{"title":"An Update on Clinical and Pathogenic Spectra of Leishmaniasis.","authors":"Angamuthu Selvapandiyan, Shital Shital, Diya A'gitok Sangma, Manju Jain, Nadira Karunaweera, Nirmal K Ganguly","doi":"10.1017/erm.2025.4","DOIUrl":"10.1017/erm.2025.4","url":null,"abstract":"<p><p>Leishmaniasis, classified as a neglected tropical disease, exerts its impact on millions globally. Its clinical spectrum encompasses diverse forms, from benign self-resolving skin lesions (cutaneous leishmaniasis) to life-threatening visceral infections (visceral leishmaniasis or kala-azar). This review aims to comprehensively explore the spectrum of the disease as an outcome of often-overlooked parasite variants. Additionally, it addresses the emerging challenges faced in the pursuit towards disease elimination. The evolving landscape of leishmaniasis demands the development of molecular surveillance tools to detect the heterogeneous parasite strains that contribute to the emergence of new endemic foci. Such surveillance poses formidable challenges to current elimination strategies. As the disease landscape continues to evolve, understanding the molecular intricacies of causative parasite strains becomes paramount. This knowledge not only aids the understanding of the basis of emerging/shifting endemic areas but also facilitates the search for and the design of targeted interventions. In this context, this review will navigate through the dynamic terrain of leishmaniasis, the various causative species of <i>Leishmania</i> parasites emphasising the urgency for the development of robust surveillance mechanisms and innovative approaches to confront the evolving challenges in our quest for global disease elimination.</p>","PeriodicalId":50462,"journal":{"name":"Expert Reviews in Molecular Medicine","volume":" ","pages":"e27"},"PeriodicalIF":5.5,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143755889","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}
Sara Ouaidat, Alessandro Bellapianta, Franziska Ammer-Pickhardt, Tara Taghipour, Matthias Bolz, Ahmad Salti
{"title":"Exploring organoid and assembloid technologies: a focus on retina and brain.","authors":"Sara Ouaidat, Alessandro Bellapianta, Franziska Ammer-Pickhardt, Tara Taghipour, Matthias Bolz, Ahmad Salti","doi":"10.1017/erm.2025.9","DOIUrl":"10.1017/erm.2025.9","url":null,"abstract":"<p><strong>Background: </strong>The recent emergence of three-dimensional organoids and their utilization as in vitro disease models confirmed the complexities behind organ-specific functions and unravelled the importance of establishing suitable human models for various applications. Also, in light of persistent challenges associated with their use, researchers have been striving to establish more advanced structures (i.e. assembloids) that can help address the limitations presented in the current organoids.</p><p><strong>Methods: </strong>In this review, we discuss the distinct organoid types that are available to date, with a special focus on retinal and brain organoids, and highlight their importance in disease modelling.</p><p><strong>Results: </strong>We refer to published research to explore the extent to which retinal and brain organoids can serve as potential alternatives to organ/cell transplants and direct our attention to the topic of photostimulation in retinal organoids. Additionally, we discuss the advantages of incorporating microfluidics and organ-on-a-chip devices for boosting retinal organoid performance. The challenges of organoids leading to the subsequent development of assembloid fusion models are also presented.</p><p><strong>Conclusion: </strong>In conclusion, organoid technology has laid the foundation for generating upgraded models that not only better replicate in vivo systems but also allow for a deeper comprehension of disease pathophysiology.</p>","PeriodicalId":50462,"journal":{"name":"Expert Reviews in Molecular Medicine","volume":" ","pages":"e14"},"PeriodicalIF":4.5,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12011387/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143722447","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":"Plant-derived products as anti-leishmanials which target mitochondria: a review.","authors":"Chandrima Shaha","doi":"10.1017/erm.2025.8","DOIUrl":"10.1017/erm.2025.8","url":null,"abstract":"<p><strong>Background: </strong>The global incidences of leishmaniasis are increasing due to changing environmental conditions and growing poverty. Leishmaniasis, caused by the <i>Leishmania</i> parasite, presents itself in six different clinical forms, the cutaneous and the visceral diseases being the most prevalent. While the cutaneous form causes disfigurement, the visceral form could be fatal if not treated. With no available vaccines combined with serious side effects of current medications and emerging drug resistance, it is crucial to discover new drugs whether as novel compounds or as repurposed existing pharmaceuticals. In the realm of drug development, mitochondria are recognized as important pharmacological targets due to their critical role in energy control, which, when disrupted, leads to irreversible cell damage. Certain plant-based compounds able to target the parasite mitochondrion, have been studied for their potential anti-leishmanial effects.</p><p><strong>Search results: </strong>These compounds have shown promising effects in eliminating the <i>Leishmania</i> parasite. Artemisinin and chloroquine, two anti-malarial drugs that target mitochondria, exert strong anti-leishmanial effectiveness in both <i>in vitro</i> cultures and <i>in vivo</i> animal models. Quinolones, coumarins and quercetin are other compounds with leishmanicidal properties, which disrupt mitochondrial activity to effectively eliminate parasites in animal models of the disease and could be considered as potential drugs.</p><p><strong>Conclusions: </strong>Therefore, plant-based compounds hold promise as potential candidates for anti-leishmanial drug development.</p>","PeriodicalId":50462,"journal":{"name":"Expert Reviews in Molecular Medicine","volume":" ","pages":"e15"},"PeriodicalIF":4.5,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12043268/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143710991","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}
Esra Atalay-Sahar, Ece Yildiz-Ozturk, Su Ozgur, Arzu Aral, Emre Dayanc, Tuncay Goksel, Ralph Meuwissen, Ozlem Yesil-Celiktas, Ozlem Goksel
{"title":"Novel Approach Methodologies in Modeling Complex Bioaerosol Exposure in Asthma and Allergic Rhinitis Under Climate Change.","authors":"Esra Atalay-Sahar, Ece Yildiz-Ozturk, Su Ozgur, Arzu Aral, Emre Dayanc, Tuncay Goksel, Ralph Meuwissen, Ozlem Yesil-Celiktas, Ozlem Goksel","doi":"10.1017/erm.2025.7","DOIUrl":"10.1017/erm.2025.7","url":null,"abstract":"<p><p>The undeniable impact of climate change and air pollution on respiratory health has led to increasing cases of asthma, allergic rhinitis and other chronic non-communicable immune-mediated upper and lower airway diseases. Natural bioaerosols, such as pollen and fungi, are essential atmospheric components undergoing significant structural and functional changes due to industrial pollution and atmospheric warming. Pollutants like particulate matter(PMx), polycyclic aromatic hydrocarbons(PAHs), nitrogen dioxide(NO<sub>2</sub>), sulfur dioxide(SO<sub>2</sub>) and carbon monoxide(CO) modify the surface and biological properties of atmospheric bioaerosols such as pollen and fungi, enhancing their allergenic potentials. As a result, sensitized individuals face heightened risks of asthma exacerbation, and these alterations likely contribute to the rise in frequency and severity of allergic diseases. NAMs, such as precision-cut lung slices(PCLS), air-liquid interface(ALI) cultures and lung-on-a-chip models, along with the integration of data from these innovative models with computational models, provide better insights into how environmental factors influence asthma and allergic diseases compared to traditional models. These systems simulate the interaction between pollutants and the respiratory system with higher precision, helping to better understand the health implications of bioaerosol exposure. Additionally, NAMs improve preclinical study outcomes by offering higher throughput, reduced costs and greater reproducibility, enhancing the translation of data into clinical applications. This review critically evaluates the potential of NAMs in researching airway diseases, with a focus on allergy and asthma. It highlights their advantages in studying the increasingly complex structures of bioaerosols under conditions of environmental pollution and climate change, while also addressing the existing gaps, challenges and limitations of these models.</p>","PeriodicalId":50462,"journal":{"name":"Expert Reviews in Molecular Medicine","volume":" ","pages":"e13"},"PeriodicalIF":4.5,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11964095/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143607000","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}
Shuoqi Lin, Genggeng Zheng, Yuxiang Yan, Tesen Liao, Bohua Su, Dali Zheng
{"title":"Targeting the Kynurenine Pathway: A Novel Approach in Tumor Therapy.","authors":"Shuoqi Lin, Genggeng Zheng, Yuxiang Yan, Tesen Liao, Bohua Su, Dali Zheng","doi":"10.1017/erm.2025.5","DOIUrl":"10.1017/erm.2025.5","url":null,"abstract":"","PeriodicalId":50462,"journal":{"name":"Expert Reviews in Molecular Medicine","volume":" ","pages":"1-33"},"PeriodicalIF":5.5,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12315670/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143558702","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":"Review of microRNA detection workflows from liquid biopsy for disease diagnostics.","authors":"Dulguunnaran Naranbat, Emilia Herdes, Nikos Tapinos, Anubhav Tripathi","doi":"10.1017/erm.2025.2","DOIUrl":"10.1017/erm.2025.2","url":null,"abstract":"<p><p>MicroRNAs have emerged as effective biomarkers in disease diagnostics, particularly cancer, due to their role as regulatory sequences. More recently, microRNAs have been detected in liquid biopsies, which hold immense potential for early disease diagnostics. This review comprehensively analyses distinct liquid biopsy microRNA detection methods validated with clinical samples. Each step in the microRNA detection workflow, including sample collection, RNA isolation, processing, and detection of target microRNAs, has been thoroughly assessed. The review discusses the advantages and limitations of established and novel techniques in microRNA detection workflows, discussing their diagnostic capabilities and potential for future implementation at scale.</p>","PeriodicalId":50462,"journal":{"name":"Expert Reviews in Molecular Medicine","volume":" ","pages":"e11"},"PeriodicalIF":4.5,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11879380/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143257218","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":"Lactylation and human disease.","authors":"Linlin Wan, HuiJuan Zhang, Jialing Liu, Qian He, Jiumei Zhao, Chenglong Pan, Kepu Zheng, Yu Tang","doi":"10.1017/erm.2025.3","DOIUrl":"10.1017/erm.2025.3","url":null,"abstract":"<p><strong>Background: </strong>Lactylation, a new epigenetic modification, is an important way in which lactate exerts physiological functions. There is a close relationship between increased lactylations caused by lactate and glycolysis, which can interact and play a role in disease through lactate as an intermediate mediator. Current research on lactylations has focused on histone lactylation, but non-histone lactylation also has greater research potential. Due to the ubiquity of lactate modifications in mammalian cells, an increasing number of studies have found that lactate modifications play important roles in tumour cell metabolism, gene transcription and immunity.</p><p><strong>Methods: </strong>A systematic literature search was carried out using search key terms and synonyms. Full-paper screening was performed based on specific inclusion and exclusion criteria.</p><p><strong>Results: </strong>Many literatures have reported that the lactylation of protein plays an important role in human diseases and is involved in the occurrence and development of human diseases.</p><p><strong>Conclusions: </strong>This article summary the correlation between lactylation and glycolysis, histones and non-histone proteins; the relationship between lactonation modifications and tumour development; and the current existence of lactylation-related inhibitors, with a view to provide new basic research ideas and clinical therapeutic tools for lactylation-related diseases.</p>","PeriodicalId":50462,"journal":{"name":"Expert Reviews in Molecular Medicine","volume":" ","pages":"e10"},"PeriodicalIF":4.5,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11879378/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143081633","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}
Hana Selvi, Anke Brüning-Richardson, Davide Danovi
{"title":"Systematic Review of Pre-Clinical Systems Using Artificial Microenvironments and Anti-Migratory Drugs to Control Migration of Glioblastoma Cells.","authors":"Hana Selvi, Anke Brüning-Richardson, Davide Danovi","doi":"10.1017/erm.2024.33","DOIUrl":"10.1017/erm.2024.33","url":null,"abstract":"<p><strong>Background: </strong>Glioblastoma multiforme (GBM) is the most prevalent primary brain tumour, with an incidence of 2 per 100,000. The standard clinical treatments do not sufficiently target cell migration and invasion, leading to recurrence after surgical resection and resistance after chemotherapy and radiotherapy. Pre-clinical studies are being conducted to construct artificial substrates that can mimic the tumour microenvironment (TME) to prevent GBM cells from migrating along their primary route through blood vessels and white matter tracts. Alongside, targeted therapies using anti-migratory or ‘migrastatic’ drugs are also being developed. This study aimed to review the therapeutic translational strategies emerging from the study of the GBM microenvironment and anti-migratory drugs.</p><p><strong>Methods: </strong>A systematic literature search was carried out using search key terms and synonyms. Full-paper screening was performed based on specific inclusion and exclusion criteria.</p><p><strong>Results: </strong>From the systems interrogated, the ‘Nanofibre’ assay is suitable to simulate white matter tracts, while hydrogel-based invasion assays and GBM cerebral organoid (GLICO) mimic the brain extracellular matrix. Inhibitors with anti-migratory activity found in this study are active involving distinct molecular mechanisms and have been tested on cell migration assays.</p><p><strong>Conclusion: </strong>Overall, we have analysed therapeutic strategies emerging from an artificial GBM TME approach and from the identification of anti-migratory inhibitors. Both carry potential to improve treatment options to prevent tumour dissemination and spread for GBM.</p>","PeriodicalId":50462,"journal":{"name":"Expert Reviews in Molecular Medicine","volume":"27 ","pages":"e6"},"PeriodicalIF":5.5,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11803519/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143025007","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}
Olivia Battistoni, Ryan H Huston, Chaitenya Verma, Thalia Pacheco-Fernandez, Sara Abul-Khoudoud, Alison Campbell, Abhay R Satoskar
{"title":"Understanding Sex-biases in Kinetoplastid Infections: Leishmaniasis and Trypanosomiasis.","authors":"Olivia Battistoni, Ryan H Huston, Chaitenya Verma, Thalia Pacheco-Fernandez, Sara Abul-Khoudoud, Alison Campbell, Abhay R Satoskar","doi":"10.1017/erm.2024.41","DOIUrl":"10.1017/erm.2024.41","url":null,"abstract":"<p><strong>Background: </strong>Leishmaniasis, Chagas disease (CD), and Human African Trypanosomiasis (HAT) are neglected tropical diseases in humans caused by intracellular parasites from the class <i>Kinetoplastida</i>. Leishmaniasis is one infectious disease that exhibits sex-bias not explained solely by behavioral or cultural differences. However, HAT and CD have less well documented and understood sex-related differences, either due to a lack of differences or insufficient research and reporting.</p><p><strong>Methods: </strong>This paper reviews the rate of disease and disease severity among male and females infected with CD, HAT, and leishmaniasis. We further review the specific immune response to each pathogen and potential sex-based mechanisms which could impact immune responses and disease outcomes.</p><p><strong>Results: </strong>These mechanisms include sex hormone modulation of the immune response, sex-related genetic differences, and socio-cultural factors impacting risky behaviors in men and women. The mechanistic differences in immune response among sexes and pathogens provide important insights and identification of areas for further research.</p><p><strong>Conclusions: </strong>This information can aid in future development of inclusive, targeted, safe, and effective treatments and control measures for these neglected diseases and other infectious diseases.</p>","PeriodicalId":50462,"journal":{"name":"Expert Reviews in Molecular Medicine","volume":" ","pages":"e7"},"PeriodicalIF":4.5,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11803520/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142958274","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}
Isabele Cristiana Iser, Ana Paula Santin Bertoni, Liziane Raquel Beckenkamp, Marcia Edilaine Lopes Consolaro, Silvya Stuchi Maria-Engler, Marcia Rosângela Wink
{"title":"Adenosinergic Signalling in Cervical Cancer Microenvironment.","authors":"Isabele Cristiana Iser, Ana Paula Santin Bertoni, Liziane Raquel Beckenkamp, Marcia Edilaine Lopes Consolaro, Silvya Stuchi Maria-Engler, Marcia Rosângela Wink","doi":"10.1017/erm.2024.30","DOIUrl":"https://doi.org/10.1017/erm.2024.30","url":null,"abstract":"<p><p>Despite the emergence of the first human papillomavirus vaccine, the incidence of cervical cancer is still responsible for more than 350,000 deaths yearly. Over the past decade, ecto-5'-nucleotidase (CD73/5'-NT) and extracellular adenosine (ADO) signalling has been the subject of many investigations to target cancer progression. In general, the adenosinergic axis has been linked to tumourigenic effects. However, CD73 can play contradictory effects, probably dependent on the tumour type, tumour microenvironment and tumour stage, thus being in some circumstances, inversely related to tumour progression. We herein reviewed the pathophysiological function of CD73 in cervical cancer and performed <i>in silico</i> analysis of the main components of the adenosinergic signalling in human tissues of cervical cancer compared to non-tumour cervix tissue. Our data showed that the <i>NT5E</i> gene, that encoded CD73, is hypermethylated, leading to a decreased CD73 expression in cervical cancer cells compared to normal cells. Consequently, the high availability of ADO cytoplasmatic/extracellular leads to its conversion to AMP by ADK, culminating in global hypermethylation. Therefore, epigenetic modulation may reveal a new role for CD73 in cervical cancer.</p>","PeriodicalId":50462,"journal":{"name":"Expert Reviews in Molecular Medicine","volume":"27 ","pages":"e5"},"PeriodicalIF":4.5,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11707834/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142958275","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}