Sepsis is a life-threatening response to infection associated with inflammation, oxidative stress and mitochondrial dysfunction. We investigated differential effects of three forms of vitamin E, which accumulate in different cellular compartments, on oxidative stress, mitochondrial function, mRNA and protein expression profiles associated with the human Toll-like receptor (TLR) -2 and -4 pathways. Human endothelial cells were exposed to lipopolysaccharide (LPS)/peptidoglycan G (PepG) to mimic sepsis, MitoVitE, α-tocopherol, or Trolox. Oxidative stress, mitochondrial function, mitochondrial membrane potential and metabolic activity were measured. NFκB-P65, total and phosphorylated inhibitor of NFκB alpha (NFκBIA), and STAT-3 in nuclear extracts, interleukin (IL)-6 and IL-8 production in culture supernatants and cellular mRNA expression of 32 genes involved in Toll-like receptor-2 and -4 pathways were measured. Exposure to LPS/PepG caused increased total radical production ( = 0.022), decreased glutathione ratio ( = 0.016), reduced membrane potential and metabolic activity (both < 0.0001), increased nuclear NFκB-P65 expression ( = 0.016) and increased IL-6/8 secretion (both < 0.0001). MitoVitE, α- tocopherol and Trolox were similar in reducing oxidative stress, NFκB activation and interleukin secretion. MitoVitE had widespread downregulatory effects on gene expression. Despite differences in site of actions, all forms of vitamin E were protective under conditions mimicking sepsis. These results challenge the concept that protection inside mitochondria provides better protection.
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http://dx.doi.org/10.3390/antiox9030195 | DOI Listing |
ACS Nano
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Department of Urology, Peking University First Hospital, Beijing 100034, China.
Although considered an "eco-friendly" biodegradable plastic, polylactic acid (PLA) microplastic (PLA-MP) poses a growing concern for human health, yet its effects on male reproductive function remain underexplored. This study investigated the reproductive toxicity of PLA in male mice and its potential mechanisms. To this end, our in vivo and in vitro experiments demonstrated that after degradation in the digestive system, a significant number of PLA-MP-derived nanoparticles could penetrate the blood-testis barrier (BTB) and localize within the spermatogenic microenvironment.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
February 2025
Aix-Marseille Université-CNRS UMR 7283, Institut de Microbiologie de la Méditerranée and Turing Center for Living Systems, Marseille 13009, France.
Despite growing awareness of their importance in soil ecology, the genetic and physiological traits of bacterial predators are still relatively poorly understood. In the course of a predator evolution experiment, we identified a class of genotypes leading to enhanced predation against diverse species. RNA-seq analysis demonstrated that this phenotype is linked to the constitutive activation of a predation-specific program.
View Article and Find Full Text PDFChem Rev
January 2025
Center for Theoretical Interdisciplinary Sciences Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, Zhejiang 325001, P. R. China.
Nanozymes have shown significant potential in cancer catalytic therapy by strategically catalyzing tumor-associated substances and metabolites into toxic reactive oxygen species (ROS) , thereby inducing oxidative stress and promoting cancer cell death. However, within the complex tumor microenvironment (TME), the rational design of nanozymes and factors like activity, reaction substrates, and the TME itself significantly influence the efficiency of ROS generation. To address these limitations, recent research has focused on exploring the factors that affect activity and developing nanozyme-based cascade catalytic systems, which can trigger two or more cascade catalytic processes within tumors, thereby producing more therapeutic substances and achieving efficient and stable cancer therapy with minimal side effects.
View Article and Find Full Text PDFISME J
January 2025
State Key Laboratory for Ecological Security of Regions and Cities, Ningbo Urban Environment Observation and Research Station, Institute of Urban Environment, Chinese Academy of Sciences, 1799 Jimei Road, Xiamen 361021, China.
Protozoa, as primary predators of soil bacteria, represent an overlooked natural driver in the dissemination of antibiotic resistance genes. However, the effects of protozoan predation on antibiotic resistance genes dissemination at the community level, along with the underlying mechanisms, remain unclear. Here we used fluorescence-activated cell sorting, qPCR, combined with metagenomics and reverse transcription quantitative PCR, to unveil how protozoa (Colpoda steinii and Acanthamoeba castellanii) influence the plasmid-mediated transfer of antibiotic resistance genes to soil microbial communities.
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Special Research Incubator Unit of Fermentomics, Department of Biotechnology, Faculty of Agro-Industry, Kasetsart University, Bangkok 10900, Thailand.
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