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}
Alexandra Mititelu, Alina Grama, Marius-Cosmin Colceriu, Tudor L Pop
{"title":"Overview of the cellular and immune mechanisms involved in acute pancreatitis: In search of new prognosis biomarkers.","authors":"Alexandra Mititelu, Alina Grama, Marius-Cosmin Colceriu, Tudor L Pop","doi":"10.1017/erm.2024.40","DOIUrl":"10.1017/erm.2024.40","url":null,"abstract":"<p><p>Acute pancreatitis (AP) is an acute-onset gastrointestinal disease characterized by a significant inflammation of the pancreas. Most of the time, AP does not leave substantial changes in the pancreas after the resolution of the symptoms but the severe forms are associated with local or systemic complications. The pathogenesis of AP has long been investigated and, lately, the importance of intracellular mechanisms and the immune system has been described. The initial modifications in AP take place in the acinar cell. There are multiple mechanisms by which cellular homeostasis is impaired, one of the most important being calcium overload. Necrotic pancreatic cells initiate the inflammatory response by secreting inflammatory mediators and attracting immune cells. From this point on, the inflammation is sustained by the involvement of innate and adaptive immune systems. Multiple studies have demonstrated the importance of the first 48 h for identifying patients at risk for developing severe forms. For this reason, there is a need to find new, easy-to-use and reliable markers for accurate predictions of these forms. This review provides an overview of the main pathogenetic mechanisms involved in AP development and the most promising biomarkers for severity stratification.</p>","PeriodicalId":50462,"journal":{"name":"Expert Reviews in Molecular Medicine","volume":" ","pages":"e9"},"PeriodicalIF":4.5,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11879381/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142933372","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}
Rakesh Arya, Surendra Kumar, Joseph M Vinetz, Jong Joo Kim, Reetika Chaurasia
{"title":"Unlocking the potential of miRNAs in detecting pulmonary tuberculosis: prospects and pitfalls.","authors":"Rakesh Arya, Surendra Kumar, Joseph M Vinetz, Jong Joo Kim, Reetika Chaurasia","doi":"10.1017/erm.2024.29","DOIUrl":"10.1017/erm.2024.29","url":null,"abstract":"<p><p>Tuberculosis (TB) is one of the deadliest infectious diseases globally, ranking as 13th leading cause of mortality and morbidity. According to the Global Tuberculosis Report 2022, TB claimed the lives of 1.6 million people worldwide in 2021. Among the casualties, 1 870 000 individuals with HIV co-infections contributed to 6.7% of the total fatalities, accounting TB as the second most lethal infectious disease following COVID-19. In the quest to identify biomarkers for disease progression and anti-TB therapy, microRNAs (miRNAs) have gained attention due to their precise regulatory role in gene expression in disease stages and their ability to distinguish latent and active TB, enabling the development of early TB prognostic signatures. miRNAs are stable in biological fluids and therefore will be useful for non-invasive and broad sample collection. However, their inherent lack of specificity and experimental variations may lead to false-positive outcomes. These limitations can be overcome by integrating standard protocols with machine learning, presenting a novel tool for TB diagnostics and therapeutics. This review summarizes, discusses and highlights the potential of miRNAs as a biomarker, particularly their differential expression at disease stages. The review assesses the advantages and obstacles associated with miRNA-based diagnostic biomarkers in pulmonary TB and facilitates rapid, point-of-care testing.</p>","PeriodicalId":50462,"journal":{"name":"Expert Reviews in Molecular Medicine","volume":"26 ","pages":"e32"},"PeriodicalIF":4.5,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11629464/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142787623","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}
Yuwen Han, Yuanshuai Zhou, Jinlin Pan, Minxuan Sun, Jiao Yang
{"title":"MAN2B1 in immune system-related diseases, neurodegenerative disorders and cancers: functions beyond α-mannosidosis.","authors":"Yuwen Han, Yuanshuai Zhou, Jinlin Pan, Minxuan Sun, Jiao Yang","doi":"10.1017/erm.2024.34","DOIUrl":"10.1017/erm.2024.34","url":null,"abstract":"<p><p>Glycosylation modifications of proteins and glycan hydrolysis are critical for protein function in biological processes. Aberrations in glycosylation enzymes are linked to lysosomal storage disorders (LSDs), immune interactions, congenital disorders and tumour progression. Mannosidase alpha class 2B member 1 (MAN2B1) is a lysosomal hydrolase from the α-mannosidase family. Dysfunction of MAN2B1 has been implicated as causative factors in mannosidosis, a lysosomal storage disorder characterised by cognitive impairment, hearing loss and immune system and skeletal anomalies. Despite decades of research, its role in pathogenic infections, autoimmune conditions, cancers and neurodegenerative pathologies is highly ambiguous. Future studies are required to shed more light on the intricate functioning of MAN2B1. To this end, we review the biological functions, expression patterns, enzymatic roles and potential implications of MAN2B1 across various cell types and disease contexts. Additionally, the novel insights presented in this review may aid in understanding the role of MAN2B1 in immune cells, thereby paving the way for targeted therapeutic interventions in immune-related disorders.</p>","PeriodicalId":50462,"journal":{"name":"Expert Reviews in Molecular Medicine","volume":" ","pages":"e4"},"PeriodicalIF":4.5,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11707832/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142773925","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}
Gabriella Crawford, Olivia Soper, Eunchai Kang, Daniel A Berg
{"title":"Advancing insights into virus-induced neurodevelopmental disorders through human brain organoid modelling.","authors":"Gabriella Crawford, Olivia Soper, Eunchai Kang, Daniel A Berg","doi":"10.1017/erm.2024.35","DOIUrl":"10.1017/erm.2024.35","url":null,"abstract":"<p><p>Human neurodevelopment is a complex process vulnerable to disruptions, particularly during the prenatal period. Maternal viral infections represent a significant environmental factor contributing to a spectrum of congenital defects with profound and enduring impacts on affected offspring. The advent of induced pluripotent stem cell (iPSC)-derived three-dimensional (3D) human brain organoids has revolutionised our ability to model prenatal viral infections and associated neurodevelopmental disorders. Notably, human brain organoids provide a distinct advantage over traditional animal models, whose brain structures and developmental processes differ markedly from those of humans. These organoids offer a sophisticated platform for investigating viral pathogenesis, infection mechanisms and potential therapeutic interventions, as demonstrated by their pivotal role during the 2016 Zika virus outbreak. This review critically examines the utilisation of brain organoids in elucidating the mechanisms of TORCH viral infections, their impact on human brain development and contribution to associated neurodevelopmental disorders.</p>","PeriodicalId":50462,"journal":{"name":"Expert Reviews in Molecular Medicine","volume":" ","pages":"e1"},"PeriodicalIF":4.5,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11707831/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142717646","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}
Faria Hasanzadeh Haghighi, Shaho Menbari, Roghayeh Mohammadzadeh, Abbas Pishdadian, Hadi Farsiani
{"title":"Developing a potent vaccine against <i>Helicobacter pylori</i>: critical considerations and challenges.","authors":"Faria Hasanzadeh Haghighi, Shaho Menbari, Roghayeh Mohammadzadeh, Abbas Pishdadian, Hadi Farsiani","doi":"10.1017/erm.2024.19","DOIUrl":"10.1017/erm.2024.19","url":null,"abstract":"<p><p><i>Helicobacter pylori</i> (<i>H. pylori)</i> is closely associated with gastric cancer and peptic ulcers. The effectiveness of antibiotic treatment against <i>H. pylori</i> is diminished by the emergence of drug-resistant strains, side effects, high cost and reinfections. Given the circumstances, it is imperative to develop a potent vaccination targeting <i>H. pylori.</i> Understanding <i>H. pylori</i>'s pathogenicity and the host's immune response is essential to developing a vaccine. Furthermore, vaccine evaluation necessitates the careful selection of design formulation. This review article aims to provide a concise overview of the considerations involved in selecting the optimal antigen, adjuvant, vaccine delivery system and laboratory animal model for vaccine formulation. Furthermore, we will discuss some significant obstacles in the realm of developing a potent vaccination against <i>H. pylori.</i></p>","PeriodicalId":50462,"journal":{"name":"Expert Reviews in Molecular Medicine","volume":" ","pages":"e12"},"PeriodicalIF":4.5,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11964096/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142711851","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":"Exercise Mediates Noncoding RNAs in Cardiovascular Diseases: Pathophysiological Roles and Clinical Application.","authors":"Changyong Wu, Xiaocui Chen, Lu Yang, Huang Sun, Suli Bao, Haojie Li, Lihui Zheng, Huiling Zeng, Ruijie Li, Yunzhu Peng","doi":"10.1017/erm.2024.25","DOIUrl":"10.1017/erm.2024.25","url":null,"abstract":"<p><p>Exercise-based cardiac rehabilitation is effective in improving cardiovascular disease risk factor management, cardiopulmonary function, and quality of life. However, the precise mechanisms underlying exercise-induced cardioprotection remain elusive. Recent studies have shed light on the beneficial functions of noncoding RNAs in either exercise or illness models, but only a limited number of noncoding RNAs have been studied in both contexts. Hence, the present study aimed to elucidate the pathophysiological implications and molecular mechanisms underlying the association among exercise, noncoding RNAs, and cardiovascular diseases. Additionally, the present study analysed the most effective and personalized exercise prescription, serving as a valuable reference for guiding the clinical implementation of cardiac rehabilitation in patients with cardiovascular diseases.</p>","PeriodicalId":50462,"journal":{"name":"Expert Reviews in Molecular Medicine","volume":" ","pages":"e2"},"PeriodicalIF":4.5,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11707833/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142683311","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":"Exploring the Antifibrotic Mechanisms of Ghrelin: Modulating TGF-β Signalling in Organ Fibrosis.","authors":"Mei Li, Chang Zheng, Huiyi Wang, Shan Wang","doi":"10.1017/erm.2024.38","DOIUrl":"10.1017/erm.2024.38","url":null,"abstract":"<p><strong>Background: </strong>Fibrosis is a pathological condition that affects various organs by increasing fibrous connective tissue while reducing parenchymal cells. This imbalance can lead to compromised organ function and potential failure, posing significant health risks. The condition's complexity necessitates the exploration of effective treatments to mitigate its progression and adverse outcomes.</p><p><strong>Aims: </strong>This study aims to investigate the role of ghrelin, a peptide hormone known for its anti-inflammatory and anti-fibrotic properties, in modulating fibrosis across different organs. By binding to the growth hormone secretagogue receptor type 1a (GHSR-1a), ghrelin has shown potential in attenuating the fibrotic process, particularly through its interaction with the TGF-β signalling pathway.</p><p><strong>Methods: </strong>An extensive review of clinical and animal model studies focusing on liver, kidney, lung, and myocardial fibrosis was conducted. The primary focus was on examining how ghrelin influences the TGF-β signalling pathway, with an emphasis on the regulation of TGF-β expression and the suppression of Smad signalling molecules. The methodology involved analysing data from various studies to understand ghrelin's molecular mechanisms in combating fibrosis.</p><p><strong>Results: </strong>The findings from the reviewed studies indicate that ghrelin exerts significant anti-fibrotic effects across multiple organ systems. Specifically, ghrelin was found to downregulate TGF-β expression and suppress Smad signalling molecules, leading to a marked reduction in fibrous tissue accumulation and preservation of organ function. In liver fibrosis models, ghrelin reduced TGF-β1 levels and Smad3 phosphorylation, while in kidney and cardiac fibrosis, similar protective effects were observed. The data also suggest that ghrelin's effects are mediated through both canonical and non-canonical TGF-β pathways.</p><p><strong>Conclusions: </strong>Ghrelin presents a promising therapeutic agent in the management of fibrosis due to its potent anti-inflammatory and anti-fibrotic actions. Its ability to modulate the TGF-β signalling pathway underscores a vital molecular mechanism through which ghrelin can mitigate fibrotic progression in various organs. Future research should focus on further elucidating ghrelin's molecular interactions and potential clinical applications in fibrosis treatment, offering new avenues for developing effective anti-fibrotic therapies.</p>","PeriodicalId":50462,"journal":{"name":"Expert Reviews in Molecular Medicine","volume":" ","pages":"e8"},"PeriodicalIF":4.5,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11879379/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142683322","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}
Yangyang Lu, Rongjing Shi, Wenqin He, Qi An, Jingwen Zhao, Xinnan Gao, Baiyan Zhang, Liyun Zhang, Ke Xu, Dan Ma
{"title":"Cell therapy in Sjögren's syndrome: opportunities and challenges.","authors":"Yangyang Lu, Rongjing Shi, Wenqin He, Qi An, Jingwen Zhao, Xinnan Gao, Baiyan Zhang, Liyun Zhang, Ke Xu, Dan Ma","doi":"10.1017/erm.2024.21","DOIUrl":"https://doi.org/10.1017/erm.2024.21","url":null,"abstract":"<p><p>Sjögren's syndrome (SS) is a chronic autoimmune disease caused by immune system disorders. The main clinical manifestations of SS are dry mouth and eyes caused by the destruction of exocrine glands, such as the salivary and lacrimal glands, and systemic manifestations, such as interstitial pneumonia, interstitial nephritis and vasculitis. The pathogenesis of this condition is complex. However, this has not been fully elucidated. Treatment mainly consists of glucocorticoids, disease-modifying antirheumatic drugs and biological agents, which can only control inflammation but not repair the tissue. Therefore, identifying methods to regulate immune disorders and repair damaged tissues is imperative. Cell therapy involves the transplantation of autologous or allogeneic normal or bioengineered cells into the body of a patient to replace damaged cells or achieve a stronger immunomodulatory capacity to cure diseases, mainly including stem cell therapy and immune cell therapy. Cell therapy can reduce inflammation, relieve symptoms and promote tissue repair and regeneration of exocrine glands such as the salivary glands. It has broad application prospects and may become a new treatment strategy for patients with SS. However, there are various challenges in cell preparation, culture, storage and transportation. This article reviews the research status and prospects of cell therapies for SS.</p>","PeriodicalId":50462,"journal":{"name":"Expert Reviews in Molecular Medicine","volume":"26 ","pages":"e28"},"PeriodicalIF":4.5,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11505611/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142512264","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}