Over the past decade, significant advances have been made in our understanding of how NACHT-, leucine-rich-repeat-, and pyrin domain-containing protein 3 (NLRP3) inflammasomes are activated. These findings provide detailed insights into the transcriptional and posttranslational regulatory processes, the structural–functional relationship of the activation processes, and the spatiotemporal dynamics of NLRP3 activation. Notably, the multifaceted mechanisms underlying the licensing of NLRP3 inflammasome activation constitute a focal point of intense research. Extensive research has revealed the interactions of NLRP3 and its inflammasome components with partner molecules in terms of positive and negative regulation. In this Review, we provide the current understanding of the complex molecular networks that play pivotal roles in regulating NLRP3 inflammasome priming, licensing and assembly. In addition, we highlight the intricate and interconnected mechanisms involved in the activation of the NLRP3 inflammasome and the associated regulatory pathways. Furthermore, we discuss recent advances in the development of therapeutic strategies targeting the NLRP3 inflammasome to identify potential therapeutics for NLRP3-associated inflammatory diseases. As research continues to uncover the intricacies of the molecular networks governing NLRP3 activation, novel approaches for therapeutic interventions against NLRP3-related pathologies are emerging.

Sohn KM, et al. J Korean Med Sci. 2020 Aug;35(38):e343. https://doi.org/10.3346/jkms.2020.35.e343

Yuk JM, et al. Immune Netw. 2024 Jan;24(1):e4. https://doi.org/10.4110/in.2024.24.e4

Peroxisome proliferator-activated receptors (PPARs) α, β, and γ are nuclear receptors that orchestrate the transcriptional regulation of genes involved in a variety of biological responses, such as energy metabolism and homeostasis, regulation of inflammation, cellular development, and differentiation. The many roles played by the PPAR signaling pathways indicate that PPARs may be useful targets for various human diseases, including metabolic and inflammatory conditions and tumors. Accumulating evidence suggests that each PPAR plays prominent but different roles in viral, bacterial, and parasitic infectious disease development. In this review, we discuss recent PPAR research works that are focused on how PPARs control various infections and immune responses. In addition, we describe the current and potential therapeutic uses of PPAR agonists/antagonists in the context of infectious diseases. A more comprehensive understanding of the roles played by PPARs in terms of host-pathogen interactions will yield potential adjunctive personalized therapies employing PPAR-modulating agents.

Health is increasingly recognized as a dynamic state of physiological equilibrium rather than the mere absence of disease. Traditional clinical biomarkers capture only limited aspects of physiology and fail to reflect the multidimensional and dynamic nature of human homeostasis. Metabolomics, by comprehensively profiling small-molecule metabolites downstream of genetic, proteomic, environmental, and lifestyle influences, offers a sensitive and functional readout of an individual’s physiological state. This review catalogues current advances in applying metabolomics to characterize metabolic features of health, focusing on the influence of age, sex, body mass index, physical activity, diet, lifestyle behaviors, microbiome composition, and population heterogeneity. Numerous cohort studies have shown that substantial metabolic variability exists amongst individuals within apparent healthy populations, underscoring the need for stratified and contextual reference frameworks. We further discuss major challenges in defining a standardized metabolic baseline, including analytical platform heterogeneity, biofluid specificity, population diversity, and the predominance of cross-sectional study designs. Finally, we highlight the role of large-scale longitudinal cohorts, biobanks, multi-omics integration, and artificial intelligence–driven tools in overcoming these barriers. Establishing robust, dynamic, and personalized metabolic baselines will be critical for redefining health, enabling early intervention, and supporting predictive and preventive medicine.