Aspects of molecular medicine最新文献

{"title":"Advances in RNA cancer therapeutics: New insight into exosomes as miRNA delivery","authors":"Luca Volpini ,&nbsp;Federica Monaco ,&nbsp;Lory Santarelli ,&nbsp;Jiri Neuzil ,&nbsp;Marco Tomasetti","doi":"10.1016/j.amolm.2023.100005","DOIUrl":"10.1016/j.amolm.2023.100005","url":null,"abstract":"<div><p>We are now entering a new era of RNA therapies, such that mRNA-based vaccines and RNA interference approaches such as siRNA have already been launched on the pharmaceutical market. However, there are no FDA-approved RNA-based therapeutics for cancer treatment. Among RNA molecules, miRNAs represent a promising solution against cancer. Despite the ability to target multiple pathways, miRNA-based therapeutics struggle to reach phase 3 clinical trial. A reason of this delay is linked to complications of selective administration of miRNAs to their target, the tumor cell. Because of this, an efficient delivery system is necessary. In this sense, exosomes are considered the most promising miRNA-based therapeutic carriers in terms of safety and efficient cargo delivery. Furthermore, researchers have developed a new strategy to overcome the tumor capacity by using exosomes to release unnecessary miRNAs, shedding light on a new generation therapy of cancer treatment. The review describes recent advances in the application of miRNAs in the treatment of cancer, the use of exosomes for miRNA delivery, focusing on new approaches to overcome the limits of miRNA-loaded exosomes in clinical applications.</p></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"1 ","pages":"Article 100005"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47624218","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unusual Monkeypox virus outbreak in 2022: Phenotypic and molecular characteristics","authors":"Alberta Azzi","doi":"10.1016/j.amolm.2023.100001","DOIUrl":"https://doi.org/10.1016/j.amolm.2023.100001","url":null,"abstract":"<div><p>Monkeypox virus, first identified in 1958 in Asian monkeys employed for experiments in a laboratory in Denmark and then in 1970 in humans in Africa, in the Democratic Republic of Congo (DRC), has continued to circulate for about 50 years in some regions of Africa, indicated as Congo Basin (CB) and West Africa (WA) where it has become endemic. Rare outbreaks have occurred outside endemic countries, linked to importation of the virus from endemic areas. Suddenly, since early May 2022, cases of MPX developed outside the endemic areas and their number increased rapidly. Important differences in the epidemiology of 2022 MPX compared to previous MPX spread have begun to be observed soon. First, the 2022 cases could not be traced to contacts with infected cases or animals from endemic countries. The 2022 cases are due to human-to-human transmission and not to contact with infected animals; among the transmission routes the sexual route seems to predominate, particularly among men who have sex with men (MSM). Affected countries are located on several continents, mainly in America and Europe, but also in Asia and Australia. As of mid-November 2022, 110 countries have reported MPX cases, for a total of more than 79,000 confirmed cases and 50 deaths. What is behind this new MPXV behavior and what consequences might it have? This review aims to clarify the possible underpinnings of this 2022 MPX outbreak, with a focus on the molecular mechanisms, through an analysis of the literature. Most of the studies undertaken for this purpose are concerned with the molecular genetics of MPXVs and have been based on analysis and sequence comparison of the different species of the OPXV genus, of isolates of the two different MPXV Clades, of MPXVs in circulation before and during 2022, as well as of MPXVs identified from May 2022 onwards. These studies, reveal some variations mainly in the sequences of the Inverted Terminal Repeats (ITRs), known, on the other hand, as more variable regions of the viral genome. These are variations mainly in the genes involved in the virus-host relationship, virulence and immune evasion. However, further studies are needed to confirm the real significance of these variations in virus evolution. Of particular interest is the observation, shared by many authors, of the frequency of mutations in the MPXVs 2022 genome associated with APOBEC activity. These mutations may in fact represent a marker of human-to-human transmission that characterizes the new MPXV isolates. Overall, the variability of the MPXVs 2022, grouped in the B.1 lineage of Clade IIb, is not particularly high compared, for example, to many RNA viruses. However, it is still much higher than that of the previously circulated MPXV. Even if the epidemiological curve has changed trend in the past 3 months, it remains important to shed full light on the causes the multinational MPX outbreak of 2022.</p></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"1 ","pages":"Article 100001"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49773632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rapid isothermal point-of-care test for screening of SARS-CoV-2 (COVID-19)","authors":"Jean-Marc Zingg ,&nbsp;Yu-Ping Yang ,&nbsp;Spencer Seely ,&nbsp;Pratibha Joshi ,&nbsp;Md Harun Or Roshid ,&nbsp;Fabiola Iribarren Latasa ,&nbsp;Gregory O'Connor ,&nbsp;Jennifer Alfaro ,&nbsp;Eduardo Riquelme ,&nbsp;Sebastian Bernales ,&nbsp;Emre Dikici ,&nbsp;Sapna Deo ,&nbsp;Sylvia Daunert","doi":"10.1016/j.amolm.2023.100002","DOIUrl":"10.1016/j.amolm.2023.100002","url":null,"abstract":"<div><p>Rapid on-site diagnosis of emerging pathogens is key for early identification of infected individuals and for prevention of further spreading in a population. Currently available molecular diagnostic tests are instrument-based whereas rapid antibody and antigen tests are often not sufficiently sensitive for detection in pre-symptomatic subjects. There is a need for rapid point of care molecular screening tests that can be easily adapted to emerging pathogens and are selective, sensitive, reliable in different settings around the world. We have developed a simple, rapid (&lt;30 ​min), and inexpensive test for SARS-CoV-2 that is based on combination of isothermal reverse transcription recombinase polymerase amplification (RT-RPA) using modified primers and visual detection with paper-based microfluidics. Our test (CoRapID) is specific for SARS-CoV-2 (alpha to omicron variants) and does not detect other coronaviruses and pathogens by in silico and in vitro analysis. A two-step test protocol was developed with stable lyophilized reagents that reduces handling by using portable and disposable components (droppers, microapplicators/swabs, paper-strips). After optimization of assay components and conditions, we have achieved a limit of detection (LoD) of 1 copy/reaction by adding a blocking primer to the lateral flow assay. Using a set of 138 clinical samples, a sensitivity of 88.1% (P ​&lt; ​0.05, CI: 78.2–93.8%) and specificity of 93.9% (P ​&lt; ​0.05, CI: 85.4–97.6%) was determined. The lack of need for instrumentation for our CoRapID makes it an ideal on-site primary screening tool for local hospitals, doctors’ offices, senior homes, workplaces, and in remote settings around the world that often do not have access to clinical laboratories.</p></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"1 ","pages":"Article 100002"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9890548/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10108372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Parvovirus B19: Insights and implication for pathogenesis, prevention and therapy","authors":"K. Zakrzewska ,&nbsp;R. Arvia ,&nbsp;G. Bua ,&nbsp;F. Margheri ,&nbsp;G. Gallinella","doi":"10.1016/j.amolm.2023.100007","DOIUrl":"10.1016/j.amolm.2023.100007","url":null,"abstract":"<div><p>Parvovirus B19 (B19V) is a small ssDNA non-enveloped virus, member of <em>Parvoviridae</em> family. The infection is widely diffused and is responsible for a broad range of clinical manifestations including fifth disease in children, transient aplastic crisis in patients with haematological disorders, non-immune hydrops fetalis in pregnant women, persistent anaemia in immunocompromised patients, arthropathy and inflammation of various other tissues. B19V infects and replicates in erythroid progenitor cells (EPCs) in the bone marrow. The depletion of infected EPCs represents the pathogenetic mechanisms of some haematological B19V-associate diseases.</p><p>Following a primary infection, the virus can establish lifelong persistence in several tissues. Currently, the pathological potential of persistent virus on the cellular signalling pathways remains unclear. In non-erythroid tissues, the infection is usually, abortive, and the virus seems to exert its pathological role through indirect mechanisms, such as induction of inflammatory and autoimmune processes, or through virus-induced apoptosis mediated by viral proteins. In addition to the diseases for which the etiological role of B19V has been fully demonstrated, there are several clinical conditions, including autoimmune diseases, that are presumably, but not certainly, associated with B19V infection.</p><p>In this review, we describe recent findings that may give us new insight into the pathogenic role of B19V in systemic sclerosis, an autoimmune disease of unknown multifactorial aetiology. Furthermore, we describe the latest findings on the intrauterine B19V infections. Moreover, since there are some ongoing interesting studies focused on vaccine development and antiviral drug discovery for the prevention and treatment of parvovirus B19 infection we described some advances in this field of research.</p></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"1 ","pages":"Article 100007"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44064264","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TTV and other anelloviruses: The astonishingly wide spread of a viral infection","authors":"Pietro Giorgio Spezia ,&nbsp;Daniele Focosi ,&nbsp;Andreina Baj ,&nbsp;Federica Novazzi ,&nbsp;Francesca Drago Ferrante ,&nbsp;Fabrizio Carletti ,&nbsp;Claudia Minosse ,&nbsp;Giulia Matusali ,&nbsp;Fabrizio Maggi","doi":"10.1016/j.amolm.2023.100006","DOIUrl":"10.1016/j.amolm.2023.100006","url":null,"abstract":"<div><p>The broad family of viruses known as anelloviruses (AV) infects both humans and numerous animal species. They have a tiny, covalently closed single-stranded DNA genome and the astonishing capacity to infect a very high percentage of healthy and ill people with chronic infections that could last a lifetime. AV, and particularly the prototype Torquetenovirus, have established a successful interaction with the host's immune system and the rate at which they replicate is a gauge to measure overall immune function, even though many aspects of their life cycle and pathogenesis are still poorly understood.</p></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"1 ","pages":"Article 100006"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10308510/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9743934","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extracellular vesicles engagement during respiratory viruses infection","authors":"Maria Alfreda Stincarelli ,&nbsp;Rosaria Arvia ,&nbsp;Simone Giannecchini","doi":"10.1016/j.amolm.2023.100004","DOIUrl":"10.1016/j.amolm.2023.100004","url":null,"abstract":"<div><p>Respiratory viruses infection is a worldwide human concern annually. The main viral respiratory diseases are caused by a variety of viruses sharing similar threats and affecting the respiratory system. Among all, influenza viruses, respiratory syncytial virus, parainfluenza viruses, respiratory adenoviruses, rhinoviruses, human bocaviruses, human metapneumovirus and coronaviruses are the main common respiratory viruses affecting human population. The recent coronavirus disease 19 pandemic has revealed critical knowledge gaps required to update in the transmission and pathological induced pathways for respiratory viruses. To date, several evidences suggest that human viruses can hijack extracellular vesicles (EVs) to deliver proteins, mRNAs, microRNAs and whole viral particles during viral life cycle in the host. Thus, several investigations have reported that also respiratory viruses use EVs to deliver viral nucleic acid and proteins, even including the potentiality of carrying whole viral particle. This evidence demonstrates the ability of the EVs produced in infected cells to deliver respiratory viral components to uninfected cells, positively or negatively counteracting new viral infection. Additionally, EVs derived from biological fluids of clinical samples may increase the risk to induce severe respiratory viruses-associated diseases in site far from the respiratory tract and for prolonged time. Here, it has been reviewed the advantages of the respiratory viruses EVs interaction regarding their ability to enhance viral infection, to evade antiviral response, to regulate virus-immune response and to mediate diseases. All these data confirm a potential role of the association between EVs and respiratory viruses infection. This suggests that further studies to define the implication of this interaction in viral life cycle in human population are needed.</p></div>","PeriodicalId":72320,"journal":{"name":"Aspects of molecular medicine","volume":"1 ","pages":"Article 100004"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42546285","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}