Progress in Molecular Biology and Translational Science最新文献

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.

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.

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.

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.

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.

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.

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.

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.

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.

Cell death is a fundamental process that plays a role in the development of multicellular organisms, tissue homeostasis, and fighting infections. Dysfunctional cell death signaling is associated with many diseases, including cancer. Most studied among multiple possible cell death pathways is apoptosis that is essential for various biological functions, including embryogenesis, aging, and the development of numerous diseases. This regulated cell death enables the removal of cells in a controlled manner, maintaining tissue homeostasis and aiding organismal development. Understanding cell death pathways can help develop new therapeutic strategies for treating diseases like cancer. For example, tumor cells often avoid apoptosis, which can lead to treatment resistance. Various groups of researchers believe that studying other cell death pathways, like necroptosis, pyroptosis, ferroptosis, and cuproptosis, may have high potential for cancer therapy. Numerous biochemical methods exist to detect, quantify, and analyze cell death pathways, each with unique principles, advantages, and limitations. A comprehensive understanding of these methods enables researchers to select appropriate techniques for their experimental contexts. This chapter systematically discusses the molecular and cellular changes related to various cell death pathways and the conventional and non-conventional methods used to investigate these processes.