{"title":"Pyroptosis and cancer: Linking inflammatory cell death to tumorigenesis and therapy.","authors":"Abhinay Pathania, Rajeev Kumar Pandey, Sanjana Mehrotra","doi":"10.1016/bs.pmbts.2025.06.021","DOIUrl":"https://doi.org/10.1016/bs.pmbts.2025.06.021","url":null,"abstract":"<p><p>Pyroptosis is a new form of programmed cell death (PCD) that is characterized by the activation of inflammasomes, and release of pro-inflammatory cytokines including IL-1β and IL-18. In the recent years, interest in pyroptosis has surged, owing to its emerging and dual role in tumorigenesis. While pyroptosis can act as a defense mechanism by eliminating cancerous cells through inflammatory cell death, it can also promote chronic inflammation in the tumor microenvironment, thereby facilitating cancer progression. In this chapter, we summarise the molecular mechanisms that govern pyroptosis, and discusses how epigenetic regulation, non-coding RNAs, pathogens, metabolites, and post-translational modifications influence pyroptosis. Detailed sections are devoted to its impact across various cancer types, followed by an in-depth review of therapeutic strategies that aim to restore or suppress pyroptosis for anticancer treatment.</p>","PeriodicalId":49280,"journal":{"name":"Progress in Molecular Biology and Translational Science","volume":"217 ","pages":"163-196"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145126384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bhupendra Puri, Yogesh A Kulkarni, Anil Bhanudas Gaikwad
{"title":"Advances in CRISPR-Cas systems for kidney diseases.","authors":"Bhupendra Puri, Yogesh A Kulkarni, Anil Bhanudas Gaikwad","doi":"10.1016/bs.pmbts.2024.07.020","DOIUrl":"10.1016/bs.pmbts.2024.07.020","url":null,"abstract":"<p><p>Recent advances in CRISPR-Cas systems have revolutionised the study and treatment of kidney diseases, including acute kidney injury (AKI), chronic kidney disease (CKD), diabetic kidney disease (DKD), lupus nephritis (LN), and polycystic kidney disease (PKD). CRISPR-Cas technology offers precise and versatile tools for genetic modification in monogenic kidney disorders such as PKD and Alport syndrome. Recent advances in CRISPR technology have also shown promise in addressing other kidney diseases like AKI, CKD, and DKD. CRISPR-Cas holds promise to edit genetic mutations underlying these conditions, potentially leading to more effective and long-lasting treatments. Furthermore, the adaptability of CRISPR-Cas systems allows for developing tailored therapeutic strategies that specifically target the genetic and molecular mechanisms contributing to different kidney diseases. Beyond DNA modifications, CRISPR-Cas technologies also enable editing noncoding RNA, such as lncRNAs and miRNAs, in kidney diseases. Despite these advancements, significant challenges persist, including delivery efficiency to specific kidney cells and potential off-target effects. However, the rapid progress in CRISPR-Cas technology suggests a transformative impact on the future management of kidney diseases, offering the potential for enhanced patient outcomes through personalised and precise therapeutic approaches. This chapter highlights the recent advancement of CRISPR-Cas systems and their potential applications in various kidney diseases.</p>","PeriodicalId":49280,"journal":{"name":"Progress in Molecular Biology and Translational Science","volume":"210 ","pages":"149-162"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143014958","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hue Vu-Thi, Huy Than Quang, Vu-Hung Nguyen, Ha-Trang Le, Thu-Trang Cao Thi, Minh-Phuc Le Mau, Dinh-Toi Chu
{"title":"Informatics and data science in cell death research.","authors":"Hue Vu-Thi, Huy Than Quang, Vu-Hung Nguyen, Ha-Trang Le, Thu-Trang Cao Thi, Minh-Phuc Le Mau, Dinh-Toi Chu","doi":"10.1016/bs.pmbts.2025.06.016","DOIUrl":"https://doi.org/10.1016/bs.pmbts.2025.06.016","url":null,"abstract":"<p><p>Cell death are essential for maintaining cell balance, including remove the damage or harmful cells. Disorders of cell death related to the progression of various diseases, such as cancer, and autoimmune disorders. However, some challenge about quantify, define the types, or detecting in cell death still occur. To overcome the challenges, scientists have been focusing on the applications of informatics and data science in cell death research due to the advantages and the potentials over traditional methods. The implementations of informatics and data science in cell death research have shown results in improving the efficiency of the complex data processes and modeling biological systems, thus improving the performances of diagnostic methods and procedures. The aim of this chapter is to provide an overview of the existing informatics and data science applications in cell death research. In addition, this chapter discusses the main advantages and limitations of traditional cell death research methods, with the implementation of informatics, data science, and AI to overcome the challenges. From the evidence on the topic, researchers can based on the existing findings to come up with a suitable and effective research plan, hence improving the cell death research methods in the future.</p>","PeriodicalId":49280,"journal":{"name":"Progress in Molecular Biology and Translational Science","volume":"217 ","pages":"67-79"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145126379","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Osmolytes as structure-function regulators of intrinsically disordered casein proteins.","authors":"Mohd Younus Bhat","doi":"10.1016/bs.pmbts.2024.09.003","DOIUrl":"10.1016/bs.pmbts.2024.09.003","url":null,"abstract":"<p><p>Intrinsically disordered proteins (IDPs), despite lacking a stable structure, play crucial role in majority of the cellular processes. Casein, a key milk protein, represents this category of proteins, due to its dynamic and flexible structure which contributes towards the nutritional and functional properties of milk. The present chapter summarizes the role of osmolytes (small molecular weight organic molecules generally accumulated by cells to protect against denaturing stresses) in regulating the structure-function integrity of intrinsically disordered casein proteins. Osmolyte - casein interplay is of particular interest as these osmolytes have been found to affect the conformational flexibility and functional properties of casein proteins and thus can affect their overall behavior in the cellular environment. The present chapter delves into this by discussing the unique structural and functional properties of casein IDPs and the influence of osmolytes on their structure, stability, and chaperone activity. Elucidation of the osmolyte effects on the structural-functional integrity of caseins should advance our understanding of the dynamics of protein structure and function in complex biological environments and also offer practical perceptions for their future applications.</p>","PeriodicalId":49280,"journal":{"name":"Progress in Molecular Biology and Translational Science","volume":"211 ","pages":"17-38"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143415895","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Analysis of the immune response in COVID-19.","authors":"Altijana Hromić-Jahjefendić, Alaa A A Aljabali","doi":"10.1016/bs.pmbts.2024.10.004","DOIUrl":"https://doi.org/10.1016/bs.pmbts.2024.10.004","url":null,"abstract":"<p><p>The COVID-19 pandemic, instigated by the novel coronavirus SARS-CoV-2, has emerged as a significant global health challenge, demanding a profound grasp of the immune response. The innate immune system, a multifaceted network encompassing pattern recognition receptors (PRRs) and effector cells, assumes a pivotal function in detecting and countering this viral assailant. Toll-like receptors (TLRs), situated on immune cell surfaces and within endosomes, play a central role in recognizing SARS-CoV-2. TLR-2 and TLR-4 discern specific viral constituents, such as the spike (S) protein, setting off inflammatory signaling cascades and catalyzing the generation of type I interferons. Intracellular PRRs, including the RIG-I-like receptors (RLRs), RIG-I and MDA5, detect viral RNA within the cytoplasm of infected cells, provoking antiviral responses by initiating the synthesis of type I interferons. The equilibrium between interferons and pro-inflammatory cytokines dictates the outcomes of the disease. Interferons play an indispensable role in governing viral replication, while unregulated cytokine production can result in tissue harm and inflammation. This intricate dynamic underpins therapeutic strategies aimed at regulating immune responses in individuals grappling with COVID-19. Natural killer (NK) cells, with their capacity to recognize infected cells through the \"missing self\" phenomenon and activating receptors, make significant contributions to the defense against SARS-CoV-2. NK cells play a pivotal role in eliminating infected cells and boosting immune responses through antibody-dependent cell-mediated cytotoxicity (ADCC). In conclusion, comprehending the interplay among PRRs, interferons, and NK cells within innate immunity is paramount for discerning and combatting SARS-CoV-2. This comprehension illuminates therapeutic interventions and vaccine development, casting light on our endeavors to confront this worldwide health crisis.</p>","PeriodicalId":49280,"journal":{"name":"Progress in Molecular Biology and Translational Science","volume":"213 ","pages":"31-71"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144036567","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"T-cell immunobiology and cytokine storm of COVID-19.","authors":"Ahmed Eltayeb, Elrashdy M Redwan","doi":"10.1016/bs.pmbts.2024.10.003","DOIUrl":"https://doi.org/10.1016/bs.pmbts.2024.10.003","url":null,"abstract":"<p><p>The 2019 coronavirus illness (COVID 2019) first manifests as a newly identified pneumonia and may quickly escalate to acute respiratory distress syndrome, which has caused a global pandemic. Except for individualized supportive care, no curative therapy has been steadfastly advised for COVID-19 up until this point. T cells and virus-specific T lymphocytes are required to guard against viral infection, particularly COVID-19. Delayed immunological reconstitution (IR) and cytokine storm (CS) continue to be significant barriers to COVID-19 cure. While severe COVID-19 patients who survived the disease had considerable lymphopenia and increased neutrophils, especially in the elderly, their T cell numbers gradually recovered. Exhausted T lymphocytes and elevated levels of pro-inflammatory cytokines, including IL6, IL10, IL2, and IL17, are observed in peripheral blood and the lungs. It implies that while convalescent plasma, IL-6 blocking, mesenchymal stem cells, and corticosteroids might decrease CS, Thymosin α1 and adaptive COVID-19-specific T cells could enhance IR. There is an urgent need for more clinical research in this area throughout the world to open the door to COVID-19 treatment in the future.</p>","PeriodicalId":49280,"journal":{"name":"Progress in Molecular Biology and Translational Science","volume":"213 ","pages":"1-30"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144056536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mikael Kélvin de Albuquerque Mendes, Luíza Santa Brígida de Barros Góes, Michely da Silva Sousa, Emanuel Carrilho, Edivan Carvalho Vieira, Cícero Alves Lopes Júnior
{"title":"Exploring innovations in cell death for the study and treatment of non-communicable diseases.","authors":"Mikael Kélvin de Albuquerque Mendes, Luíza Santa Brígida de Barros Góes, Michely da Silva Sousa, Emanuel Carrilho, Edivan Carvalho Vieira, Cícero Alves Lopes Júnior","doi":"10.1016/bs.pmbts.2025.06.013","DOIUrl":"https://doi.org/10.1016/bs.pmbts.2025.06.013","url":null,"abstract":"<p><p>Cell death is a common occurrence in human physiological conditions which plays a pivotal role in the development and homeostasis of cells. In fact, the dysregulation of this process constitutes a scenario in the pathogenesis of several diseases, including non-communicable diseases (NCDs) such as cardiovascular diseases, cancer, diabetes, and neurological disorders. NCDs represents a staggering ca. 75% of all deaths worldwide. Although traditional treatments have played a crucial role against NCDs, innovative therapeutic strategies are urgently needed. The modulation of regulated cell death (RCD) has emerged as a promising therapy because recent research has revealed different pathways capable of killing damaged cells with the activation of a cell-specific immune response for NCD types. Apoptosis, autophagy, pyroptosis, necroptosis, ferroptosis and cuproptosis are the main forms of RCD identified. The complexity of the mechanism and interconnectivity of the different RCD pathways have constituted the greatest challenges for applied analytical approaches, but the integration of artificial intelligence and machine learning promotes an expectation to catalyze the understanding of cell death processes. By targeting RCD, new treatments may offer hope for better management and potential reversal of NCDs, thus improving the quality of life of a significant proportion of individuals and contributing to alleviating a global public health problem.</p>","PeriodicalId":49280,"journal":{"name":"Progress in Molecular Biology and Translational Science","volume":"217 ","pages":"407-439"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145126368","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M C Salinas-García, A G Sanchez-Toro, M Hernandez-Valladares
{"title":"Knowing cell death mechanisms and their applications in the management of disease.","authors":"M C Salinas-García, A G Sanchez-Toro, M Hernandez-Valladares","doi":"10.1016/bs.pmbts.2025.06.022","DOIUrl":"https://doi.org/10.1016/bs.pmbts.2025.06.022","url":null,"abstract":"<p><p>Cell death is a crucial biological process involved in development, homeostasis, and immune regulation. It can occur through multiple mechanisms, including apoptosis, necroptosis, pyroptosis, and ferroptosis. Programmed cell death is genetically regulated and essential for multicellular organisms, with dysregulation leading to various diseases. In normal development, cell death sculpts shapes and optimizes functions in the immune and central nervous systems. The field of cell death research has grown significantly, with recent efforts to standardize nomenclature, to describe the different mechanisms and to make available several assays to identify and study each of the different cell death processes. Fluorescence spectroscopy and imaging can probe cellular metabolism and detect cell death by measuring intensity or lifetime changes. In situ detection methods include DNA nick-end labeling, vital dyes, lysosomal enzyme histochemistry, and immunocytochemical detection of death-associated antigens. These diverse approaches enable researchers to investigate cell death in various contexts, from developmental processes to responses to external stimuli, contributing to our understanding of this fundamental biological phenomenon. Moreover, understanding these processes has important implications for treating diseases such as cancer, developmental abnormalities and neurological disorders.</p>","PeriodicalId":49280,"journal":{"name":"Progress in Molecular Biology and Translational Science","volume":"217 ","pages":"305-353"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145126391","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
José E Belizário, João Marcelo Occhiucci, Miguel Garay-Malpartida, José Rm Cunha da Silva
{"title":"Phageptosis: A bacterial cell death program induced by crispr-cas systems.","authors":"José E Belizário, João Marcelo Occhiucci, Miguel Garay-Malpartida, José Rm Cunha da Silva","doi":"10.1016/bs.pmbts.2025.07.003","DOIUrl":"https://doi.org/10.1016/bs.pmbts.2025.07.003","url":null,"abstract":"<p><p>Programmed cell death (PCD) is a fundamental mechanism that has evolved across both unicellular and multicellular organisms for species preservation and self-protection. In certain contexts, genetically regulated cell death can enable surviving cells to thrive, safeguarding the genotype from extinction. Recent research on bacteria and archaea has revealed an ancient defense mechanism involving CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) and Cas (CRISPR-associated) proteins. These systems identify and eliminate invading genetic elements, such as bacteriophages, transposons, and plasmids, using sequence-specific RNA-guided targeting. A protease complex called Craspase, activated by non-self RNA, regulates Cas nuclease activity, facilitating this primitive form of immunity. Interestingly, this pathway shows structural and mechanistic similarities to apoptosis, the first recognized form of programmed mammalian cell death, characterized by chromatin condensation, nuclear fragmentation, and membrane blebbing. Other regulated cell death pathways, including necroptosis and pyroptosis, also share overlapping features. Comparative genomic studies reveal a conserved molecular framework underpinning these diverse death pathways across life forms. In this article, we explore the emerging parallels and distinctions between apoptosis and CRISPR-Cas-mediated cell death, a process we refer to as \"phageptosis,\" highlighting evolutionary links and their implications for understanding cell death mechanisms.</p>","PeriodicalId":49280,"journal":{"name":"Progress in Molecular Biology and Translational Science","volume":"217 ","pages":"211-231"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145126427","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The role and regulation of cell death in cancer.","authors":"Minh Trong Quang, Minh Nam Nguyen, Van Thai Than","doi":"10.1016/bs.pmbts.2025.06.014","DOIUrl":"https://doi.org/10.1016/bs.pmbts.2025.06.014","url":null,"abstract":"<p><p>Regulated cell death (RCD) is an essential aspect of cellular homeostasis and coordinates important physiological processes, such as immune regulation, embryogenesis, and tissue remodeling. In cancer, the regulation of RCD is disrupted to allow tumor cells to resist apoptosis, modify their function to survive microenvironmental stresses, and become resistant to standard therapies. Beyond apoptosis, new modalities of RCD including necroptosis, pyroptosis, ferroptosis, and parthanatos, play multifaceted roles in tumor suppression and progression, determined by interactions with the tumor microenvironment (TME). These RCD pathways possess unique molecular regulators and exhibit distinctive immunological and pathological connotations with novel therapeutic potential. Here, in the current study, the mechanistic complexity of RCD pathways and their interactions with the TME, particularly in their immune evasion, tumor progression and therapy resistance roles, are reviewed. Furthermore, the therapeutic potential of the modulation of RCD pathways by using small-molecule inhibitors, immune checkpoint inhibitors, and combination therapies that repurpose the TME, were tested. The newly emerging technologies, such as nanotechnology and biomimetic delivery systems, are proposed to deliver novel solutions to escalating the specificity and potency of RCD-targeted therapy and confronting systemic toxicity as well as adaptive resistance. By combining mechanistic knowledge with innovative therapy, the transformative potential of RCD modulation in treating cancers is highlighted in the current review to improve precision oncology strategies that augment the efficacy of therapies and increase patient benefit.</p>","PeriodicalId":49280,"journal":{"name":"Progress in Molecular Biology and Translational Science","volume":"217 ","pages":"135-161"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145126428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}