Screening for the efficacy on lipid accumulation in 3T3-L1 cells is an effective tool for the identification of new anti-diabetic compounds

Reducing lipid accumulation in insulin target tissues is critical for the treatment of type 2 diabetes. This study aimed to develop a biochemical assay in cells for high throughput (HTP) screening of anti-diabetic drugs by reducing lipid accumulation via different mechanisms

Expanding the Applicability of Poly(Ionic Liquids) in Solid Phase Microextraction: Pyrrolidinium Coatings

Crosslinked pyrrolidinium-based poly(ionic liquids) (Pyrr-PILs) were synthesized through a fast, simple, and solventless photopolymerization scheme, and tested as solid phase microextraction (SPME) sorbents. A series of Pyrr-PILs bearing three different alkyl side chain lengths with two, eight, and fourteen carbons was prepared, characterized, and homogeneously coated on a steel wire by using a very simple procedure. The resulting coatings showed a high thermal stability, with decomposition temperatures above 350 degrees C, excellent film stability, and lifetime of over 100 injections. The performance of these PIL-based SPME fibers was evaluated using a mixture of eleven organic compounds with different molar volumes and chemical functionalities (alcohols, ketones, and monoterpenes). The Pyrr-PIL fibers were obtained as dense film coatings, with 67 mu m thickness, with an overall sorption increase of 90% and 55% as compared to commercial fibers of Polyacrylate (85 mu m) (PA85) and Polydimethylsiloxane (7 mu m) (PDMS7) coatings, respectively. A urine sample doped with the sample mixture was used to study the matrix effect and establish relative recoveries, which ranged from 60.2% to 104.1%.David J. S. Patinha, and Liliana C. Tome are grateful to FCT (Fundacao para a Ciencia e a Tecnologia) for the PhD research grant SFRH/BD/97042/2013 and the Post-Doctoral research grant (SFRH/BPD/101793/2014), respectively. David J. S. Patinha also thanks the financial support from COST-Exil Project 1206. The NMR data was acquired at CERMAX (Centro de Ressonncia Magnetica Antnio Xavier) which is a member of the National NMR network. This work was partially supported by FCT through Research Unit GREEN-it " Bioresources for Sustainability" (UID/Multi/04551/2013) and the Associate Laboratory CICECO Aveiro Institute of materials (UID/CTM/50011/2013)

The NRF2 transcription factor plays a dual role in colorectal cancer : A systematic review

Background: Colorectal cancer is one of the most common cancers worldwide, and is influenced by the interplay of various factors, including a very strong genetic component. For instance, incorrect mitochondrial biogenesis is correlated with increased risk of developing colorectal cancer. Thus, it is important to understand the consequences of changes in both the expression and the correct function of the transcription factors that regulate mitochondrial biogenesis, namely NRF2. Objectives: The main objective of this paper is to characterise the relationship between NRF2 and colorectal cancer by compiling data from an exhaustive literature search. Methods: Information was obtained by defining specific search terms and searching in several databases. After a strict selection procedure, data were tabulated and the relationships between articles were assessed by measuring heterogeneity and by constructing conceptual maps. Results and discussion: We found a general consensus in the literature that the presence of oxidizing agents as well as the inhibition of the NRF2 repressor Keap1 maintain NRF2 expression at basal levels. This predominantly exerts a cytoprotective effect on cells and decreases risk of colorectal cancer. However, if NRF2 is inhibited, protection against external agents disappears and risk of colorectal cancer increases. Interestingly, colorectal cancer risk is also increased when NRF2 becomes overexpressed. In this case, the increased risk arises from NRF2-induced inflammation and resistance to chemotherapy. Conclusion: The proper basal function of NRF2 and Keap1 are essential for preventing oncogenic processes in the colon. Consequently, any disruption to the expression of these genes can promote the genesis and progression of colon cancer

Anisotropy of particle fluxes in primary cosmic rays measured with the alpha magnetic spectrometer on the ISS

An analysis of anisotropies in the arrival directions of galactic electrons and positrons, as well as protons, Helium, Carbon and Oxygen has been performed with the Alpha Magnetic Spectrometer on the International Space Station using the first 6.5 years (electrons and positrons) and the first 7.5 years (protons, Helium, Carbon, Oxygen) of data taking. Results on a dipole signal in Galactic coordinates are reported. The arrival directions of all studied cosmic ray species are consistent with isotropy. For energies above 16 GeV a limit of δ < 0.019 (δ < 0.005) at the 95% confidence level is obtained for positrons (electrons). For rigidities above 200 GV a limit of δ < 0.0038 (δ < 0.0036, δ < 0.019,δ < 0.017) at the 95% confidence level is obtained for protons (Helium, Carbon, Oxygen). The quoted limits are based on a total of $9.9 \times 10^{4}$ ($1.3 \times 10^6,~2 \times10^6,~ 2.2 \times10^6,~ 6.1 \times10^4,~6.3 \times10^4$ ) positron (electron, proton, Helium, Carbon, Oxygen) events

Polyphenol Iongel Patches with Antimicrobial, Antioxidant and Anti-Inflammatory Properties

There is an actual need for developing materials for wound healing applications with anti-inflammatory, antioxidant, or antibacterial properties in order to improve the healing performance. In this work, we report the preparation and characterization of soft and bioactive iongel materials for patches, based on polymeric poly(vinyl alcohol) (PVA) and four ionic liquids containing the cholinium cation and different phenolic acid anions, namely cholinium salicylate ([Ch][Sal]), cholinium gallate ([Ch][Ga]), cholinium vanillate ([Ch][Van]), and cholinium caffeate ([Ch][Caff]). Within the iongels, the phenolic motif in the ionic liquids plays a dual role, acting as a PVA crosslinker and a bioactive compound. The obtained iongels are flexible, elastic, ionic conducting, and thermoreversible materials. Moreover, the iongels demonstrated high biocompatibility, non-hemolytic activity, and non-agglutination in mice blood, which are key-sought material specifications in wound healing applications. All the iongels have shown antibacterial properties, being PVA-[Ch][Sal], the one with higher inhibition halo for Escherichia Coli. The iongels also revealed high values of antioxidant activity due to the presence of the polyphenol, with the PVA-[Ch][Van] iongel having the highest activity. Finally, the iongels show a decrease in NO production in LPS-stimulated macrophages, with the PVA-[Ch][Sal] iongel displaying the best anti-inflammatory activity (>63% at 200 µg/mL).This work was funding by Marie Sklodowska-Curie Research and Innovation Staff Exchanges (RISE) under the grant agreement No 823989 “IONBIKE”, CONICET (PIP 11220200101353CO), ANPCyT (PICT-2020-03156), and the National University of the Litoral (C.A.I. + D 50620190100117LI), and Fundação para a Ciência e a Tecnologia (2020.01555.CEECIND, UIDB/50006/2020 and UIDP/50006/2020)

Short-course versus long-course therapy of the same antibiotic for community-acquired pneumonia in adolescent and adult outpatients.

Background Community-acquired pneumonia (CAP) is a lung infection that can be acquired during day-to-day activities in the community (not while receiving care in a hospital). Community-acquired pneumonia poses a significant public health burden in terms of mortality, morbidity, and costs. Shorter antibiotic courses for CAP may limit treatment costs and adverse effects, but the optimal duration of antibiotic treatment is uncertain. Objectives To evaluate the efficacy and safety of short-course versus longer-course treatment with the same antibiotic at the same daily dosage for CAP in non-hospitalised adolescents and adults (outpatients). We planned to investigate non-inferiority of short-course versus longerterm course treatment for efficacy outcomes, and superiority of short-course treatment for safety outcomes. Search methods We searched CENTRAL, which contains the Cochrane Acute Respiratory Infections Group Specialised Register,MEDLINE, Embase, five other databases, and three trials registers on 28 September 2017 together with conference proceedings, reference checking, and contact with experts and pharmaceutical companies.SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing short- and long-courses of the same antibiotic for CAP in adolescent and adult outpatients. DATA COLLECTION AND ANALYSIS: We planned to use standard Cochrane methods. MAIN RESULTS: Our searches identified 5260 records. We did not identify any RCTs that compared short- and longer-courses of the same antibiotic for the treatment of adolescents and adult outpatients with CAP.We excluded two RCTs that compared short courses (five compared to seven days) of the same antibiotic at the same daily dose because they evaluated antibiotics (gemifloxacin and telithromycin) not commonly used in practice for the treatment of CAP. In particular, gemifloxacin is no longer approved for the treatment of mild-to-moderate CAP due to its questionable risk-benefit balance, and reported adverse effects. Moreover, the safety profile of telithromycin is also cause for concern.We found one ongoing study that we will assess for inclusion in future updates of the review. AUTHORS' CONCLUSIONS: We found no eligible RCTs that studied a short-course of antibiotic compared to a longer-course (with the same antibiotic at the same daily dosage) for CAP in adolescent and adult outpatients. The effects of antibiotic therapy duration for CAP in adolescent and adult outpatients remains unclear.pre-print547 K

Gene-based mapping of trehalose biosynthetic pathway genes reveals association with source- and sink-related yield traits in a spring wheat panel

Trehalose 6-phosphate (T6P) signalling regulates carbon use and allocation and is a target to improve crop yields. However, the specific contributions of trehalose phosphate synthase (TPS) and trehalose phosphate phosphatase (TPP) genes to source- and sink-related traits remain largely unknown. We used enrichment-capture sequencing on TPS and TPP genes to estimate and partition the genetic variation of yield-related traits in a spring wheat (Triticum aestivum) breeding panel specifically built to capture the diversity across the 75,000 CIMMYT wheat cultivar collection. Twelve phenotypes were correlated to variation in TPS and TPP genes including plant height and biomass (source), spikelets per spike, spike growth, and grain filling traits (sink) which showed indications of both positive and negative gene selection. Individual genes explained proportions of heritability for biomass and grain-related traits. Three TPS1 homeologues were particularly significant for trait variation. Epistatic interactions were found within and between the TPS and TPP gene families for both plant height and grain-related traits. Gene-based prediction improved predictive ability for grain weight when gene effects were combined with the whole-genome markers. Our study has generated a wealth of information on natural variation of TPS and TPP genes related to yield potential which confirms the role for T6P in resource allocation and in affecting traits such as grain number and size confirming other studies which now opens up the possibility of harnessing natural genetic variation more widely to better understand the contribution of native genes to yield traits for incorporation into breeding programmes