Pyroptosis is a novel regulated cell death (RCD) mode associated with inflammation and innate immunity. Gasdermin E (GSDME), a crucial component of the gasdermin (GSDM) family proteins, has the ability to convert caspase-3-mediated apoptosis to pyroptosis of cancer cells and activate anti-tumor immunity. Accumulating evidence indicates that GSDME methylation holds tremendous potential as a biomarker for early detection, diagnosis, prognosis, and treatment of tumors. In fact, GSDME-mediated pyroptosis performs a dual role in anti-tumor therapy. On the one side, pyroptotic cell death in tumors caused by GSDME contributes to inflammatory cytokines release, which transform the tumor immune microenvironment (TIME) from a ‘cold’ to a ‘hot’ state and significantly improve anti-tumor immunotherapy. However, due to GSDME is expressed in nearly all body tissues and immune cells, it can exacerbate chemotherapy toxicity and partially block immune response. How to achieve a balance between the two sides is a crucial research topic. Meanwhile, the potential functions of GSDME-mediated pyroptosis in anti-programmed cell death protein 1 (PD-1) therapy, antibody-drug conjugates (ADCs) therapy, and chimeric antigen receptor T cells (CAR-T cells) therapy have not yet been fully understood, and how to improve clinical outcomes persists obscure. In this review, we systematically summarize the latest research regarding the molecular mechanisms of pyroptosis and discuss the role of GSDME-mediated pyroptosis in anti-tumor immunity and its potential applications in cancer treatment.

Pyroptosis is a novel inflammatory form of regulated cell death (RCD), characterized by cell swelling, membrane rupture, and pro-inflammatory effects. It is recognized as a potent inflammatory response required for maintaining organismal homeostasis. However, excessive and persistent pyroptosis contributes to severe inflammatory responses and accelerates the progression of numerous inflammation-related disorders. In pyroptosis, activated inflammasomes cleave gasdermins (GSDMs) and generate membrane holes, releasing interleukin (IL)-1β/18, ultimately causing pyroptotic cell death. Mechanistically, pyroptosis is categorized into caspase-1-mediated classical pyroptotic pathway and caspase-4/5/11-mediated non-classical pyroptotic pathway. Renal fibrosis is a kidney disease characterized by the loss of structural and functional units, the proliferation of fibroblasts and myofibroblasts, and extracellular matrix (ECM) accumulation, which leads to interstitial fibrosis of the kidney tubules. Histologically, renal fibrosis is the terminal stage of chronic inflammatory kidney disease. Although there is a multitude of newly discovered information regarding pyroptosis, the regulatory roles of pyroptosis involved in renal fibrosis still need to be fully comprehended, and how to improve clinical outcomes remains obscure. Hence, this review systematically summarizes the novel findings regarding the role of pyroptosis in the pathogenesis of renal fibrosis and discusses potential biomarkers and drugs for anti-fibrotic therapeutic strategies.

Pyroptosis, an inflammatory regulated cell death (RCD) mechanism, is characterized by cellular swelling, membrane rupture, and subsequent discharge of cellular contents, exerting robust proinflammatory effects. Recent studies have significantly advanced our understanding of pyroptosis, revealing that it can be triggered through inflammasome- and caspase-independent pathways, and interacts intricately with other RCD pathways (e.g., pyroptosis, necroptosis, ferroptosis, and cuproptosis). The pathogenesis of pulmonary fibrosis (PF), including idiopathic pulmonary fibrosis (IPF) and other interstitial lung diseases, involves a multifaceted interplay of factors such as pathogen infections, environmental pollutants, genetic variations, and immune dysfunction. This chronic and progressive interstitial lung disease is characterized by persistent inflammation, extracellular matrix (ECM) accumulation, and fibrotic alveolar wall thickening, which potentially contribute to deteriorated lung function. Despite recent advances in understanding pyroptosis, the mechanisms by which it regulates PF are not entirely elucidated, and effective strategies to improve clinical outcomes remain unclear. This review strives to deliver a comprehensive overview of the biological functions and molecular mechanisms of pyroptosis, exploring its roles in the pathogenesis of PF. Furthermore, it examines potential biomarkers and therapeutic agents for anti-fibrotic treatments.

Voriconazole, a broad-spectrum antifungal agent, is considered the first-line treatment for invasive aspergillosis. In this article, we report three cases of patients who experienced visual disturbances and hallucinations following voriconazole therapy for invasive pulmonary aspergillosis. These symptoms appeared within 1 week after initiating voriconazole administration and resolved upon discontinuation or dose reduction of the drug. Considering the absence of any identifiable alternative cause and the temporal relationship with voriconazole initiation, these symptoms were attributed to the adverse effects of voriconazole. All three patients had trough concentrations exceeding 5 μg/mL at the time of adverse reactions, leading to subsequent therapeutic drug monitoring and dose adjustment. The clinical characteristics and management strategies of voriconazole-induced hallucinations and/or visual disturbances have been rarely reported previously. Therefore, our study reviewed and analyzed relevant case reports since 2014. This study highlights the importance of recognizing the potential risk of hallucinations and visual disturbances associated with voriconazole. Furthermore, our findings indicate that the route of voriconazole administration does not influence the frequency of these adverse events. Additionally, special attention should be given to monitoring adverse events related to voriconazole in Asian populations due to their higher prevalence of CYP2C19 poor metabolizers. In the event of adverse reactions to voriconazole, diligent monitoring of therapeutic drug levels and dosage adjustments is crucial. These clinical characteristics and management strategies offer advantages in terms of enhancing drug efficacy, ensuring treatment continuity, and minimizing the incidence of other severe adverse reactions.