Molecular Aspects of Medicine最新文献_第6页

Ubiquitin proteasome system and glaucoma: A survey of genetics and molecular biology studies supporting a link with pathogenic and therapeutic relevance 泛素蛋白酶体系统和青光眼:遗传学和分子生物学研究的调查支持与致病和治疗相关性的联系。

IF 10.6 2区医学

Molecular Aspects of Medicine Pub Date : 2023-11-10 DOI: 10.1016/j.mam.2023.101226

Irene Pandino , Sara Giammaria , Gabriele Antonio Zingale , Gloria Roberti , Manuele Michelessi , Massimo Coletta , Gianluca Manni , Luca Agnifili , Alice Verticchio Vercellin , Alon Harris , Francesco Oddone , Diego Sbardella

{"title":"Ubiquitin proteasome system and glaucoma: A survey of genetics and molecular biology studies supporting a link with pathogenic and therapeutic relevance","authors":"Irene Pandino , Sara Giammaria , Gabriele Antonio Zingale , Gloria Roberti , Manuele Michelessi , Massimo Coletta , Gianluca Manni , Luca Agnifili , Alice Verticchio Vercellin , Alon Harris , Francesco Oddone , Diego Sbardella","doi":"10.1016/j.mam.2023.101226","DOIUrl":"10.1016/j.mam.2023.101226","url":null,"abstract":"<div><p>Glaucoma represents a group of progressive neurodegenerative diseases characterized by the loss of retinal ganglion cells (RGCs) and their axons with subsequent visual field impairment. The disease develops through largely uncharacterized molecular mechanisms, that are likely to occur in different localized cell types, either in the anterior (e.g., trabecular meshwork cells) or posterior (e.g., Muller glia, retinal ganglion cells) segments of the eye. Genomic and preclinical studies suggest that glaucoma pathogenesis may develop through altered ubiquitin (Ub) signaling. Ubiquitin conjugation, referred to as ubiquitylation, is a major post-synthetic modification catalyzed by E1-E2-E3 enzymes, that profoundly regulates the turnover, trafficking and biological activity of the targeted protein. The development of new technologies, including proteomics workflows, allows the biology of ubiquitin signaling to be described in health and disease. This post-translational modification is emerging as a key role player in neurodegeneration, gaining relevance for novel therapeutic options, such as in the case of Proteolysis Targeting Chimeras technology. Although scientific evidence supports a link between Ub and glaucoma, their relationship is still not well-understood. Therefore, this review provides a detailed research-oriented discussion on current evidence of Ub signaling in glaucoma. A review of genomic and genetic data is provided followed by an in-depth discussion of experimental data on ASB10, parkin and optineurin, which are proteins that play a key role in Ub signaling and have been associated with glaucoma.</p></div>","PeriodicalId":49798,"journal":{"name":"Molecular Aspects of Medicine","volume":null,"pages":null},"PeriodicalIF":10.6,"publicationDate":"2023-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89720265","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

Vaccines for HPV-associated diseases HPV相关疾病的疫苗。

IF 10.6 2区医学

Molecular Aspects of Medicine Pub Date : 2023-11-04 DOI: 10.1016/j.mam.2023.101224

Jeffrey M. Skolnik, Matthew P. Morrow

{"title":"Vaccines for HPV-associated diseases","authors":"Jeffrey M. Skolnik, Matthew P. Morrow","doi":"10.1016/j.mam.2023.101224","DOIUrl":"10.1016/j.mam.2023.101224","url":null,"abstract":"<div><p>Human papillomavirus (HPV) infection represents a significant global health concern owing to its role in the etiology of conditions ranging from benign low-grade lesions to cancers of the cervix, head and neck, anus, vagina, vulva, and penis. Prophylactic vaccination programs, primarily targeting adolescent girls, have achieved dramatic reductions in rates of HPV infection and cervical cancer in recent years. However, there is a clear demand for a strategy to manage the needs of the many people who are already living with persistent HPV infection and/or HPV-associated conditions. Unlike prophylactic vaccines, which act to prevent HPV infection, therapeutic vaccination presents an opportunity to induce cellular immunity against established HPV infections and lesions and prevent progression to cancer. Several HPV vaccines are undergoing clinical development, using a range of platforms. Peptide- or protein-based vaccines, vector-based vaccines, whole-cell vaccines, and nucleic acid vaccines each offer relative merits and limitations for the delivery of HPV antigens and the subsequent generation of targeted immune responses. There has been particular interest in DNA-based vaccines, which elicit both cellular and humoral immune responses to provide long-lasting immunity. DNA vaccines offer several practical advantages over other vaccine platforms, including the potential for rapid and scalable manufacturing, targeting of many different antigens, and potential for repeat boosting. Furthermore, unlike vectored approaches, DNA vaccines are thermostable over extended time periods, which may enable shipping and storage. Several delivery strategies are available to address the main challenge of DNA vaccines, namely their relatively low transfection efficiency. We review the latest clinical data supporting the development of DNA vaccines and reflect on this exciting prospect in the management of HPV-related disease.</p></div>","PeriodicalId":49798,"journal":{"name":"Molecular Aspects of Medicine","volume":null,"pages":null},"PeriodicalIF":10.6,"publicationDate":"2023-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71488123","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

Computational methods in glaucoma research: Current status and future outlook 青光眼研究中的计算方法：现状和未来展望。

IF 10.6 2区医学

Molecular Aspects of Medicine Pub Date : 2023-11-03 DOI: 10.1016/j.mam.2023.101222

Minjae J. Kim , Cole A. Martin , Jinhwa Kim , Monica M. Jablonski

{"title":"Computational methods in glaucoma research: Current status and future outlook","authors":"Minjae J. Kim , Cole A. Martin , Jinhwa Kim , Monica M. Jablonski","doi":"10.1016/j.mam.2023.101222","DOIUrl":"10.1016/j.mam.2023.101222","url":null,"abstract":"<div><p>Advancements in computational techniques have transformed glaucoma research, providing a deeper understanding of genetics, disease mechanisms, and potential therapeutic targets. Systems genetics integrates genomic and clinical data, aiding in identifying drug targets, comprehending disease mechanisms, and personalizing treatment strategies for glaucoma. Molecular dynamics simulations offer valuable molecular-level insights into glaucoma-related biomolecule behavior and drug interactions, guiding experimental studies and drug discovery efforts. Artificial intelligence (AI) technologies hold promise in revolutionizing glaucoma research, enhancing disease diagnosis, target identification, and drug candidate selection. The generalized protocols for systems genetics, MD simulations, and AI model development are included as a guide for glaucoma researchers. These computational methods, however, are not separate and work harmoniously together to discover novel ways to combat glaucoma. Ongoing research and progresses in genomics technologies, MD simulations, and AI methodologies project computational methods to become an integral part of glaucoma research in the future.</p></div>","PeriodicalId":49798,"journal":{"name":"Molecular Aspects of Medicine","volume":null,"pages":null},"PeriodicalIF":10.6,"publicationDate":"2023-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71488122","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

Advances in understanding glaucoma pathogenesis: A multifaceted molecular approach for clinician scientists 了解青光眼发病机制的进展:临床医生科学家的多面分子方法

IF 10.6 2区医学

Molecular Aspects of Medicine Pub Date : 2023-10-27 DOI: 10.1016/j.mam.2023.101223

Eren Ekici , Sasan Moghimi

{"title":"Advances in understanding glaucoma pathogenesis: A multifaceted molecular approach for clinician scientists","authors":"Eren Ekici , Sasan Moghimi","doi":"10.1016/j.mam.2023.101223","DOIUrl":"https://doi.org/10.1016/j.mam.2023.101223","url":null,"abstract":"<div><p><span><span>Glaucoma, a leading cause of irreversible blindness worldwide, is a spectrum of neurodegenerative diseases characterized by the gradual deterioration of retinal ganglion cells (RGCs) and optic neuropathy. With complex etiology, glaucoma's major risk factors include elevated intraocular pressure (IOP), advanced age, ethnicity, systemic vascular factors, and </span>genetic predisposition<span>. By 2040, glaucoma is expected to affect over 110 million individuals aged 40 to 80, posing a significant economic burden. Glaucoma can be classified into open-angle, angle-closure, and developmental subtypes, with primary and secondary forms. The disease often progresses silently, gradually impairing the visual field (VF) until it reaches an advanced stage. Understanding the abnormal functional changes associated with glaucoma at the tissue, cellular, molecular, and genetic levels is crucial for comprehending its pathogenesis. This review examines the published data from the past two decades to shed light on the biological mechanisms underlying glaucoma development. The most evident factors in the development of glaucomatous optic neuropathy include elevated IOP, aging, genetic influences, followed by impaired ocular blood flow regulation. These factors are interconnected processes that lead to optic nerve damage, compromised circulation, and structural changes in glial and connective tissues. Contributing factors involve extracellular matrix remodeling, </span></span>excitotoxicity<span><span>, nitric oxide, </span>oxidative stress, and neuroinflammation. Ultimately, all types of glaucoma result in RGC dysfunction and loss, causing irreversible visual impairment. While our understanding of glaucoma pathogenesis is evolving, further research is crucial for a comprehensive understanding of glaucoma pathogenesis and the development of effective treatments.</span></p></div>","PeriodicalId":49798,"journal":{"name":"Molecular Aspects of Medicine","volume":null,"pages":null},"PeriodicalIF":10.6,"publicationDate":"2023-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91985488","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 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":null,"pages":null},"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":null,"pages":null},"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":null,"pages":null},"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