Molecular Aspects of Medicine最新文献_第7页

Towards modifying the genetic predisposition for glaucoma: An overview of the contribution and interaction of genetic and environmental factors 改变青光眼的遗传易感性：遗传和环境因素的作用和相互作用综述

IF 10.6 2区医学

Molecular Aspects of Medicine Pub Date : 2023-10-01 DOI: 10.1016/j.mam.2023.101203

Kelsey V. Stuart , Louis R. Pasquale , Jae H. Kang , Paul J. Foster , Anthony P. Khawaja

{"title":"Towards modifying the genetic predisposition for glaucoma: An overview of the contribution and interaction of genetic and environmental factors","authors":"Kelsey V. Stuart , Louis R. Pasquale , Jae H. Kang , Paul J. Foster , Anthony P. Khawaja","doi":"10.1016/j.mam.2023.101203","DOIUrl":"10.1016/j.mam.2023.101203","url":null,"abstract":"<div><p>Glaucoma, the leading cause of irreversible blindness worldwide, is a complex human disease, with both genetic and environmental determinants. The availability of large-scale, population-based cohorts and biobanks, combining genotyping and detailed phenotyping, has greatly accelerated research into the aetiology of glaucoma in recent years. Hypothesis-free genome-wide association studies have furthered our understanding of the complex genetic architecture underpinning the disease, while epidemiological studies have provided advances in the identification and characterisation of environmental risk factors. It is increasingly recognised that the combined effects of genetic and environmental factors may confer a disease risk that reflects a departure from the simple additive effect of the two. These gene-environment interactions have been implicated in a host of complex human diseases, including glaucoma, and have several important diagnostic and therapeutic implications for future clinical practice. Importantly, the ability to modify the risk associated with a particular genetic makeup promises to lead to personalised recommendations for glaucoma prevention, as well as novel treatment approaches in years to come. Here we provide an overview of genetic and environmental risk factors for glaucoma, as well as reviewing the evidence and discussing the implications of gene-environment interactions for the disease.</p></div>","PeriodicalId":49798,"journal":{"name":"Molecular Aspects of Medicine","volume":null,"pages":null},"PeriodicalIF":10.6,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9995957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Advances in vaccine development for cancer prevention and treatment in Lynch Syndrome 林奇综合征癌症预防和治疗疫苗开发进展。

IF 10.6 2区医学

Molecular Aspects of Medicine Pub Date : 2023-10-01 DOI: 10.1016/j.mam.2023.101204

Ana M. Bolivar , Fahriye Duzagac , Krishna M. Sinha , Eduardo Vilar

{"title":"Advances in vaccine development for cancer prevention and treatment in Lynch Syndrome","authors":"Ana M. Bolivar , Fahriye Duzagac , Krishna M. Sinha , Eduardo Vilar","doi":"10.1016/j.mam.2023.101204","DOIUrl":"10.1016/j.mam.2023.101204","url":null,"abstract":"<div><p>Lynch Syndrome (LS) is one of the most common hereditary cancer syndromes, and is caused by mutations in one of the four DNA mismatch repair (MMR) genes, namely <em>MLH1</em>, <em>MSH2</em>, <em>MSH6</em> and <em>PMS2</em>. Tumors developed by LS carriers display high levels of microsatellite instability, which leads to the accumulation of large numbers of mutations, among which frameshift insertion/deletions (indels) within microsatellite (MS) loci are the most common. As a result, MMR-deficient (MMRd) cells generate increased rates of tumor-specific neoantigens (neoAgs) that can be recognized by the immune system to activate cancer cell killing. In this context, LS is an ideal disease to leverage immune-interception strategies. Therefore, the identification of these neoAgs is an ongoing effort for the development of LS cancer preventive vaccines. In this review, we summarize the computational methods used for <em>in silico</em> neoAg prediction, including their challenges, and the experimental techniques used for <em>in vitro</em> validation of their immunogenicity. In addition, we outline results from past and on-going vaccine clinical trials and highlight avenues for improvement and future directions.</p></div>","PeriodicalId":49798,"journal":{"name":"Molecular Aspects of Medicine","volume":null,"pages":null},"PeriodicalIF":10.6,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10528439/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10022517","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cardiac Fibrosis in heart failure: Focus on non-invasive diagnosis and emerging therapeutic strategies 心力衰竭中的心脏纤维化：关注无创诊断和新兴治疗策略

IF 10.6 2区医学

Molecular Aspects of Medicine Pub Date : 2023-10-01 DOI: 10.1016/j.mam.2023.101194

Susana Ravassa , Begoña López , Thomas A. Treibel , Gorka San José , Blanca Losada-Fuentenebro , Leire Tapia , Antoni Bayés-Genís , Javier Díez , Arantxa González

{"title":"Cardiac Fibrosis in heart failure: Focus on non-invasive diagnosis and emerging therapeutic strategies","authors":"Susana Ravassa , Begoña López , Thomas A. Treibel , Gorka San José , Blanca Losada-Fuentenebro , Leire Tapia , Antoni Bayés-Genís , Javier Díez , Arantxa González","doi":"10.1016/j.mam.2023.101194","DOIUrl":"10.1016/j.mam.2023.101194","url":null,"abstract":"<div><p>Heart failure is a leading cause of mortality and hospitalization worldwide. Cardiac fibrosis, resulting from the excessive deposition of collagen fibers, is a common feature across the spectrum of conditions converging in heart failure. Eventually, either reparative or reactive in nature, in the long-term cardiac fibrosis contributes to heart failure development and progression and is associated with poor clinical outcomes. Despite this, specific cardiac antifibrotic therapies are lacking, making cardiac fibrosis an urgent unmet medical need. In this context, a better patient phenotyping is needed to characterize the heterogenous features of cardiac fibrosis to advance toward its personalized management. In this review, we will describe the different phenotypes associated with cardiac fibrosis in heart failure and we will focus on the potential usefulness of imaging techniques and circulating biomarkers for the non-invasive characterization and phenotyping of this condition and for tracking its clinical impact. We will also recapitulate the cardiac antifibrotic effects of existing heart failure and non-heart failure drugs and we will discuss potential strategies under preclinical development targeting the activation of cardiac fibroblasts at different levels, as well as targeting additional extracardiac processes.</p></div>","PeriodicalId":49798,"journal":{"name":"Molecular Aspects of Medicine","volume":null,"pages":null},"PeriodicalIF":10.6,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10334374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Kidney fibrosis: Emerging diagnostic and therapeutic strategies 肾脏纤维化：新兴的诊断和治疗策略

IF 10.6 2区医学

Molecular Aspects of Medicine Pub Date : 2023-10-01 DOI: 10.1016/j.mam.2023.101206

Barbara Mara Klinkhammer , Peter Boor

引用次数: 0

Doxorubicin and other anthracyclines in cancers: Activity, chemoresistance and its overcoming 阿霉素和其他蒽环类药物治疗癌症的活性、耐药性及其克服

IF 10.6 2区医学

Molecular Aspects of Medicine Pub Date : 2023-10-01 DOI: 10.1016/j.mam.2023.101205

Roberto Mattioli , Andrea Ilari , Beatrice Colotti , Luciana Mosca , Francesco Fazi , Gianni Colotti

引用次数: 3

The molecular aspect of anti-glaucomatous eye drops - are we harming our patients? 抗青光眼滴眼液的分子方面——我们是否在伤害我们的患者？

IF 10.6 2区医学

Molecular Aspects of Medicine Pub Date : 2023-10-01 DOI: 10.1016/j.mam.2023.101195

Anne Hedengran , Miriam Kolko

{"title":"The molecular aspect of anti-glaucomatous eye drops - are we harming our patients?","authors":"Anne Hedengran , Miriam Kolko","doi":"10.1016/j.mam.2023.101195","DOIUrl":"10.1016/j.mam.2023.101195","url":null,"abstract":"<div><p>Glaucoma is one of the leading causes of irreversible blindness. Progression is halted with a reduction in intraocular pressure (IOP), which is most often achieved with eye drops. A major challenge in the topical treatment of glaucoma patients is the many side effects and the resulting reduced adherence. Side effects may of course be due to the molecular properties of the active pharmaceutical ingredients (APIs). There are currently six different APIs available: prostaglandin analogues, β-adrenergic inhibitors, α-adrenergic agonists, carbonic anhydrase inhibitors, rho-kinase inhibitors and muscarinic 3 agonists. But the additives used in eye drops are also known to cause damage to the ocular surface and to some extent also to the deeper tissues. Said additives are considered inactive molecular components and are added to secure for instance viscosity and pH value, and to prevent contamination. There has been an increasing focus on the harmful effects of preservatives, with the most commonly used preservative benzalkonium chloride (BAK) being particularly controversial. BAK has long been recognized as a toxin that increases the risk of ocular discomfort. This can affect the adherence and ultimately result in lack of disease control. Other issues include the addition of certain buffers, such as phosphates, and varying pH values. This review will address the different molecular components of the IOP-lowering eye drops and what to be aware of when prescribing topical glaucoma treatment.</p></div>","PeriodicalId":49798,"journal":{"name":"Molecular Aspects of Medicine","volume":null,"pages":null},"PeriodicalIF":10.6,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9995677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

Current understanding of genetics and epigenetics in pseudoexfoliation syndrome and glaucoma 目前对假剥脱综合征和青光眼的遗传学和表观遗传学的理解。

IF 10.6 2区医学

Molecular Aspects of Medicine Pub Date : 2023-09-18 DOI: 10.1016/j.mam.2023.101214

Ramani Shyam Kapuganti , Debasmita Pankaj Alone

{"title":"Current understanding of genetics and epigenetics in pseudoexfoliation syndrome and glaucoma","authors":"Ramani Shyam Kapuganti , Debasmita Pankaj Alone","doi":"10.1016/j.mam.2023.101214","DOIUrl":"10.1016/j.mam.2023.101214","url":null,"abstract":"<div><p>Pseudoexfoliation is a complex, progressive, and systemic age-related disorder. The early stage of deposition of extracellular fibrillar material on ocular and extraocular tissues is termed as pseudoexfoliation syndrome (PEXS). The severe advanced stage is known as pseudoexfoliation glaucoma (PEXG), which involves increased intraocular pressure and optic nerve damage. Through genome-wide association and candidate gene studies, PEX has been associated with numerous genetic risk variants in various gene loci. However, the genetic basis of the disease fails to explain certain features of PEX pathology, such as the progressive nature of the disease, asymmetric ocular manifestation, age-related onset, and only a subset of PEXS individuals developing PEXG. Increasing evidence shows an interplay of genetic and epigenetic factors in the pathology of complex, multifactorial diseases. In this review, we have discussed the genetic basis of the disease and the emerging contribution of epigenetic regulations in PEX pathogenesis, focusing on DNA methylation and non-coding RNAs. Aberrant methylation patterns, histone modifications, and post-transcriptional regulation by microRNAs lead to aberrant gene expression changes. We have reviewed these aberrant epigenetic changes in PEX pathology and their effect on molecular pathways associated with PEX. We have further discussed some possible genetic/epigenetic-based diagnoses and therapeutics for PEX. Although studies to understand the role of epigenetic regulations in PEX are just emerging, epigenetic modifications contribute significantly to PEX pathogenesis and may pave the way for better and targeted therapeutics.</p></div>","PeriodicalId":49798,"journal":{"name":"Molecular Aspects of Medicine","volume":null,"pages":null},"PeriodicalIF":10.6,"publicationDate":"2023-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41160740","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Gene-environment interactions that influence CVD, lipid traits, obesity, diabetes, and hypertension appear to be able to influence gene therapy 影响CVD、脂质特征、肥胖、糖尿病和高血压的基因-环境相互作用似乎能够影响基因治疗

IF 10.6 2区医学

Molecular Aspects of Medicine Pub Date : 2023-09-11 DOI: 10.1016/j.mam.2023.101213

Moataz Dowaidar

{"title":"Gene-environment interactions that influence CVD, lipid traits, obesity, diabetes, and hypertension appear to be able to influence gene therapy","authors":"Moataz Dowaidar","doi":"10.1016/j.mam.2023.101213","DOIUrl":"10.1016/j.mam.2023.101213","url":null,"abstract":"<div><p>Most mind boggling diseases are accepted to be impacted by both genetic and environmental elements. As of late, there has been a flood in the improvement of different methodologies, concentrate on plans, and measurable and logical techniques to examine gene-environment cooperations (G × Es) in enormous scope studies including human populaces. The many-sided exchange between genetic elements and environmental openings has long charmed the consideration of clinicians and researchers looking to grasp the complicated starting points of diseases. While single variables can add to disease, the blend of genetic variations and environmental openings frequently decides disease risk. The fundamental point of this paper is to talk about the Gene-Environment Associations That Impact CVD, Lipid Characteristics, Obesity, Diabetes, and Hypertension Have all the earmarks of being Ready to Impact Gene Therapy. This survey paper investigates the meaning of gene-environment collaborations (G × E) in disease advancement. The intricacy of genetic and environmental communications in disease causation is explained, underlining the multifactorial idea of many circumstances. The job of gene-environment cooperations in cardiovascular disease, lipid digestion, diabetes, obesity, and hypertension is investigated. This audit fixates on Gene by Environment (G × E) collaborations, investigating their importance in disease etiology.</p></div>","PeriodicalId":49798,"journal":{"name":"Molecular Aspects of Medicine","volume":null,"pages":null},"PeriodicalIF":10.6,"publicationDate":"2023-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10234364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Neuroprotection in glaucoma: Mechanisms beyond intraocular pressure lowering 青光眼的神经保护：除眼压降低外的机制

IF 10.6 2区医学

Molecular Aspects of Medicine Pub Date : 2023-08-01 DOI: 10.1016/j.mam.2023.101193

James R. Tribble , Flora Hui , Heberto Quintero , Sana El Hajji , Katharina Bell , Adriana Di Polo , Pete A. Williams

{"title":"Neuroprotection in glaucoma: Mechanisms beyond intraocular pressure lowering","authors":"James R. Tribble , Flora Hui , Heberto Quintero , Sana El Hajji , Katharina Bell , Adriana Di Polo , Pete A. Williams","doi":"10.1016/j.mam.2023.101193","DOIUrl":"10.1016/j.mam.2023.101193","url":null,"abstract":"<div><p>Glaucoma is a common, complex, multifactorial neurodegenerative disease characterized by progressive dysfunction and then loss of retinal ganglion cells, the output neurons of the retina. Glaucoma is the most common cause of irreversible blindness and affects ∼80 million people worldwide with many more undiagnosed. The major risk factors for glaucoma are genetics, age, and elevated intraocular pressure. Current strategies only target intraocular pressure management and do not directly target the neurodegenerative processes occurring at the level of the retinal ganglion cell. Despite strategies to manage intraocular pressure, as many as 40% of glaucoma patients progress to blindness in at least one eye during their lifetime. As such, neuroprotective strategies that target the retinal ganglion cell and these neurodegenerative processes directly are of great therapeutic need. This review will cover the recent advances from basic biology to on-going clinical trials for neuroprotection in glaucoma covering degenerative mechanisms, metabolism, insulin signaling, mTOR, axon transport, apoptosis, autophagy, and neuroinflammation. With an increased understanding of both the basic and clinical mechanisms of the disease, we are closer than ever to a neuroprotective strategy for glaucoma.</p></div>","PeriodicalId":49798,"journal":{"name":"Molecular Aspects of Medicine","volume":null,"pages":null},"PeriodicalIF":10.6,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10112386","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 7

Mechanisms of organ fibrosis: Emerging concepts and implications for novel treatment strategies 器官纤维化的机制：新出现的概念和新治疗策略的意义

IF 10.6 2区医学

Molecular Aspects of Medicine Pub Date : 2023-08-01 DOI: 10.1016/j.mam.2023.101191

Isabella Lurje , Nadine T. Gaisa , Ralf Weiskirchen , Frank Tacke

{"title":"Mechanisms of organ fibrosis: Emerging concepts and implications for novel treatment strategies","authors":"Isabella Lurje , Nadine T. Gaisa , Ralf Weiskirchen , Frank Tacke","doi":"10.1016/j.mam.2023.101191","DOIUrl":"10.1016/j.mam.2023.101191","url":null,"abstract":"<div><p>Fibrosis, or tissue scarring, develops as a pathological deviation from the physiological wound healing response and can occur in various organs such as the heart, lung, liver, kidney, skin, and bone marrow. Organ fibrosis significantly contributes to global morbidity and mortality. A broad spectrum of etiologies can cause fibrosis, including acute and chronic ischemia, hypertension, chronic viral infection (e.g., viral hepatitis), environmental exposure (e.g., pneumoconiosis, alcohol, nutrition, smoking) and genetic diseases (e.g., cystic fibrosis, alpha-1-antitrypsin deficiency). Common mechanisms across organs and disease etiologies involve a sustained injury to parenchymal cells that triggers a wound healing response, which becomes deregulated in the disease process. A transformation of resting fibroblasts into myofibroblasts with excessive extracellular matrix production constitutes the hallmark of disease, however, multiple other cell types such as immune cells, predominantly monocytes/macrophages, endothelial cells, and parenchymal cells form a complex network of profibrotic cellular crosstalk. Across organs, leading mediators include growth factors like transforming growth factor-β and platelet-derived growth factor, cytokines like interleukin-10, interleukin-13, interleukin-17, and danger-associated molecular patterns. More recently, insights into fibrosis regression and resolution of chronic conditions have deepened our understanding of beneficial, protective effects of immune cells, soluble mediators and intracellular signaling. Further in-depth insights into the mechanisms of fibrogenesis can provide the rationale for therapeutic interventions and the development of targeted antifibrotic agents. This review gives insight into shared responses and cellular mechanisms across organs and etiologies, aiming to paint a comprehensive picture of fibrotic diseases in both experimental settings and in human pathology.</p></div>","PeriodicalId":49798,"journal":{"name":"Molecular Aspects of Medicine","volume":null,"pages":null},"PeriodicalIF":10.6,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9789974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 8