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.
The c-Jun N-terminal kinases (JNKs) constitute one of the three major types of mitogen-activated protein kinases. Previous studies showed that JNK mediates multiple signaling transduction pathways ...implicated in cell proliferation, differentiation, inflammation, stress response and apoptosis in mammals. In the present study, we use goldfish as a model system and demonstrate that JNK kinases are necessary to promote embryonic survival and regulate eye development in vertebrates. During goldfish development, JNK1 and JNK2 are expressed at every stage from cleavage to hatching larvae. JNK3 is turned on at the gastrulation stage and then expressed at similar level to that of JNK2. JNK1 activity remains slightly fluctuated during different developmental stages. Inhibition of JNK activity caused massive apoptosis of blastula cells and significant death of goldfish embryos, which are associated with altered expression of the anti-apoptotic regulator, Mcl-1 and the proapoptotic regulator, Bak. These results provide novel information regarding the mechanisms by which JNKs promote embryonic survival. In addition, the embryos that survived inhibition of JNK activity displayed severe phenotype in the eye with clear microphthalmia and lens coloboma. To confirm that the observed phenotype is derived from JNK activity deficiency, we expressed JNK dominant negative mutant (DNM-JNK) in goldfish. Expression of DNM-JNK also caused similar phenotypes with altered expression of pax-6, Sox-2 and β-crystallin. Together, our results demonstrate that JNKs play important roles in promoting survival of vertebrate embryos and regulating development of vertebrate eye.
The first fossil chordates are found in deposits from the Cambrian period (545-490 million years ago), but their earliest record is exceptionally sporadic and is often controversial. Accordingly, it ...has been difficult to construct a coherent phylogenetic synthesis for the basal chordates. Until now, the available soft-bodied remains have consisted almost entirely of cephalochordate-like animals from Burgess Shale-type faunas.
We report an amplitude analysis and branching fraction measurement of D+s → K+K−π+ decay using a data sample of 3.19 fb−1 recorded with BESIII detector at a center-of-mass energy of 4.178 GeV. We ...perform a model-independent partial wave analysis in the low K+K− mass region to determine the K+K− S-wave line shape, followed by an amplitude analysis of our very pure high-statistics sample. With the detection efficiency based on the amplitude analysis results, the absolute branching fraction is measured to be B(D+s → K+K− π+) = (5.47 ± 0.0 8stat ± 0.13sys)%.
Based on electron-positron collision data collected with the BESIII detector operating at the Beijing Electron-Positron Collider II storage rings, the value of ...R≡σ(e^{+}e^{-}→hadrons)/σ(e^{+}e^{-}→μ^{+}μ^{-}) is measured at 14 center-of-mass energies from 2.2324 to 3.6710 GeV. The resulting uncertainties are less than 3.0% and are dominated by systematic uncertainties.
It is well established that the tumor suppressor p53 plays major roles in regulating apoptosis and cell cycle progression. In addition, recent studies have demonstrated that p53 is actively involved ...in regulating cell differentiation in muscle, the circulatory system and various carcinoma tissues. We have recently shown that p53 also controls lens differentiation. Regarding the mechanism, we reveal that p53 directly regulates c-Maf and Prox1, two important transcription factors to control cell differentiation in the ocular lens. In the present study, we present further evidence to show that p53 can regulate lens differentiation by controlling expression of the differentiation genes coding for the lens crystallins. First, the αA and βA3/A1 gene promoters or introns all contain putative p53 binding sites. Second, gel mobility shifting assays revealed that the p53 protein in nuclear extracts from lens epithelial cells directly binds to the p53 binding sites found in these crystallin gene promoters or introns. Third, exogenous wild type p53 induces dose-dependent expression of the luciferase reporter gene driven by different crystallin gene promoters and the exogenous dominant negative mutant p53 causes dose-dependent inhibition of the same crystallin genes. Fourth, ChIP assays revealed that p53 binds to crystallin gene promoters in vivo. Finally, in the p53 knockout mouse lenses, expression levels of various crystallins were found down-regulated in comparison with those from the wild type mouse lenses. Together, our results reveal that p53 directly regulates expression of different sets of genes to control lens differentiation.
We present an analysis of the process ψ(3686)→Ω^{-}Ωover ¯^{+} (Ω^{-}→K^{-}Λ, Ωover ¯^{+}→K^{+}Λover ¯, Λ→pπ^{-}, Λover ¯→pover ¯π^{+}) based on a dataset of 448×10^{6} ψ(3686) decays collected with ...the BESIII detector at the BEPCII electron-positron collider. The helicity amplitudes for the process ψ(3686)→Ω^{-}Ωover ¯^{+} and the decay parameters of the subsequent decay Ω^{-}→K^{-}Λ (Ωover ¯^{+}→K^{+}Λover ¯) are measured for the first time by a fit to the angular distribution of the complete decay chain, and the spin of the Ω^{-} is determined to be 3/2 for the first time since its discovery more than 50 years ago.
SOX2 (Sry-related high-mobility box SOX-2) is a transcription factor, which is essential for maintaining the cancer cell stemness. However, the role of microRNAs targeting SOX2 in cancer cell ...stemness remains unclear. We examined the effect of miR-590-5p, which targeted SOX2, on the breast cancer cell stemness and metastasis.
We predicted and screened microRNA targeting SOX2, and further investigated the regulatory role of miR-590-5p on the level of SOX2 with Western blot, luciferase reporting assay and qRT-PCR analysis. Flow cytometry was performed to detect the effect of miR-590-5p on the breast cancer stem cell population with ALDEFLUOR Assay. We inoculated the breast cancer cells transfected with or without miR-590-5p to NOD/SCID mice to detect the tumorigenicity in vivo. Finally, forty-nine pairs of breast cancer samples and adjacent noncancerous tissues were obtained, and immunohistochemistry (IHC) with SOX2 antibody and qRT-PCR assay were used to quantify the expression of miR-590-5p in breast cancer samples.
miR-590-5p significantly downregulated the SOX2 protein expression, and inhibition of miR-590-5p increased SOX2 expression. The luciferase reporter assay indicated that miR-590-5p decreased the SOX2 3'UTR (3' untranslated region) reporter activity but not the luciferase activity of the mutant reporter, in which the binding sites for miR-590-5p were mutated. ALDEFLUOR Assay showed that miR-590-5p significantly decreased breast cancer stem cells population. NOD/SCID nude mice experiments indicated that miR-590-5p significantly inhibited tumorigenicity of breast cancer cells. IHC assay and qRT-PCR suggested that miR-590-5p expression was downregulated in breast cancer patients, and negatively correlated with SOX2.
miR-590-5p inhibited breast cancer cell stemness through targeting SOX2. Our study indicated that miR-590-5p might be a useful strategy for breast cancer treatment.
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