Measurement of charged jet production cross sections and nuclear modification in p-Pb collisions at root s(NN)=5.02 TeV

Charged jet production cross sections in p-Pb collisions at root s(NN) = 5.02 TeV measured with the ALICE detector at the LHC are presented. Using the anti-k(T) algorithm, jets have been reconstructed in the central rapidity region from charged particles with resolution parameters R = 0.2 and R = 0.4. The reconstructed jets have been corrected for detector effects and the underlying event background. To calculate the nuclear modification factor, R-pPb, of charged jets in p-Pb collisions, a pp reference was constructed by scaling previously measured charged jet spectra at root s = 7 TeV. In the transverse momentum range 20Peer reviewe

Laccase–TEMPO as an Efficient System for Doxorubicin Removal from Wastewaters

A large number of drugs are used to treat different diseases, and thus to improve the quality of life for humans. These represent a real ecological threat, as they end up in soil or ground waters in amounts that can affect the environment. Among these drugs, doxorubicin is a highly cytotoxic compound used as anticancer medicine. Doxorubicin can be efficiently removed from wastewater or polluted water using a simple enzymatic (biocatalytic) system, employing the oxidoreductase enzyme laccase and a stable organic nitroxide-free radical, TEMPO. Results presented in this work (as percentage of removal) were obtained at pH 5 and 7, after 2, 4, 6, and 24 h, using different ratios between doxorubicin, laccase, and TEMPO. It was shown that longer time, as well as an increased amount of catalyst, led to a higher percentage of removal, up to 100%. The influence of all these parameters is also discussed. In this way it was shown that the laccase–TEMPO biocatalytic system is highly efficient in the removal of the anticancer drug doxorubicin from wastewaters

K2 Transfection System Boosts the Adenoviral Transduction of Murine Mesenchymal Stromal Cells

Adenoviral vectors are important vehicles for delivering therapeutic genes into mammalian cells. However, the yield of the adenoviral transduction of murine mesenchymal stromal cells (MSC) is low. Here, we aimed to improve the adenoviral transduction efficiency of bone marrow-derived MSC. Our data showed that among all the potential transduction boosters that we tested, the K2 Transfection System (K2TS) greatly increased the transduction efficiency. After optimization of both K2TS components, the yield of the adenoviral transduction increased from 18% to 96% for non-obese diabetic (NOD)-derived MSC, from 30% to 86% for C57BL/6-derived MSC, and from 0.6% to 63% for BALB/c-derived MSC, when 250 transduction units/cell were used. We found that MSC derived from these mouse strains expressed different levels of the coxsackievirus and adenovirus receptors (MSC from C57BL/6≥NOD>>>BALB/c). K2TS did not increase the level of the receptor expression, but desensitized the cells to foreign DNA and facilitated the virus entry into the cell. The expression of Stem cells antigen-1 (Sca-1) and 5′-nucleotidase (CD73) MSC markers, the adipogenic and osteogenic differentiation potential, and the immunosuppressive capacity were preserved after the adenoviral transduction of MSC in the presence of the K2TS. In conclusion, K2TS significantly enhanced the adenoviral transduction of MSC, without interfering with their main characteristics and properties

K2 Transfection System Boosts the Adenoviral Transduction of Murine Mesenchymal Stromal Cells

Adenoviral vectors are important vehicles for delivering therapeutic genes into mammalian cells. However, the yield of the adenoviral transduction of murine mesenchymal stromal cells (MSC) is low. Here, we aimed to improve the adenoviral transduction efficiency of bone marrow-derived MSC. Our data showed that among all the potential transduction boosters that we tested, the K2 Transfection System (K2TS) greatly increased the transduction efficiency. After optimization of both K2TS components, the yield of the adenoviral transduction increased from 18% to 96% for non-obese diabetic (NOD)-derived MSC, from 30% to 86% for C57BL/6-derived MSC, and from 0.6% to 63% for BALB/c-derived MSC, when 250 transduction units/cell were used. We found that MSC derived from these mouse strains expressed different levels of the coxsackievirus and adenovirus receptors (MSC from C57BL/6≥NOD>>>BALB/c). K2TS did not increase the level of the receptor expression, but desensitized the cells to foreign DNA and facilitated the virus entry into the cell. The expression of Stem cells antigen-1 (Sca-1) and 5′-nucleotidase (CD73) MSC markers, the adipogenic and osteogenic differentiation potential, and the immunosuppressive capacity were preserved after the adenoviral transduction of MSC in the presence of the K2TS. In conclusion, K2TS significantly enhanced the adenoviral transduction of MSC, without interfering with their main characteristics and properties

Enhanced Suppression of Immune Cells In Vitro by MSC Overexpressing FasL

Mesenchymal stromal cells (MSC) display several mechanisms of action that may be harnessed for therapeutic purposes. One of their most attractive features is their immunomodulatory activity that has been extensively characterized both in vitro and in vivo. While this activity has proven to be very efficient, it is transient. We aimed to enhance it by transforming MSC to overexpress a first apoptosis signal (Fas) ligand (FasL). In this study, our goal was to induce FasL overexpression through adenoviral transduction in MSC to improve their immunomodulatory activity. We characterized the impact of FasL overexpression on the morphology, proliferation, viability, phenotype, multilineage differentiation potential and immunomodulation of MSC. Moreover, we determined their suppressive properties in mixed reactions with A20 cells, as well as with stimulated splenocytes. Our findings demonstrate that FasL-overexpressing MSC exhibit improved immunosuppressive properties, while maintaining their MSC-characteristic features. In conclusion, we establish, in a proof-of-concept set-up, that FasL-overexpressing MSC represent good candidates for therapeutic intervention targeted at autoimmune disorders

Nanoconjugates Based on Cisplatin and Single-Walled Carbon Nanotubes for Therapy of Triple Negative Breast Cancer

Triple negative breast cancer has a phenotype characterized by the absence of progesterone and estrogen receptors and the lack of HER2 overexpression. In order to find new strategies for treatment, single-walled carbon nanotubes (SWCNT) in combination with chemotherapeutics were studied and tested as new therapeutic tools. The objective of this study was to evaluate the efficiency of SWCNT in the transport of cisplatin (CDDP) for improving its cytotoxic effects on MDA-MB-231 cells. The nanoconjugates SWCNT-COOH-CDDP were obtained by the functionalization of SWCNT with carboxyl groups (SWCNT-COOH) and conjugation with CDDP. MDA-MB-231 cells were exposed to different doses of SWCNT-COOH, SWCNT-COOH-CDDP (0.01–2 µg/mL), and CDDP (0.00632–1.26 µg/mL) for 24 and 48 h. Cellular viability was monitored through an MTT test. The level of reactive oxygen species (ROS) and reduced glutathione (GSH) were evaluated using fluorescence and spectrophotometric methods, respectively. The expressions of Nrf2, caspase-3, caspase-8, and Bid proteins were assessed by immunoblotting in the presence of 0.5 and 1 µg/mL nanoconjugates. Additionally, the effects of SWCNT-COOH-CDDP on cell migration were monitored using a wound healing assay. The cellular viability decreased and ROS level increased in a time and dose-dependent manner in the presence of nanoconjugates relative to the control. Moreover, the level of GSH rose after 24 and 48 h of exposure to 0.5 µg/mL SWCNT-COOH-CDDP, while a decrease to 78.31% was recorded after 48 h in the presence of 1 µg/mL nanoconjugates. The expression of Nrf2 decreased to 33% after 24 h of treatment with 1 µg/mL SWCNT-COOH-CDDP and increased to 80% compared to the control (100%) after 48 h. Upregulation of caspase-3 and caspase-8 and downregulation of Bid post-exposure to 1 µg/mL SWCNT-COOH-CDDP was noticed. The inhibition of cell migration was observed after 24 and 48 h of exposure to 1 µg/mL SWCNT-COOH-CDDP. In conclusion, these nanoconjugates induced apoptosis in MDA-MB-231 cells, probably by both intrinsic and extrinsic pathways, by triggering the oxidative stress mechanisms, and inhibited their migration potential