{"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}
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":"2024-11-25","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":"2024-11-25","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}
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":"2024-09-27","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}
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":"2024-09-23","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}
Mercedes Grima-Terrén , Silvia Campanario , Ignacio Ramírez-Pardo , Andrés Cisneros , Xiaotong Hong , Eusebio Perdiguero , Antonio L. Serrano , Joan Isern , Pura Muñoz-Cánoves
{"title":"Muscle aging and sarcopenia: The pathology, etiology, and most promising therapeutic targets","authors":"Mercedes Grima-Terrén , Silvia Campanario , Ignacio Ramírez-Pardo , Andrés Cisneros , Xiaotong Hong , Eusebio Perdiguero , Antonio L. Serrano , Joan Isern , Pura Muñoz-Cánoves","doi":"10.1016/j.mam.2024.101319","DOIUrl":"10.1016/j.mam.2024.101319","url":null,"abstract":"<div><div>Sarcopenia is a progressive muscle wasting disorder that severely impacts the quality of life of elderly individuals. Although the natural aging process primarily causes sarcopenia, it can develop in response to other conditions. Because muscle function is influenced by numerous changes that occur with age, the etiology of sarcopenia remains unclear. However, recent characterizations of the aging muscle transcriptional landscape, signaling pathway disruptions, fiber and extracellular matrix compositions, systemic metabolomic and inflammatory responses, mitochondrial function, and neurological inputs offer insights and hope for future treatments. This review will discuss age-related changes in healthy muscle and our current understanding of how this can deteriorate into sarcopenia. As our elderly population continues to grow, we must understand sarcopenia and find treatments that allow individuals to maintain independence and dignity throughout an extended lifespan.</div></div>","PeriodicalId":49798,"journal":{"name":"Molecular Aspects of Medicine","volume":"100 ","pages":"Article 101319"},"PeriodicalIF":8.7,"publicationDate":"2024-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142308930","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":"2024-09-11","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}
{"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":"2024-09-10","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}
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":"2024-09-09","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}
Won-Ki Pang, Ekaterina Kuznetsova, Hélène Holota, Angélique De Haze, Claude Beaudoin, David H. Volle
{"title":"Understanding the role of endocrine disrupting chemicals in testicular germ cell cancer: Insights into molecular mechanisms","authors":"Won-Ki Pang, Ekaterina Kuznetsova, Hélène Holota, Angélique De Haze, Claude Beaudoin, David H. Volle","doi":"10.1016/j.mam.2024.101307","DOIUrl":"10.1016/j.mam.2024.101307","url":null,"abstract":"<div><p>This comprehensive review examines the complex interplay between endocrine disrupting chemicals (EDCs) and the development of testicular germ cell tumors (TGCTs). Despite the high cure rates of TGCTs, challenges in diagnosis and treatment remain, necessitating a deeper understanding of the etiology of the disease. Here, we emphasize current knowledge on the role of EDCs as potential risk factors for TGCTs, focusing on pesticides and perfluorinated and polyfluoroalkyl substances (PFAs/PFCs). Evidence suggests that EDCs disrupt endocrine pathways and induce epigenetic changes that contribute to the development of TGCTs. However, the direct link between EDCs and TGCTs remains elusive and requires further investigation of the molecular mechanisms. We also highlighted the importance of studying nuclear receptors as potential targets for understanding TGCT etiology. In addition, recent evidence implicates PFAs/PFCs in TGCT incidence, highlighting the need for further research into their impact on human health. Overall, this review provides valuable insights into the potential role of EDCs in TGCT development and suggests avenues for future research, while also highlighting how understanding their influence may pave the way for novel therapeutic approaches to improve disease management.</p></div>","PeriodicalId":49798,"journal":{"name":"Molecular Aspects of Medicine","volume":"99 ","pages":"Article 101307"},"PeriodicalIF":8.7,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142097214","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}