Dynamic Control of the Self-Assembling Properties of Cyclodextrins by the Interplay of Aromatic and Host-Guest Interactions

The presence of a doubly-linked naphthylene clip at the O-2I and O-3II positions in the secondary ring of β-cyclodextrin (βCD) derivatives promoted their self-assembly into head-to-head supramolecular dimers in which the aromatic modules act either as cavity extension walls (if the naphthalene moiety is 1,8-disubstituted) or as folding screens that separate the individual βCD units (if 2,3-disubstituted). Dimer architecture is governed by the conformational properties of the monomer constituents, as determined by NMR, fluorescence, circular dichroism, and computational techniques. In a second supramolecular organization level, the topology of the assembly directs host-guest interactions and, reciprocally, guest inclusion impacts the stability of the supramolecular edifice. Thus, inclusion of adamantane carboxylate, a well-known βCD cavity-fitting guest, was found to either preserve the dimeric arrangement, leading to multicomponent species, or elicit dimer disruption. The ensemble of results highlights the potential of the approach to program self-organization and external stimuli responsiveness of CD devices in a controlled manner while keeping full diastereomeric purity.Spanish Ministerio de Economía y Competitividad CTQ2015-64425-C2-1-R, CTQ2016-80600-P and SAF2016- 76083-RJunta de Andalucía contract number FQM2012-1467UAH CCGP2017-EXP/02

Pasaporte a la profesión en el Grado de Farmacia

La incorporació del sistema universitari espanyol al Espai Europeu d’Educació Superior (EEES) ha implicat una sèrie d’adaptacions dels graus. Entre aquests s’ha de destacar un període de pràctiques externes a la pròpia universitat, lo que ha comportar una sèrie de canvis considerables en els plans d’estudis de manera que s’aconsegueixi un balanç més equilibrat entre la formació teòrica i pràctica rebuda pels estudiants. Aquest nou marc de treball ha estat confirmat legalment pel Govern espanyol (Real Decreto 1393/2007, de 20 d’octubre i Real Decreto 1707/2011 de 18 de novembre) i en el cas de la Universitat de Barcelona amb la publicació d’una normativa de pràctiques (Normativa de pràctiques acadèmiques externes dels estudiants de la Universitat de Barcelona). Aprofitant aquesta oportunitat per adaptar el Grau de Farmàcia a la realitat social actual, l’equip deganal de la Facultat de Farmàcia amb el recolzament del personal administratiu i el Servei d’atenció a l’estudiant, va assumir el repte d’incloure una nova assignatura en el pla docent del Grau de Farmàcia, que es va denominar “Pràctiques en empreses”. En paral·lel a la posta en marxa d’aquesta assignatura, es va iniciar una nova activitat per assegurar que els estudiants escollirien adequadament la companyia/departament/lloc de treball i donar-los les nocions bàsiques per poder afrontar amb les millors garanties d’èxit l’entrevista laboral. Sota el nom “Passaport a la professió”, s’han programat una sèrie de deu sessions per cada any acadèmic. Aquestes sessions inclouen temes d’una amplia varietat per proveir als estudiants amb les eines bàsiques per aprofitar al màxim el període de practiques i afrontar amb èxit el seu futur professional quan acabin els estudis de grau. A més, s’han celebrat tres workshops i dos taules rodones per apropar el mon de l’empresa a la universitat. S’ha de destacar que el projecte s’ha ampliat a nivell internacional, ja que una empresa farmacèutica amb seu en el Regne Unit cada any contracta a dos o tres estudiants de grau durant un any. Les dades estadístiques obtingudes en el procés s’han analitzat per tenir una millor comprensió de l’activitat i poder millorar el programa

Trifaceted Mickey Mouse Amphiphiles for Programmable Self-Assembly, DNA Complexation and Organ-Selective Gene Delivery

Instilling segregated cationic and lipophilic domains with an angular disposition in a trehalose-based trifaceted macrocyclic scaffold allows engineering patchy molecular nanoparticles leveraging directional interactions that emulate those controlling self-assembling processes in viral capsids. The resulting trilobular amphiphilic derivatives, featuring a Mickey Mouse architecture, can electrostatically interact with plasmid DNA (pDNA) and further engage in hydrophobic contacts to promote condensation into transfectious nanocomplexes. Notably, the topology and internal structure of the cyclooligosaccharide/pDNA co-assemblies can be molded by fine-tuning the valency and characteristics of the cationic and lipophilic patches, which strongly impacts the transfection efficacy in vitro and in vivo. Outstanding organ selectivities can then be programmed with no need of incorporating a biorecognizable motif in the formulation. The results provide a versatile strategy for the construction of fully synthetic and perfectly monodisperse nonviral gene delivery systems uniquely suited for optimization schemes by making cyclooligosaccharide patchiness the focus.Ministerio de Ciencia, Innovación y Universidades y Agencia Estatal de Investigación de España. RTI2018-097609-B-C21, RTI2018-097609-B-C22 y PID2019-105858RB-I00Universidad de Alcalá de Henares, Madrid. CCG19/CC-03

Clinical Management of COVID-19 in Cancer Patients with the STAT3 Inhibitor Silibinin

COVID-19 pathophysiology is caused by a cascade of respiratory and multiorgan failures arising, at least in part, from the SARS-CoV-2-driven dysregulation of the master transcriptional factor STAT3. Pharmacological correction of STAT3 over-stimulation, which is at the root of acute respiratory distress syndrome (ARDS) and coagulopathy/thrombosis events, should be considered for treatment of severe COVID-19. In this perspective, we first review the current body of knowledge on the role of STAT3 in the pathogenesis of severe COVID-19. We then exemplify the potential clinical value of treating COVID-19 disease with STAT3 inhibitors by presenting the outcomes of two hospitalized patients with active cancer and COVID-19 receiving oral Legalon(R)-a nutraceutical containing the naturally occurring STAT3 inhibitor silibinin. Both patients, which were recruited to the clinical trial SIL-COVID19 (EudraCT number: 2020-001794-77) had SARS-CoV-2 bilateral interstitial pneumonia and a high COVID-GRAM score, and showed systemic proinflammatory responses in terms of lymphocytopenia and hypoalbuminemia. Both patients were predicted to be at high risk of critical COVID-19 illness in terms of intensive care unit admission, invasive ventilation, or death. In addition to physician's choice of best available therapy or supportive care, patients received 1050 mg/day Legalon(R) for 10 days without side-effects. Silibinin-treated cancer/COVID-19+ patients required only minimal oxygen support (2-4 L/min) during the episode, exhibited a sharp decline of the STAT3-regulated C-reactive protein, and demonstrated complete resolution of the pulmonary lesions. These findings might inspire future research to advance our knowledge and improve silibinin-based clinical interventions aimed to target STAT3-driven COVID-19 pathophysiology

Incidence and Survival Trends of Pancreatic Cancer in Girona: Impact of the Change in Patient Care in the Last 25 Years.

(1) Background: We investigated the incidence and survival trends for pancreatic cancer (PC) over the last 25 years in the Girona region, Catalonia, Spain; (2) Methods: Data were extracted from the population-based Girona Cancer Registry. Incident PC cases during 1994-2015 were classified using the International Classification of Diseases for Oncology Third Edition (ICD-O-3). Incidence rates age-adjusted to the European standard population (ASRE) and world standard population (ASRW) were obtained. Trends were assessed using the estimated annual percentage of change (EAPC) of the ASRE13. Observed and relative survivals (RS) were estimated with the Kaplan-Meier and Pohar Perme methods, respectively; (3) Results: We identified 1602 PC incident cases. According to histology, 44.4% of cases were exocrine PC, 4.1% neuroendocrine, and 51.1% malignant-non-specified. The crude incidence rate (CR) for PC was 11.43 cases-per-100,000 inhabitants/year. A significant increase of incidence with age and over the study period was observed. PC overall 5-year RS was 7.05% (95% confidence interval (CI) 5.63; 8.84). Longer overall survival was observed in patients with neuroendocrine tumours (5-year RS 61.45%; 95% CI 47.47; 79.55). Trends in 5-year RS for the whole cohort rose from 3.27% (95% CI 1.69-6.35) in 1994-1998 to 13.1% (95% CI 9.98; 17.2) in 2010-2015; (4) Conclusions: Incidence rates of PC in Girona have increased in the last two decades. There is a moderate but encouraging increase in survival thorough the study period. These results can be used as baseline for future research.S

Hormonal study in patients with prostate cancer with PSA at diagnosis between 4-10 ng/ml and PSA free/total <20%

Objetivo: El objetivo de este estudio es analizar los parámetros hormonales en pacientes con adenocarcinoma de próstata con PSA entre 4-10 ng/ml (cociente libre/total <20%) en el momento del diagnóstico. Material y Métodos: Desde enero a diciembre de 2014, se incluyen en este estudio hombres con PSA entre 4-10 ng/ ml y cociente libre/total <20%, candidatos a biopsia de próstata. Se excluyen del estudio pacientes que estén tomando inhibidores de la 5 alfa-reductasa y pacientes con biopsias de próstata previamente realizadas. Se analiza edad, PSA total, testosterona total, libre y biodisponible, FSH, LH, SHBG, 17-hidroxiprogesterona, Androstendiona, volumen prostático (medido por ecografía transrectal), cocientes testosterona total/PSA, testosterona libre/PSA, testosterona biodisponible/PSA y Densidad de PSA, testosterona total/volumen próstata, testosterona libre/volumen próstata y testosterona biodisponible/volumen próstata. Análisis estadístico con SPSS 20.0 y significación estadística p≤0.05. Resultados: Un total de 109 pacientes han sido incluídos, sólo el 44.9% de los mismos presenta adenocarcinoma de próstata en la biopsia, incluyéndose en este estudio. Destaca un volumen prostático de 37.6 cc, una densidad PSA de 0.24, unos niveles de testosterona total de 4.51 ng/ml, de testosterona libre de 0.076 ng/ml y de testosterona biodisponible de 1.94 ng/ml. Además es destacable un cociente testosterona total/volumen próstata de 0.15, testosterona libre/volumen próstata de 0.002 y testosterona biodisponible/volumen próstata de 0.06. Existe relación lineal positiva y significativa entre niveles de PSA y grado de Gleason y entre SHBG y grado de Gleason. Además se observa relación lineal negativa y significativa entre el volumen de próstata y el ratio testosterona/PSA. Conclusión: Los niveles de PSA y SHBG se asocian con un mayor gleason de la biopsia y por tanto con un mayor riesgo histológico.Objective: The aim of this study is to analyze the hormonal parameters in patients with prostate adenocarcinoma with PSA between 4-10 ng / ml (free / total ratio <20%) at the time of diagnosis. Material and Methods: From January to December 2014 were included in this study men with PSA between 4-10 ng / ml and free / total <20%, candidates for prostate biopsy ratio. Excluded from the study patients taking inhibitors of 5 alpha-reductase and patients with prostate biopsies previously made. Parameters analyzed: Age, total PSA, total, free and bioavailable testosterone, FSH, LH, SHBG, 17-hydroxyprogesterone, Androstenedione, prostate volume (measured by transrectal ultrasound), ratios total testosterone/PSA, free testosterone/PSA, bioavailable testosterone/PSA and PSA density, total testosterone/prostate volume, free testosterone/prostate volume and bioavailable testosterone/prostate volume. Statistical analysis with SPSS 20.0 and statistical significance p≤0.05. Results: A total of 109 patients were included, only 44.9% of them presented prostate adenocarcinoma on biopsy, including in this study. A prostate volume of 37.6 cc with a PSA density of 0.24, total testosterone levels of 4.51 ng/ml, free testosterone 0.076 ng/ml and bioavailable testosterone 1.94 ng/ml. It is also remarkable ratio total testosterone/prostate volume of 0.15, free testosterone/prostate volume of 0.002 and bioavailable testosterone/prostate volume of 0.06. There is a significant linear relationship between PSA and Gleason score and between SHBG and Gleason score. Besides significant negative linear relationship between volume and prostate testosterone/PSA ratio was observed. Conclusion: PSA levels and SHBG levels are associated with a higher Gleason biopsy and therefore with greater histological risk

Autobeca

Projecte presentat al 3r Premi a la Qualitat de la Gestió Universitària, convocat pel Consell Social de la UPCAward-winnin

Markers of endothelial damage in patients with chronic kidney disease on hemodialysis

Patients with Stage 5 chronic kidney disease who are on hemodialysis (HD) remain in a chronic inflammatory state, characterized by the accumulation of uremic toxins that induce endothelial damage and cardiovascular disease (CVD). Our aim was to examine microvesicles (MVs), monocyte subpopulations, and angiopoietins (Ang) to identify prognostic markers in HD patients with or without diabetes mellitus (DM). A total of 160 prevalent HD patients from 10 centers across Spain were obtained from the Biobank of the Nephrology Renal Network (Madrid, Spain): 80 patients with DM and 80 patients without DM who were matched for clinical and demographic criteria. MVs from plasma and several monocyte subpopulations (CD142+/CD16+, CD14+/CD162+) were analyzed by flow cytometry, and the plasma concentrations of Ang1 and Ang2 were quantified by ELISA. Data on CVD were gathered over the 5.5 yr after these samples were obtained. MV level, monocyte subpopulations (CD14+/CD162+ and CD142+/CD16+), and Ang2-to-Ang1 ratios increased in HD patients with DM compared with non-DM patients. Moreover, MV level above the median (264 MVs/µl) was associated independently with greater mortality. MVs, monocyte subpopulations, and Ang2-to-Ang1 ratio can be used as predictors for CVD. In addition, MV level has a potential predictive value in the prevention of CVD in HD patients. These parameters undergo more extensive changes in patients with DM.Support for this work was provided by Plan Nacional de IDi Proyectos de Investigación en Salud of Instituto de Salud Carlos III (ISCIII)–Subdirección General de Evaluación, Fondos de desarrollo regional (FEDER; PI11/01536, PI12/01489, PI14/00806, PI15/01785); Junta de Andalucía grants (P010-CTS-6337, P11-CTS-7352); and Fundación Nefrológica. P. Buendía, A. Carmona, and C. Luna-Ruiz are fellows from Consejería de Innovacion, Ciencia y Empresa, Junta de Andalucía