department of Medicine, Surgery and Dentistry, University of Salerno, Baronissi (Salerno), Italy
| | - Guido Parodi
- Department of Cardiology, ASL4 Liguria, Lavagna, Italy
| | - Fernando Scudiero
- Cardiology Department, Azienda Ospedaliera Bolognini Seriate, Seriate, Italy
| | - Eduardo Bossone
- Department of Cardiology, Antonio Cardarelli Hospital, Naples, Italy
| | - Marco Di Maio
- Department of Medicine, Surgery and Dentistry, University of Salerno, Baronissi (Salerno), Italy
| | - Olga Vriz
- Cardiology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
| | - Michele Bellino
- Department of Medicine, Surgery and Dentistry, University of Salerno, Baronissi (Salerno), Italy
| | - Concetta Zito
- Department of Clinical and Experimental Medicine - Cardiology, University of Messina, Messina, Italy
| | - Gennaro Provenza
- Cardiovascular Department, Azienda Ospedaliera Universitaria 'San Giovanni di Dio e Ruggi d'Aragona', Salerno, Italy
| | - Ilaria Radano
- Cardiovascular Department, Azienda Ospedaliera Universitaria 'San Giovanni di Dio e Ruggi d'Aragona', Salerno, Italy
| | - Cesare Baldi
- Cardiovascular Department, Azienda Ospedaliera Universitaria 'San Giovanni di Dio e Ruggi d'Aragona', Salerno, Italy
| | | | - Giuseppina Novo
- Dipartimento di Promozione della Salute, Materno-Infantile, di Medicina Interna e Specialistica di Eccellenza (PROMISE), Università degli Studi di Palermo, Palermo, Italy
| | - Ciro Mauro
- Department of Cardiology, Antonio Cardarelli Hospital, Naples, Italy
| | - Fausto Rigo
- Department of Cardiology, Ospedale dell'Angelo Mestre-Venice, Mestre, Italy
| | - Pasquale Innelli
- Department of Cardiovascular Imaging, San Carlo Hospital, Potenza, Italy
| | | | - Matteo Cameli
- Department of Medical Biotechnologies, University of Siena, Siena, Italy
| | - Carmine Vecchione
- Department of Medicine, Surgery and Dentistry, University of Salerno, Baronissi (Salerno), Italy
- Vascular Physiopathology Unit, IRCCS Neuromed, Pozzilli, Italy
| | - Francesco Antonini Canterin
- Department of Cardiology, High Specialization Rehabilitation Hospital Motta di Livenza, Motta di Livenza, Italy
| | - Gennaro Galasso
- Department of Medicine, Surgery and Dentistry, University of Salerno, Baronissi (Salerno), Italy
| | - Rodolfo Citro
- Cardiovascular Department, Azienda Ospedaliera Universitaria 'San Giovanni di Dio e Ruggi d'Aragona', Salerno, Italy
- Vascular Physiopathology Unit, IRCCS Neuromed, Pozzilli, Italy
| |
Collapse
|
|
40
|
Rossi M, Talbot J, Piris P, Grand ML, Montero MP, Matteudi M, Agavnian-Couquiaud E, Appay R, Keime C, Williamson D, Buric D, Bourgarel V, Padovani L, Clifford SC, Ayrault O, Pasquier E, André N, Carré M. Beta-blockers disrupt mitochondrial bioenergetics and increase radiotherapy efficacy independently of beta-adrenergic receptors in medulloblastoma. EBioMedicine 2022; 82:104149. [PMID: 35816899 PMCID: PMC9283511 DOI: 10.1016/j.ebiom.2022.104149] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2022] [Revised: 06/20/2022] [Accepted: 06/22/2022] [Indexed: 11/03/2022] Open
Abstract
Background Medulloblastoma is the most frequent brain malignancy of childhood. The current multimodal treatment comes at the expense of serious and often long-lasting side effects. Drug repurposing is a strategy to fast-track anti-cancer therapy with low toxicity. Here, we showed the ability of β-blockers to potentiate radiotherapy in medulloblastoma with bad prognosis. Methods Medulloblastoma cell lines, patient-derived xenograft cells, 3D spheroids and an innovative cerebellar organotypic model were used to identify synergistic interactions between β-blockers and ionising radiations. Gene expression profiles of β-adrenergic receptors were analysed in medulloblastoma samples from 240 patients. Signaling pathways were explored by RT-qPCR, RNA interference, western blotting and RNA sequencing. Medulloblastoma cell bioenergetics were evaluated by measuring the oxygen consumption rate, the extracellular acidification rate and superoxide production. Findings Low concentrations of β-blockers significantly potentiated clinically relevant radiation protocols. Although patient biopsies showed detectable expression of β-adrenergic receptors, the ability of the repurposed drugs to potentiate ionising radiations did not result from the inhibition of the canonical signaling pathway. We highlighted that the efficacy of the combinatorial treatment relied on a metabolic catastrophe that deprives medulloblastoma cells of their adaptive bioenergetics capacities. This led to an overproduction of superoxide radicals and ultimately to an increase in ionising radiations-mediated DNA damages. Interpretation These data provide the evidence of the efficacy of β-blockers as potentiators of radiotherapy in medulloblastoma, which may help improve the treatment and quality of life of children with high-risk brain tumours. Funding This study was funded by institutional grants and charities.
Collapse
|
|
41
|
He Y, Zhu R, Cai Y, Zhang Y, Zhang Y, Pan S, Schneider RJ, Zhang Y. Transcriptomics and protein biomarkers reveal the detoxifying mechanisms of UV radiation for nebivolol toward zebrafish (Danio rerio) embryos/larvae. AQUATIC TOXICOLOGY (AMSTERDAM, NETHERLANDS) 2022; 249:106241. [PMID: 35868139 DOI: 10.1016/j.aquatox.2022.106241] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/11/2021] [Revised: 06/20/2022] [Accepted: 07/11/2022] [Indexed: 06/15/2023]
Abstract
Nebivolol (NEB), a β-blocker frequently used to treat cardiovascular diseases, has been widely detected in aquatic environments, and can be degraded under exposure to UV radiation, leading to the formation of certain transformation products (UV-TPs). Thus, the toxic effects of NEB and its UV-TPs on aquatic organisms are of great importance for aquatic ecosystems. In the present study, the degradation pathway of NEB under UV radiation was investigated. Subsequently, zebrafish embryos/larvae were used to assess the median lethal concentration (LC50) of NEB, and to clarify the sub-lethal effects of NEB and its UV-TPs for the first time. It was found that UV radiation could reduce the toxic effects of NEB on the early development of zebrafish. Transcriptomic analysis identified the top 20 enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways in zebrafish larvae exposed to NEB, most of which were associated with the antioxidant, nervous, and immune systems. The number of differentially expressed genes (DEGs) in the pathways were reduced after UV radiation. Furthermore, the analysis of protein biomarkers, including CAT and GST (antioxidant response), AChE and ACh (neurotoxicity), CRP and LYS (immune response), revealed that NEB exposure reduced the activity of these biomarkers, whereas UV radiation could alleviate the effects. The present study provides initial insights into the mechanisms underlying toxic effects of NEB and the detoxification effects of UV radiation on the early development of zebrafish. It highlights the necessity of considering the toxicity of UV-TPs when evaluating the toxicity of emerging pollutants in aquatic systems.
Collapse
Affiliation(s)
- Yide He
- School of Environmental Science and Engineering, Nanjing Tech University, Nanjing 211800, PR China.
| | - Rongwen Zhu
- School of Environmental Science and Engineering, Nanjing Tech University, Nanjing 211800, PR China
| | - Yujie Cai
- School of Environmental Science and Engineering, Nanjing Tech University, Nanjing 211800, PR China
| | - Yiqun Zhang
- School of Environmental Science and Engineering, Nanjing Tech University, Nanjing 211800, PR China
| | - Yunhai Zhang
- School of Environmental Science and Engineering, Nanjing Tech University, Nanjing 211800, PR China
| | - Shunlong Pan
- School of Environmental Science and Engineering, Nanjing Tech University, Nanjing 211800, PR China
| | - Rudolf J Schneider
- BAM Federal Institute for Materials Research and Testing, Richard-Willstaetter -Str. 11, Berlin D-12489, Germany
| | - Yongjun Zhang
- School of Environmental Science and Engineering, Nanjing Tech University, Nanjing 211800, PR China.
| |
Collapse
|
|
42
|
Melhado EM, Santos PSF, Kaup AO, da Costa ATNM, Roesler CADP, Piovesan ÉJ, Sarmento EM, Theotonio GOM, de Campos HC, Fortini I, de Souza JA, Maciel JA, Segundo JBA, de Carvalho JJF, Speziali JG, Calia LC, Barea LM, Queiroz LP, Souza MNP, Figueiredo MRCF, Costa MENDM, Peres MFP, Jurno ME, Peixoto PM, Kowacs PA, Rocha-Filho PAS, Moreira PF, Silva-Neto RP, Fragoso YD. Consensus of the Brazilian Headache Society (SBCe) for the Prophylactic Treatment of Episodic Migraine: part I. ARQUIVOS DE NEURO-PSIQUIATRIA 2022; 80:845-861. [PMID: 36252594 PMCID: PMC9703891 DOI: 10.1055/s-0042-1756441] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
The Brazilian Headache Society (Sociedade Brasileira de Cefaleia, SBCe, in Portuguese) nominated a Committee of Authors with the aim of establishing a consensus with recommendations regarding prophylactic treatment for episodic migraine based on articles published in the worldwide literature, as well as personal experience. Migraine affects 1 billion people around the world and more than 30 million Brazilians. In addition, it is an underdiagnosed and undertreated disorder. It is well known within the medical community of neurologists, and especially among headache specialists, that there is a need to disseminate knowledge about prophylactic treatment for migraine. For this purpose, together with the need for drug updates and to expand knowledge of the disease itself (frequency, intensity, duration, impact and perhaps the progression of migraine), this Consensus was developed, following a full online methodology, by 12 groups who reviewed and wrote about the pharmacological categories of the drugs used and, at the end of the process, met to read and establish conclusions for this document. The drug classes studied were: anticonvulsants, tricyclic antidepressants, monoclonal anti-calcitonin gene-related peptide (anti-CGRP) antibodies, beta-blockers, antihypertensives, calcium channel inhibitors, other antidepressants (selective serotonin reuptake inhibitors, SSRIs, and dual-action antidepressants), other drugs, and polytherapy. Hormonal treatment and anti-inflammatories and triptans in minimum prophylaxis schemes (miniprophylaxis) will be covered in a specific chapter. The drug classes studied for part I of the Consensus were: anticonvulsants, tricyclic antidepressants, monoclonal anti-CGRP antibodies, and beta-blockers.
Collapse
Affiliation(s)
- Eliana Meire Melhado
- Centro Universitário Padre Albino, Faculdade de Medicina, Departamento de Neurologia, Catanduva SP, Brazil
| | - Paulo Sergio Faro Santos
- Instituto de Neurologia de Curitiba, Departamento de Neurologia, Setor de Cefaleia e Dor Orofacial, Curitiba PR, Brazil
| | - Alexandre Ottoni Kaup
- Houston Headache Clinic, Houston TX, United States,Universidade Federal de São Paulo, Departamento de Neurologia, São Paulo SP, Brazil,Universidade de Santo Amaro, São Paulo SP, Brazil
| | | | | | - Élcio Juliato Piovesan
- Universidade Federal do Paraná, Departamento de Clínica Médica, Disciplina de Neurologia, Curitiba PR, Brazil
| | | | | | | | - Ida Fortini
- Universidade de São Paulo, Faculdade de Medicina, Departamento de Neurologia, São Paulo SP, Brazil
| | - Jano Alves de Souza
- Universidade Federal Fluminense, Departamento de Medicina Clínica, Disciplina de Neurologia, Niterói RJ, Brazil
| | - Jayme Antunes Maciel
- Universidade Estadual de Campinas, Faculdade de Ciências Médicas, Departamento de Neurologia, Campinas SP, Brazil
| | | | - João José Freitas de Carvalho
- Unichristus, Curso de Medicina, Disciplina de Neurologia, Fortaleza CE, Brazil,Hospital Geral de Fortaleza, Serviço de Neurologia, Núcleo de Cefaleias, Fortaleza CE, Brazil
| | - José Geraldo Speziali
- Universidade de São Paulo, Faculdade de Medicina de Ribeirão Preto, Departamento de Neurologia, Ribeirão Preto SP, Brazil
| | - Leandro Cortoni Calia
- Universidade Federal de São Paulo, Escola Paulista de Medicina, São Paulo SP, Brazil
| | - Liselotte Menke Barea
- Fundação Universidade Federal de Ciências da Saúde de Porto Alegre, Disciplina de Neurologia, Porto Alegre RS, Brazil
| | - Luiz Paulo Queiroz
- Universidade Federal de Santa Catarina, Hospital Universitário, Serviço de Neurologia, Florianópolis SC, Brazil
| | | | | | | | | | - Mauro Eduardo Jurno
- Fundação José Bonifácio Lafayette de Andrada, Faculdade de Medicina de Barbacena, Barbacena MG, Brazil,Fundação Hospitalar do Estado de Minas Gerais, Hospital Regional de Barbacena Dr. José Américo, Barbacena MG, Brazil
| | | | - Pedro André Kowacs
- Instituto de Neurologia de Curitiba, Serviço de Neurologia, Curitiba PR, Brazil,Universidade Federal do Paraná, Complexo Hospital de Clínicas, Serviço de Neurologia, Curitiba PR, Brazil
| | - Pedro Augusto Sampaio Rocha-Filho
- Universidade Federal de Pernambuco, Centro de Ciências Médicas, Área de Neuropsquiatria, Recife PE, Brazil,Universidade de Pernambuco, Hospital Universitário Oswaldo Cruz, Ambulatório de Cefaleias, Recife PR, Brazil
| | - Pedro Ferreira Moreira
- Universidade Federal Fluminense, Hospital Universitário Antônio Pedro, Departamento de Medicina Clínica, Niterói RJ, Brazil
| | | | | |
Collapse
|
|
43
|
Fu L, Jin W, Zhang J, Zhu L, Lu J, Zhen Y, Zhang L, Ouyang L, Liu B, Yu H. Repurposing non-oncology small-molecule drugs to improve cancer therapy: Current situation and future directions. Acta Pharm Sin B 2022; 12:532-557. [PMID: 35256933 PMCID: PMC8897051 DOI: 10.1016/j.apsb.2021.09.006] [Citation(s) in RCA: 37] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2021] [Revised: 07/05/2021] [Accepted: 08/27/2021] [Indexed: 12/25/2022] Open
Abstract
Drug repurposing or repositioning has been well-known to refer to the therapeutic applications of a drug for another indication other than it was originally approved for. Repurposing non-oncology small-molecule drugs has been increasingly becoming an attractive approach to improve cancer therapy, with potentially lower overall costs and shorter timelines. Several non-oncology drugs approved by FDA have been recently reported to treat different types of human cancers, with the aid of some new emerging technologies, such as omics sequencing and artificial intelligence to overcome the bottleneck of drug repurposing. Therefore, in this review, we focus on summarizing the therapeutic potential of non-oncology drugs, including cardiovascular drugs, microbiological drugs, small-molecule antibiotics, anti-viral drugs, anti-inflammatory drugs, anti-neurodegenerative drugs, antipsychotic drugs, antidepressants, and other drugs in human cancers. We also discuss their novel potential targets and relevant signaling pathways of these old non-oncology drugs in cancer therapies. Taken together, these inspiring findings will shed new light on repurposing more non-oncology small-molecule drugs with their intricate molecular mechanisms for future cancer drug discovery.
Collapse
|
|
44
|
Sikiric P, Skrtic A, Gojkovic S, Krezic I, Zizek H, Lovric E, Sikiric S, Knezevic M, Strbe S, Milavic M, Kokot A, Blagaic AB, Seiwerth S. Cytoprotective gastric pentadecapeptide BPC 157 resolves major vessel occlusion disturbances, ischemia-reperfusion injury following Pringle maneuver, and Budd-Chiari syndrome. World J Gastroenterol 2022; 28:23-46. [PMID: 35125818 PMCID: PMC8793015 DOI: 10.3748/wjg.v28.i1.23] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/21/2021] [Revised: 05/14/2021] [Accepted: 12/21/2021] [Indexed: 02/06/2023] Open
Abstract
The stable gastric pentadecapeptide BPC 157 counteracts various venous occlusion-induced syndromes. Summarized are all these arguments, in the Robert's cytoprotection concept, to substantiate the resolution of different major vessel occlusion disturbances, in particular ischemia-reperfusion injury following the Pringle maneuver and Budd-Chiari syndrome, which was obtained by BPC 157 therapy. Conceptually, there is a new point, namely, endothelium maintenance to epithelium maintenance (the recruitment of collateral blood vessels to compensate for vessel occlusion and reestablish blood flow or bypass the occluded or ruptured vessel). In this paper, we summarize the evidence of the native cytoprotective gastric pentadecapeptide BPC 157, which is stable in the human gastric juice, is a membrane stabilizer and counteracts gut-leaky syndrome. As a particular target, it is distinctive from the standard peptide growth factors, involving particular molecular pathways and controlling VEGF and NO pathways. In the early 1990s, BPC 157 appeared as a late outbreak of the Robert's and Szabo's cytoprotection-organoprotection concept, like the previous theoretical/practical breakthrough in the 1980s and the brain-gut axis and gut-brain axis. As the time went on, with its reported effects, it is likely most useful theory practical implementation and justification. Meantime, several reviews suggest that BPC 157, which does not have a lethal dose, has profound cytoprotective activity, used to be demonstrated in ulcerative colitis and multiple sclerosis trials. Likely, it may bring the theory to practical application, starting with the initial argument, no degradation in human gastric juice for more than 24 h, and thereby, the therapeutic effectiveness (including via a therapeutic per-oral regimen) and pleiotropic beneficial effects.
Collapse
Affiliation(s)
- Predrag Sikiric
- Department of Pharmacology, School of Medicine, University of Zagreb, Zagreb 10000, Croatia
| | - Anita Skrtic
- Department of Pathology, School of Medicine, University of Zagreb, Zagreb 10000, Croatia
| | - Slaven Gojkovic
- Department of Pharmacology, School of Medicine, University of Zagreb, Zagreb 10000, Croatia
| | - Ivan Krezic
- Department of Pharmacology, School of Medicine, University of Zagreb, Zagreb 10000, Croatia
| | - Helena Zizek
- Department of Pharmacology, School of Medicine, University of Zagreb, Zagreb 10000, Croatia
| | - Eva Lovric
- Department of Pathology, School of Medicine, University of Zagreb, Zagreb 10000, Croatia
| | - Suncana Sikiric
- Department of Pathology, School of Medicine, University of Zagreb, Zagreb 10000, Croatia
| | - Mario Knezevic
- Department of Pharmacology, School of Medicine, University of Zagreb, Zagreb 10000, Croatia
| | - Sanja Strbe
- Department of Pharmacology, School of Medicine, University of Zagreb, Zagreb 10000, Croatia
| | - Marija Milavic
- Department of Pathology, School of Medicine, University of Zagreb, Zagreb 10000, Croatia
| | - Antonio Kokot
- Department of Anatomy and Neuroscience, Faculty of Medicine Osijek, J.J.Strossmayer University of Osijek, Osijek 31000, Croatia
| | - Alenka Boban Blagaic
- Department of Pharmacology, School of Medicine, University of Zagreb, Zagreb 10000, Croatia
| | - Sven Seiwerth
- Department of Pathology, School of Medicine, University of Zagreb, Zagreb 10000, Croatia
| |
Collapse
|
|
45
|
Español P, Luna R, Soler C, Caruana P, Altés-Arranz A, Rodríguez F, Porta O, Sanchez O, Llurba E, Rovira R, Céspedes MV. Neural plasticity of the uterus: New targets for endometrial cancer? WOMEN'S HEALTH (LONDON, ENGLAND) 2022; 18:17455057221095537. [PMID: 35465787 PMCID: PMC9047769 DOI: 10.1177/17455057221095537] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Endometrial carcinoma is the most common gynecological malignancy in Western countries and is expected to increase in the following years because of the high index of obesity in the population. Recently, neural signaling has been recognized as part of the tumor microenvironment, playing an active role in tumor progression and invasion of different solid tumor types. The uterus stands out for the physiological plasticity of its peripheral nerves due to cyclic remodeling brought on by estrogen and progesterone hormones throughout the reproductive cycle. Therefore, a precise understanding of nerve-cancer crosstalk and the contribution of the organ-intrinsic neuroplasticity, mediated by estrogen and progesterone, of the uterine is urgently needed. The development of new and innovative medicines for patients with endometrial cancer would increase their quality of life and health. This review compiles information on the architecture and function of autonomous uterine neural innervations and the influence of hormone-dependent nerves in normal uterus and tumor progression. It also explores new therapeutic possibilities for endometrial cancer using these endocrine and neural advantages.
Collapse
Affiliation(s)
- Pia Español
- Gynecology and Oncology Peritoneal Group, Institut d'Investigacions Biomèdiques Sant Pau, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.,Department of Obstetrics and Gynecology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
| | - Rocio Luna
- Gynecology and Oncology Peritoneal Group, Institut d'Investigacions Biomèdiques Sant Pau, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.,Department of Obstetrics and Gynecology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
| | - Cristina Soler
- Gynecology and Oncology Peritoneal Group, Institut d'Investigacions Biomèdiques Sant Pau, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.,Department of Obstetrics and Gynecology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
| | - Pablo Caruana
- Gynecology and Oncology Peritoneal Group, Institut d'Investigacions Biomèdiques Sant Pau, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
| | - Amanda Altés-Arranz
- Gynecology and Oncology Peritoneal Group, Institut d'Investigacions Biomèdiques Sant Pau, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
| | - Francisco Rodríguez
- Gynecology and Oncology Peritoneal Group, Institut d'Investigacions Biomèdiques Sant Pau, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
| | - Oriol Porta
- Gynecology and Oncology Peritoneal Group, Institut d'Investigacions Biomèdiques Sant Pau, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.,Department of Obstetrics and Gynecology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
| | - Olga Sanchez
- Women and Perinatal Health Research Group, Obstetrics and Gynaecology Department, Hospital Sant Pau and Universitat Autònoma de Barcelona, Barcelona, Spain.,Maternal and Child Health and Development Network, Instituto Salud Carlos III, Madrid, Spain
| | - Elisa Llurba
- Department of Obstetrics and Gynecology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.,Women and Perinatal Health Research Group, Obstetrics and Gynaecology Department, Hospital Sant Pau and Universitat Autònoma de Barcelona, Barcelona, Spain.,Maternal and Child Health and Development Network, Instituto Salud Carlos III, Madrid, Spain
| | - Ramón Rovira
- Gynecology and Oncology Peritoneal Group, Institut d'Investigacions Biomèdiques Sant Pau, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.,Department of Obstetrics and Gynecology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
| | - María Virtudes Céspedes
- Gynecology and Oncology Peritoneal Group, Institut d'Investigacions Biomèdiques Sant Pau, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.,CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Barcelona, Spain
| |
Collapse
|
|
46
|
Tian W, Liu Y, Cao C, Zeng Y, Pan Y, Liu X, Peng Y, Wu F. Chronic Stress: Impacts on Tumor Microenvironment and Implications for Anti-Cancer Treatments. Front Cell Dev Biol 2021; 9:777018. [PMID: 34869378 PMCID: PMC8640341 DOI: 10.3389/fcell.2021.777018] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2021] [Accepted: 11/02/2021] [Indexed: 12/12/2022] Open
Abstract
Chronic stress is common among cancer patients due to the psychological, operative, or pharmaceutical stressors at the time of diagnosis or during the treatment of cancers. The continuous activations of the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system (SNS), as results of chronic stress, have been demonstrated to take part in several cancer-promoting processes, such as tumorigenesis, progression, metastasis, and multi-drug resistance, by altering the tumor microenvironment (TME). Stressed TME is generally characterized by the increased proportion of cancer-promoting cells and cytokines, the reduction and malfunction of immune-supportive cells and cytokines, augmented angiogenesis, enhanced epithelial-mesenchymal transition, and damaged extracellular matrix. For the negative effects that these alterations can cause in terms of the efficacies of anti-cancer treatments and prognosis of patients, supplementary pharmacological or psychotherapeutic strategies targeting HPA, SNS, or psychological stress may be effective in improving the prognosis of cancer patients. Here, we review the characteristics and mechanisms of TME alterations under chronic stress, their influences on anti-cancer therapies, and accessory interventions and therapies for stressed cancer patients.
Collapse
Affiliation(s)
- Wentao Tian
- Department of Oncology, The Second Xiangya Hospital, Central South University, Changsha, China.,Xiangya School of Medicine, Central South University, Changsha, China
| | - Yi Liu
- Xiangya School of Public Health, Central South University, Changsha, China
| | - Chenghui Cao
- Department of Oncology, The Second Xiangya Hospital, Central South University, Changsha, China.,Xiangya School of Medicine, Central South University, Changsha, China
| | - Yue Zeng
- Department of Oncology, The Second Xiangya Hospital, Central South University, Changsha, China
| | - Yue Pan
- Department of Oncology, The Second Xiangya Hospital, Central South University, Changsha, China
| | - Xiaohan Liu
- Department of Oncology, The Second Xiangya Hospital, Central South University, Changsha, China
| | - Yurong Peng
- Department of Oncology, The Second Xiangya Hospital, Central South University, Changsha, China
| | - Fang Wu
- Department of Oncology, The Second Xiangya Hospital, Central South University, Changsha, China.,Hunan Cancer Mega-Data Intelligent Application and Engineering Research Centre, Changsha, China.,Hunan Key Laboratory of Tumor Models and Individualized Medicine, The Second Xiangya Hospital, Central South University, Changsha, China.,Hunan Key Laboratory of Early Diagnosis and Precision Therapy in Lung Cancer, The Second Xiangya Hospital, Central South University, Changsha, China
| |
Collapse
|
|
47
|
Kang LL, Chen PE, Tung TH, Chien CW. Association Between Asthma and Migraine: A Systematic Review and Meta-Analysis of Observational Studies. FRONTIERS IN ALLERGY 2021; 2:741135. [PMID: 35386963 PMCID: PMC8974722 DOI: 10.3389/falgy.2021.741135] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2021] [Accepted: 10/18/2021] [Indexed: 11/17/2022] Open
Abstract
Objectives: The purpose of this study was to determine the association between asthma and migraine and assess the risk for migraine in patients with asthma. Methods: We systematically searched the Cochrane Library, PubMed, Medical Literature Analysis and Retrieval System Online (MEDLINE), and Excerpta Medica dataBASE (EMBASE) databases from inception to September 26, 2021, for indexed observational studies that examined either the odds or risk of migraine in subjects with asthma. The qualities of the included studies were evaluated using the Newcastle-Ottawa Scale. A random-effects meta-analysis was performed to calculate the odds ratio for case-control and cross-sectional studies and the risk ratio for cohort studies. Results: Seven observational studies (four cross-sectional and three cohort studies) with a total of 549,534 study subjects were included in this systematic review and meta-analysis and selected for data extraction. Four articles were considered to be of moderate quality; other studies were considered to be of high quality. Asthma was associated with increased odds (OR, 1.85; 95%CI, 1.39-2.45) and risk of migraine (RR, 1.70; 95%CI, 1.52-1.90). Conclusions: The available evidence that supports the existence of an association between asthma and migraine is limited. Clinicians should be aware that patients with asthma show both increased prevalence and incidence of migraine. Further studies are warranted to further clarify the relationship between asthma and migraine. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=185881, identifier: CRD42020185881.
Collapse
Affiliation(s)
- Lin-Lin Kang
- Institute for Hospital Management, Tsing Hua University, Shenzhen, China
| | - Pei-En Chen
- Institute of Health Policy and Management, National Taiwan University, Taipei, Taiwan
- Taiwan Association of Health Industry Management and Development, Taipei, Taiwan
| | - Tao-Hsin Tung
- Evidence-Based Medicine Center, Public Laboratory, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, China
| | - Ching-Wen Chien
- Institute for Hospital Management, Tsing Hua University, Shenzhen, China
| |
Collapse
|
|
48
|
Safaryan AS, Nebieridze DV. Sympathetic hyperactivity in patients with hypertension: pathogenesis and treatment. Part II. КАРДИОВАСКУЛЯРНАЯ ТЕРАПИЯ И ПРОФИЛАКТИКА 2021. [DOI: 10.15829/1728-8800-2021-2845] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2022] Open
Abstract
The second part of the review considers different classes of drugs affecting blood pressure in increased activity of the sympathetic nervous system. Additional possibilities are discussed on how to reduce the negative effect of sympathetic hyperactivity on cardiovascular system and improve the prognosis.
Collapse
Affiliation(s)
- A. S. Safaryan
- National Medical Research Center for Therapy and Preventive Medicine
| | - D. V. Nebieridze
- National Medical Research Center for Therapy and Preventive Medicine
| |
Collapse
|
|
49
|
Del Mauro JS, Prince PD, Santander Plantamura Y, Allo MA, Parola L, Fernandez Machulsky N, Morettón MA, Bin EP, González GE, Bertera FM, Carranza A, Berg G, Taira CA, Donato M, Chiappetta DA, Polizio AH, Höcht C. Nebivolol is more effective than atenolol for blood pressure variability attenuation and target organ damage prevention in L-NAME hypertensive rats. Hypertens Res 2021; 44:791-802. [PMID: 33612826 DOI: 10.1038/s41440-021-00630-4] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2020] [Revised: 12/06/2020] [Accepted: 12/27/2020] [Indexed: 02/07/2023]
Abstract
β-Adrenergic blockers are no longer recommended as first-line therapy due to the reduced cardioprotection of traditional β-blockers compared with other antihypertensive drugs. It is unknown whether third-generation β-blockers share the limitations of traditional β-blockers. The aim of the present study was to compare the effects of nebivolol or atenolol on central and peripheral systolic blood pressure (SBP) and its variability and target organ damage (TOD) in N-nitro-L-arginine methyl ester (L-NAME) hypertensive rats. Male Wistar rats were treated with L-NAME for 8 weeks together with oral administration of nebivolol 30 mg/kg (n = 8), atenolol 90 mg/kg (n = 8), or vehicle (n = 8). The control group was composed of vehicle-treated Wistar rats. SBP and its variability, as well as echocardiographic parameters, were assessed during the last 2 weeks of treatment. Tissue levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and transforming growth factor β (TGF-β), and histopathological parameters were evaluated in the left ventricle and aorta. Nebivolol had a greater ability than atenolol to decrease central SBP and mid-term and short-term blood pressure variability (BPV) in L-NAME rats. Echocardiographic analysis showed that nebivolol was more effective than atenolol on E/A wave ratio normalization. Compared with atenolol treatment, nebivolol had a greater protective effect on different TOD markers, inducing a decrease in collagen deposition and a reduction in the proinflammatory cytokines IL-6 and TNF-α in the left ventricle and aorta. Our findings suggest that the adverse hemodynamic profile and the reduced cardiovascular protection reported with traditional β-blockers must not be carried forward to third-generation β-blockers.
Collapse
Affiliation(s)
- Julieta S Del Mauro
- Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Departamento de Farmacología, Buenos Aires, Argentina.
| | - Paula D Prince
- Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Cátedra de Físicoquímica, Instituto de Bioquímica y Medicina Molecular (IBIMOL), Buenos Aires, Argentina
| | - Yanina Santander Plantamura
- Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Departamento de Farmacología, Buenos Aires, Argentina
| | - Miguel A Allo
- Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Departamento de Farmacología, Buenos Aires, Argentina
| | - Luciano Parola
- Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Departamento de Farmacología, Buenos Aires, Argentina
| | - Nahuel Fernandez Machulsky
- Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Departamento de Bioquímica Clínica, Laboratorio de Lípidos y Aterosclerosis, Buenos Aires, Argentina.,Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Instituto de Fisiopatología y Bioquímica Clínica (INFIBIOC), Buenos Aires, Argentina
| | - Marcela A Morettón
- Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Departamento de Tecnología Farmacéutica, Buenos Aires, Argentina
| | - Eliana P Bin
- Universidad de Buenos Aires, Facultad de Medicina, Instituto de Fisiopatología Cardiovascular (INFICA), Departamento de Patología, Buenos Aires, Argentina
| | - Germán E González
- Instituto de Investigaciones Biomédicas (BIOMED UCA-CONICET), Laboratorio de Patología Cardiovascular Experimental e Hipertensión Arterial, Buenos Aires, Argentina
| | - Facundo M Bertera
- Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Departamento de Farmacología, Buenos Aires, Argentina.,Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Instituto de Fisiopatología y Bioquímica Clínica (INFIBIOC), Buenos Aires, Argentina
| | - Andrea Carranza
- Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Departamento de Farmacología, Buenos Aires, Argentina
| | - Gabriela Berg
- Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Departamento de Bioquímica Clínica, Laboratorio de Lípidos y Aterosclerosis, Buenos Aires, Argentina.,Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Instituto de Fisiopatología y Bioquímica Clínica (INFIBIOC), Buenos Aires, Argentina
| | - Carlos A Taira
- Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Departamento de Farmacología, Buenos Aires, Argentina.,Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Instituto de Fisiopatología y Bioquímica Clínica (INFIBIOC), Buenos Aires, Argentina
| | - Martín Donato
- Universidad de Buenos Aires, Facultad de Medicina, Instituto de Fisiopatología Cardiovascular (INFICA), Departamento de Patología, Buenos Aires, Argentina
| | - Diego A Chiappetta
- Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Departamento de Tecnología Farmacéutica, Buenos Aires, Argentina
| | - Ariel H Polizio
- Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Departamento de Farmacología, Buenos Aires, Argentina
| | - Christian Höcht
- Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Departamento de Farmacología, Buenos Aires, Argentina.,Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Instituto de Fisiopatología y Bioquímica Clínica (INFIBIOC), Buenos Aires, Argentina
| |
Collapse
|
|
50
|
Cojocariu SA, Maștaleru A, Sascău RA, Stătescu C, Mitu F, Leon-Constantin MM. Neuropsychiatric Consequences of Lipophilic Beta-Blockers. ACTA ACUST UNITED AC 2021; 57:medicina57020155. [PMID: 33572109 PMCID: PMC7914867 DOI: 10.3390/medicina57020155] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2020] [Revised: 02/04/2021] [Accepted: 02/06/2021] [Indexed: 12/21/2022]
Abstract
Beta-blockers are a class of drugs with important benefits in cardiovascular pathology. In this paper, we aim to highlight their adverse and therapeutic effects in the neuropsychiatric field. With respect to permeability, we would like to mention that most beta-blockers are lipophilic and can cross the blood–brain barrier. Observational studies show the presence of neuropsychiatric side effects when taking beta-blockers, and is the reason for which caution is recommended in their use in patients with depressive syndrome. From a therapeutic point of view, most current evidence is for the use of beta-blockers in migraine attacks, essential tremor, and akathisia. Beta-blockers appear to be effective in the treatment of aggressive behavior, beneficial in the prevention of posttraumatic stress syndrome and may play a role in the adjuvant treatment of obsessive–compulsive disorder, which is refractory to standard therapy. In conclusion, the relationship between beta-blockers and the central nervous system appears as a two-sided coin. Summarizing the neuropsychiatric side effects of beta-blockers, we suggest that clinicians pay special attention to the pharmacological properties of different beta-blockers.
Collapse
Affiliation(s)
- Sabina Alexandra Cojocariu
- Department of Medical Specialties (I), Faculty of Medicine, “Grigore T Popa” University of Medicine and Pharmacy, University Street nr 16, 700115 Iasi, Romania; (S.A.C.); (R.A.S.); (C.S.); (F.M.); (M.M.L.-C.)
| | - Alexandra Maștaleru
- Department of Medical Specialties (I), Faculty of Medicine, “Grigore T Popa” University of Medicine and Pharmacy, University Street nr 16, 700115 Iasi, Romania; (S.A.C.); (R.A.S.); (C.S.); (F.M.); (M.M.L.-C.)
- Clinical Rehabilitation Hospital–Cardiovascular Rehabilitation Clinic, Pantelimon Halipa Street nr 14, 700661 Iasi, Romania
- Correspondence:
| | - Radu Andy Sascău
- Department of Medical Specialties (I), Faculty of Medicine, “Grigore T Popa” University of Medicine and Pharmacy, University Street nr 16, 700115 Iasi, Romania; (S.A.C.); (R.A.S.); (C.S.); (F.M.); (M.M.L.-C.)
- Institute of Cardiovascular Disease “Prof. Dr. George. I.M. Georgescu”, Carol I Boulevard nr 50, 700503 Iasi, Romania
| | - Cristian Stătescu
- Department of Medical Specialties (I), Faculty of Medicine, “Grigore T Popa” University of Medicine and Pharmacy, University Street nr 16, 700115 Iasi, Romania; (S.A.C.); (R.A.S.); (C.S.); (F.M.); (M.M.L.-C.)
- Institute of Cardiovascular Disease “Prof. Dr. George. I.M. Georgescu”, Carol I Boulevard nr 50, 700503 Iasi, Romania
| | - Florin Mitu
- Department of Medical Specialties (I), Faculty of Medicine, “Grigore T Popa” University of Medicine and Pharmacy, University Street nr 16, 700115 Iasi, Romania; (S.A.C.); (R.A.S.); (C.S.); (F.M.); (M.M.L.-C.)
- Clinical Rehabilitation Hospital–Cardiovascular Rehabilitation Clinic, Pantelimon Halipa Street nr 14, 700661 Iasi, Romania
| | - Maria Magdalena Leon-Constantin
- Department of Medical Specialties (I), Faculty of Medicine, “Grigore T Popa” University of Medicine and Pharmacy, University Street nr 16, 700115 Iasi, Romania; (S.A.C.); (R.A.S.); (C.S.); (F.M.); (M.M.L.-C.)
- Clinical Rehabilitation Hospital–Cardiovascular Rehabilitation Clinic, Pantelimon Halipa Street nr 14, 700661 Iasi, Romania
| |
Collapse
|