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":null,"pages":null},"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}
{"title":"Radiation drives tertiary lymphoid structures to reshape TME for synergized antitumour immunity.","authors":"Shuling Li, Kuifei Chen, Zhenwei Sun, Meng Chen, Wenhu Pi, Suna Zhou, Haihua Yang","doi":"10.1017/erm.2024.27","DOIUrl":"https://doi.org/10.1017/erm.2024.27","url":null,"abstract":"<p><p>Radiotherapy (RT) plays a key role in the tumour microenvironment (TME), impacting the immune response via cellular and humoral immunity. RT can induce local immunity to modify the TME. It can stimulate dendritic cell maturation and T-cell infiltration. Moreover, B cells, macrophages and other immune cells may also be affected. Tertiary lymphoid structure (TLS) is a unique structure within the TME and a class of aggregates containing T cells, B cells and other immune cells. The maturation of TLS is determined by the presence of mature dendritic cells, the density of TLS is determined by the number of immune cells. TLS maturation and density both affect the antitumour immune response in the TME. This review summarized the recent research on the impact and the role of RT on TLS, including the changes of TLS components and formation conditions and the mechanism of how RT affects TLS and transforms the TME. RT may promote TLS maturation and density to modify the TME regarding enhanced antitumour immunity.</p>","PeriodicalId":50462,"journal":{"name":"Expert Reviews in Molecular Medicine","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11505612/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142512265","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}
Madhura Shekhar Patil, Emma Richter, Lara Fanning, Jolien Hendrix, Arne Wyns, Laura Barrero Santiago, Jo Nijs, Lode Godderis, Andrea Polli
{"title":"Epigenetic changes in patients with post-acute COVID-19 symptoms (PACS) and long-COVID: A systematic review.","authors":"Madhura Shekhar Patil, Emma Richter, Lara Fanning, Jolien Hendrix, Arne Wyns, Laura Barrero Santiago, Jo Nijs, Lode Godderis, Andrea Polli","doi":"10.1017/erm.2024.32","DOIUrl":"10.1017/erm.2024.32","url":null,"abstract":"<p><strong>Background: </strong>Up to 30% of people infected with SARS-CoV-2 report disabling symptoms 2 years after the infection. Over 100 persistent symptoms have been associated with Post-Acute COVID-19 Symptoms (PACS) and/or long-COVID, showing a significant clinical heterogeneity. To develop effective, patient-targeted treatment, a better understanding of underlying mechanisms is needed. Epigenetics has helped elucidating the pathophysiology of several health conditions and it might help unravelling inter-individual differences in patients with PACS and long-COVID. As accumulating research is exploring epigenetic mechanisms in PACS and long-COVID, we systematically summarized the available literature on the topic.</p><p><strong>Methods: </strong>We interrogated five databases (Medline, Embase, Web of Science, Scopus and medXriv/bioXriv) and followed PRISMA and SWiM guidelines to report our results.</p><p><strong>Results: </strong>Eight studies were included in our review. Six studies explored DNA methylation in PACS and/or long-COVID, while two studies explored miRNA expression in long-COVID associated with lung complications. Sample sizes were mostly small and study quality was low or fair. The main limitation of the included studies was a poor characterization of the patient population that made a homogeneous synthesis of the literature challenging. However, studies on DNA methylation showed that mechanisms related to the immune and the autonomic nervous system, and cell metabolism might be implicated in the pathophysiology of PACS and long-COVID.</p><p><strong>Conclusion: </strong>Epigenetic changes might help elucidating PACS and long-COVID underlying mechanisms, aid subgrouping, and point towards tailored treatments. Preliminary evidence is promising but scarce. Biological and epigenetic research on long-COVID will benefit millions of people suffering from long-COVID and has the potential to be transferable and benefit other conditions as well, such as Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). We urge future research to employ longitudinal designs and provide a better characterization of included patients.</p>","PeriodicalId":50462,"journal":{"name":"Expert Reviews in Molecular Medicine","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11505605/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142479703","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":"Advances in multifunctional metal-organic framework (MOF)-based nanoplatforms for cancer starvation therapy.","authors":"Jinghan Cai, Yan Xu, Fei Liao","doi":"10.1017/erm.2024.28","DOIUrl":"https://doi.org/10.1017/erm.2024.28","url":null,"abstract":"<p><p>Cancer remains a significant threat to human health today. Even though starvation therapy and other treatment methods have recently advanced to a new level of rapid development in tumour treatment, their limited therapeutic effectiveness and unexpected side effects prevent them from becoming the first option in clinical treatment. With rapid advancement in nanotechnology, the utilization of nanomaterials in therapeutics offers the potential to address the shortcomings in cancer treatment. Notably, multifunctional metal-organic framework (MOF) has been widely employed in cancer therapy due to their customizable shape, adjustable diameter, high porosity, diverse compositions, large specific surface area, high degree of functionalization and strong biocompatibility. This paper reviews the current progress and success of MOF-based multifunctional nanoplatforms for cancer starvation therapy, as well as the prospects and potential barriers for the application of MOF nanoplatforms in cancer starvation therapy.</p>","PeriodicalId":50462,"journal":{"name":"Expert Reviews in Molecular Medicine","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11488333/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142479702","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}
Ahmad Suhail Khazali, Waqiyuddin Hilmi Hadrawi, Fatimah Ibrahim, Shatrah Othman, Nurshamimi Nor Rashid
{"title":"Thrombocytopenia in dengue infection: mechanisms and a potential application.","authors":"Ahmad Suhail Khazali, Waqiyuddin Hilmi Hadrawi, Fatimah Ibrahim, Shatrah Othman, Nurshamimi Nor Rashid","doi":"10.1017/erm.2024.18","DOIUrl":"https://doi.org/10.1017/erm.2024.18","url":null,"abstract":"<p><p>Thrombocytopenia is a common symptom and one of the warning signs of dengue virus (DENV) infection. Platelet depletion is critical as it may lead to other severe dengue symptoms. Understanding the molecular events of this condition during dengue infection is challenging because of the multifaceted factors involved in DENV infection and the dynamics of the disease progression. Platelet levels depend on the balance between platelet production and platelet consumption or clearance. Megakaryopoiesis and thrombopoiesis, two interdependent processes in platelet production, are hampered during dengue infection. Conversely, platelet elimination via platelet activation, apoptosis and clearance processes are elevated. Together, these anomalies contribute to thrombocytopenia in dengue patients. Targeting the molecular events of dengue-mediated thrombocytopenia shows great potential but still requires further investigation. Nonetheless, the application of new knowledge in this field, such as immature platelet fraction analysis, may facilitate physicians in monitoring the progression of the disease.</p>","PeriodicalId":50462,"journal":{"name":"Expert Reviews in Molecular Medicine","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11488332/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142479704","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}
Akshat D Modi, Hira Zahid, Ashlyn Chase Southerland, Dharmeshkumar M Modi
{"title":"Epitranscriptomics and cervical cancer: the emerging role of m<sup>6</sup>A, m<sup>5</sup>C and m<sup>1</sup>A RNA modifications.","authors":"Akshat D Modi, Hira Zahid, Ashlyn Chase Southerland, Dharmeshkumar M Modi","doi":"10.1017/erm.2024.20","DOIUrl":"10.1017/erm.2024.20","url":null,"abstract":"<p><p>Cervical cancer (CC), one of the most prevalent and detrimental gynaecologic cancers, evolves through genetic and epigenetic alterations resulting in the promotion of oncogenic activity and dysfunction of tumour-suppressing mechanisms. Despite medical advancement, the prognosis for advanced-stage patients remains extremely low due to high recurrence rates and resistance to existing treatments. Thereby, the search for potential prognostic biomarkers is heightened to unravel new modalities of CC pathogenesis and to develop novel anti-cancer therapies. Epitranscriptomic modifications, reversible epigenetic RNA modifications, regulate various biological processes by deciding RNA fate to mediating RNA interactions. This narrative review provides insight into the cellular and molecular roles of endogenous RNA-editing proteins and their associated epitranscriptomic modifications, especially <i>N<sup>6</sup></i>-methyladenosine (m<sup>6</sup>A), 5-methylcytosine (m<sup>5</sup>C) and <i>N<sup>1</sup></i>-methyladenosine (m<sup>1</sup>A), in governing the development, progression and metastasis of CC. We discussed the in-depth epitranscriptomic mechanisms underlying the regulation of over 50 RNAs responsible for tumorigenesis, proliferation, migration, invasion, survival, autophagy, stemness, epithelial-mesenchymal transition, metabolism (glucose, lipid, glutamate and glutamine), resistance (drug and radiation), angiogenesis and recurrence of CC. Additionally, we provided a concise overview of the therapeutic potential of targeting the altered expression of endogenous RNA-editing proteins and aberrant deposition of RNA modifications on both coding and non-coding RNAs in CC.</p>","PeriodicalId":50462,"journal":{"name":"Expert Reviews in Molecular Medicine","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11488341/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142394923","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":"Repulsive guidance molecules b (RGMb): molecular mechanism, function and role in diseases.","authors":"Jie Zhang, Yijing Jiang, Zijian Zhang, Shilin Li, Haowen Fan, Jinhua Gu, Renfang Mao, Xiaohong Xu","doi":"10.1017/erm.2024.24","DOIUrl":"10.1017/erm.2024.24","url":null,"abstract":"<p><p>Repulsive guidance molecule b (RGMb), a glycosylphosphatidylinositol-anchored member of the RGM family, is initially identified as a co-receptor of bone morphogenetic protein (BMP) in the nervous system. The expression of RGMb is transcriptionally regulated by dorsal root ganglion 11 (DRG11), which is a transcription factor expressed in embryonic DRG and dorsal horn neurons and plays an important role in the development of sensory circuits. RGMb is involved in important physiological processes such as embryonic development, immune response, intercellular adhesion and tumorigenesis. Furthermore, RGMb is mainly involved in the regulation of RGMb-neogenin-Rho and BMP signalling pathways. The recent discovery of programmed death-ligand 2 (PD-L2)-RGMb binding reveals that the cell signalling network and functional regulation centred on RGMb are extremely complex. The latest report suggests that down-regulation of the PD-L2-RGMb pathway in the gut microbiota promotes an anti-tumour immune response, which defines a potentially effective immune strategy. However, the biological function of RGMb in a variety of human diseases has not been fully determined, and will remain an active research field. This article reviews the properties and functions of RGMb, focusing on its role under various physiological and pathological conditions.</p>","PeriodicalId":50462,"journal":{"name":"Expert Reviews in Molecular Medicine","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11488336/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142394825","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":"Understanding the autophagic functions in cancer stem cell maintenance and therapy resistance.","authors":"Niharika, Minal Garg","doi":"10.1017/erm.2024.23","DOIUrl":"10.1017/erm.2024.23","url":null,"abstract":"<p><p>Complex tumour ecosystem comprising tumour cells and its associated tumour microenvironment (TME) constantly influence the tumoural behaviour and ultimately impact therapy failure, disease progression, recurrence and poor overall survival of patients. Crosstalk between tumour cells and TME amplifies the complexity by creating metabolic changes such as hypoxic environment and nutrient fluctuations. These changes in TME initiate stem cell-like programmes in cancer cells, contribute to tumoural heterogeneity and increase tumour robustness. Recent studies demonstrate the multifaceted role of autophagy in promoting fibroblast production, stemness, cancer cell survival during longer periods of dormancy, eventual growth of metastatic disease and disease resistance. Recent ongoing studies examine autophagy/mitophagy as a powerful survival strategy in response to environmental stress including nutrient deprivation, hypoxia and environmental stress in TME. It prevents irreversible senescence, promotes dormant stem-like state, induces epithelial-mesenchymal transition and increases migratory and invasive potential of tumour cells. The present review discusses various theories and mechanisms behind the autophagy-dependent induction of cancer stem cell (CSC) phenotype. Given the role of autophagic functions in CSC aggressiveness and therapeutic resistance, various mechanisms and studies based on suppressing cellular plasticity by blocking autophagy as a powerful therapeutic strategy to kill tumour cells are discussed.</p>","PeriodicalId":50462,"journal":{"name":"Expert Reviews in Molecular Medicine","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11488345/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142394826","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":"ADP-ribose hydrolases: biological functions and potential therapeutic targets.","authors":"Jingpeng Wang, Zhao-Qi Wang, Wen Zong","doi":"10.1017/erm.2024.17","DOIUrl":"10.1017/erm.2024.17","url":null,"abstract":"<p><p>ADP-ribosylation (ADPRylation), which encompasses poly(ADP-ribosyl)ation and mono(ADP-ribosyl)ation, is an important post-translational modification catalysed by the poly(ADP-ribose) polymerase (PARP) enzyme superfamily. The process involves writers (PARPs) and erasers (ADP-ribose hydrolases), which work together to precisely regulate diverse cellular and molecular responses. Although the PARP-mediated synthesis of ADP-ribose (ADPr) has been well studied, ADPr degradation by degrading enzymes deserves further investigation. Nonetheless, recent studies have provided important new insights into the biology and functions of ADPr hydrolases. Notably, research has illuminated the significance of the poly(ADP-ribose) degradation pathway and its activation by the coordinated actions of poly(ADP-ribose) glycohydrolase and other ADPr hydrolases, which have been identified as key components of ADPRylation signalling networks. The degradation pathway has been proposed to play crucial roles in key cellular processes, such as DNA damage repair, chromatin dynamics, transcriptional regulation and cell death. A deep understanding of these ADPr erasing enzymes provides insights into the biological roles of ADPRylation in human health and disease aetiology and paves the road for the development of novel therapeutic strategies. This review article provides a summary of current knowledge about the biochemical and molecular functions of ADPr erasers and their physiological implications in human pathology.</p>","PeriodicalId":50462,"journal":{"name":"Expert Reviews in Molecular Medicine","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11488344/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142394921","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}
Katie Hanna, Anna-Lena Asiedu, Thomas Theurer, David Muirhead, Valerie Speirs, Yara Oweis, Rasha Abu-Eid
{"title":"Advances in Raman spectroscopy for characterising oral cancer and oral potentially malignant disorders.","authors":"Katie Hanna, Anna-Lena Asiedu, Thomas Theurer, David Muirhead, Valerie Speirs, Yara Oweis, Rasha Abu-Eid","doi":"10.1017/erm.2024.26","DOIUrl":"10.1017/erm.2024.26","url":null,"abstract":"<p><p>Oral cancer survival rates have seen little improvement over the past few decades. This is mainly due to late detection and a lack of reliable markers to predict disease progression in oral potentially malignant disorders (OPMDs). There is a need for highly specific and sensitive screening tools to enable early detection of malignant transformation. Biochemical alterations to tissues occur as an early response to pathological processes; manifesting as modifications to molecular structure, concentration or conformation. Raman spectroscopy is a powerful analytical technique that can probe these biochemical changes and can be exploited for the generation of novel disease-specific biomarkers. Therefore, Raman spectroscopy has the potential as an adjunct tool that can assist in the early diagnosis of oral cancer and the detection of disease progression in OPMDs. This review describes the use of Raman spectroscopy for the diagnosis of oral cancer and OPMDs based on ex vivo and liquid biopsies as well as in vivo applications that show the potential of this powerful tool to progress from benchtop to chairside.</p>","PeriodicalId":50462,"journal":{"name":"Expert Reviews in Molecular Medicine","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11488342/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142394922","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}