Tuberculosis de la sínfisis del pubis : a propósito de un caso clínico.

Se presenta un caso muy infrecuente de tuberculosis osteoarticular de localización en la sínfisis del pubis. Destaca la dificultad de su diagnóstico por lo inespecífico de su clínica, por el desconocimiento de enfermedad pulmonar o lesión primaria tuberculosa, y la dificultad para aislar al propio bacilo tuberculoso. Establecemos los diagnósticos diferenciales más importantes con los que se puede confundir esta patología antes de llegar a un diagnóstico certero y se valoran los síntomas, signos y hallazgos radiológicos más frecuentes que contribuyen al diagnóstico, así como el tratamiento específico empleado.We presen t a cas e o f an infrecuen t locatio n o f osteoarticula r tuber - culosis a t th e pubi x xymphisis. This patolog y is difficult t o determine , specil y if ther e doe s no t exit a pulmonar y o r primar y TBC lesion . Also , th e difficult t o obtai n a positiv e microbiolog y cultur e increase s th e dela y i n diagnosis. We establis h all posibl e differencia l diagnoses. Whic h ca n lea d t o confusio n i n this typ e o f pathology . A carefu l evaluatio n o f most commo n simptoms, sign s an d radiologien e fínding s ar e described , a s wel l as, th e specifi c treatmen t employe d i n this particuler e case

Turning carbon dots into selenium bearing nanoplatforms with in vitro GPx-like activity and pro-oxidant activity

Selenium (Se) has been defined as the “Janus element”, with one face showing antioxidant activity and the other pro-oxidant activity. The biological effect of Se depends on both dose and speciation. Se nanoparticles are attracting major interest, although their large-scale preparation for biomedical applications is not trivial. We hypothesize that acid anhydride-coated carbon dots (AACD) are an attractive platform for preparing nanoparticles containing chemically defined Se. The reaction of AA-CD with 3- selenocyanatopropan-1-amine yields carbon dots bearing selenocyanate and carboxylate groups (CD-SeCN) that allow for tuning the hydrosolubility. CD-SeCN has a Se content of 0.36 μmol per mg of nanoparticles, and they show the typical photoluminescence of carbon dots. The selenocyanate groups (SeCN) exhibited glutathione peroxidase-like activity and cytotoxicity. Data show that antioxidant behavior differs between normal and tumor cells, and the evaluation on HEK293 and A549 cells reveals that the toxicity of CD-SeCN depends on dose, time, and intracellular glutathione (GSH) content. The toxicity of CD-SeCN decreases with the time of incubation and the cell death mechanism switches from necrosis to apoptosis, indicating that CD-SeCN is neutralized. Additionally, high levels of intracellular GSH exert a protective effect. These results support a pharmacological potential in cancers with low levels of intracellular GSH. The use of AA-CD as nanoplatforms is a general strategy that paves the way for the engineering of advanced nanosystemsSpanish institution Ministerio de Ciencia, Innovacion y Universidades (No. CTQ2017- 86125-P)Unit of Excellence in Chemistry Applied to Biomedicine and the EnvironmentCentro de Instrumentacion Cientifica (Universidad de Granada)Universidad de Granada/CBUASpringer Natur

Técnicas de protección del patrimonio arqueológico excavado

Los yacimientos arqueológicos presentan problemas para la protección ambiental de los restos que se hallan en ellos. Los materiales de las excavaciones suelen ser adobe, tapiales o piedras, materiales que sufren una gran degradación a la intemperie. Generalmente durante el proceso de degradación las construcciones pierden en primer lugar la techumbre por lo que el agua de lluvia penetra directamente sobre el interior de los yacimientos, actuando sobre revestimientos, bajorrelieves, pinturas, etc. También la cota de los restos arqueológicos suele ser inferior a los niveles actuales de las calles, por lo que el agua freática o de lluvia termina acumulándose en ellos, e incluso el viento termina transportando basuras y materiales finos sobre los restos, ayudado especialmente por los a veces maleducados visitantes

Vinyl sulfone silica: application of an open preactivated support to the study of transnitrosylation of plant proteins by S-nitrosoglutathione

Background S-nitrosylaton is implicated in the regulation of numerous signaling pathways with a diversity of regulatory roles. The high lability of the S-NO bond makes the study of proteins regulated by S-nitrosylation/denitrosylation a challenging task and most studies have focused on already S-nitrosylated proteins. We hypothesize that: i) S-nitrosoglutathione (GSNO) transnitrosylation is a feasible mechanism to account for the physiological S-nitrosylation of rather electropositive sulfur atoms from proteins, ii) affinity chromatography is a suitable approach to isolate proteins that are prone to undergo S-transnitrosylation and iii) vinyl sulfone silica is a suitable chromatographic bead.Results The combination of vinyl sulfone silica with GSNO yielded an affinity resin that withstood high ionic strength without shrinking or deforming and that it was suitable to isolate potential GSNO transnitrosylation target candidates. Fractions eluted at 1500 mM NaCl resulted in a symmetrical peak for both, protein and S-nitrosothiols, supporting the idea of transnitrosylation by GSNO as a selective process that involves strong and specific interactions with the target protein. Proteomic analysis led to the identification of 22 physiological significant enzymes that differ with the tissue analyzed, being regulatory proteins the most abundant group in hypocotyls. The identification of chloroplastidic FBPase, proteasome, GTP-binding protein, heat shock Hsp70, syntaxin, catalase I, thioredoxin peroxidase and cytochrome P450 that have already been reported as S-nitrosylated by other techniques can be considered as internal positive controls that validate our experimental approach. An additional validation was provided by the prediction of the S-nitrosylation sites in 19 of the GSNO transnitrosylation target candidates.Conclusions Vinyl sulfone silica is an open immobilization support that can be turned ad hoc and in a straightforward manner into an affinity resin. Its potential in omic sciences was successfully put to test in the context of the analysis of post-translational modification by S-nitrosylation with two different tissues: mature pea leaves and embryogenic sunflower hypocotyls. The identified proteins reveal an intriguing overlap among S-nitrosylation and both tyrosine nitration and thioredoxin regulation. Chloroplastidic FBPase is a paradigm of such overlap of post-translational modifications since it is reversible modified by thioredoxin and S-nitrosylation and irreversibly by tyrosine nitration. Our results suggest a complex interrelation among different modulation mechanisms mediated by NO-derived molecules.Financial Support was provided by Dirección General de Investigacion Cientıfica y Técnica (DGICYT) (CTQ2008-01754), Junta de Andalucía (P07-FQM-02899), Universidad de Jaén campus de Excelencia Internacional Agroalimentario ceiA3 and by ERDF-cofinanced grants from Ministry of Science and Innovation (BIO2012-33904) and Junta de Andalucía (research groups BIO286 and BIO192). We also acknowledge support of the publication fee by the CSIC Open Access Publication Support Initiative through its Unit of Information Resources for Research (URICI)

Single chain variable fragment fused to maltose binding protein: a modular nanocarrier platform for the targeted delivery of antitumorals

This work was supported by grants CTQ2014-55474-C2-1-R, CTQ2014-55474-C2-2-R and CTQ2017-86125-P from the Ministerio Economia, Industria y Competitividad (co-financed by FEDER funds). SP is supported by a FPU fellowship (FPU17/ 04749). We acknowledge the University of Granada (Spain) cell culture, animal and microscopy central facilities (CIC-UGR).The use of the specific binding properties of monoclonal antibody fragments such as single-chain variable fragments (ScFv) for the selective delivery of antitumor therapeutics for cancer cells is attractive due to their smaller size, low immunogenicity, and low-cost production. Although covalent strategies for the preparation of such ScFv-based therapeutic conjugates are prevalent, this approach is not straightforward, as it requires prior chemical activation and/or modification of both the ScFv and the therapeutics for the application of robust chemistries. A non-covalent alternative based on ScFv fused to maltose-binding protein (MBP) acting as a binding adapter is proposed for active targeted delivery. MBP-ScFv proves to be a valuable modular platform to synergistically bind maltose-derivatized therapeutic cargos through the MBP, while preserving the targeting competences provided by the ScFv. The methodology has been tested by using a mutated maltose-binding protein (MBP I334W) with an enhanced affinity toward maltose and an ScFv coding sequence toward the human epidermal growth factor receptor 2 (HER2). Non-covalent binding complexes of the resulting MBP-ScFv fusion protein with diverse maltosylated therapeutic cargos (a near-infrared dye, a maltosylated supramolecular beta-cyclodextrin container for doxorubicin, and non-viral polyplex gene vector) were easily prepared and characterized. In vitro and in vivo assays using cell lines that express or not the HER2 epitope, and mice xenografts of HER2 expressing cells demonstrated the capability and versatility of MBP-ScFv for diagnosis, imaging, and drug and plasmid active targeted tumor delivery. Remarkably, the modularity of the MBP-ScFv platform allows the flexible interchange of both the cargos and the coding sequence for the ScFv, allowing ad hoc solutions in targeting delivery without any further optimization since the MBP acts as a pivotal element.Ministerio Economia, Industria y Competitividad - FEDER funds CTQ2014-55474-C2-1-R CTQ2014-55474-C2-2-R CTQ2017-86125-PSpanish Government FPU17/0474

Poly(ethylene-imine)-Functionalized Magnetite Nanoparticles Derivatized with Folic Acid: Heating and Targeting Properties

Magnetite nanoparticles (MNPs) coated by branched poly (ethylene-imine) (PEI) were synthesized in a one-pot. Three molecular weights of PEI were tested, namely, 1.8 kDa (sample MNP-1), 10 kDa (sample MNP-2), and 25 kDa (sample MNP-3). The MNP-1 particles were further functionalized with folic acid (FA) (sample MNP-4). The four types of particles were found to behave magnetically as superparamagnetic, with MNP-1 showing the highest magnetization saturation. The particles were evaluated as possible hyperthermia agents by subjecting them to magnetic fields of 12 kA/m strength and frequencies ranging between 115 and 175 kHz. MNP-1 released the maximum heating power, reaching 330 W/g at the highest frequency, in the high side of reported values for spherical MNPs. In vitro cell viability assays of MNP-1 and MNP-4 against three cell lines expressing different levels of FA receptors (FR), namely, HEK (low expression), and HeLa (high expression), and HepG2 (high expression), demonstrated that they are not cytotoxic. When the cells were incubated in the presence of a 175 kHz magnetic field, a significant reduction in cell viability and clone formation was obtained for the high expressing FR cells incubated with MNP-4, suggesting that MNP-4 particles are good candidates for magnetic field hyperthermia and active targeting.Spanish Institutions: Ministerio de Ciencia, Innovación y Universidades (PGC2018-098770-B-I00 and CTQ2017-86125-P)Junta de Andalucía (ProgramaOperativo FEDER 2014-2020, grants B-FQM-141-UGR18, A1-FQM-341-UGR-18, C-FQM-497-UGR18

Biological Evaluation and Docking Studies of Synthetic Oleananetype Triterpenoids

Saponins are potential wide-spectrum antitumor drugs, and copper(I) catalyzed azide−alkyne 1,3-dipolar cycloaddition is a suitable approach to synthesizing saponinlike compounds by regioselective glycosylation of the C2/C3 hydroxyl and C28 carboxylic groups of triterpene aglycones maslinic acid (MA) and oleanolic acid (OA). Biological studies on the T-84 human colon carcinoma cell line support the role of the hydroxyl groups at C2/C3, the influence of the aglycone, and the bulky nature of the substituents in C28. OA bearing a α-D-mannose moiety at C28 (compound 18) focused our interest because the estimated inhibitory concentration 50 was similar to that reported for ginsenoside Rh2 against colon cancer cells and it inhibits the G1−S phase transition affecting the cell viability and apoptosis. Considering that triterpenoids from natural sources have been identified as inhibitors of nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB) signaling, docking studies were conducted to evaluate whether NF-κB may be a potential target. Results are consistent with the biological study and predict a similar binding mode of MA and compound 18 to the p52 subunit from NF- κB but not for OA. The fact that the binding site is shared by the NF-κB inhibitor 6,6-dimethyl-2-(phenylimino)-6,7- dihydrobenzo[d][1,3]oxathiol-4(5H)-one supports the result and points to NF-κB as a potential target of both MA and compound 18.This work was supported by a grant from Ramón Areces Foundation (Madrid, Spain) and by grant CTQ2014-55474- C2-1-R from the Spanish Ministerio de Economia y Competitividad (MINECO) co-financed by FEDER funds

Amphiphilic-like carbon dots as antitumoral drug vehicles and phototherapeutical agents

The work was financially supported by the Spanish institutions Ministerio de Ciencia, Innovacion y Universidades (PGC2018-098770-B-I00 and CTQ2017-86125-P) and Junta de Andalucia (ProgramaOperativo FEDER 2014-2020, grants B-FQM-141-UGR18, A1-FQM-341-UGR-18, C-FQM-497-UGR18).Water-insoluble carbon dots are recognized as promising materials, although their applications in nanomedicine are rarely explored, despite their lipophilic character and foreseen compatibility with biological membranes. In this article, we exploit the anhydride functionalization of carbon dots obtained by thermolysis of citric acid to synthesize amphiphilic-like carbon dots (LCDs) by reaction with alkyl amines. A differential feature of this approach is that the hydrophobicity of LCDs is a balance between the ionization of the carboxylic groups resulting from the reaction and the hydrophobicity from the grafted amines. The alkyl chains allow LCDs to entrap hydrophobic molecules and the ionization of the carboxylic groups increases the hydrosolubility, permitting the transfer between organic and aqueous phases. The biomedical interest of these features is illustrated by analyzing the application of LCDs as carriers of the drug campothecin and their evaluation on a battery of cancer cell lines, as well as the transformation of LCDs into a phototherapeutic agent by the formation of a complex with IR780 dye. Results demonstrate that LCDs behave as nanocarriers in a manner that resembles other supramolecular hosts with two differential features: (i) the length of the alkyl chains determines the size of the hosted guest, and (ii) the hydrosolubility of the complex can be modulated by pH.Ministerio de Ciencia, Innovacion y Universidades PGC2018-098770-B-I00 CTQ2017-86125-PJunta de Andalucia B-FQM-141-UGR18 A1-FQM-341-UGR-18 C-FQM-497-UGR1

Conserving Ecosystem Diversity in the Tropical Andes

Documenting temporal trends in the extent of ecosystems is essential to monitoring their status but combining this information with the degree of protection helps us assess the effectiveness of societal actions for conserving ecosystem diversity and related ecosystem services. We demonstrated indicators in the Tropical Andes using both potential (pre-industrial) and recent (~2010) distribution maps of terrestrial ecosystem types. We measured long-term ecosystem loss, representation of ecosystem types within the current protected areas, quantifying the additional representation offered by protecting Key Biodiversity Areas. Six (4.8%) ecosystem types (i.e., measured as 126 distinct vegetation macrogroups) have lost >50% in extent across four Andean countries since pre-industrial times. For ecosystem type representation within protected areas, regarding the pre-industrial extent of each type, a total of 32 types (25%) had higher representation (>30%) than the post-2020 Convention on Biological Diversity (CBD) draft target in existing protected areas. Just 5 of 95 types (5.2%) within the montane Tropical Andes hotspot are currently represented with >30% within the protected areas. Thirty-nine types (31%) within these countries could cross the 30% CBD 2030 target with the addition of Key Biodiversity Areas. This indicator is based on the Essential Biodiversity Variables (EBV) and responds directly to the needs expressed by the users of these countries