2'-Fucosyllactose (2FL) is the most abundant component of the oligosaccharide content in human milk. It has been reported that 2FL has the ability to protect against infectious disease caused by bacterial pathogens. In this study, we investigated the protective effects of 2FL on particulate matter (PM)-induced pro-inflammatory cytokines in HaCaT keratinocytes. 2FL reduced PM-induced excess expression of interleukin (IL)-6, IL-8, IL-1α and IL-1β in HaCaT keratinocytes. In addition, PM also increased hypoxia-inducible factor (HIF)-1α protein levels; however, 2FL inhibited the accumulation of HIF-1α protein and the phosphorylation of phosphatidylinositol 3-kinase (PI3K)/Akt stimulated by PM. Furthermore, 2FL improved PM-induced the decrease in epidermal thickness and integrity of the cornified layer in the reconstructed human epidermal skin model (RHE). In our results, 2FL inhibited PM-induced pro-inflammatory mediators by regulating the HIF-1α/PI3K/Akt pathway and protected the skin epidermis against PM irritation. Taken together, these results suggest that 2FL can be used as a primary ingredient in cosmeceutical products to alleviate skin irritation and inflammation caused by urban air pollution.
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In Vitro Model
February 2024
Faculty of Engineering, Tokyo University of Agriculture and Technology, 2-24-16 Naka-Cho, Koganei, Tokyo 184-8588 Japan.
Unlabelled: Engineered three-dimensional (3D) tissue culture platforms are useful for reproducing and elucidating complex in vivo biological phenomena. Spheroids, 3D aggregates of living cells, are produced based on physicochemical or microfabrication technologies and are commonly used even in cancer pathology research. However, conventional methods have difficulties in constructing 3D structures depending on the cell types, and require specialized techniques/lab know-how to reproducibly control the spheroid size and shape.
View Article and Find Full Text PDFFront Cell Neurosci
January 2025
Hainan General Hospital and Hainan Affiliated Hospital of Hainan Medical University, Haikou, China.
Protein lactylation is a new form of post-translational modification that has recently been proposed. Lactoyl groups, derived mainly from the glycolytic product lactate, have been linked to protein lactylation in brain tissue, which has been shown to correlate with increased neuronal excitability. Ischemic stroke may promote neuronal glycolysis, leading to lactate accumulation in brain tissue.
View Article and Find Full Text PDFClin Pharmacol Ther
January 2025
Leiden Experts on Advanced Pharmacokinetics and Pharmacodynamics (LAP&P), Leiden, The Netherlands.
Daprodustat, a novel oral hypoxia-inducible factor prolyl hydroxylase inhibitor is approved in the United States for the treatment of anemia due to chronic kidney disease (CKD) in adults receiving dialysis for at least 4 months. Pharmacodynamic dose-hemoglobin (Dose-Hgb) models were developed as daprodustat progressed through development. To support global phase III development, a dose-titration algorithm, guided by simulations from the initial Dose-Hgb model based on phase II clinical data, was implemented.
View Article and Find Full Text PDFJ Dent Res
January 2025
Department of Preventive and Restorative Dental Sciences, School of Dentistry, University of California, San Francisco, CA, USA.
The upstream mechanobiological pathways that regulate the downstream mineralization rates in periodontal tissues are limitedly understood. Herein, we spatially colocalized and correlated compression and tension strain profiles with the expressions of mechanosensory ion channels (MS-ion) TRPV4 and PIEZO1, biometal zinc, mitochondrial function marker (), cell senescence indicator (), and oxygen status marker hypoxia-inducible factor-1α () in rats fed hard and soft foods. The observed zinc and related cellular homeostasis in vivo were ascertained by TRPV4 and PIEZO1 agonists and antagonists on human periodontal ligament fibroblasts ex vivo.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
February 2025
Cardiovascular Research Institute, University of California San Francisco, San Francisco, CA 94158.
The ε4 variant of human apolipoprotein E () is a key genetic risk factor for neurodegeneration in Alzheimer's disease and elevated all-cause mortality in humans. Understanding the factors and mechanisms that can mitigate the harmful effects of has significant implications. In this study, we find that inactivating the VHL-1 (Von Hippel-Lindau) protein can suppress mortality, neural and behavioral pathologies caused by transgenic human in .
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