Effects of Space Flight on Inflammasome Activation in the Brain of MiceRoy, Hadad, Rodriguez
et alCells (2025) 14 (6)
Abstract: Space flight exposes astronauts to stressors that alter the immune response, rendering them vulnerable to infections and diseases. In this study, we aimed to determine the levels of inflammasome activation in the brains of mice that were housed in the International Space Station (ISS) for 37 days. C57BL/6 mice were launched to the ISS as part of NASA's Rodent Research 1 Mission on SpaceX-4 CRS-4 Dragon cargo spacecraft from 21 September 2014 to 25 October 2014. Dissected mouse brains from that mission were analyzed by immunoblotting of inflammasome signaling proteins and Electrochemiluminescence Immunoassay (ECLIA) for inflammatory cytokine levels. Our data indicate decreased inflammasome activation in the brains of mice that were housed in the ISS for 37 days when compared to the brains of mice that were maintained on the ground, and in mice corresponding to the baseline group that were sacrificed at the time of launching of SpaceX-4. Moreover, we did not detect any significant changes in the expression levels of the pro-inflammatory cytokines TNF-α, IL-2, IFN-γ, IL-5, IL-6, IL-12p70 and IL-10 between the ground control and the flight groups. Together, these studies suggest that spaceflight results in a decrease in the levels of innate immune signaling molecules that govern inflammasome signaling in the brain of mice.
Caco2/HT-29 In Vitro Cell Co-Culture: Barrier Integrity, Permeability, and Tight Junctions' Composition During Progressive Passages of Parental CellsDonetti, Bendinelli, Correnti
et alBiology (Basel) (2025) 14 (3)
Abstract: Epithelial linings are crucial for the maintenance of physiological barriers. The intestinal epithelial barrier (IEB) consists of enterocytes through tight junctions and mucus-secreting cells and can undergo physiological modifications throughout life. To reproduce as closely as possible the IEB main features over time, in vitro co-cultures of Caco2/HT-29 70/30 formed by parental Caco2 and HT-29 cells sub-cultivated for more than 40 passages were set up. The measurements of the transepithelial electrical resistance (TEER) identified two populations: physiological TEER co-cultures (PC) with values > 50 Ωcm2 formed by parental cells with fewer than 40 passages, and leaky TEER co-cultures (LC) with values < 50 Ωcm2 formed by parental cells with more than 40 passages. In LC, paracellular permeability increased in parallel. By immunofluorescence and Western blot analysis, an increase in claudin 2 was observed in LC vs. PC, with no differences in occludin expression. MUC-2 immunoreactivity was stronger in PC than in LC. LC also showed an enhanced vulnerability to TNFα+IFN-γ. These results reproduce the main morpho-functional modifications reported in the human leaky/aged gut and support the usefulness of our in vitro cell model for studying the molecular processes underlying these modifications and testing drug/nutraceutical treatments to ameliorate leaky gut aging.
Evaluation of the Antiaging Potential of the Dendropanax morbiferus-Derived Compound Dendropanoxide in TNF-α-Stimulated Human Dermal FibroblastsAhn, Lee, Kim
et alCurr Issues Mol Biol (2025) 47 (3)
Abstract: In this study, we investigated the antiaging potential of dendropanoxide (DP), an active compound derived from Dendropanax morbiferus, in human dermal fibroblasts (NHDFs) induced by Tumor Necrosis Factor-alpha (TNF-α) and in human epidermal keratinocytes (NHEKs) induced by TNF-α and interferon gamma (IFN-γ). We induced oxidative stress related to ultraviolet (UV) radiation with TNF-α and IFN-γ and then treated the cells with various concentrations of DP to evaluate its effects on reactive oxygen species (ROS) production, matrix metalloproteinase-1 (MMP-1) expression, collagen synthesis, inflammatory cytokine expression, and skin barrier protection. The results showed that DP significantly reduced ROS production, indicating its potential to alleviate oxidative stress in the skin. Additionally, DP effectively inhibited MMP-1 production, suggesting that it could prevent collagen degradation in the dermis, significantly increase the secretion of pro-collagen I, promote collagen synthesis, and protect the dermal extracellular matrix (ECM). Moreover, DP significantly reduced the expression of inflammatory cytokines IL-1β and IL-6, thereby inhibiting excessive inflammatory responses in the skin. DP also enhanced the gene expression of key factors involved in skin barrier maintenance, including Kazal-type 5 (SPINK5), loricrin (LOR), aquaporin-3 (AQP3), filaggrin (FLG), and keratin 1 (KRT1), suggesting its potential to maintain and protect the skin barrier. Western blot analysis revealed that DP inhibited TNF-α-induced phosphorylation of JNK and p38, implying that DP exerts antiaging effects through the regulation of the JNK and p38 signaling pathways. Collectively, these findings suggest that DP has significant potential as an antiaging agent.
In silico construction of a multi-epitope vaccine (RGME-VAC/ATS-1) against the Rickettsia genus using immunoinformaticsFelice, Rodrigues, Marques
et alMem Inst Oswaldo Cruz (2025) 120, e240201
Abstract: Rickettsia is a genus of Gram-negative bacteria that causes various diseases, including epidemic typhus, Rocky Mountain spotted fever, and Mediterranean spotted fever. Ticks transmit these diseases and commonly found in developing regions with poor sanitation. As a result, it is difficult to estimate the number of these diseases cases, making it challenging to create prevention and diagnostic mechanisms.Thus, this study aimed to develop an in silico multi-epitope vaccine against Rickettsia.Eight proteins were previously identified as potential vaccine candidates through reverse vaccinology and were screened for epitopes that bind to MHC class I and II molecules. The epitopes were then analysed for antigenicity, allergenicity, and toxicity. The selected epitopes were linked with AAY and GPGPG sequences peptide and a known adjuvant, the B-chain of Escherichia coli heat-labile enterotoxin, to form a chimeric multi-epitope protein. The protein's three-dimensional structure was predicted, and molecular docking analysis was performed against the toll-like receptor 4 (TLR4). Finally, the immune response to the protein was simulated using C-ImmSim tool.A total of 26 immunogenic epitopes, formed the multi-epitope vaccine RGME-VAC/ATS-1. The vaccine showed excellent immunogenic parameters and was predicted to do not be toxic or allergenic to the host. It also showed good potential stimulation of immune cells, with a propensity to generate memory cells and elicit IFN-γ secretion.The in silico validations suggest that our study successfully designed an innovative multi-epitope vaccine against Rickettsia, addressing the challenges posed by the elusive nature of diseases caused by this genus. We provide a promising potential for further experimental exploration and the development of targeted prevention and diagnostic strategies for these diseases.
膜杰作
Star Staining
