Molecular Aspects of Medicine最新文献_第9页

The role of the microbiota in glaucoma 微生物群在青光眼中的作用。

IF 10.6 2区医学

Molecular Aspects of Medicine Pub Date : 2023-10-21 DOI: 10.1016/j.mam.2023.101221

Ling Huang , Yiwen Hong , Xiangyu Fu , Haishan Tan , Yongjiang Chen , Yujiao Wang , Danian Chen

{"title":"The role of the microbiota in glaucoma","authors":"Ling Huang , Yiwen Hong , Xiangyu Fu , Haishan Tan , Yongjiang Chen , Yujiao Wang , Danian Chen","doi":"10.1016/j.mam.2023.101221","DOIUrl":"10.1016/j.mam.2023.101221","url":null,"abstract":"<div><p>Glaucoma is a common irreversible vision loss disorder because of the gradual loss of retinal ganglion cells (RGCs) and the optic nerve axons. Major risk factors include elder age and high intraocular pressure (IOP). However, high IOP is neither necessary nor sufficient to cause glaucoma. Some non-IOP signaling cascades can mediate RGC degeneration. In addition, gender, diet, obesity, depression, or anxiety also contribute to the development of glaucoma. Understanding the mechanism of glaucoma development is crucial for timely diagnosis and establishing new strategies to improve current IOP-reducing therapies. The microbiota exerts a marked influence on the human body during homeostasis and disease. Many glaucoma patients have abnormal compositions of the microbiota (dysbiosis) in multiple locations, including the ocular surface, intraocular cavity, oral cavity, stomach, and gut. Here, we discuss findings in the last ten years or more about the microbiota and metabolite changes in animal models, patients with three risk factors (aging, obesity, and depression), and glaucoma patients. Antigenic mimicry and heat stress protein (HSP)-specific T-cell infiltration in the retina may be responsible for commensal microbes contributing to glaucomatous RGC damage. LPS-TLR4 pathway may be the primary mechanism of oral and ocular surface dysbiosis affecting glaucoma. Microbe-derived metabolites may also affect glaucoma pathogenesis. Homocysteine accumulation, inflammatory factor release, and direct dissemination may link gastric <em>H. pylori</em> infection and anterior chamber viral infection (such as cytomegalovirus) to glaucoma. Potential therapeutic protocols targeting microbiota include antibiotics, modified diet, and stool transplant. Later investigations will uncover the underlying molecular mechanism connecting dysbiosis to glaucoma and its clinical applications in glaucoma management.</p></div>","PeriodicalId":49798,"journal":{"name":"Molecular Aspects of Medicine","volume":"94 ","pages":"Article 101221"},"PeriodicalIF":10.6,"publicationDate":"2023-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49693438","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

Understanding the complex genetics and molecular mechanisms underlying glaucoma 了解青光眼的复杂遗传学和分子机制。

IF 10.6 2区医学

Molecular Aspects of Medicine Pub Date : 2023-10-17 DOI: 10.1016/j.mam.2023.101220

Weiwei Wang , Huaizhou Wang

引用次数: 0

Signalling pathways and cell death mechanisms in glaucoma: Insights into the molecular pathophysiology 青光眼的信号通路和细胞死亡机制：对分子病理生理学的见解。

IF 10.6 2区医学

Molecular Aspects of Medicine Pub Date : 2023-10-17 DOI: 10.1016/j.mam.2023.101216

Devaraj Basavarajappa , Caridad Galindo-Romero , Vivek Gupta , Marta Agudo-Barriuso , Veer B. Gupta , Stuart L. Graham , Nitin Chitranshi

{"title":"Signalling pathways and cell death mechanisms in glaucoma: Insights into the molecular pathophysiology","authors":"Devaraj Basavarajappa , Caridad Galindo-Romero , Vivek Gupta , Marta Agudo-Barriuso , Veer B. Gupta , Stuart L. Graham , Nitin Chitranshi","doi":"10.1016/j.mam.2023.101216","DOIUrl":"10.1016/j.mam.2023.101216","url":null,"abstract":"<div><p>Glaucoma is a complex multifactorial eye disease manifesting in retinal ganglion cell (RGC) death and optic nerve degeneration, ultimately causing irreversible vision loss. Research in recent years has significantly enhanced our understanding of RGC degenerative mechanisms in glaucoma. It is evident that high intraocular pressure (IOP) is not the only contributing factor to glaucoma pathogenesis. The equilibrium of pro-survival and pro-death signalling pathways in the retina strongly influences the function and survival of RGCs and optic nerve axons in glaucoma. Molecular evidence from human retinal tissue analysis and a range of experimental models of glaucoma have significantly contributed to unravelling these mechanisms. Accumulating evidence reveals a wide range of molecular signalling pathways that can operate -either alone or via intricate networks - to induce neurodegeneration. The roles of several molecules, including neurotrophins, interplay of intracellular kinases and phosphates, caveolae and adapter proteins, serine proteases and their inhibitors, nuclear receptors, amyloid beta and tau, and how their dysfunction affects retinal neurons are discussed in this review. We further underscore how anatomical alterations in various animal models exhibiting RGC degeneration and susceptibility to glaucoma-related neuronal damage have helped to characterise molecular mechanisms in glaucoma. In addition, we also present different regulated cell death pathways that play a critical role in RGC degeneration in glaucoma.</p></div>","PeriodicalId":49798,"journal":{"name":"Molecular Aspects of Medicine","volume":"94 ","pages":"Article 101216"},"PeriodicalIF":10.6,"publicationDate":"2023-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49684185","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

Molecular aspects of optic nerve autophagy in glaucoma 青光眼视神经自噬的分子方面。

IF 10.6 2区医学

Molecular Aspects of Medicine Pub Date : 2023-10-14 DOI: 10.1016/j.mam.2023.101217

Yasushi Kitaoka , Kana Sase

引用次数: 0

Therapeutic strategies for glaucoma and optic neuropathies 青光眼和视神经病变的治疗策略。

IF 10.6 2区医学

Molecular Aspects of Medicine Pub Date : 2023-10-13 DOI: 10.1016/j.mam.2023.101219

Jung Lo , Kamakshi Mehta , Armaan Dhillon , Yu-Kai Huang , Ziming Luo , Mi-Hyun Nam , Issam Al Diri , Kun-Che Chang

{"title":"Therapeutic strategies for glaucoma and optic neuropathies","authors":"Jung Lo , Kamakshi Mehta , Armaan Dhillon , Yu-Kai Huang , Ziming Luo , Mi-Hyun Nam , Issam Al Diri , Kun-Che Chang","doi":"10.1016/j.mam.2023.101219","DOIUrl":"10.1016/j.mam.2023.101219","url":null,"abstract":"<div><p>Glaucoma is a neurodegenerative eye disease that causes permanent vision impairment. The main pathological characteristics of glaucoma are retinal ganglion cell (RGC) loss and optic nerve degeneration. Glaucoma can be caused by elevated intraocular pressure (IOP), although some cases are congenital or occur in patients with normal IOP. Current glaucoma treatments rely on medicine and surgery to lower IOP, which only delays disease progression. First-line glaucoma medicines are supported by pharmacotherapy advancements such as Rho kinase inhibitors and innovative drug delivery systems. Glaucoma surgery has shifted to safer minimally invasive (or microinvasive) glaucoma surgery, but further trials are needed to validate long-term efficacy. Further, growing evidence shows that adeno-associated virus gene transduction and stem cell-based RGC replacement therapy hold potential to treat optic nerve fiber degeneration and glaucoma. However, better understanding of the regulatory mechanisms of RGC development is needed to provide insight into RGC differentiation from stem cells and help choose target genes for viral therapy. In this review, we overview current progress in RGC development research, optic nerve fiber regeneration, and human stem cell-derived RGC differentiation and transplantation. We also provide an outlook on perspectives and challenges in the field.</p></div>","PeriodicalId":49798,"journal":{"name":"Molecular Aspects of Medicine","volume":"94 ","pages":"Article 101219"},"PeriodicalIF":10.6,"publicationDate":"2023-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41240337","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

The changing epidemiology of fungal infections 真菌感染的流行病学变化。

IF 10.6 2区医学

Molecular Aspects of Medicine Pub Date : 2023-10-05 DOI: 10.1016/j.mam.2023.101215

Cornelia Lass-Flörl, Stephan Steixner

引用次数: 0

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":"93 ","pages":"Article 101203"},"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":"93 ","pages":"Article 101204"},"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":"93 ","pages":"Article 101194"},"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