Fucoidan refined from Saccharina japonica ameliorates ambient particulate matter-induced inflammation in keratinocytes, underlying fibroblasts, and 12-O-tetradecanoylphorbol 13-acetate-induced ear edema in mice.

Fucoidan from Saccharina japonica (SJF) was isolated and characterized, and its anti-inflammatory effects on fine dust/ambient particulate matter (PM)-stimulated HaCaT keratinocytes were investigated. SJF increased cell viability by reducing intracellular ROS production in PM-stimulated HaCaT keratinocytes. Moreover, SJF downregulated the expression/production of inflammatory cytokines (IL-6, IL-8, IL-13, IL-25, IL-33, TNF-α, IFN-γ, and TSLP) and chemokines (MDC and TARC) through modulating NF-κB/MAPK signaling in PM-stimulated HaCaT keratinocytes. Extended studies investigated the impact of SJF-treated HaCaT keratinocyte culture media on HDFs. Interestingly, media from SJF-treated HaCaT keratinocytes on HDFs demonstrated a notable downregulation of the production of inflammatory mediators such as TSLP, IL-6, IL-8, IL-13, and TNF-α, as well as TARC and MDC. Furthermore, the study examined the impact of SJF on 12-O-tetradecanoylphorbol 13-acetate (TPA) induced ear edema in BALB/c mice and results indicated the reduced ear thickness and decreased iNOS and COX-2 expression. Our study confirmed the effectiveness of SJF in ameliorating PM-induced skin inflammation in in vitro experiments, along with the TPA-induced in vivo inflammatory model.

The secreted protein Amuc_1409 from Akkermansia muciniphila improves gut health through intestinal stem cell regulation.

Akkermansia muciniphila has received great attention because of its beneficial roles in gut health by regulating gut immunity, promoting intestinal epithelial development, and improving barrier integrity. However, A. muciniphila-derived functional molecules regulating gut health are not well understood. Microbiome-secreted proteins act as key arbitrators of host-microbiome crosstalk through interactions with host cells in the gut and are important for understanding host-microbiome relationships. Herein, we report the biological function of Amuc_1409, a previously uncharacterised A. muciniphila-secreted protein. Amuc_1409 increased intestinal stem cell (ISC) proliferation and regeneration in ex vivo intestinal organoids and in vivo models of radiation- or chemotherapeutic drug-induced intestinal injury and natural aging with male mice. Mechanistically, Amuc_1409 promoted E-cadherin/ß-catenin complex dissociation via interaction with E-cadherin, resulting in the activation of Wnt/ß-catenin signaling. Our results demonstrate that Amuc_1409 plays a crucial role in intestinal homeostasis by regulating ISC activity in an E-cadherin-dependent manner and is a promising biomolecule for improving and maintaining gut health.

Particulate Matter Induces Oxidative Stress and Ferroptosis in Human Lung Epithelial Cells.

Numerous toxicological studies have highlighted the association between urban particulate matter (PM) and increased respiratory infections and lung diseases. The adverse impact on the lungs is directly linked to the complex composition of particulate matter, initiating reactive oxygen species (ROS) production and consequent lipid peroxidation. Excessive ROS, particularly within mitochondria, can destroy subcellular organelles through various pathways. In this study, we confirmed the induction of ferroptosis, an iron-dependent cell death, upon exposure to an urban PM using RT-qPCR and signaling pathway analysis. We used KRISS CRM 109-02-004, the certified reference material for the analysis of particulate matter, produced by the Korea Research Institute of Standards and Science (KRISS). To validate that ferroptosis causes lung endothelial toxicity, we assessed intracellular mitochondrial potential, ROS overproduction, lipid peroxidation, and specific ferroptosis biomarkers. Following exposure to the urban PM, a significant increase in ROS generation and a decrease in mitochondrial potential were observed. Furthermore, it induced hallmarks of ferroptosis, including the accumulation of lipid peroxidation, the loss of antioxidant defenses, and cellular iron accumulation. In addition, the occurrence of oxidative stress as a key feature of ferroptosis was confirmed by increased expression levels of specific oxidative stress markers such as NQO1, CYP1B1, FTH1, SOD2, and NRF. Finally, a significant increase in key ferroptosis markers was observed, including xCT/SLC7A11, NQO1, TRIM16, HMOX-1, FTL, FTH1, CYP1B1, CHAC1, and GPX4. This provides evidence that elevated ROS levels induce oxidative stress, which ultimately triggers ferroptosis. In conclusion, our results show that the urban PM, KRISS CRM, induces cellular and mitochondrial ROS production, leading to oxidative stress and subsequent ferroptosis. These results suggest that it may induce ferroptosis through ROS generation and may offer potential strategies for the treatment of lung diseases.

A potential role of protein extractions from Metagonimus yokogawai in amelionating inflammation in patients with ankylosing spondylitis.

Helminth infections and their components has been recognized to have a positive impact on the immune system. This study aimed to investigate the potential of Metagonimus yokogawai-derived proteins (MYp) to provide protection against ankylosing spondylitis (AS) through modulation of immune responses. The cytotoxicity of MYp at various doses was first assessed using MTS and flow cytometry. Peripheral blood mononuclear cells (PBMCs) were collected from AS patients, and the production of inflammatory cytokines was analyzed through flow cytometry. In the experiments with SKG mice, MYp or vehicle was administered and inflammation was evaluated through immunohistochemistry and enzyme-linked immunosorbent assay. The results showed that MYp did not decrease cell viability of PBMCs even after 48 h. Additionally, the frequencies of IFN-γ and IL-17A producing cells were significantly reduced after MYp treatment in the PBMC cultures. Furthermore, MYp treatment significantly suppressed arthritis and enthesitis in the SKG mouse model. The results suggest the first evidence that MYp can effectively alleviate clinical symptoms and restore cytokine balance in patients with AS.

Development of Human Rhinovirus RNA Reference Material Using Digital PCR.

The human rhinovirus (RV) is a positive-stranded RNA virus that causes respiratory tract diseases affecting both the upper and lower halves of the respiratory system. RV enhances its replication by concentrating RNA synthesis within a modified host membrane in an intracellular compartment. RV infections often occur alongside infections caused by other respiratory viruses, and the RV virus may remain asymptomatic for extended periods. Alongside qualitative detection, it is essential to accurately quantify RV RNA from clinical samples to explore the relationships between RV viral load, infections caused by the virus, and the resulting symptoms observed in patients. A reference material (RM) is required for quality evaluation, the performance evaluation of molecular diagnostic products, and evaluation of antiviral agents in the laboratory. The preparation process for the RM involves creating an RV RNA mixture by combining RV viral RNA with RNA storage solution and matrix. The resulting RV RNA mixture is scaled up to a volume of 25 mL, then dispensed at 100 µL per vial and stored at -80 °C. The process of measuring the stability and homogeneity of RV RMs was conducted by employing reverse transcription droplet digital polymerase chain reaction (RT-ddPCR). Digital PCR is useful for the analysis of standards and can help to improve measurement compatibility: it represents the equivalence of a series of outcomes for reference materials and samples being analyzed when a few measurement procedures are employed, enabling objective comparisons between quantitative findings obtained through various experiments. The number of copies value represents a measured result of approximately 1.6 × 105 copies/µL. The RM has about an 11% bottle-to-bottle homogeneity and shows stable results for 1 week at temperatures of 4 °C and -20 °C and for 12 months at a temperature of -80 °C. The developed RM can enhance the dependability of RV molecular tests by providing a precise reference value for the absolute copy number of a viral target gene. Additionally, it can serve as a reference for diverse studies.