Correction: Anti-inflammatory effects of cold atmospheric plasma irradiation on the THP-1 human acute monocytic leukemia cell line.

[This corrects the article DOI: 10.1371/journal.pone.0292267.].

Anti-inflammatory effects of cold atmospheric plasma irradiation on the THP-1 human acute monocytic leukemia cell line.

Cold atmospheric plasma (CAP) has been studied and clinically applied to treat chronic wounds, cancer, periodontitis, and other diseases. CAP exerts cytotoxic, bactericidal, cell-proliferative, and anti-inflammatory effects on living tissues by generating reactive species. Therefore, CAP holds promise as a treatment for diseases involving chronic inflammation and bacterial infections. However, the cellular mechanisms underlying these anti-inflammatory effects of CAP are still unclear. Thus, this study aimed to elucidate the anti-inflammatory mechanisms of CAP in vitro. The human acute monocytic leukemia cell line, THP-1, was stimulated with lipopolysaccharide and irradiated with CAP, and the cytotoxic effects of CAP were evaluated. Time-course differentiation of gene expression was analyzed, and key transcription factors were identified via transcriptome analysis. Additionally, the nuclear localization of the CAP-induced transcription factor was examined using western blotting. The results indicated that CAP showed no cytotoxic effects after less than 70 s of irradiation and significantly inhibited interleukin 6 (IL6) expression after more than 40 s of irradiation. Transcriptome analysis revealed many differentially expressed genes (DEGs) following CAP irradiation at all time points. Cluster analysis classified the DEGs into four distinct groups, each with time-dependent characteristics. Gene ontology and gene set enrichment analyses revealed CAP-induced suppression of IL6 production, other inflammatory responses, and the expression of genes related to major histocompatibility complex (MHC) class II. Transcription factor analysis suggested that nuclear factor erythroid 2-related factor 2 (NRF2), which suppresses intracellular oxidative stress, is the most activated transcription factor. Contrarily, regulatory factor X5, which regulates MHC class II expression, is the most suppressed transcription factor. Western blotting revealed the nuclear localization of NRF2 following CAP irradiation. These data suggest that CAP suppresses the inflammatory response, possibly by promoting NRF2 nuclear translocation.

Improved Production of Induced Pluripotent Stem Cells Using Dot Pattern Culture Plates.

The rate of cell proliferation is a crucial factor in cell production under good manufacturing practice (GMP) control. In this study, we identified a culture system for induced pluripotent cells (iPSCs) that supports cell proliferation and viability and maintains the cells in an undifferentiated state even at 8 days after seeding. This system involves the use of dot pattern culture plates that have been coated with a chemically defined scaffold which has high biocompatibility. Under cell starvation conditions, where medium exchange was not performed for 7 days or where the amount of medium exchange was reduced to half or a quarter, iPSC viability and lack of differentiation were maintained. The rate of cell viability in this culture system was greater than generally obtained by standard culture methods. The cells in this compartmentalized culture system could be induced to differentiate in a controlled and consistent manner: differentiation of endoderm occurred in a controlled and consistent manner: endoderm, mesoderm, and ectoderm could be consistently induced to differentiate in the cultures. In conclusion, we have developed a culture system that supports high viability in iPSCs and allows their controlled differentiation. This system has the potential for use in GMP-based production of iPSCs for clinical purposes.

Antibacterial and Bioactive Surface Modifications of Titanium Implants by PCL/TiO2 Nanocomposite Coatings.

Surface modification of biomedical implants is an established strategy to improve tissue regeneration, osseointegration and also to minimize the bacterial accumulation. In the present study, electrospun poly(ε-caprolactone)/titania (PCL/TiO2) nanocomposite coatings were developed on commercially pure titanium (cpTi) substrates for an improved biological and antibacterial properties for bone tissue engineering. TiO2 nanoparticles in various amounts (2, 5, and 7 wt %) were incorporated into a biodegradable PCL matrix to form a homogeneous solution. Further, PCL/TiO2 coatings on cpTi were obtained by electrospinning of PCL/TiO2 solution onto the substrate. The resulted coatings were structurally characterized and inspected by employing scanning electron microscope (SEM), X-ray diffraction (XRD), and Fourier transform infrared (FTIR) spectroscopy. Given the potential biological applications of PCL/TiO2 coated cpTi substrates, the apatite-forming capacity was examined by immersing in simulated body fluid (SBF) for upto 21 days. Biocompatibility has been evaluated through adhesion/proliferation of hFOB osteoblast cell lines and cytotoxicity by MTT assay. Antimicrobial activity of PCL/TiO2 nanocomposites has been tested using UV light against gram-positive Staphylococcus aureus (S.aureus). The resulting surface displays good bioactive properties against osteoblast cell lines with increased viability of 40% at day 3 and superior antibacterial property against S.aureus with a significant reduction of bacteria to almost 76%. Surface modification by PCL/TiO2 nanocomposites makes a viable approach for improving dual properties, i.e., biological and antibacterial properties on titanium implants which might be used to prevent implant-associated infections and promoting cell attachment of orthopedic devices at the same time.