Francesca Ruzzi , Federica Riccardo , Laura Conti , Lidia Tarone , Maria Sofia Semprini , Elisabetta Bolli , Giuseppina Barutello , Elena Quaglino , Pier-Luigi Lollini , Federica Cavallo
{"title":"Cancer vaccines: Target antigens, vaccine platforms and preclinical models","authors":"Francesca Ruzzi , Federica Riccardo , Laura Conti , Lidia Tarone , Maria Sofia Semprini , Elisabetta Bolli , Giuseppina Barutello , Elena Quaglino , Pier-Luigi Lollini , Federica Cavallo","doi":"10.1016/j.mam.2024.101324","DOIUrl":"10.1016/j.mam.2024.101324","url":null,"abstract":"<div><div>This review provides a comprehensive overview of the evolving landscape of cancer vaccines, highlighting their potential to revolutionize tumor prevention. Building on the success of vaccines against virus-related cancers, such as HPV- and HBV-associated cervical and liver cancers, the current challenge is to extend these achievements to the prevention of non-viral tumors and the treatment of preneoplastic or early neoplastic lesions. This review analyzes the critical aspects of preventive anti-cancer vaccination, focusing on the choice of target antigens, the development of effective vaccine platforms and technologies, and the use of various model systems for preclinical testing, from laboratory rodents to companion animals.</div></div>","PeriodicalId":49798,"journal":{"name":"Molecular Aspects of Medicine","volume":"101 ","pages":"Article 101324"},"PeriodicalIF":8.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142781700","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":"An updated systematic review about various effects of microplastics on cancer: A pharmacological and in-silico based analysis","authors":"Akmaral Baspakova , Afshin Zare , Roza Suleimenova , Aidar B. Berdygaliev , Bibigul Karimsakova , Kymbat Tussupkaliyeva , Nadiar M. Mussin , Kulyash R. Zhilisbayeva , Nader Tanideh , Amin Tamadon","doi":"10.1016/j.mam.2024.101336","DOIUrl":"10.1016/j.mam.2024.101336","url":null,"abstract":"<div><div>Microplastics (MPs) are known as substantial environmental and health threats because of their pervasive existence and potential function in human diseases. This study is the first research in which a comprehensive analysis of various impacts of MPs on cancer cells is performed through pharmacological and in silico approaches. Moreover, our results demonstrate that MPs have both promotive and suppressive impacts on cancer cells, changing some of the important features of these kinds of cells including cellular viability, migration, metastasis, and apoptosis. Furthermore, the present study displayed that AP-2 complex subunit mu-1 (AP2M1), Asialoglycoprotein receptor 2 (ASGR2), Bax inhibitor-1 (BI-1), and Ferritin Heavy Chain, and pivotal role in the progression of cancers mediated by MPs. Moreover, our in-silico analysis identified Goserelin, Paclitaxel, Raloxifene, Exemestane, Epirubicin, Trametinib, Vemurafenib, Pactitaxel, and Sorafenib as potential anticancer agents for curing MPS-based cancer. Besides, our results demonstrated that MPs can exacerbate the development of tumor cells by affecting some important mechanisms including oxidative stress, immune suppression, and adjusting of critical signaling pathways. Interestingly, some sorts of MPs also displayed suppressive effects on cancer cells in some particular contexts, highlighting their complicated biological roles in different biological interactions. Ultimately the present survey tries to demonstrate the crucial roles of MPs in cancer cells and the different mechanisms that occur in the mentioned cells in order to emphasize performing more studies about clarifying the roles of MPs in carcinogenesis.</div></div>","PeriodicalId":49798,"journal":{"name":"Molecular Aspects of Medicine","volume":"101 ","pages":"Article 101336"},"PeriodicalIF":8.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142933363","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":"Vaccines for cancer prevention and treatment","authors":"Federica Cavallo, Pier-Luigi Lollini","doi":"10.1016/j.mam.2024.101334","DOIUrl":"10.1016/j.mam.2024.101334","url":null,"abstract":"","PeriodicalId":49798,"journal":{"name":"Molecular Aspects of Medicine","volume":"101 ","pages":"Article 101334"},"PeriodicalIF":8.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142824564","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}
Mariana Weigel Muñoz, Débora J. Cohen, Vanina G. Da Ros, Soledad N. González, Abril Rebagliati Cid, Valeria Sulzyk, Patricia S. Cuasnicu
{"title":"Physiological and pathological aspects of epididymal sperm maturation","authors":"Mariana Weigel Muñoz, Débora J. Cohen, Vanina G. Da Ros, Soledad N. González, Abril Rebagliati Cid, Valeria Sulzyk, Patricia S. Cuasnicu","doi":"10.1016/j.mam.2024.101321","DOIUrl":"10.1016/j.mam.2024.101321","url":null,"abstract":"<div><div>In mammals, sperm that leave the testes are nonfunctional and require a complex post-testicular maturation process to acquire their ability to recognize and fertilize the egg. The crucial maturation changes that provide sperm their fertilizing capability occur while passing through the epididymis. Due to the widespread use of assisted reproductive technologies to address male infertility, there has been a significant decrease in research focusing on the mechanisms underlying the maturation process over the past decades. Considering that up to 40% of male infertility is idiopathic and could be reflecting sperm maturation defects, the study of post-testicular sperm maturation will clearly contribute to a better understanding of the causes of male infertility and to the development of both new approaches to maturing sperm <em>in vitro</em> and safer male contraceptive methods. Based on this, the present review focuses on the physiopathology of the epididymis as well as on current approaches under investigation to improve research in sperm maturation and as potential therapeutic options for male infertility.</div></div>","PeriodicalId":49798,"journal":{"name":"Molecular Aspects of Medicine","volume":"100 ","pages":"Article 101321"},"PeriodicalIF":8.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142326560","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}
Kathleen Duffin , Rod T. Mitchell , Mark F.H. Brougham , Geert Hamer , Ans M.M. van Pelt , Callista L. Mulder
{"title":"Impacts of cancer therapy on male fertility: Past and present","authors":"Kathleen Duffin , Rod T. Mitchell , Mark F.H. Brougham , Geert Hamer , Ans M.M. van Pelt , Callista L. Mulder","doi":"10.1016/j.mam.2024.101308","DOIUrl":"10.1016/j.mam.2024.101308","url":null,"abstract":"<div><p>Over the past two decades, advances in cancer therapy have significantly improved survival rates, particularly in childhood cancers. Still, many treatments pose a substantial risk for diminishing future fertility potential due to the gonadotoxic nature of many cancer regimens, justifying fertility preservation programs for both childhood and adult cancer patients. To assure a balance between offering fertility preservation and actual chance of infertility post-treatment, guidelines are in place. However, assessing the actual risk of infertility after treatment remains challenging, given the multi-faceted approach of many cancer treatment plans, which are continuously evolving. This review discusses the evolution of cancer therapy over the past 20 years and attempts to assess their impact on fertility after treatment. Overall, cancer regimens have shifted from broadly killing fast dividing cells to more targeting therapies, reducing collateral damage in general. Although progress has been made to reduce overall toxicity, unfortunately this does not automatically translate to reduced gonadotoxicity. Therefore, current fertility preservation programs continue to be an important part of cancer care.</p></div>","PeriodicalId":49798,"journal":{"name":"Molecular Aspects of Medicine","volume":"100 ","pages":"Article 101308"},"PeriodicalIF":8.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0098299724000670/pdfft?md5=8f19f2533a69786ae7ab55463531c34d&pid=1-s2.0-S0098299724000670-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142161506","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}
Kevin Núño , Anne Sophie Jensen , Gregory O'Connor , Tiffani Janae Houston , Emre Dikici , Jean Marc Zingg , Sapna Deo , Sylvia Daunert
{"title":"Insights into Women's health: Exploring the vaginal microbiome, quorum sensing dynamics, and therapeutic potential of quorum sensing quenchers","authors":"Kevin Núño , Anne Sophie Jensen , Gregory O'Connor , Tiffani Janae Houston , Emre Dikici , Jean Marc Zingg , Sapna Deo , Sylvia Daunert","doi":"10.1016/j.mam.2024.101304","DOIUrl":"10.1016/j.mam.2024.101304","url":null,"abstract":"<div><p>The vaginal microbiome is an important aspect of women's health that changes dynamically with various stages of the woman's life. Just like the gut microbiome, the vaginal microbiome can also be affected by pathologies that dramatically change the typical composition of native vaginal microorganisms. However, the mechanism as to how both vaginal endemic and gut endemic opportunistic microbes can express pathogenicity in vaginal polymicrobial biofilms is poorly understood. Quorum sensing is the cellular density-dependent bacterial and fungal communication process in which chemical signaling molecules, known as autoinducers, activate expression for genes responsible for virulence and pathogenicity, such as biofilm formation and virulence factor production. Quorum sensing inhibition, or quorum quenching, has been explored as a potential therapeutic route for both bacterial and fungal infections. By applying these quorum quenchers, one can reduce biofilm formation of opportunistic vaginal microbes and combine them with antibiotics for a synergistic effect. This review aims to display the relationship between the vaginal and gut microbiome, the role of quorum sensing in polymicrobial biofilm formation which cause pathology in the vaginal microbiome, and how quorum quenchers can be utilized to attenuate the severity of bacterial and fungal infections.</p></div>","PeriodicalId":49798,"journal":{"name":"Molecular Aspects of Medicine","volume":"100 ","pages":"Article 101304"},"PeriodicalIF":8.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142161509","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}
Anna-Lisa V. Nguyen , Sania Julian , Ninglu Weng , Ryan Flannigan
{"title":"Advances in human In vitro spermatogenesis: A review","authors":"Anna-Lisa V. Nguyen , Sania Julian , Ninglu Weng , Ryan Flannigan","doi":"10.1016/j.mam.2024.101320","DOIUrl":"10.1016/j.mam.2024.101320","url":null,"abstract":"<div><div>Recent advances surrounding in vitro spermatogenesis (IVS) have shown potential in creating a new paradigm of regenerative medicine in the future of fertility treatments for males experiencing non-obstructive azoospermia (NOA). Male infertility is a common condition affecting approximately 15% of couples, with azoospermia being present in 15% of infertile males (Cocuzza et al., 2013; Esteves et al., 2011a). Treatment for patients with NOA has primarily been limited to surgical sperm retrieval combined with in vitro fertilization intracytoplasmic sperm injection (IVF-ICSI); however, sperm retrieval is successful in only half of these patients, and live birth rates typically range between 10 and 25% (Aljubran et al., 2022). Therefore, a significant need exists for regenerative therapies in this patient population.</div><div>IVS has been considered as a model for further understanding the molecular and cellular processes of spermatogenesis and as a potential regenerative therapeutic approach. While 2D cell cultures using human testicular cells have been attempted in previous research, lack of proper spatial arrangement limits germ cell differentiation and maturation, posing challenges for clinical application. Recent research suggests that 3D technology may have advantages for IVS due to mimicry of the native cytoarchitecture of human testicular tissue along with cell-cell communication directly or indirectly. 3D organotypic cultures, scaffolds, organoids, microfluidics, testis-on-a-chip, and bioprinting techniques have all shown potential to contribute to the technology of regenerative treatment strategies, including in vitro fertilization (IVF).</div><div>Although promising, further work is needed to develop technology for successful, replicable, and safe IVS for humans. The intersection between tissue engineering, molecular biology, and reproductive medicine in IVS development allows for multidisciplinary involvement, where challenges can be overcome to realize regenerative therapies as a viable option.</div></div>","PeriodicalId":49798,"journal":{"name":"Molecular Aspects of Medicine","volume":"100 ","pages":"Article 101320"},"PeriodicalIF":8.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142312281","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":"Immunomodulation: A new approach to cancer cachexia, potentially suitable for aging","authors":"Fabio Penna, Giacomo Rubini, Paola Costelli","doi":"10.1016/j.mam.2024.101318","DOIUrl":"10.1016/j.mam.2024.101318","url":null,"abstract":"<div><p>Cancer cachexia is the prototypical example of comorbidity, occurring in most of cancer patients. It is a direct consequence of tumor growth and of the associated inflammatory/immune response. Cachexia can be exacerbated by anti-cancer therapies, frequently resulting in dose limitation and/or treatment delay or discontinuation. The pathogenesis of cancer cachexia is still unclear and includes nutritional, metabolic, hormonal and immunological components.</p><p>Tumor ability to shape the immune response to its own advantage is now well accepted, while the possibility that such an altered immune response could play a role in the onset of cachexia is still an undefined issue. Indeed, most of the immune-related research on cachexia mainly focused on pro-inflammatory mediators, almost totally disregarding the interactions among immune cells and the homeostasis of peripheral tissues. The present review provides an overview of the immune system dysregulations occurring in cancer cachexia, focusing on the possibility that immunomodulating strategies, mainly developed to stimulate the anti-cancer immune response, could be useful to counteract cachexia as well.</p><p>Cancer and cachexia are frequent comorbidities of aging. Along this line, cancer- and aging-associated muscle wasting likely coexist in the same patients. Since both conditions share some of the underlying mechanisms, the potential effectiveness of immunomodulation on sarcopenia of aging is discussed.</p></div>","PeriodicalId":49798,"journal":{"name":"Molecular Aspects of Medicine","volume":"100 ","pages":"Article 101318"},"PeriodicalIF":8.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0098299724000773/pdfft?md5=8d6de41398a219ac4fb6b6a41a8067fc&pid=1-s2.0-S0098299724000773-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142161510","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}
Shu-Yun Li , Sudeep Kumar , Xiaowei Gu , Tony DeFalco
{"title":"Testicular immunity","authors":"Shu-Yun Li , Sudeep Kumar , Xiaowei Gu , Tony DeFalco","doi":"10.1016/j.mam.2024.101323","DOIUrl":"10.1016/j.mam.2024.101323","url":null,"abstract":"<div><div>The testis is a unique environment where immune responses are suppressed to allow the development of sperm that possess autoimmunogenic antigens. There are several contributors responsible for testicular immune privilege, including the blood-testis barrier, testicular immune cells, immunomodulation by Sertoli cells, and high levels of steroid hormones. Despite multiple mechanisms in place to regulate the testicular immune environment, pathogens that disrupt testicular immunity can lead to long-term effects such as infertility. If testicular immunity is disturbed, autoimmune reactions can also occur, leading to aberrant immune cell infiltration and subsequent attack of autoimmunogenic germ cells. Here we discuss cellular and molecular factors underlying testicular immunity and how testicular infection or autoimmunity compromise immune privilege. We also describe infections and autoimmune diseases that impact the testis. Further research into testicular immunity will reveal how male fertility is maintained and will help update therapeutic strategies for infertility and other testicular disorders.</div></div>","PeriodicalId":49798,"journal":{"name":"Molecular Aspects of Medicine","volume":"100 ","pages":"Article 101323"},"PeriodicalIF":8.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142698138","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}
Fernando Millan-Domingo , Esther Garcia-Dominguez , Juan Gambini , Gloria Olaso-Gonzalez , Jose Viña , Maria Carmen Gomez-Cabrera
{"title":"Diet and exercise in frailty and sarcopenia. Molecular aspects","authors":"Fernando Millan-Domingo , Esther Garcia-Dominguez , Juan Gambini , Gloria Olaso-Gonzalez , Jose Viña , Maria Carmen Gomez-Cabrera","doi":"10.1016/j.mam.2024.101322","DOIUrl":"10.1016/j.mam.2024.101322","url":null,"abstract":"<div><div>Function declines throughout life although phenotypical manifestations in terms of frailty or disability are only seen in the later periods of our life. The causes underlying lifelong function decline are the aging process “per se”, chronic diseases, and lifestyle factors. These three etiological causes result in the deterioration of several organs and systems which act synergistically to finally produce frailty and disability. Regardless of the causes, the skeletal muscle is the main organ affected by developing sarcopenia.</div><div>In the first section of the manuscript, as an introduction, we review the quantitative and qualitative age-associated skeletal muscle changes leading to frailty and sarcopenia and their impact in the quality of life and independence in the elderly. The reversibility of frailty and sarcopenia are discussed in the second and third sections of the manuscript. The most effective intervention to delay and even reverse frailty is exercise training. We review the role of different training programs (resistance exercise, cardiorespiratory exercise, multicomponent exercise, and real-life interventions) not only as a preventive but also as a therapeutical strategy to promote healthy aging. We also devote a section in the text to the sexual dimorphic effects of exercise training interventions in aging. How to optimize the skeletal muscle anabolic response to exercise training with nutrition is also discussed in our manuscript. The concept of anabolic resistance and the evidence of the role of high-quality protein, essential amino acids, creatine, vitamin D, β-hydroxy-β-methylbutyrate, and Omega-3 fatty acids, is reviewed. In the last section of the manuscript, the main genetic interventions to promote robustness in preclinical models are discussed. We aim to highlight the molecular pathways that are involved in frailty and sarcopenia. The possibility to effectively target these signaling pathways in clinical practice to delay muscle aging is also discussed.</div></div>","PeriodicalId":49798,"journal":{"name":"Molecular Aspects of Medicine","volume":"100 ","pages":"Article 101322"},"PeriodicalIF":8.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142698139","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}