•We proposed the efficacy of DRIAs and dietary supplement on endometriosis.•DRIAs inhibit cell proliferation in human endometriotic stromal cells.•DRIAs reduce inflammatory cytokines and exhibit ...ERβ-mediated activity.•DRIAs reduce the extent of endometriosis-like lesions in a mouse model.•DRIAs might be a potential therapeutic option for management of endometriosis.
Endometriosis is an estrogen-dependent disease, and isoflavones interact with estrogen receptors. The purposes of this study are to investigate the in vitro and in vivo effects of daidzein-rich isoflavone aglycones (DRIAs), dietary supplements, on cellular proliferation in endometriosis. Stromal cells isolated from ovarian endometrioma (OESCs) and normal endometrium (NESCs) were cultured with DRIAs, i.e., each of the DRIA components (daidzein, genistein, or glycitein), or isoflavone glycosides (IG; DRIA precursors). A mouse model of endometriosis was established by transplanting donor-mouse uterine fragments into recipient mice. Our results showed that DRIAs (0.2–20 μM) inhibited the proliferation of OESCs (P < 0.05 for 0.2 μM; P < 0.01 for 2 and 20 μM) but not of NESCs. However, daidzein, genistein, glycitein, and IG did not inhibit their proliferation. DRIA-induced suppression was reversed by inhibition of the estrogen receptor (ER)β by an antagonist, PHTPP, or by ERβ siRNA (P < 0.05), but not by MPP, an ERα antagonist. In OESCs, DRIAs led to reduced expression of IL-6, IL-8, COX-2, and aromatase, as well as reduced aromatase activity, serum glucocorticoid-regulated kinase levels, and PGE2 levels (P < 0.05). Western blot and immunofluorescence assays revealed that DRIAs inhibited TNF-α-induced IκB phosphorylation and p65 uptake into the nuclei of OESCs. In the mouse model, a DRIA-containing feed significantly decreased the number, weight, and Ki-67 proliferative activity of endometriosis-like lesions compared to in mice fed with an IG-containing feed and the control feed (P < 0.01). In conclusion, DRIAs inhibit cellular proliferation in endometriosis, thus representing a potential therapeutic option for the management of endometriosis.
Super-Kamiokande (SK) can search for weakly interacting massive particles (WIMPs) by detecting neutrinos produced from WIMP annihilations occurring inside the Sun. In this analysis, we include ...neutrino events with interaction vertices in the detector in addition to upward-going muons produced in the surrounding rock. Compared to the previous result, which used the upward-going muons only, the signal acceptances for light (few-GeV/c^{2}-200-GeV/c^{2}) WIMPs are significantly increased. We fit 3903 days of SK data to search for the contribution of neutrinos from WIMP annihilation in the Sun. We found no significant excess over expected atmospheric-neutrino background and the result is interpreted in terms of upper limits on WIMP-nucleon elastic scattering cross sections under different assumptions about the annihilation channel. We set the current best limits on the spin-dependent WIMP-proton cross section for WIMP masses below 200 GeV/c^{2} (at 10 GeV/c^{2}, 1.49×10^{-39} cm^{2} for χχ→bbover ¯ and 1.31×10^{-40} cm^{2} for χχ→τ^{+}τ^{-} annihilation channels), also ruling out some fraction of WIMP candidates with spin-independent coupling in the few-GeV/c^{2} mass range.
Background
Maternal fish oil supplementation during pregnancy has been associated with altered infant immune responses and a reduced risk of infant sensitization and eczema.
Objective
To examine the ...effect of early postnatal fish oil supplementation on infant cellular immune function at 6 months of age in the context of allergic disease.
Methods
In a double‐blind randomized controlled trial (ACTRN12606000281594), 420 infants of high atopic risk received fish oil containing 280 mg docosahexaenoic acid (DHA) and 110 mg eicosapentanoic acid (EPA) or control oil daily from birth to 6 months. One hundred and twenty infants had blood collected at 6 months of age. Fatty acid levels, induced cytokine responses, T cell subsets and monocyte HLA‐DR expression were assessed at 6 months of age. Infant allergies were assessed at 6 and 12 months of age.
Results
DHA and EPA levels were significantly higher in the fish oil group and erythrocyte arachidonic acid (AA) levels were lower (all P < 0.05). Infants in the fish oil group had significantly lower IL‐13 responses (P = 0.036) to house dust mite (HDM) and higher IFNγ (P = 0.035) and TNF (P = 0.017) responses to phytohaemaglutinin (PHA). Infants with relatively high DHA levels had lower Th2 responses to allergens including lower IL‐13 to β‐lactoglobulin (BLG) (P = 0.020), and lower IL‐5 to BLG (P = 0.045).
Conclusions and clinical relevance
Postnatal fish oil supplementation increased infant n‐3 polyunsaturated fatty acid (PUFA) levels and associated with lowered allergen‐specific Th2 responses and elevated polyclonal Th1 responses. Our results add to existing evidence of n‐3 PUFA having immunomodulatory properties that are potentially allergy‐protective.
We recently demonstrated that acute myeloid leukemia (AML) cell lines and patient-derived blasts release exosomes that carry RNA and protein; following an in vitro transfer, AML exosomes produce ...proangiogenic changes in bystander cells. We reasoned that paracrine exosome trafficking may have a broader role in shaping the leukemic niche. In a series of in vitro studies and murine xenografts, we demonstrate that AML exosomes downregulate critical retention factors (Scf, Cxcl12) in stromal cells, leading to hematopoietic stem and progenitor cell (HSPC) mobilization from the bone marrow. Exosome trafficking also regulates HSPC directly, and we demonstrate declining clonogenicity, loss of CXCR4 and c-Kit expression, and the consistent repression of several hematopoietic transcription factors, including c-Myb, Cebp-β and Hoxa-9. Additional experiments using a model of extramedullary AML or direct intrafemoral injection of purified exosomes reveal that the erosion of HSPC function can occur independent of direct cell-cell contact with leukemia cells. Finally, using a novel multiplex proteomics technique, we identified candidate pathways involved in the direct exosome-mediated modulation of HSPC function. In aggregate, this work suggests that AML exosomes participate in the suppression of residual hematopoietic function that precedes widespread leukemic invasion of the bone marrow directly and indirectly via stromal components.
Abstract
The scientific and technical advances continue to support novel discoveries by allowing scientists to acquire new insights into the structure and properties of matter using new tools and ...sources. Notably, neutrons are among the most valuable sources in providing such a capability. At the Institute of Laser Engineering, Osaka, the first steps are taken towards the development of a table-top laser-driven neutron source, capable of producing a wide range of energies with high brightness and temporal resolution. By employing a pure hydrogen moderator, maintained at cryogenic temperature, a cold neutron (
$$\le 25\hbox { meV}$$
≤
25
meV
) flux of
$$\sim 2\times 10^3\hbox { n/cm}^2$$
∼
2
×
10
3
n/cm
2
/pulse was measured at the proximity of the moderator exit surface. The beam duration of hundreds of ns to tens of
$$\upmu \hbox {s}$$
μ
s
is evaluated for neutron energies ranging from 100s keV down to meV via Monte-Carlo techniques. Presently, with the upcoming J-EPoCH high repetition rate laser at Osaka University, a cold neutron flux in orders of
$$\sim 1\times 10^{9}\hbox { n/cm}^2/\hbox {s}$$
∼
1
×
10
9
n/cm
2
/
s
is expected to be delivered at the moderator in a compact beamline.
The aim of this study was to examine the ability of the Vigileo-FloTrac system to measure cardiac output (CO) and track changes in CO induced by increased vasomotor tone, under different states of ...systemic vascular resistance (SVR).
Forty patients undergoing cardiac surgery were enrolled. Haemodynamic variables including CO measured by the Vigileo-FloTrac system (version 3.02) (APCO), CO measured by a pulmonary artery catheter (ICO), and SVR index (SVRI) were recorded before (T1) and 2 min after (T2) phenylephrine administration (100 μg). Bland and Altman analysis was used to compare ICO and APCO at T1. We used four-quadrant plots and polar plots to compare the trending abilities between ICO and APCO. Patients were divided into three groups according to the SVRI value at T1, with low (<1200 dyn cm−5 m2), normal (1200–2500 dyn cm−5 m2), and high (>2500 dyn cm−5 m2) SVRI states.
A total of 155 paired data were collected. The adjusted percentage error was 46.3%, 26.4%, and 61.4%, and the concordance rate between ΔICO and ΔAPCO was 67.5%, 28.8%, and 7.7% in the low, normal, and high SVRI state, respectively. The polar plot analysis showed that the mean angular bias was −22.3°, −46.0°, and −3.51°, and the radial limits of agreement were 70°, 85°, and 87°, in the low, normal, and high SVRI state, respectively.
These results indicate that the reliability of the Vigileo-FloTrac system to measure CO and track changes in CO induced by phenylephrine administration was not clinically acceptable.
The impact of the conditioning intensity and TBI on acute GVHD (aGVHD) is still a matter of debate. We analyzed 6848 adult recipients who received allogeneic hematopoietic cell transplants (HCT) ...between 2006 and 2011 in Japan. The subjects were divided into groups who had received myeloablative conditioning (MAC) or reduced-intensity conditioning (RIC), either with or without TBI. There was a significant difference in the incidence of aGVHD 2-4 among the different conditioning types: 39% in TBI-MAC, 35% in TBI-RIC and 32% in both no-TBI MAC and no-TBI-RIC (P<0.001). In a multivariate analysis, TBI-MAC, but not no-TBI MAC, was significantly associated with an increased risk of aGVHD 2-4 (hazard ratio (HR) 1.33, P<0.01), whereas TBI-RIC was associated with an increased risk of GVHD 3-4 (HR 1.36, P=0.048). TBI-MAC and TBI-RIC were significantly associated with skin and gastrointestinal aGVHD. Subgroup analyses demonstrated that not only TBI-MAC, but also TBI-RIC, was significantly associated with aGVHD 2-4 in older patients. Furthermore, high-dose TBI only had an adverse impact on aGVHD 2-4 in HLA-matched HCT. Impacts of intensity and TBI on aGVHD differ by patient backgrounds, and this difference should be considered to establish a risk-adapted strategy for the prevention of aGVHD.
Although monoclonal antibodies have demonstrated clinical potentials as tumor targeting agents, poor tumor penetration of the antibodies due to the size of molecules and liver/bone marrow toxicity by ...non-specific uptake of the antibodies are the two major limitations of antibody therapy. Peptidic targeting agents may ease the problems associated with antibody cancer therapy. Combinatorial libraries displayed on microorganisms have successfully been utilized to discover cell surface-binding peptides, which can be tumor-targeting agents. Among many molecular display techniques, phage display has been the most popular approach. Peptides can be used as targeting molecules of receptor-targeted toxins and gene therapy, imaging and/or therapeutic agents, and nano-medical technologies. Recent results from preclinical studies with various peptides support their targeting potential and suggest that the role of peptides as targeting molecules in drug development should be further exploited.
La-doped ZnO nanoparticles with different La contents were synthesized and characterized by various sophisticated techniques such as XRD, UV–vis, AFM, XPS, and HR-SEM. The XRD results revealed that ...La
3+ is uniformly dispersed on ZnO nanoparticles in the form of small La
2O
3 cluster. It was found that the particle size of La-doped ZnO is much smaller as compared to that of pure ZnO and decreases with increasing La loading. Rough and high porous surface of La-doped ZnO was observed by AFM, which is critical for enhancing the photocatalytic activity. The photocatalytic activity of La-doped ZnO in the degradation of monocrotophos (MCP) was studied. The effects of the adsorption of MCP, lights of wavelength, and the solution pH on the photocatalytic activity of La-doped ZnO with different La loading were studied and the results were compared with pure ZnO and pure TiO
2. It was observed that the rate of degradation of MCP over La-doped ZnO increases with increasing La loading up to 0.8
wt% and then decreases. It was found that the doping of La in ZnO helps to achieve complete mineralization of MCP within a short irradiation time. Among the catalyst studied, the 0.8
wt% La-doped ZnO was the most active, showing high relative photonic efficiencies and high photocatalytic activity for the degradation of MCP.
La-doped ZnO nanoparticles with different La contents were synthesized and characterized by various sophisticated techniques such as XRD, UV–vis, AFM, XPS, and HR-SEM. It was found that the particle size of La-doped ZnO is much smaller as compared to that of pure ZnO and decreases with increasing La loading. The effects of the adsorption of MCP, lights of wavelength, and the solution pH on the photocatalytic activity of La-doped ZnO with different La loading were studied and the results were compared with pure ZnO and pure TiO
2. It was observed that the rate of degradation of MCP over La-doped ZnO increases with increasing La loading up to 0.8
wt% and then decreases. Among the catalyst studied, the 0.8
wt% La-doped ZnO was the most active, showing high relative photonic efficiencies and high photocatalytic activity for the degradation of MCP (see figure).
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