Molecular Aspects of Medicine最新文献

{"title":"The molecular aspect of anti-glaucomatous eye drops - are we harming our patients?","authors":"Anne Hedengran ,&nbsp;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":"93 ","pages":"Article 101195"},"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}

{"title":"Current understanding of genetics and epigenetics in pseudoexfoliation syndrome and glaucoma","authors":"Ramani Shyam Kapuganti ,&nbsp;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":"94 ","pages":"Article 101214"},"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}

{"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":"94 ","pages":"Article 101213"},"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}

{"title":"Neuroprotection in glaucoma: Mechanisms beyond intraocular pressure lowering","authors":"James R. Tribble ,&nbsp;Flora Hui ,&nbsp;Heberto Quintero ,&nbsp;Sana El Hajji ,&nbsp;Katharina Bell ,&nbsp;Adriana Di Polo ,&nbsp;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":"92 ","pages":"Article 101193"},"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}

{"title":"Mechanisms of organ fibrosis: Emerging concepts and implications for novel treatment strategies","authors":"Isabella Lurje ,&nbsp;Nadine T. Gaisa ,&nbsp;Ralf Weiskirchen ,&nbsp;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":"92 ","pages":"Article 101191"},"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}

{"title":"Antifungal prophylaxis and pre-emptive therapy: When and how?","authors":"Rosanne Sprute ,&nbsp;Julia A. Nacov ,&nbsp;Dionysios Neofytos ,&nbsp;Matteo Oliverio ,&nbsp;Juergen Prattes ,&nbsp;Ilana Reinhold ,&nbsp;Oliver A. Cornely ,&nbsp;Jannik Stemler","doi":"10.1016/j.mam.2023.101190","DOIUrl":"10.1016/j.mam.2023.101190","url":null,"abstract":"<div><p>The growing pool of critically ill or immunocompromised patients leads to a constant increase of life-threatening invasive infections by fungi such as <em>Aspergillus</em> spp., <em>Candida</em> spp. and <em>Pneumocystis jirovecii</em>.</p><p>In response to this, prophylactic and pre-emptive antifungal treatment strategies have been developed and implemented for high-risk patient populations. The benefit by risk reduction needs to be carefully weighed against potential harm caused by prolonged exposure against antifungal agents. This includes adverse effects and development of resistance as well as costs for the healthcare system.</p><p>In this review, we summarise evidence and discuss advantages and downsides of antifungal prophylaxis and pre-emptive treatment in the setting of malignancies such as acute leukaemia, haematopoietic stem cell transplantation, CAR-T cell therapy, and solid organ transplant. We also address preventive strategies in patients after abdominal surgery and with viral pneumonia as well as individuals with inherited immunodeficiencies.</p><p>Notable progress has been made in haematology research, where strong recommendations regarding antifungal prophylaxis and pre-emptive treatment are backed by data from randomized controlled trials, whereas other critical areas still lack high-quality evidence. In these areas, paucity of definitive data translates into centre-specific strategies that are based on interpretation of available data, local expertise, and epidemiology.</p><p>The development of novel immunomodulating anticancer drugs, high-end intensive care treatment and the development of new antifungals with new modes of action, adverse effects and routes of administration will have implications on future prophylactic and pre-emptive approaches.</p></div>","PeriodicalId":49798,"journal":{"name":"Molecular Aspects of Medicine","volume":"92 ","pages":"Article 101190"},"PeriodicalIF":10.6,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9725419","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}

{"title":"Microorganisms-derived antigens for preventive anti-cancer vaccines","authors":"Luigi Buonaguro ,&nbsp;Beatrice Cavalluzzo ,&nbsp;Angela Mauriello ,&nbsp;Concetta Ragone ,&nbsp;Anna Lucia Tornesello ,&nbsp;Franco M. Buonaguro ,&nbsp;Maria Lina Tornesello ,&nbsp;Maria Tagliamonte","doi":"10.1016/j.mam.2023.101192","DOIUrl":"10.1016/j.mam.2023.101192","url":null,"abstract":"<div><p>Cancer prevention is one of the aim with the highest priority in order to reduce the burden of cancer diagnosis and treatment on individuals as well as on healthcare systems.</p><p>To this aim, vaccines represent the most efficient primary cancer prevention strategy. Indeed, anti-cancer immunological memory elicited by preventive vaccines might promptly expand and prevent tumor from progressing.</p><p>Antigens derived from microorganisms (MoAs), represent the obvious target for developing highly effective preventive vaccines for virus-induced cancers. In this respect, the drastic reduction in cancer incidence following HBV and HPV preventive vaccines are the paradigmatic example of such evidence. More recently, experimental evidences suggest that MoAs may represent a “natural” anti-cancer preventive vaccination or can be exploited for developing vaccines to prevent cancers presenting highly homologous tumor-associated antigens (TAAs) (e.g. molecular mimicry).</p><p>The present review describes the different preventive anti-cancer vaccines based on antigens derived from pathogens at the different stages of development.</p></div>","PeriodicalId":49798,"journal":{"name":"Molecular Aspects of Medicine","volume":"92 ","pages":"Article 101192"},"PeriodicalIF":10.6,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9726396","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}

{"title":"Vaccination against Helicobacter pylori – An approach for cancer prevention?","authors":"Verena Friedrich,&nbsp;Markus Gerhard","doi":"10.1016/j.mam.2023.101183","DOIUrl":"10.1016/j.mam.2023.101183","url":null,"abstract":"<div><p>The gram-negative bacterium <em>Helicobacter pylori</em> is the most common chronic bacterial infection and the main cause of gastric cancer. Due to the increasing antimicrobial resistance of <em>H. pylori</em>, the development of an efficacious vaccine is a valid option to protect from disease or infection and ultimately prevent gastric cancer. However, despite more than 30 years of research, no vaccine has entered the market yet. This review highlights the most relevant previous preclinical and clinical studies to allow conclusions to be drawn on which parameters need special attention in the future to develop an efficacious vaccine against <em>H. pylori</em> and thus prevent gastric cancer.</p></div>","PeriodicalId":49798,"journal":{"name":"Molecular Aspects of Medicine","volume":"92 ","pages":"Article 101183"},"PeriodicalIF":10.6,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9732679","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}

{"title":"Protein structure-based in-silico approaches to drug discovery: Guide to COVID-19 therapeutics","authors":"Yash Gupta ,&nbsp;Oleksandr V. Savytskyi ,&nbsp;Matt Coban ,&nbsp;Amoghavarsha Venugopal ,&nbsp;Vasili Pleqi ,&nbsp;Caleb A. Weber ,&nbsp;Rohit Chitale ,&nbsp;Ravi Durvasula ,&nbsp;Christopher Hopkins ,&nbsp;Prakasha Kempaiah ,&nbsp;Thomas R. Caulfield","doi":"10.1016/j.mam.2022.101151","DOIUrl":"10.1016/j.mam.2022.101151","url":null,"abstract":"<div><p>With more than 5 million fatalities and close to 300 million reported cases, COVID-19 is the first documented pandemic due to a coronavirus that continues to be a major health challenge. Despite being rapid, uncontrollable, and highly infectious in its spread, it also created incentives for technology development and redefined public health needs and research agendas to fast-track innovations to be translated. Breakthroughs in computational biology peaked during the pandemic with renewed attention to making all cutting-edge technology deliver agents to combat the disease. The demand to develop effective treatments yielded surprising collaborations from previously segregated fields of science and technology. The long-standing pharmaceutical industry's aversion to repurposing existing drugs due to a lack of exponential financial gain was overrun by the health crisis and pressures created by front-line researchers and providers. Effective vaccine development even at an unprecedented pace took more than a year to develop and commence trials. Now the emergence of variants and waning protections during the booster shots is resulting in breakthrough infections that continue to strain health care systems. As of now, every protein of SARS-CoV-2 has been structurally characterized and related host pathways have been extensively mapped out. The research community has addressed the druggability of a multitude of possible targets. This has been made possible due to existing technology for virtual computer-assisted drug development as well as new tools and technologies such as artificial intelligence to deliver new leads. Here in this article, we are discussing advances in the drug discovery field related to target-based drug discovery and exploring the implications of known target-specific agents on COVID-19 therapeutic management. The current scenario calls for more personalized medicine efforts and stratifying patient populations early on for their need for different combinations of prognosis-specific therapeutics. We intend to highlight target hotspots and their potential agents, with the ultimate goal of using rational design of new therapeutics to not only end this pandemic but also uncover a generalizable platform for use in future pandemics.</p></div>","PeriodicalId":49798,"journal":{"name":"Molecular Aspects of Medicine","volume":"91 ","pages":"Article 101151"},"PeriodicalIF":10.6,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9613808/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10198404","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}

{"title":"In vitro high-content tissue models to address precision medicine challenges","authors":"Samson Afewerki ,&nbsp;Thiago Domingues Stocco ,&nbsp;André Diniz Rosa da Silva ,&nbsp;André Sales Aguiar Furtado ,&nbsp;Gustavo Fernandes de Sousa ,&nbsp;Guillermo U. Ruiz-Esparza ,&nbsp;Thomas J. Webster ,&nbsp;Fernanda R. Marciano ,&nbsp;Maria Strømme ,&nbsp;Yu Shrike Zhang ,&nbsp;Anderson Oliveira Lobo","doi":"10.1016/j.mam.2022.101108","DOIUrl":"10.1016/j.mam.2022.101108","url":null,"abstract":"<div><p>The field of precision medicine allows for tailor-made treatments specific to a patient and thereby improve the efficiency and accuracy of disease prevention, diagnosis, and treatment and at the same time would reduce the cost, redundant treatment, and side effects of current treatments. Here, the combination of organ-on-a-chip and bioprinting into engineering high-content <em>in vitro</em> tissue models is envisioned to address some precision medicine challenges. This strategy could be employed to tackle the current coronavirus disease 2019 (COVID-19), which has made a significant impact and paradigm shift in our society. Nevertheless, despite that vaccines against COVID-19 have been successfully developed and vaccination programs are already being deployed worldwide, it will likely require some time before it is available to everyone. Furthermore, there are still some uncertainties and lack of a full understanding of the virus as demonstrated in the high number new mutations arising worldwide and reinfections of already vaccinated individuals. To this end, efficient diagnostic tools and treatments are still urgently needed. In this context, the convergence of bioprinting and organ-on-a-chip technologies, either used alone or in combination, could possibly function as a prominent tool in addressing the current pandemic. This could enable facile advances of important tools, diagnostics, and better physiologically representative <em>in vitro</em> models specific to individuals allowing for faster and more accurate screening of therapeutics evaluating their efficacy and toxicity. This review will cover such technological advances and highlight what is needed for the field to mature for tackling the various needs for current and future pandemics as well as their relevancy towards precision medicine.</p></div>","PeriodicalId":49798,"journal":{"name":"Molecular Aspects of Medicine","volume":"91 ","pages":"Article 101108"},"PeriodicalIF":10.6,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9384546/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9283979","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}