Carboxylated-xyloglucan and peptide amphiphile co-assembly in wound healing

Hydrogel wound dressings can play critical roles in wound healing protecting the wound from trauma or contamination and providing an ideal environment to support the growth of endogenous cells and promote wound closure. This work presents a self-assembling hydrogel dressing that can assist the wound repair process mimicking the hierarchical structure of skin extracellular matrix. To this aim, the co-assembly behaviour of a carboxylated variant of xyloglucan (CXG) with a peptide amphiphile (PA-H3) has been investigated to generate hierarchical constructs with tuneable molecular composition, structure, and properties. Transmission electron microscopy and circular dichroism at a low concentration shows that CXG and PA-H3 co-assemble into nanofibres by hydrophobic and electrostatic interactions and further aggregate into nanofibre bundles and networks. At a higher concentration, CXG and PA-H3 yield hydrogels that have been characterized for their morphology by scanning electron microscopy and for the mechanical properties by small-amplitude oscillatory shear rheological measurements and compression tests at different CXG/PAH3 ratios. A preliminary biological evaluation has been carried out both in vitro with HaCat cells and in vivo in a mouse model

An AFM Approach of RBC Micro and Nanoscale Topographic Features During Storage

Blood gamma irradiation is the only available method to prevent transfusion-associated graft versus host disease (TA-GVHD). However, when blood is irradiated, determine blood shelf time is crucial. Non-irradiated blood has a self-time from 21 to 35 days when is preserved with an anticoagulated solution and stored at 4°C. During their storage, red blood cells (RBC) undergo a series of biochemical, biomechanical and molecular changes involving what is known as storage lesion (SL). SL include loss of structural integrity of RBC, a decrease of 2,3-diphosphatidylglyceric acid levels, and an increase of both ion potassium concentration and hemoglobin (Hb). On the other hand, Atomic force Microscopy (AFM) represents a versatile tool for a nano-scale high-resolution topographic analysis in biological systems. In order to evaluate SL in irradiated and non-irradiated blood, RBC topography and morphometric parameters were obtained from an AFM XE-BIO system. Cell viability was followed using flow cytometry. Our results showed that early markers as nanoscale roughness, allow us to evaluate blood quality since another perspective

Independent genomic polymorphisms in the PknH serine threonine kinase locus during evolution of the Mycobacterium tuberculosis Complex affect virulence and host preference

Species belonging to the Mycobacterium tuberculosis Complex (MTBC) show more than 99% genetic identity but exhibit distinct host preference and virulence. The molecular genetic changes that underly host specificity and infection phenotype within MTBC members have not been fully elucidated. Here, we analysed RD900 genomic region across MTBC members using whole genome sequences from 60 different MTBC strains so as to determine its role in the context of MTBC evolutionary history. The RD900 region comprises two homologous genes, pknH1 and pknH2, encoding a serine/threonine protein kinase PknH flanking the tbd2 gene. Our analysis revealed that RD900 has been independently lost in different MTBC lineages and different strains, resulting in the generation of a single pknH gene. Importantly, all the analysed M. bovis and M. caprae strains carry a conserved deletion within a proline rich-region of pknH, independent of the presence or absence of RD900. We hypothesized that deletion of pknH proline rich-region in M. bovis may affect PknH function, having a potential role in its virulence and evolutionary adaptation. To explore this hypothesis, we constructed two M. bovis ‘knock-in’ strains containing the M. tuberculosis pknH gene. Evaluation of their virulence phenotype in mice revealed a reduced virulence of both M. bovis knock-in strains compared to the wild type, suggesting that PknH plays an important role in the differential virulence phenotype of M. bovis vs M. tuberculosis

Solution-Processed Ni-Based Nanocomposite Electrocatalysts: An Approach to Highly Efficient Electrochemical Water Splitting

In this study, we report an up-scalable and low-cost solution-processed method to in situ synthesize an earth-abundant non-stoichiometric NiOx-based electrocatalytic film for water oxidation. The catalytic activity was found to be inversely proportional to the baking temperature, which varied from 50 to 500 °C. We found the formation of a hybrid nanocomposite thin film of NiOx nanocrystals (<2 nm size) inside an acetate-based organic matrix at low temperatures (<200 °C). The defective and short-range structural order of the NiOx-based nanocomposite electrocatalysts, compatible with lattice stress, low electrical conductivity, and high density of catalytically active surface species, and higher Fe incorporation were responsible for the enhanced electrocatalytic activity. Our champion NiOx catalyst features a 358 mV overpotential at 10 mA cm–2 and more than 60 h of continuous operation without significant losses, which is a remarkable milestone for undoped NiOx electrocatalysts synthesized at nearly room temperature by a solution-processed up-scalable method.Funding for open access charge: CRUE-Universitat Jaume IThe authors acknowledge the financial support from the Ministerio de Ciencia, Innovación y Universidades of Spain through funded projects ENE2017-85087-C3-1-R, RYC-2015-18349, and TEC2017-86102-C2-1-R and Agencia Valenciana de la Innovacion (AVI) INNVAL10/18/032. The authors thank the Central Support Service for Experimental Research (SCSIE) (XRD and SEM facilities) and the Institute of Materials Science (TGA and DTA equipment) of the University of Valencia and the Central Service of Scientific Instrumentation (SCIC) at University Jaume I. The authors also thank Prof. Juan P. Martinez-Pastor for his constructive suggestions and scientific discussions

Role of the human concentrative nucleoside transporter (hCNT1) in the cytotoxic action of 5[Prime]-deoxy-5-fluorouridine, an active intermediate metabolite of capecitabine, a novel oral anticancer drug.

We attempt to identify the plasma membrane transporter involved in the uptake of 5'-deoxy-5-fluorouridine (5'-DFUR), an intermediate metabolite of capecitabine. This novel oral fluoropyrimidine is used in cancer treatments and is a direct precursor of the cytostatic agent 5'-fluorouracil. We also examine the role of the transporter in 5'-DFUR cytotoxicity. The human concentrative nucleoside transporter (hCNT1) was cloned from human fetal liver and expressed in Xenopus laevis oocytes. The two-electrode voltage-clamp technique was used to demonstrate that 5'-DFUR, but not capecitabine or 5'-FU, is an hCNT1 substrate. Then, hCNT1 was heterologously expressed in the mammalian cell line Chinese hamster ovary-K1. Functional expression was demonstrated by monitoring transport of radiolabeled substrates and by using a monospecific polyclonal antibody generated against the transporter. hCNT1-expressing cells were more sensitive to 5'-DFUR than vector-transfected or wild-type cells. The sensitivity of the three cell types to other agents such as cisplatin or 5'-FU was identical. In conclusion, this study shows that 1) the pharmacological profile of a nucleoside transporter can be determined by an electrophysiological approach; 2) the hCNT1 transporter is involved in 5'-DFUR uptake; and 3) hCNT1 expression may increase cell sensitivity to 5'-DFUR treatment. This study also reports for the first time the generation of an antibody against hCNT1, which may be useful in the elucidation of the relationship between hCNT1 expression and tumor response to capecitabine treatmen

Bacteriemia secundaria a balanitis por pseudomona aeruginosa XDR en paciente con LLC con inmunosupresión severa prolongada

PB-071 Introducción: La neutropenia severa (7- 10 días) es indicación de profilaxis antibiótica en pacientes de alto riesgo para desarrollo de infección según guías de recomendación. En enfermedades con clonalidad linfoide como la leucemia linfática crónica (LLC), se añade frecuentemente el desarrollo de hipogamaglobulinemia, que produce afectación de la inmunidad innata y humoral, aumentando el riesgo infeccioso de base. Caso clínico: Paciente de 70 años con antecedentes de colicitis ulcerosa (CU) y LLC estadío Rai 4 Binet C desde mayo de 2017, con cadena pesada de las inmunoglobulinas y p53 normales, que recibió Ibrutinib durante 20 días en diciembre de 2017, suspendiéndose por múltiples complicaciones infecciosas: NAC, bacteriemia por E. Coli, gripe A y aspergilosis pulmonar invasiva. Ingresa en hematología en abril de 2018 por diarrea, disuria y balanitis prepucial de una semana de evolución. Presenta fiebre en contexto de neutropenia severa y prolongada, con posible foco infeccioso digestivo y/o urinario. Se inicia tratamiento antibiótico empírico y se continúa tratamiento antifúngico previo. Digestivo descarta que la diarrea sea secundaria a brote de CU. Presenta mejoría de cuadro diarreico con empeoramiento de balanitis, documentándose tándose aislamiento de P. aeruginosa XDR en orina y exudado uretral. Se realizó cambio de antibiótico a aztreonam y colistina según antibiograma recogido en Tabla 1. Durante la evolución, se reactiva infección por CMV y se decide inicio de valganciclovir sin evidencia de lesión orgánica o enfermedad por CMV. Se descarta infección fúngica invasiva activa durante la hospitalización. Debido a progresión clínica de adenopatías y aumento de hepatoesplenomegalia, además de neutropenia persistente, secundarios a infiltración por LLC; se decide inicio de quimioterapia con esquema R-Clorambucilo y reinicio de G-CSF (G-CSF inefectivo en ingresos previos). Se descarta transformación de hemopatía de base mediante biopsia de médula ósea. Se produce reducción importante de adenopatías axilares e inguinales con menor respuesta del conglomerado adenopático abdominal. ..

A multiproxy study distinguishes environmental change from diagenetic alteration in the recent sedimentary record of the inner Cadiz Bay (SW Spain)

In this study, we reconstruct the recent environmental evolution of the inner Cadiz Bay using sedimentary records reaching back as far as AD 1700. We report lithological descriptions of the sediments and extensive mineralogical and geochemical analyses. An extraction technique that identifies different Fe phases provides an assessment of diagenetic alteration, which allows an estimation of the original organic matter inputs to the inner Cadiz Bay. Downcore variations in Corg/N ratios, δ13Corg and δ15N are related to changes in organic matter sources and the trophic state of the water column. The downcore records of selected trace metals (e.g. Pb, Zn and Cu) are interpreted to reflect changes in heavy metal pollution in the bay, while records of other elements (e.g. Mn and P) are likely overprinted by diagenetic alteration. Major environmental shifts took place during the 20th century, when the population around Cadiz Bay increased exponentially. Increases in sediment accumulation rates, organic matter inputs and heavy metal contents, in parallel with increases in δ13Corg and δ15N over this period, are interpreted as direct effects of the increasing anthropogenic influence in the area. The results of this study suggest that multiproxy approaches and detailed consideration of diagenetic overprinting are required to reconstruct past environmental conditions from coastal sediments

Glomerulonefritis membranoproliferativa paraneoplásica en leucemia linfática crónica: a propósito de un caso

PB-070 Introducción: La leucemia linfática crónica (LLC) es una neoplasia hematológica con alta incidencia en la población general. Sin embargo, la incidencia de afectación extranodal o extramedular secundaria a procesos paraneoplásicos es rara. En las series de casos encontradas en la literatura, la incidencia de afectación sintomática a nivel genitourinario o ginecológico es inferior al 10%, pero en autopsias se ha encontrado infiltración asintomática hasta en un 90% de los casos. La glomerulonefritis membranoproliferativa (GNMP) es la afectación paraneoplásica más frecuentemente encontrada a nivel renal y se presenta generalmente con insuficiencia renal o síndrome nefrótico. Caso clínico: Paciente de 81 años con antecedentes de HTA, dislipemia, fibrilación auricular, HBP e hipoacusia crónica. Ingresa en Nefrología en septiembre de 2018 por insuficiencia renal progresiva desde una creatinina basal de 1.26 mg/dL hasta 2.54 mg/dL, asociado a microhematuria y proteinuria; sin proceso intercurrente ni exposición a nefrotóxicos. Se encuentra asintomático, sin hallazgos patológicos a la exploración física. Se objetiva proteinuria de 7.7 gramos en orina de 24 horas, proteinuria de Bence Jones negativa y hematuria persistente. Así mismo, se objetiva una linfocitosis de 5.8x103/microL. Se completa el estudio etiológico mediante biopsia renal, con el diagnóstico de GNMP. En las pruebas de inmunohistoquímica, se objetiva un infiltrado linfocítico en cápsula renal CD20 positivo, CD23 y CD5 focalmente positivos; compatible con infiltración por LLC. En la citometría de flujo de sangre periférica, se halla un 38, 1% de linfocitos B maduros, siendo un 96% elementos clonales con inmunofenotipo de LLC con coexpresión de CD20, CD19, CD23, CD200 y CD5. En la citogenética se obtiene trisomía del cromosoma 12. Presenta biología molecular no mutada para TP53 y VH. En la serie ósea no se objetivan imágenes osteolíticas. En diciembre de 2018, Nefrología inicia tratamiento con ..