EGR3-HDAC6-IL-27 Axis Mediates Allergic Inflammation and Is Necessary for Tumorigenic Potential of Cancer Cells Enhanced by Allergic Inflammation-Promoted Cellular Interactions

The objective of this study was to investigate mechanisms of allergic inflammation both in vitro and in vivo in details. For this, RNA sequencing was performed. Early growth response 3 gene (Egr3) was one of the most highly upregulated genes in rat basophilic leukemia (RBL2H3) cells stimulated by antigen. The role of Egr3 in allergic inflammation has not been studied extensively. Egr3 was necessary for passive cutaneous anaphylaxis (PCA) and passive systemic anaphylaxis (PSA). Egr3 promoter sequences contained potential binding site for NF-κB p65. NF-κB p65 directly regulated Egr3 expression and mediated allergic inflammation in vitro. Histone deacetylases (HDACs) is known to be involved in allergic airway inflammation. HDAC6 promoter sequences contained potential binding site for EGR3. EGR3 showed binding to promoter sequences of HDAC6. EGR3 was necessary for increased expression of histone deacetylase 6 (HDAC6) in antigen-stimulated RBL2H3 cells. HDAC6 mediated allergic inflammation in vitro and PSA. TargetScan analysis predicted that miR-182-5p was a negative regulator of EGR3. Luciferase activity assay confirmed that miR-182-5p was a direct regulator of EGR3. MiR-182-5p mimic inhibited allergic inflammation both in vitro and in vivo. Cytokine array showed that HDAC6 was necessary for increased interleukin-27 (IL-27) expression in BALB/C mouse model of PSA. Antigen stimulation did not affect expression of EBI3, another subunit of IL-27 in RBL2H3 cells or BALB/C mouse model of PCA or PSA. IL-27 receptor alpha was shown to be able to bind to HDAC6. IL-27 p28 mediated allergic inflammation in vitro, PCA, and PSA. Mouse recombinant IL-27 protein promoted features of allergic inflammation in an antigen-independent manner. HDAC6 was necessary for tumorigenic and metastatic potential enhanced by PSA. PSA enhanced the metastatic potential of mouse melanoma B16F1 cells in an IL-27-dependent manner. Experiments employing culture medium and mouse recombinant IL-27 protein showed that IL-27 mediated and promoted cellular interactions involving B16F1 cells, lung macrophages, and mast cells during allergic inflammation. IL-27 was present in exosomes of antigen-stimulated RBL2H3 cells. Exosomes from antigen-stimulated RBL2H3 cells enhanced invasion of B16F1 melanoma cells in an IL-27-dependemt manner. These results present evidence that EGR3-HDAC6-IL-27 axis can regulate allergic inflammation by mediating cellular interactions

Human Adipose Tissue-Derived Mesenchymal Stem Cells Attenuate Atopic Dermatitis by Regulating the Expression of MIP-2, miR-122a-SOCS1 Axis, and Th1/Th2 Responses

The objective of this study was to investigate the effect of human adipose tissue-derived mesenchymal stem cells (AdMSCs) on atopic dermatitis (AD) in the BALB/c mouse model. The AdMSCs attenuated clinical symptoms associated with AD, decreased numbers of degranulated mast cells (MCs), IgE level, amount of histamine released, and prostaglandin E2 level. Atopic dermatitis increased the expression levels of cytokines/chemokines, such as interleukin-5 (IL-5), macrophage inflammatory protein-1ß (MIP-1ß), MIP-2, chemokine (C-C motif) ligand 5 (CCL5), and IL-17, in BALB/c mouse. The AdMSCs showed decreased expression levels of these cytokines in the mouse model of AD. In vivo downregulation of MIP-2 attenuated the clinical symptoms associated with AD. Atopic dermatitis increased the expression levels of hallmarks of allergic inflammation, induced interactions of FcRIβ with histone deacetylase 3 (HDAC3) and Lyn, increased ß-hexosaminidase activity, increased serum IgE level, and increased the amount of histamine released in an MIP-2-dependent manner. Downregulation of MIP-2 increased the levels of several miRNAs, including miR-122a-5p. Mouse miR-122a-5p mimic inhibited AD, while suppressor of cytokine signaling 1 (SOCS1), a predicted downstream target of miR-122a-5p, was required for AD. The downregulation of SOCS1 decreased the expression levels of MIP-2 and chemokine (C-X-C motif) ligand 13 (CXCL13) in the mouse model of AD. The downregulation of CXCL13 attenuated AD and allergic inflammation such as passive cutaneous anaphylaxis. The role of T cell transcription factors in AD was also investigated. Atopic dermatitis increased the expression levels of T-bet and GATA-3 [transcription factors of T-helper 1 (Th1) and T-helper 2 (Th2) cells, respectively] but decreased the expression of Foxp3, a transcription factor of regulatory T (Treg) cells, in an SOCS1-dependent manner. In addition to this, miR-122a-5p mimic also prevented AD from regulating the expression of T-bet, GATA-3, and Foxp3. Atopic dermatitis increased the expression of cluster of differentiation 163 (CD163), a marker of M2 macrophages, but decreased the expression of inducible nitric oxide synthase (iNOS), a marker of M1 macrophages. Additionally, SOCS1 and miR-122a-5p mimic regulated the expression of CD163 and iNOS in the mouse model of AD. Experiments employing conditioned medium showed interactions between MCs and macrophages in AD. The conditioned medium of AdMSCs, but not the conditioned medium of human dermal fibroblasts, negatively inhibited the features of allergic inflammation. In summary, we investigated the anti-atopic effects of AdMSCs, identified targets of AdMSCs, and determined the underlying mechanism for the anti-atopic effects of AdMSCs

MiR-135-5p-p62 Axis Regulates Autophagic Flux, Tumorigenic Potential, and Cellular Interactions Mediated by Extracellular Vesicles During Allergic Inflammation

The objective of this study was to investigate the relationship between autophagy and allergic inflammation. In vitro allergic inflammation was accompanied by an increased autophagic flux in rat basophilic leukemia (RBL2H3) cells. 3-MA, an inhibitor of autophagic processes, negatively regulated allergic inflammation both in vitro and in vivo. The role of p62, a selective receptor of autophagy, in allergic inflammation was investigated. P62, increased by antigen stimulation, mediated in vitro allergic inflammation, passive cutaneous anaphylaxis (PCA), and passive systemic anaphylaxis (PSA). P62 mediated cellular interactions during allergic inflammation. It also mediated tumorigenic and metastatic potential of cancer cells enhanced by PSA. TargetScan analysis predicted that miR-135-5p was a negative regulator of p62. Luciferase activity assay showed that miR-135-5p directly regulated p62. MiR-135-5p mimic negatively regulated features of allergic inflammation and inhibited tumorigenic and metastatic potential of cancer cells enhanced by PSA. MiR-135-5p mimic also inhibited cellular interactions during allergic inflammation. Extracellular vesicles mediated allergic inflammation both in vitro and in vivo. Extracellular vesicles were also necessary for cellular interactions during allergic inflammation. Transmission electron microscopy showed p62 within extracellular vesicles of antigen-stimulated rat basophilic leukemia cells (RBL2H3). Extracellular vesicles isolated from antigen-stimulated RBL2H3 cells induced activation of macrophages and enhanced invasion and migration potential of B16F1 mouse melanoma cells in a p62-dependent manner. Extracellular vesicles isolated from PSA-activated BALB/C mouse enhanced invasion and migration potential of B16F1 cells, and induced features of allergic inflammation in RBL2H3 cells. Thus, miR-135-5p-p62 axis might serve as a target for developing anti-allergy drugs

Synthesis and electrochemical properties of lithium-electroactive surface-stabilized silicon quantum dots

Highly lithium-electroactive Si quantum dots (n-Si), coated with an amorphous carbon layer, were prepared by of butyl-capped Si annealing at 700 or 900 ??C. The ordering of the carbon layer structure increased with increasing annealing temperature while the thickness decreased to 1 from 2 nm due to the increased ordering of carbon. n-Si, annealed at 900 ??C, had the same particle size (5 nm) as n-Si annealed at 700 ??C. In contrast to Si nanocrystals with an average particle size of 30 nm that had a first charge capacity of 225 mAh/g with a very small coulombic efficiency of 4%, n-Si that annealed at 900 ??C possessed a first charge capacity of 1257 mAh/g with a significantly enhanced coulombic efficiency of 71%. This improvement was due to the uniform distribution of n-Si with a carbon layer that prohibited n-Si aggregation during cycling.close192

Role of HDAC3-miRNA-CAGE Network in Anti-Cancer Drug-Resistance

Histone modification is associated with resistance to anti-cancer drugs. Epigenetic modifications of histones can regulate resistance to anti-cancer drugs. It has been reported that histone deacetylase 3 (HDAC3) regulates responses to anti-cancer drugs, angiogenic potential, and tumorigenic potential of cancer cells in association with cancer-associated genes (CAGE), and in particular, a cancer/testis antigen gene. In this paper, we report the roles of microRNAs that regulate the expression of HDAC3 and CAGE involved in resistance to anti-cancer drugs and associated mechanisms. In this review, roles of HDAC3-miRNAs-CAGE molecular networks in resistance to anti-cancer drugs, and the relevance of HDAC3 as a target for developing anti-cancer drugs are discussed

Sn0.9Si0.1/carbon core-shell nanoparticles for high-density lithium storage materials

Sn0.9Si0.1 core/carbon shell nanoparticles, with the sizes of 16 and 10 nm, were prepared by annealing as-prepared butyl-capped Sn0.9Si0.1 particles with an average particle size of 1 ??m. Even though as-prepared samples were severely encapsulated by butyl terminators, annealing led to pulverization of the bulky particles into core - shell nanoparticles with a shell thickness dependent on the annealing temperature. The core Sn0.9Si0.1 size was estimated to be constant at 6 nm, and the carbon shell thickness decreased from 10 to 4 nm with increasing annealing temperature from 600 to 700??C, respectively. In addition, the carbon shell was found to be more ordered at 700??C than at 600??C. Sn0.9Si0.1 core/carbon shell nanoparticles exhibited excellent lithium storage ability at a high current rate, resulting in a value of 964 mA??h/g at a rate of 0.3 C (1 C = 1200 mA/g), and demonstrated good capacity retention after 50 cycles.close363

FcεRI-HDAC3-MCP1 Signaling Axis Promotes Passive Anaphylaxis Mediated by Cellular Interactions

Anaphylaxis is an acute and life-threatening systemic reaction. Food, drug, aero-allergen and insect sting are known to induce anaphylaxis. Mast cells and basophils are known to mediate Immunoglobulin E (IgE)-dependent anaphylaxis, while macrophages, neutrophils and basophils mediate non IgE-dependent anaphylaxis. Histone deacetylases (HDACs) play various roles in biological processes by deacetylating histones and non-histones proteins. HDAC inhibitors can increase the acetylation of target proteins and affect various inflammatory diseases such as cancers and allergic diseases. HDAC3, a class I HDAC, is known to act as epigenetic and transcriptional regulators. It has been shown that HDAC3 can interact with the high-affinity Immunoglobulin E receptor (FcεRI), to mediate passive anaphylaxis and cellular interactions during passive anaphylaxis. Effects of HDAC3 on anaphylaxis, cellular interactions involving mast cells and macrophages during anaphylaxis, and any tumorigenic potential of cancer cells enhanced by mast cells will be discussed in this review. Roles of microRNAs that form negative feedback loops with hallmarks of anaphylaxis such as HDAC3 in anaphylaxis and cellular interactions will also be discussed. The roles of MCP1 regulated by HDAC3 in cellular interactions during anaphylaxis are discussed. Roles of exosomes in cellular interactions mediated by HDAC3 during anaphylaxis are also discussed. Thus, review might provide clues for development of drugs targeting passive anaphylaxis

Effect of capping agents in tin nanoparticles on electrochemical cycling

Tin particles that were prepared using three different capping agents, hydrobenzamide, citrate, and polyvinyl pyrrolidone (PVP) exhibited different particle sizes. The hydrobenzamide-capped Sn had the smallest particle size (∼50 nm) and uniform distribution while the citrate and PVP-capped Sn had particle sizes of ∼100 and ∼300 nm, respectively, with severe particle aggregation. However, there was no SnO2 or SnO detected on the particle surfaces. The cycling results using coin-type half cells confirmed that the hydrobenzamide-capped Sn had the highest charge capacity of 994 mAh/g between 1.5 and 0 V and the best capacity retention. In contrast, the citrate and PVP-capped Sn showed severe capacity decay. Further analysis using cycled electrodes showed that the hydrobenzamide-capped Sn showed the least particle agglomeration and growth, compared with the others. From Fourier transform magnitude (FT) of Sn LIII-edge energy dispersive X-ray analysis spectra, these facts could be supported by the strong coordination formed as a result of chemical bonding between the nitrogen of the hydrobenzamide capping agent effectively inhibiting the particle growth during cycling.close202

Amorphous carbon-coated tin anode material for lithium secondary battery

The use of amorphous carbon-coated tin particles as an alternative material to ensure the dimensional integrity during Sn alloy/dealloy was highlighted. Inductively coupled plasma mass spectroscopy (ICP_MS) analysis of the Sn in the coated carbon showed that Sn wt% was 80, and the remaining 20 wt% was estimated to be carbon. It was indicated that most hydroxyl groups in glucose were removed during the hydrothermal reaction. It was found that an almost uniform amorphous carbon coating on the tin nanoparticles was prepared from aqueous glucose solutions using a hydrothermal method at 180??C, which facilitated enhanced dimensional stability during Li alloying/dealloying.close14914