59 research outputs found

    Rational design of polyarginine nanocapsules intended to help peptides overcoming intestinal barriers

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    The aim of this work was to rationally design and characterize nanocapsules (NCs) composed of an oily core and a polyarginine (PARG) shell, intended for oral peptide delivery. The cationic polyaminoacid, PARG, and the oily core components were selected based on their penetration enhancing properties. Insulin was adopted as a model peptide to assess the performance of the NCs. After screening numerous formulation variables, including different oils and surfactants, we defined a composition consisting of oleic acid, sodium deoxycholate (SDC) and Span 80. This selected NCs composition, produced by the solvent displacement technique, exhibited the following key features: (i) an average size of 180 nm and a low polydispersity (0.1), (ii) a high insulin association efficacy (80–90% AE), (iii) a good colloidal stability upon incubation in simulated intestinal fluids (SIF, FaSSIF-V2, FeSSIF-V2), and (iv) the capacity to control the release of the associated insulin for > 4 h. Furthermore, using the Caco-2 model cell line, PARG nanocapsules were able to interact with the enterocytes, and reversibly modify the TEER of the monolayer. Both cell adhesion and membrane permeabilization could account for the pronounced transport of the NCs-associated insulin (3.54%). This improved interaction was also visualized by confocal fluorescent microscopy following oral administration of PARG nanocapsulesto mice. Finally, in vivo efficacy studies performed in normoglycemic rats showed a significant decrease in their plasma glucose levels after treatment. In conclusion, here we disclose key formulation elements for making possible the oral administration of peptidesThis work was supported by the European TRANS-INT Consortium, which received funding from the European Union's Seventh Framework Programme for research, technological development and demonstration under grant agreement No. 281035. Z. Niu also would like to thank the Chinese Scholarship Council for his scholarshipS

    Acidic microenvironment plays a key role in human melanoma progression through a sustained exosome mediated transfer of clinically relevant metastatic molecules

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    Background: Microenvironment cues involved in melanoma progression are largely unknown. Melanoma is highly influenced in its aggressive phenotype by the changes it determinates in its microenvironment, such as pH decrease, in turn influencing cancer cell invasiveness, progression and tissue remodelling through an abundant secretion of exosomes, dictating cancer strategy to the whole host. A role of exosomes in driving melanoma progression under microenvironmental acidity was never described. Methods: We studied four differently staged human melanoma lines, reflecting melanoma progression, under microenvironmental acidic pHs pressure ranging between pH 6.0-6.7. To estimate exosome secretion as a function of tumor stage and environmental pH, we applied a technique to generate native fluorescent exosomes characterized by vesicles integrity, size, density, markers expression, and quantifiable by direct FACS analysis. Functional roles of exosomes were tested in migration and invasion tests. Then we performed a comparative proteomic analysis of acid versus control exosomes to elucidate a specific signature involved in melanoma progression. Results: We found that metastatic melanoma secretes a higher exosome amount than primary melanoma, and that acidic pH increases exosome secretion when melanoma is in an intermediate stage, i.e. metastatic non-invasive. We were thus able to show that acidic pH influences the intercellular cross-talk mediated by exosomes. In fact when exposed to exosomes produced in an acidic medium, pH naïve melanoma cells acquire migratory and invasive capacities likely due to transfer of metastatic exosomal proteins, favoring cell motility and angiogenesis. A Prognoscan-based meta-analysis study of proteins enriched in acidic exosomes, identified 11 genes (HRAS, GANAB, CFL2, HSP90B1, HSP90AB1, GSN, HSPA1L, NRAS, HSPA5, TIMP3, HYOU1), significantly correlating with poor prognosis, whose high expression was in part confirmed in bioptic samples of lymph node metastases. Conclusions: A crucial step of melanoma progression does occur at melanoma intermediate -stage, when extracellular acidic pH induces an abundant release and intra-tumoral uptake of exosomes. Such exosomes are endowed with pro-invasive molecules of clinical relevance, which may provide a signature of melanoma advancement

    Measurement of the proton form factor by studying e+e−→ppˉe^{+} e^{-}\rightarrow p\bar{p}

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    Using data samples collected with the BESIII detector at the BEPCII collider, we measure the Born cross section of e+e−→ppˉe^{+}e^{-}\rightarrow p\bar{p} at 12 center-of-mass energies from 2232.4 to 3671.0 MeV. The corresponding effective electromagnetic form factor of the proton is deduced under the assumption that the electric and magnetic form factors are equal (∣GE∣=∣GM∣)(|G_{E}|= |G_{M}|). In addition, the ratio of electric to magnetic form factors, ∣GE/GM∣|G_{E}/G_{M}|, and ∣GM∣|G_{M}| are extracted by fitting the polar angle distribution of the proton for the data samples with larger statistics, namely at s=\sqrt{s}= 2232.4 and 2400.0 MeV and a combined sample at s\sqrt{s} = 3050.0, 3060.0 and 3080.0 MeV, respectively. The measured cross sections are in agreement with recent results from BaBar, improving the overall uncertainty by about 30\%. The ∣GE/GM∣|G_{E}/G_{M}| ratios are close to unity and consistent with BaBar results in the same q2q^{2} region, which indicates the data are consistent with the assumption that ∣GE∣=∣GM∣|G_{E}|=|G_{M}| within uncertainties.Comment: 13 pages, 24 figure

    Confirmation of a charged charmoniumlike state Zc(3885)∓Z_c(3885)^{\mp} in e+e−→π±(DDˉ∗)∓e^+e^-\to\pi^{\pm}(D\bar{D}^*)^\mp with double DD tag

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    We present a study of the process e+e−→π±(DDˉ∗)∓e^+e^-\to\pi^{\pm}(D\bar{D}^*)^{\mp} using data samples of 1092~pb−1^{-1} at s=4.23\sqrt{s}=4.23~GeV and 826~pb−1^{-1} at s=4.26\sqrt{s}=4.26~GeV collected with the BESIII detector at the BEPCII storage ring. With full reconstruction of the DD meson pair and the bachelor π±\pi^{\pm} in the final state, we confirm the existence of the charged structure Zc(3885)∓Z_c(3885)^{\mp} in the (DDˉ∗)∓(D\bar{D}^*)^{\mp} system in the two isospin processes e+e−→π+D0D∗−e^+e^-\to\pi^+D^0D^{*-} and e+e−→π+D−D∗0e^+e^-\to\pi^+D^-D^{*0}. By performing a simultaneous fit, the statistical significance of Zc(3885)∓Zc(3885)^{\mp} signal is determined to be greater than 10σ\sigma, and its pole mass and width are measured to be MpoleM_{\rm{pole}}=(3881.7±\pm1.6(stat.)±\pm1.6(syst.))~MeV/c2c^2 and Γpole\Gamma_{\rm{pole}}=(26.6±\pm2.0(stat.)±\pm2.1(syst.))~MeV, respectively. The Born cross section times the (DDˉ∗)∓(D\bar{D}^*)^{\mp} branching fraction (σ(e+e−→π±Zc(3885)∓)×Br(Zc(3885)∓→(DDˉ∗)∓)\sigma(e^+e^-\to\pi^{\pm}Z_{c}(3885)^{\mp}) \times Br(Z_{c}(3885)^{\mp}\to(D\bar{D}^*)^{\mp})) is measured to be (141.6±7.9(stat.)±12.3(syst.)) pb(141.6\pm7.9(\text{stat.})\pm12.3(\text{syst.}))~\text{pb} at s=4.23\sqrt{s}=4.23~GeV and (108.4±6.9(stat.)±8.8(syst.)) pb(108.4\pm6.9(\text{stat.})\pm8.8(\text{syst.}))~\text{pb} at s=4.26\sqrt{s}=4.26~GeV. The polar angular distribution of the π±\pi^{\pm}-Zc(3885)∓Z_c(3885)^{\mp} system is consistent with the expectation of a quantum number assignment of JP=1+J^P=1^+ for Zc(3885)∓Z_c(3885)^{\mp}

    Observation of the isospin-violating decay J/ψ→ϕπ0f0(980)J/\psi \to \phi\pi^{0}f_{0}(980)

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    Using a sample of 1.31 billion J/ψJ/\psi events collected with the BESIII detector at the BEPCII collider, the decays J/ψ→ϕπ+π−π0J/\psi \to \phi \pi^{+}\pi^{-}\pi^{0} and J/ψ→ϕπ0π0π0J/\psi \to \phi \pi^{0}\pi^{0}\pi^{0} are investigated. The isospin violating decay J/ψ→ϕπ0f0(980)J/\psi \to \phi \pi^{0} f_{0}(980) with f0(980)→ππf_{0}(980) \to \pi\pi, is observed for the first time. The width of the f0(980)f_{0}(980) obtained from the dipion mass spectrum is found to be much smaller than the world average value. In the π0f0(980)\pi^{0} f_{0}(980) mass spectrum, there is evidence of f1(1285)f_1(1285) production. By studying the decay J/ψ→ϕη′J/\psi \to \phi\eta', the branching fractions of η′→π+π−π0\eta' \to \pi^{+}\pi^{-}\pi^{0} and η′→π0π0π0\eta' \to \pi^{0}\pi^{0}\pi^{0}, as well as their ratio, are also measured.Comment: 10 pages, 10 figures, published in Phys. Rev.

    An amplitude analysis of the π0π0\pi^{0}\pi^{0} system produced in radiative J/ψJ/\psi decays

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    An amplitude analysis of the π0π0\pi^{0}\pi^{0} system produced in radiative J/ψJ/\psi decays is presented. In particular, a piecewise function that describes the dynamics of the π0π0\pi^{0}\pi^{0} system is determined as a function of Mπ0π0M_{\pi^{0}\pi^{0}} from an analysis of the (1.311±0.011)×109(1.311\pm0.011)\times10^{9} J/ψJ/\psi decays collected by the BESIII detector. The goal of this analysis is to provide a description of the scalar and tensor components of the π0π0\pi^0\pi^0 system while making minimal assumptions about the properties or number of poles in the amplitude. Such a model-independent description allows one to integrate these results with other related results from complementary reactions in the development of phenomenological models, which can then be used to directly fit experimental data to obtain parameters of interest. The branching fraction of J/ψ→γπ0π0J/\psi \to \gamma \pi^{0}\pi^{0} is determined to be (1.15±0.05)×10−3(1.15\pm0.05)\times10^{-3}, where the uncertainty is systematic only and the statistical uncertainty is negligible.Comment: Submitted to Phys. Rev. D 19 pages, 4 figure

    Measurement of the e+e−→ηJ/ψe^{+}e^{-} \to \eta J/\psi cross section and search for e+e−→π0J/ψe^{+}e^{-} \to \pi^{0} J/\psi at center-of-mass energies between 3.810 and 4.600~GeV

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    Using data samples collected with the BESIII detector operating at the BEPCII collider at center-of-mass energies from 3.810 to 4.600 GeV, we perform a study of e+e−→ηJ/ψe^{+}e^{-} \to \eta J/\psi and π0J/ψ\pi^0 J/\psi. Statistically significant signals of e+e−→ηJ/ψe^{+}e^{-} \to \eta J/\psi are observed at s\sqrt{s} = 4.190, 4.210, 4.220, 4.230, 4.245, 4.260, 4.360 and 4.420 GeV, while no signals of e+e−→π0J/ψe^{+}e^{-} \to \pi^{0} J/\psi are observed. The measured energy-dependent Born cross section for e+e−→ηJ/ψe^{+}e^{-} \to \eta J/\psi shows an enhancement around 4.2~GeV. The measurement is compatible with an earlier measurement by Belle, but with a significantly improved precision

    Search for the Y(4140)Y(4140) via e+e−→γϕJ/ψe^{+} e^{-} \to \gamma \phi J/\psi at s=\sqrt{s}= 4.23, 4.26 and 4.36 GeV

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    Using data samples collected at center-of-mass energies s=4.23\sqrt{s} = 4.23, 4.26, and 4.36 GeV with the BESIII detector operating at the BEPCII storage ring, we search for the production of the charmoniumlike state Y(4140)Y(4140) through a radiative transition followed by its decay to ϕJ/ψ\phi J/\psi. No significant signal is observed and upper limits on σ[e+e−→γY(4140)]⋅B(Y(4140)→ϕJ/ψ)\sigma[e^{+} e^{-} \rightarrow \gamma Y(4140)] \cdot \mathcal{B}(Y(4140)\rightarrow \phi J/\psi) at the 90%90\% confidence level are estimated as 0.35, 0.28, and 0.33 pb at s=4.23\sqrt{s} = 4.23, 4.26, and 4.36 GeV, respectively

    Robust estimation of bacterial cell count from optical density

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    Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data
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