Background and aims
Mast cells are the major effector cells in allergic disorders and many other informatory disorders. The mechanism of mast cell stabilization is not fully understood. Cumulative ...reports indicate that vitamin D (VitD) contributes to the homeostasis in the body. This study tests a hypothesis that VitD is required in the maintenance of the stability of mast cells.
Methods
The stability of mast cell lines, HMC1 cells, RBL‐2H3 cells, p815 cells, and mouse bone marrow‐derived mast cells (BMMC) was tested in the presence or absence of VitD3.
Results
Mast cells activated automatically in a VitD‐deficient environment. Exposure to calcitriol in the culture increased the expression of VitD receptor (VDR) in mast cells. VDR formed complexes with Lyn in mast cells to inhibit the binding of Lyn to the β chain of FcεRI and MyD88, which decreased the phosphorylation of Syk, decreased the levels of MAPK and NF‐κB. VDR bound to the promoter of TNF‐α to decrease the acetylation of histone H3/H4, RNA polymerase II and OCT1 (a transcription factor of TNF‐α) at the promoter locus and repressed the expression of TNF‐α in mast cells.
Conclusions
The data demonstrate that VitD is required to maintain the stability of mast cells. The deficiency of VitD results in mast cell activation.
Background and aims
The function of interleukin (IL)‐10‐producing B cells (B10 cell) is compromised in patients with allergic diseases. Protease‐activated receptor (PAR)‐2 has immunoregulatory ...functions. This study aimed to elucidate the role of PAR2 in the suppression of IL‐10 expression in peripheral B cells.
Methods
Peripheral blood B cells were collected from patients with allergic rhinitis (AR). A correlation between the expression of Bcl2‐like protein 12 (Bcl2L12) and IL‐10 in the B cells was analyzed. An AR mouse model was developed.
Results
We observed that the expression of IL‐10 was lower in the peripheral B cells from patients with airway allergy. A negative correlation was identified between the expression of IL‐10 and PAR2 in B cells. Activation of PAR2 of B cells increased the expression of Bcl2L12 and suppression of LPS‐induced IL‐10 expression, which were inhibited by knocking down the Bcl2L12 gene. Treating B cells from AR patients with Bcl2L12‐shRNA‐carrying liposomes reversed the capability of IL‐10 expression and the immunosuppressive function. Administration of Bcl2L12 shRNA‐carrying liposomes attenuated experimental AR in mice.
Conclusions
Activation of PAR2 inhibits the expression of IL‐10 in B cells, which can be reversed by treating B cells with Bcl2L12 shRNA‐carrying liposomes. The data suggest that regulation of Bcl2L12 may be a novel approach in the treatment for AR.
Background
The overproduction of IgE plays a critical role in the pathogenesis of allergy; the mechanism is unclear. Histone‐acetyltransferase (HAT) activities are required in gene transcription of a ...large number of molecules in the immune system of the body.
Objectives
This study tests a hypothesis that HAT Tat‐interactive protein 60 (Tip60) plays an important role in the initiation of IgE‐mediated allergy.
Methods
The effects of Tip60 on regulating IgE expression were assessed with B cells. An intestinal allergy mouse model was developed to assess the role of Tip60 in the induction of IgE‐mediated allergic inflammation.
Results
High levels of Tip60 were observed in the peripheral B cells of patients with FA. Tat‐interactive protein 60 (Tip60) was required in the expression of IgE and IgG1 in B cells by inducing the chromatin remolding at the gene locus, in which histone acetylation, signal transducer and activator of transcription 6 (STAT6), and nuclear factor‐κB at the locus of Iε promoter were markedly increased. Blocking Tip60 significantly attenuated the allergic inflammation in the mouse intestinal mucosa.
Conclusions
Tat‐interactive protein 60 (Tip60) plays an important role in the induction of IgE in B cells. Blocking Tip60 inhibits the allergic inflammation in the intestine, suggesting Tip60 inhibitor may be a potential anti‐allergy drug.
The 3D printed bulk samples fabricated by selective laser melting (SLM) of the additive manufacturing technique are usually considered to be 3D isotropic in microstructures and mechanical responses. ...This study systematically investigates the anisotropic responses in terms of hardness and electrochemical resistance for the X-, Y- and Z-planes of the SLM Ti-6Al-4V bulk samples fabricated with the zigzag laser path strategy. Results show that all SLM planes exhibit no significant difference in Young's modulus compared to the mechanically rolled plate. However, the X-plane, referred to the cross-sectional plane perpendicular to the laser moving direction, is found ~20% lower hardness and the lowest corrosion resistance compared to the Y- and Z-planes. The underlying reasoning is researched and discussed. The microstructure observations indicate that artifact holes are induced in the X-plane due to un-uniform laser intensity distribution between two neighboring printing lines. Alternatively, the Y- and Z-planes exhibit dense morphology due to multiple heating while zigzag scanning. Experimental results also indicate that the SLM materials exhibit higher corrosion resistance than the commercial rolled materials.
The Chinese government promotes the Belt and Road Initiative (BRI) as a global strategy for regional integration and infrastructure investment. With a projected US$1 trillion commitment from Chinese ...financial institutions, and at least 138 countries participating, the BRI is attracting intense debate. Yet most analysis to date focuses on broad drivers, risks, and opportunities, largely considered to be emanating from a coherent policy imposed by Beijing. In this special issue, we instead examine the BRI as a relational, contested process - a bundle of intertwined discourses, policies, and projects that sometimes align but are sometimes contradictory. We move beyond policy-level, macro-economic, and classic geopolitical analysis to study China's global investments “from the ground”. Our case studies reveal the BRI to be dynamic and unstable, rhetorically appropriated for different purposes that sometimes but do not always coalesce as a coherent geopolitical and geoeconomic strategy. The papers in this special issue provide one of the first collections of deep empirical work on the BRI and a useful approach for grounding China's role in globalization in the critical contexts of complex local realities.
Fe3O4@C microcapsules were prepared using carbon-coated α-FeOOH nanorods as precursors, which were synthesized via two-step hydrothermal reactions. During the subsequent sintering procedure, α-FeOOH ...was reduced to Fe3O4 by carbon, accompanied by the formation of mesopores. In Fe3O4@C microcapsules, mesoporous Fe3O4 nanorods are coated with amorphorous carbon layers. The Fe3O4/C composites with such special structures demonstrate high specific capacity and good cyclic stability as anode materials in Li test cells.
The primary aim of this study was to evaluate the antitumor efficacy of the bromodomain inhibitor JQ1 in pancreatic ductal adenocarcinoma (PDAC) patient-derived xenograft (tumorgraft) models. A ...secondary aim of the study was to evaluate whether JQ1 decreases expression of the oncogene c-Myc in PDAC tumors, as has been reported for other tumor types. We used five PDAC tumorgraft models that retain specific characteristics of tumors of origin to evaluate the antitumor efficacy of JQ1. Tumor-bearing mice were treated with JQ1 (50 mg/kg daily for 21 or 28 days). Expression analyses were performed with tumors harvested from host mice after treatment with JQ1 or vehicle control. An nCounter PanCancer Pathways Panel (NanoString Technologies) of 230 cancer-related genes was used to identify gene products affected by JQ1. Quantitative RT-PCR, immunohistochemistry and immunoblots were carried out to confirm that changes in RNA expression reflected changes in protein expression. JQ1 inhibited the growth of all five tumorgraft models (P<0.05), each of which harbors a KRAS mutation; but induced no consistent change in expression of c-Myc protein. Expression profiling identified CDC25B, a regulator of cell cycle progression, as one of the three RNA species (TIMP3, LMO2 and CDC25B) downregulated by JQ1 (P<0.05). Inhibition of tumor progression was more closely related to decreased expression of nuclear CDC25B than to changes in c-Myc expression. JQ1 and other agents that inhibit the function of proteins with bromodomains merit further investigation for treating PDAC tumors. Work is ongoing in our laboratory to identify effective drug combinations that include JQ1.
Background and Aims
Mast cell activation interferes with the effects of allergen‐specific immunotherapy (SIT). Galectin‐1 (Gal‐1) is capable of regulating immune cells’ functions. This study tests ...the hypothesis that administration of Gal‐1 promotes and prolongs the efficacy of SIT via suppressing mast cell activation.
Methods
An intestinal allergy mouse model was developed. The coadministration of SIT and Gal‐1 on suppression of the allergic responses, prevention of mast cell activation, and generation of antigen‐specific regulatory T cells (Treg) in the intestine was observed in sensitized mice.
Results
The coadministration of Gal‐1 and SIT markedly suppressed the allergic responses in the mouse intestine vs the use of either SIT alone or Gal‐1 alone. The Gal‐1 binds to the IgE/FcɛRI complexes on the surface of mast cells to prevent mast cell activation during SIT. Gal‐1 promoted the SIT‐generated allergen‐specific Tregs in the intestine of sensitized mice. Coadministration of Gal‐1 and SIT significantly enhanced the efficacy of immunotherapy in suppressing allergic responses in the intestine, which lasted for at least for 12 months.
Conclusions
Long‐term effects of specific immunotherapy on intestinal allergy can be achieved with Gal‐1/SIT therapy by inhibiting mast cell activation and facilitating Treg development.
Phthalates are known endocrine disruptors and associated with decreased fecundity, pregnancy loss, and adverse obstetrical outcomes, however the underlying mechanisms remain to be established. ...Environmental factors can influence gene expression and cell function by modifying epigenetic marks, impacting the developing embryo as well as future generations of offspring. The impact of phthalates on placental gene methylation and expression is largely unknown. We studied the effect of maternal phthalate exposure on the human placental DNA methylome and transcriptome. We determined epigenome-wide DNA methylation marks (Illumina Infinium Human Methylation 850k BeadChip) and gene expression (Agilent whole human genome array) associated with phthalate exposure in first trimester placenta. Integrative genomic analysis of candidate genes was performed to define gene methylation-expression relationships. We identified 39 genes with significantly altered methylation and gene expression in the high phthalate exposure group. Most of these relationships were inversely correlated. This analysis identified epidermal growth factor receptor (EGFR) as a critical candidate gene mediating the effects of phthalates on early placental function. Although additional studies are needed to determine the functional consequences of these changes, our findings are consistent with the model that phthalates impact placental function by modulating the expression of critical placental genes through epigenetic regulation.
We report the first results of a light weakly interacting massive particles (WIMPs) search from the CDEX-10 experiment with a 10 kg germanium detector array immersed in liquid nitrogen at the China ...Jinping Underground Laboratory with a physics data size of 102.8 kg day. At an analysis threshold of 160 eVee, improved limits of 8×10^{-42} and 3×10^{-36} cm^{2} at a 90% confidence level on spin-independent and spin-dependent WIMP-nucleon cross sections, respectively, at a WIMP mass (m_{χ}) of 5 GeV/c^{2} are achieved. The lower reach of m_{χ} is extended to 2 GeV/c^{2}.
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