Bromate determination in water after membrane complexation and total reflection X-ray fluorescence analysis

A new method for the determination of trace levels of bromates by selective membrane collection is presented. Various membranes containing a few micrograms of different complexing reagents in a poly(vinyl chloride) matrix were tested. These membranes were produced on the surface of quartz glass (reflectors), and they were immersed in solutions containing bromate and bromide ions. At the first stage the prepared membranes collected both bromate and bromide ions, so different bromide masking agents were put in the analyzed solutions to avoid bromide collection. By the end of the equilibration time, the reflectors were left to dry, and they were analyzed by total reflection X-ray fluorescence (TXRF). The poly(vinyl chloride) with aliquat-336 membrane and o-dianisidin complexing agent gave the best results. The minimum detection limit was equal to 0.9 ng/mL for ultrapure water and 1.0 ng/mL for drinking water.     

Elucidating Carfilzomib’s Induced Cardiotoxicity in an In Vivo Model of Aging: Prophylactic Potential of Metformin

Background: Carfilzomib is a first-line proteasome inhibitor indicated for relapsed/refractory multiple myeloma (MM), with its clinical use being hampered by cardiotoxic phenomena. We have previously established a translational model of carfilzomib cardiotoxicity in young adult mice, in which metformin emerged as a prophylactic therapy. Considering that MM is an elderly disease and that age is an independent risk factor for cardiotoxicity, herein, we sought to validate carfilzomib’s cardiotoxicity in an in vivo model of aging. Methods: Aged mice underwent the translational two- and four-dose protocols without and with metformin. Mice underwent echocardiography and were subsequently sacrificed for molecular analyses in the blood and cardiac tissue. Results: Carfilzomib decreased proteasomal activity both in PBMCs and myocardium in both protocols. Carfilzomib induced mild cardiotoxicity after two doses and more pronounced cardiomyopathy in the four-dose protocol, while metformin maintained cardiac function. Carfilzomib led to an increased Bip expression and decreased AMPKα phosphorylation, while metformin coadministration partially decreased Bip expression and induced AMPKα phosphorylation, leading to enhanced myocardial LC3B-dependent autophagy. Conclusion: Carfilzomib induced cardiotoxicity in aged mice, an effect significantly reversed by metformin. The latter possesses translational importance as it further supports the clinical use of metformin as a potent prophylactic therapy.     

Polyurethane Foam Rafts Supported In Vitro Cultures of Rindera graeca Roots for Enhanced Production of Rinderol,Potent Proapoptotic Naphthoquinone Compound

Unique phytochemical profile of plants belonging to Boraginaceae family provides a prolific resource of lipophilic pigments from the group of naphthoquinone derivatives. To overcome low compound content, the major obstacle of plant-based production, immobilization of Rindera graeca roots in in vitro cultures was implemented for efficient production of rinderol, novel furanonaphthoquinone derivative with anticancer properties. Chromatographic procedures revealed rinderol presence in extracts of all investigated root lines, derived both from root biomass and post-culture medium. Unexpectedly, in the second stage of the experiment, rinderol production was ceased in control, unmodified culture systems. On the contrary, roots immobilized on PUF rafts uniformly and stably produced rinderol, and its highest amount was noted for transformed root lines after 42 days of cultivation (222.98 ± 10.47 µg/flask). PUF occurred to be the main place of compound accumulation. Moreover, investigation of rinderol biological activity revealed its fast-acting cell death induction in HeLa cervical cancer cells at relatively low concentrations. Presented results revealed successful application of R. graeca roots immobilization on PUF rafts for production and in situ product removal of rinderol, novel lipophilic furanonaphthoquinone with suggested proapoptotic activity.     

Towards Understanding Excited-State Properties of Organic Molecules Using Time-Resolved Soft X-ray Absorption Spectroscopy

The extension of the pump-probe approach known from UV/VIS spectroscopy to very short wavelengths together with advanced simulation techniques allows a detailed analysis of excited-state dynamics in organic molecules or biomolecular structures on a nanosecond to femtosecond time level. Optical pump soft X-ray probe spectroscopy is a relatively new approach to detect and characterize optically dark states in organic molecules, exciton dynamics or transient ligand-to-metal charge transfer states. In this paper, we describe two experimental setups for transient soft X-ray absorption spectroscopy based on an LPP emitting picosecond and sub-nanosecond soft X-ray pulses in the photon energy range between 50 and 1500 eV. We apply these setups for near-edge X-ray absorption fine structure (NEXAFS) investigations of thin films of a metal-free porphyrin, an aggregate forming carbocyanine and a nickel oxide molecule. NEXAFS investigations have been carried out at the carbon, nitrogen and oxygen K-edge as well as on the Ni L-edge. From time-resolved NEXAFS carbon, K-edge measurements of the metal-free porphyrin first insights into a long-lived trap state are gained. Our findings are discussed and compared with density functional theory calculations.     

Circulating miRNA Expression Profiles and Machine Learning Models in Association with Response to Irinotecan-Based Treatment in Metastatic Colorectal Cancer

Colorectal cancer represents a leading cause of cancer-related morbidity and mortality. Despite improvements, chemotherapy remains the backbone of colorectal cancer treatment. The aim of this study is to investigate the variation of circulating microRNA expression profiles and the response to irinotecan-based treatment in metastatic colorectal cancer and to identify relevant target genes and molecular functions. Serum samples from 95 metastatic colorectal cancer patients were analyzed. The microRNA expression was tested with a NucleoSpin miRNA kit (Machnery-Nagel, Germany), and a machine learning approach was subsequently applied for microRNA profiling. The top 10 upregulated microRNAs in the non-responders group were hsa-miR-181b-5p, hsa-miR-10b-5p, hsa-let-7f-5p, hsa-miR-181a-5p, hsa-miR-181d-5p, hsa-miR-301a-3p, hsa-miR-92a-3p, hsa-miR-155-5p, hsa-miR-30c-5p, and hsa-let-7i-5p. Similarly, the top 10 downregulated microRNAs were hsa-let-7d-5p, hsa-let-7c-5p, hsa-miR-215-5p, hsa-miR-143-3p, hsa-let-7a-5p, hsa-miR-10a-5p, hsa-miR-142-5p, hsa-miR-148a-3p, hsa-miR-122-5p, and hsa-miR-17-5p. The upregulation of microRNAs in the miR-181 family and the downregulation of those in the let-7 family appear to be mostly involved with non-responsiveness to irinotecan-based treatment.     

Glycidyl Methacrylate-Based Copolymers as Healing Agents of Waterborne Polyurethanes

Self-healing materials and self-healing mechanisms are two topics that have attracted huge scientific interest in recent decades. Macromolecular chemistry can provide appropriately tailored functional polymers with desired healing properties. Herein, we report the incorporation of glycidyl methacrylate-based (GMA) copolymers in waterborne polyurethanes (WPUs) and the study of their potential healing ability. Two types of copolymers were synthesized, namely the hydrophobic P(BA-co-GMAy) copolymers of GMA with n-butyl acrylate (BA) and the amphiphilic copolymers P(PEGMA-co-GMAy) of GMA with a poly(ethylene glycol) methyl ether methacrylate (PEGMA) macromonomer. We demonstrate that the blending of these types of copolymers with two WPUs leads to homogenous composites. While the addition of P(BA-co-GMAy) in the WPUs leads to amorphous materials, the addition of P(PEGMA-co-GMAy) copolymers leads to hybrid composite systems varying from amorphous to semi-crystalline, depending on copolymer or blend composition. The healing efficiency of these copolymers was explored upon application of two external triggers (addition of water or heating). Promising healing results were exhibited by the final composites when water was used as a healing trigger.     

Effect of inulin on texture and clarity of gellan gels

The effect of inulin on the gelation of 0.5 wt% low acyl gellan in the presence of increasing concentrations of potassium chloride was investigated by large deformation compression experiments and visible light absorbance. The sugar and salt concentrations varied from 0 to 15 wt% and 40-100 mM, respectively. Stress and strain at failure along with Young’s modulus were calculated from each compression curve. Samples prior to compression were refrigerated at 5 °C for 24 h. Reduced gel strength and firmness were observed for all inulin and salt concentrations. Increasing amounts of inulin resulted in an increase in gel strength which was greater for higher potassium concentrations. Elasticity values did not exhibit great diversion. Inulin at concentrations of 5 and 10 wt% led to less turbid gels than those with only gellan. Samples containing 15 wt% inulin gave absorbance readings greater than 1.     

Reevaluation of antimicrobial and antioxidant activity of Thymus spp. extracts before and after encapsulation in liposomes

The antioxidant and antimicrobial activity of four Thymus species (boissieri, longicaulis, leucospermus, and ocheus) extracts were determined. Two methods (Rancimat and malondialdehyde by high-performance liquid chromatography) were used to measure the antioxidant action in comparison with common commercial antioxidants, including butylated hydroxytoluene and alpha-tocopherol. The extracts that presented high antioxidant activity were encapsulated in liposomes and their antioxidant action was again estimated. Thermal-oxidative decomposition of the samples (pure liposomes and encapsulating extracts) was studied using the differential scanning calorimetry method. The modification of the main transition temperature for the lipid mixture and the splitting of the calorimetric peak in the presence of the antioxidants were also demonstrated by differential scanning calorimetry. All extracts showed antioxidant and antimicrobial activities. Some extracts showed superior or equal antioxidant activity to alpha-tocopherol. When the extracts were encapsulated in liposomes, their antioxidant as well as antimicrobial activities proved to be superior from the same extracts in pure form.     

Reconstruction procedure for 3D micro X-ray absorption fine structure

A new approach for chemical speciation in stratified systems using 3D Micro-XAFS spectroscopy is developed by combining 3D Micro X-ray Fluorescence Spectroscopy (3D Micro-XRF) and conventional X-ray Absorption Fine Structure Spectroscopy (XAFS). A prominent field of application is stratified materials within which depth-resolved chemical speciation is required. Measurements are collected in fluorescence mode which in general lead to distorted spectra due to absorption effects. Developing a reliable reconstruction algorithm for obtaining undistorted spectra for superficial and in-depth layers is proposed and validated. The developed algorithm calculates the attenuation coefficients of the analyte for the successive layers facilitating a new spectroscopic tool for three-dimensionally resolved nondestructive chemical speciation.