Expert Reviews in Molecular Medicine最新文献

{"title":"The compartmentalised nature of neuronal mitophagy: molecular insights and implications.","authors":"Fivos Borbolis,&nbsp;Konstantinos Palikaras","doi":"10.1017/erm.2022.31","DOIUrl":"https://doi.org/10.1017/erm.2022.31","url":null,"abstract":"<p><p>The maintenance of a healthy mitochondrial network and the ability to adjust organelle population in response to internal or external stimuli are essential for the function and the survival of eukaryotic cells. Over the last two decades several studies have demonstrated the paramount importance of mitophagy, a selective form of autophagy that removes damaged and/or superfluous organelles, in organismal physiology. Post-mitotic neuronal cells are particularly vulnerable to mitochondrial damage, and mitophagy impairment has emerged as a causative factor in multiple neurodegenerative pathologies, including Alzheimer's disease and Parkinson's disease among others. Although mitochondrial turnover is a multifaceted process, neurons have to tackle additional complications, arising from their pronounced bioenergetic demands and their unique architecture and cellular polarisation that render the degradation of distal organelles challenging. Mounting evidence indicates that despite the functional conservation of mitophagy pathways, the unique features of neuronal physiology have led to the adaptation of compartmentalised solutions, which serve to ensure seamless mitochondrial removal in every part of the cell. In this review, we summarise the current knowledge concerning the molecular mechanisms that mediate mitophagy compartmentalisation and discuss their implications in various human pathologies.</p>","PeriodicalId":50462,"journal":{"name":"Expert Reviews in Molecular Medicine","volume":"24 ","pages":"e38"},"PeriodicalIF":6.2,"publicationDate":"2022-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9884780/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10677987","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":"Roles of CCR10/CCL27-CCL28 axis in tumour development: mechanisms, diagnostic and therapeutic approaches, and perspectives.","authors":"Ermias Mergia Terefe,&nbsp;Maria Jade Catalan Opulencia,&nbsp;Amir Rakhshani,&nbsp;Mohammad Javed Ansari,&nbsp;Sergushina Elena Sergeevna,&nbsp;Sura A Awadh,&nbsp;Djamila Sh Polatova,&nbsp;Adnan Hashim Abdulkadhim,&nbsp;Yasser Fakri Mustafa,&nbsp;Hamzah H Kzar,&nbsp;Moaed E Al-Gazally,&nbsp;Mustafa M Kadhim,&nbsp;Gholamali Taherian","doi":"10.1017/erm.2022.28","DOIUrl":"https://doi.org/10.1017/erm.2022.28","url":null,"abstract":"<p><p>Cancer is now one of the major causes of death across the globe. The imbalance of cytokine and chemokine secretion has been reported to be involved in cancer development. Meanwhile, CC chemokines have received considerable interest in cancer research. CCR10, as the latest identified CC chemokine receptor (CCR), has been implicated in the recruitment and infiltration of immune cells, especially lymphocytes, into epithelia such as skin via ligation to two ligands, CCL27 and CCL28. Other than homoeostatic function, several mechanisms have been shown to dysregulate CCR10/CCL27-CCL28 expression in the tumour microenvironment. As such, these receptors and ligands mediate T-cell trafficking in the tumour microenvironment. Depending on the types of lymphocytes recruited, CCR10/CCL27-CCL28 interaction has been shown to play conflicting roles in cancer development. If they were T helper and cytotoxic T cells and natural killer cells, the role of this axis would be tumour-suppressive. In contrast, if CCR10/CCL27-CCL28 recruited regulatory T cells, cancer-associated fibroblasts or myeloid-derived suppressor cells, it would lead to tumour progression. In addition to the trafficking of lymphocytes and immune cells, CCR10 also leads to the migration of tumour cells or endothelial cells (called angiogenesis and lymphangiogenesis) to promote tumour metastasis. Furthermore, CCR10 signalling triggers tumour-promoting signalling such as PI3K/AKT and mitogen-activated protein kinase/extracellular signal-regulated kinase, resulting in tumour cell growth. Since CCR10/CCL27-CCL28 is dysregulated in the tumour tissues, it is suggested that analysis and measurement of them might predict tumour development. Finally, it is hoped using therapeutic approaches based on this axis might increase our knowledge to overcome tumour progression.</p>","PeriodicalId":50462,"journal":{"name":"Expert Reviews in Molecular Medicine","volume":"24 ","pages":"e37"},"PeriodicalIF":6.2,"publicationDate":"2022-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10504325","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":"Possibilities of using T-cell biophysical biomarkers of ageing.","authors":"Blanca González-Bermúdez, Aldo Abarca-Ortega, Mónica González-Sánchez, Mónica De la Fuente, Gustavo R Plaza","doi":"10.1017/erm.2022.29","DOIUrl":"10.1017/erm.2022.29","url":null,"abstract":"<p><p>Ageing is interrelated with the development of immunosenescence. This article focuses on one of the cell sets of the adaptive immune system, T cells, and provides a review of the known changes in T cells associated with ageing. Such fundamental changes affect both cell molecular content and internal ordering. However, acquiring a complete description of the changes at these levels would require extensive measurements of parameters and, furthermore, important fine details of the internal ordering that may be difficult to detect. Therefore, an alternative approach for the characterisation of cells consists of the performance of physical measurements of the whole cell, such as deformability measurements or migration measurements: the physical parameters, complementing the commonly used chemical biomarkers, may contribute to a better understanding of the evolution of T-cell states during ageing. Mechanical measurements, among other biophysical measurements, have the advantage of their relative simplicity: one single parameter agglutinates the complex effects of the variety of changes that gradually appear in cells during ageing.</p>","PeriodicalId":50462,"journal":{"name":"Expert Reviews in Molecular Medicine","volume":"24 ","pages":"e35"},"PeriodicalIF":4.5,"publicationDate":"2022-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9884748/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10729802","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":"Unveil the pain of endometriosis: from the perspective of the nervous system.","authors":"Peiya Fan,&nbsp;Tian Li","doi":"10.1017/erm.2022.26","DOIUrl":"https://doi.org/10.1017/erm.2022.26","url":null,"abstract":"<p><p>Endometriosis is a chronic inflammatory disease with pelvic pain and uncharacteristic accompanying symptoms. Endometriosis-associated pain often persists despite treatment of the disease, thus it brings a deleterious impact on their personal lives as well as imposing a substantial economic burden on them. At present, mechanisms underlie endometriosis-associated pain including inflammatory reaction, injury, aberrant blood vessels and the morphological and functional anomaly of the peripheral and central nervous systems. The nerve endings are influenced by the physical and chemical factors surrounding the lesion, via afferent nerve to the posterior root of the spinal nerve, then to the specific cerebral cortex involved in nociception. However, our understanding of the aetiology and mechanism of this complex pain process caused by endometriosis remains incomplete. Identifying the pathogenesis of endometriosis is crucial to disease management, offering proper treatment, and helping patients to seek novel targets for the maintenance and contributors of chronic pain. The main aim of this review is to focus on every possible mechanism of pain related to endometriosis in both peripheral and central nervous systems, and to present related mechanisms of action from the interaction between peripheral lesions and nerves to the changes in transmission of pain, resulting in hyperalgesia and the corresponding alterations in cerebral cortex and brain metabolism.</p>","PeriodicalId":50462,"journal":{"name":"Expert Reviews in Molecular Medicine","volume":"24 ","pages":"e36"},"PeriodicalIF":6.2,"publicationDate":"2022-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10497439","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":"Mismatch repair is a double-edged sword in the battle against microsatellite instability.","authors":"Carson J Miller,&nbsp;Karen Usdin","doi":"10.1017/erm.2022.16","DOIUrl":"https://doi.org/10.1017/erm.2022.16","url":null,"abstract":"<p><p>Roughly 3% of the human genome consists of microsatellites or tracts of short tandem repeats (STRs). These STRs are often unstable, undergoing high-frequency expansions (increases) or contractions (decreases) in the number of repeat units. Some microsatellite instability (MSI) is seen at multiple STRs within a single cell and is associated with certain types of cancer. A second form of MSI is characterised by expansion of a single gene-specific STR and such expansions are responsible for a group of 40+ human genetic disorders known as the repeat expansion diseases (REDs). While the mismatch repair (MMR) pathway prevents genome-wide MSI, emerging evidence suggests that some MMR factors are directly involved in generating expansions in the REDs. Thus, MMR suppresses some forms of expansion while some MMR factors promote expansion in other contexts. This review will cover what is known about the paradoxical effect of MMR on microsatellite expansion in mammalian cells.</p>","PeriodicalId":50462,"journal":{"name":"Expert Reviews in Molecular Medicine","volume":"24 ","pages":"e32"},"PeriodicalIF":6.2,"publicationDate":"2022-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9884765/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10669021","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":"The emerging role of NOTCH3 receptor signalling in human lung diseases.","authors":"Manish Bodas,&nbsp;Bharathiraja Subramaniyan,&nbsp;Harry Karmouty-Quintana,&nbsp;Peter F Vitiello,&nbsp;Matthew S Walters","doi":"10.1017/erm.2022.27","DOIUrl":"https://doi.org/10.1017/erm.2022.27","url":null,"abstract":"<p><p>The mammalian respiratory system or lung is a tree-like branching structure, and the main site of gas exchange with the external environment. Structurally, the lung is broadly classified into the proximal (or conducting) airways and the distal alveolar region, where the gas exchange occurs. In parallel with the respiratory tree, the pulmonary vasculature starts with large pulmonary arteries that subdivide rapidly ending in capillaries adjacent to alveolar structures to enable gas exchange. The NOTCH signalling pathway plays an important role in lung development, differentiation and regeneration post-injury. Signalling via the NOTCH pathway is mediated through activation of four NOTCH receptors (NOTCH1-4), with each receptor capable of regulating unique biological processes. Dysregulation of the NOTCH pathway has been associated with development and pathophysiology of multiple adult acute and chronic lung diseases. This includes accumulating evidence that alteration of NOTCH3 signalling plays an important role in the development and pathogenesis of chronic obstructive pulmonary disease, lung cancer, asthma, idiopathic pulmonary fibrosis and pulmonary arterial hypertension. Herein, we provide a comprehensive summary of the role of NOTCH3 signalling in regulating repair/regeneration of the adult lung, its association with development of lung disease and potential therapeutic strategies to target its signalling activity.</p>","PeriodicalId":50462,"journal":{"name":"Expert Reviews in Molecular Medicine","volume":"24 ","pages":"e33"},"PeriodicalIF":6.2,"publicationDate":"2022-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9884775/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10671308","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":"Erythrocyte oxidative stress and thrombosis.","authors":"Alessandra Bettiol,&nbsp;Silvia Galora,&nbsp;Flavia Rita Argento,&nbsp;Eleonora Fini,&nbsp;Giacomo Emmi,&nbsp;Irene Mattioli,&nbsp;Giacomo Bagni,&nbsp;Claudia Fiorillo,&nbsp;Matteo Becatti","doi":"10.1017/erm.2022.25","DOIUrl":"https://doi.org/10.1017/erm.2022.25","url":null,"abstract":"<p><p>Thrombosis is a common disorder with a relevant burden of morbidity and mortality worldwide, particularly among elderly patients. Growing evidence demonstrated a direct role of oxidative stress in thrombosis, with various cell types contributing to this process. Among them, erythrocytes produce high quantities of intracellular reactive oxygen species (ROS) by NADPH oxidase activation and haemoglobin autoxidation. Concomitantly, extracellular ROS released by other cells in the blood flow can be uptaken and accumulate within erythrocytes. This oxidative milieu can alter erythrocyte membrane structure, leading to an impaired erythrocyte function, and promoting erythrocytes lysis, binding to endothelial cells, activation of platelet and of coagulation factors, phosphatidylserine exposure and release of microvesicles. Moreover, these abnormal erythrocytes are able to adhere to the vessel wall, contributing to thrombin generation within the thrombus. This process results in accelerated haemolysis and in a hypercoagulable state, in which structurally impaired erythrocytes contribute to increase thrombus size, to reduce its permeability and susceptibility to lysis. However, the wide plethora of mechanisms by which oxidised erythrocytes contribute to thrombosis is not completely elucidated. This review discusses the main biochemical aspects linking erythrocytes, oxidative stress and thrombosis, addressing their potential implication for clinical and therapeutic management.</p>","PeriodicalId":50462,"journal":{"name":"Expert Reviews in Molecular Medicine","volume":"24 ","pages":"e31"},"PeriodicalIF":6.2,"publicationDate":"2022-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9884766/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10669016","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":"Obesity-related genomic instability and altered xenobiotic metabolism: possible consequences for cancer risk and chemotherapy.","authors":"Ezgi Eyluel Bankoglu,&nbsp;Helga Stopper","doi":"10.1017/erm.2022.22","DOIUrl":"https://doi.org/10.1017/erm.2022.22","url":null,"abstract":"<p><p>The increase in the prevalence of obesity has led to an elevated risk for several associated diseases including cancer. Several studies have investigated the DNA damage in human blood samples and showed a clear trend towards increased DNA damage in obesity. Reduced genomic stability is thus one of the consequences of obesity, which may contribute to the related cancer risk. Whether this is influenced by compromised DNA repair has not been elucidated sufficiently yet. On the other hand, obesity has also been linked to reduced therapy survival and increased adverse effects during chemotherapy, although the available data are controversial. Despite some indications that obesity might alter hepatic metabolism, current literature in humans is insufficient, and results from animal studies are inconclusive. Here we have summarised published data on hepatic drug metabolism to understand the impact of obesity on cancer therapy better. Furthermore, we highlight knowledge gaps in the interrelationship between obesity and drug metabolism from a toxicological perspective.</p>","PeriodicalId":50462,"journal":{"name":"Expert Reviews in Molecular Medicine","volume":"24 ","pages":"e28"},"PeriodicalIF":6.2,"publicationDate":"2022-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9884759/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9240220","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":"The potential role of FNDC5/irisin in various liver diseases: awakening the sleeping beauties","authors":"Xiaoyu Wang, Lihong Mao, Chaoqun Li, Yang-yang Hui, Zi-han Yu, Mingyu Sun, Yifan Li, Gaoyue Guo, Wanting Yang, Binxin Cui, Xiaofei Fan, Chao Sun","doi":"10.1017/erm.2022.19","DOIUrl":"https://doi.org/10.1017/erm.2022.19","url":null,"abstract":"Abstract Fibronectin type III domain-containing protein 5 (FNDC5) is a transmembrane protein and the precursor of irisin, which serves as a systemic exerkine/myokine with multiple origins. Since its discovery in 2012, this hormone-like polypeptide has rapidly evolved to a component significantly involved in a gamut of metabolic dysregulations and various liver diseases. After a decade of extensive investigation on FNDC5/irisin, we are still surrounded by lots of open questions regarding its diagnostic and therapeutic values. In this review, we first concentrated on the structure–function relationship of FNDC5/irisin. Next, we comprehensively summarised the current knowledge and research findings regarding pathogenic roles/therapeutic applications of FNDC5/irisin in the context of non-alcoholic fatty liver disease, fibrosis, liver injury due to multiple detrimental insults, hepatic malignancy and intrahepatic cholestasis of pregnancy. Moreover, the prominent molecules involved in the underlying mechanisms and signalling pathways were highlighted. As a result, emerging evidence reveals FNDC5/irisin may act as a proxy for diagnosing liver disease pathology, a sensitive biomarker for assessing damage severity, a predisposing factor for surveilling illness progression and a treatment option with protective/preventive impact, all of which are highly dependent on disease grading and contextually pathological features.","PeriodicalId":50462,"journal":{"name":"Expert Reviews in Molecular Medicine","volume":" ","pages":""},"PeriodicalIF":6.2,"publicationDate":"2022-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46423056","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":"TNF-<i>α</i>/anti-TNF-<i>α</i> drugs and its effect on pregnancy outcomes.","authors":"Fang-Fang Dai,&nbsp;Min Hu,&nbsp;Yu-Wei Zhang,&nbsp;Rong-Hui Zhu,&nbsp;Li-Ping Chen,&nbsp;Zhi-Dian Li,&nbsp;Yan-Jie Huang,&nbsp;Wei Hu,&nbsp;Yan-Xiang Cheng","doi":"10.1017/erm.2022.18","DOIUrl":"https://doi.org/10.1017/erm.2022.18","url":null,"abstract":"<p><p>Pregnancy is a complex biological process. The establishment and maintenance of foetal-maternal interface are pivotal events. Decidual immune cells and inflammatory cytokines play indispensable roles in the foetal-maternal interface. The disfunction of decidual immune cells leads to adverse pregnancy outcome. Tumour necrosis factor (TNF)-<i>α</i>, a common inflammatory cytokine, has critical roles in different stages of normal pregnancy process. However, the relationship between the disorder of TNF-<i>α</i> and adverse pregnancy outcomes, including preeclampsia (PE), intrauterine growth restriction (IUGR), spontaneous abortion (SA), preterm birth and so on, is still indefinite. In this review, we thoroughly reviewed the effect of TNF-<i>α</i> disorder on pathological conditions. Moreover, we summarized the reports about the adverse pregnancy outcomes (PE, IUGR, SA and preterm birth) of using anti-TNF-<i>α</i> drugs (infliximab, etanercept and adalimumab, certolizumab and golimumab) currently in the clinical studies. Overall, IUGR, SA and preterm birth are the most common adverse pregnancy outcomes of anti-TNF-<i>α</i> drugs. Our review may provide insight for the immunological treatment of pregnancy-related complication, and help practitioners make informed decisions based on the current evidences.</p>","PeriodicalId":50462,"journal":{"name":"Expert Reviews in Molecular Medicine","volume":"24 ","pages":"e26"},"PeriodicalIF":6.2,"publicationDate":"2022-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9884758/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10671544","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}