Facile, fast and green synthesis of a highly porous calcium-syringate bioMOF with intriguing triple bioactivity

A facile, fast and green strategy based on ethanol is utilized to prepare a new bioMOF, namely, CaSyr-1, with particular characteristics of full biocompatibility given by using just calcium and syringic acid, the latter being a phenolic natural product found in fruits and vegetables, permanent porosity with an outstanding surface area >1000 m2 g−1, and a micropore diameter of 1.4 nm close to mesopore values. Collectively, these data establish CaSyr-1 as one of the most porous bioMOFs reported to date, with high molecular adsorption capacity. The CaSyr-1 adsorptive behavior is revised here through the reversible adsorption of CO2 and the encapsulation of bioactive ingredients in the structure. Remarkably, CaSyr-1 enables the development of triple therapeutic entities, involving bioactive Ca2+, syringic acid and an impregnated drug

Biomimetic gradient scaffolds containing hyaluronic acid and sr/zn folates for osteochondral tissue engineering

Regenerative therapies based on tissue engineering are becoming the most promising alternative for the treatment of osteoarthritis and rheumatoid arthritis. However, regeneration of full-thickness articular osteochondral defects that reproduces the complexity of native cartilage and osteochondral interface still remains challenging. Hence, in this work, we present the fabrication, physic-chemical characterization, and in vitro and in vivo evaluation of biomimetic hierarchical scaffolds that mimic both the spatial organization and composition of cartilage and the osteochondral interface. The scaffold is composed of a composite porous support obtained by cryopolymerization of poly(ethylene glycol) dimethacrylate (PEGDMA) in the presence of biodegradable poly(D,L-lactide-co-glycolide) (PLGA), bioactive tricalcium phosphate β-TCP and the bone promoting strontium folate (SrFO), with a gradient biomimetic photo-polymerized methacrylated hyaluronic acid (HAMA) based hydrogel containing the bioactive zinc folic acid derivative (ZnFO). Microscopical analysis of hierarchical scaffolds showed an open interconnected porous open microstructure and the in vitro behaviour results indicated high swelling capacity with a sustained degradation rate. In vitro release studies during 3 weeks indicated the sustained leaching of bioactive compounds, i.e., Sr, Zn and folic acid, within a biologically active range without negative effects on human osteoblast cells (hOBs) and human articular cartilage cells (hACs) cultures. In vitro co-cultures of hOBs and hACs revealed guided cell colonization and proliferation according to the matrix microstructure and composition. In vivo rabbit-condyle experiments in a critical-sized defect model showed the ability of the biomimetic scaffold to promote the regeneration of cartilage-like tissue over the scaffold and neoformation of osteochondral tissue.This research was funded by Spanish MICINN (MAT201573656-JIN), AEI-MICINN (PID2020- 114086RB-100) and CAM (IND2018/BMD-9485

NADPH oxidase 1 as a new regulator of the WNT pathway and the protective effect of vitamin D in colorectal cancer

Trabajo presentado en el 43rd Annual Meeting of the SEBBM, celebrado en Barcelona (España) del 19 al 22 de julio de 2021.Worldwide, colorectal cancer (CRC) is the third most common malignant neoplasm and the second leading cause of cancer-associated mortality, with an estimated increase in global prevalence of 60% by 2030 (1,2). Mutational inactivation of adenomatous polyposis coli (APC) is the hallmark of CRC and leads to an overactivation of WNT signaling that favors the development and progression of CRC (3). Large epidemiological studies suggest that the diabetic population is at increased risk for site-specific cancers, including CRC (4). Our laboratory has shown that hyperglycemia induces the accumulation of ROS in CRC but not healthy cells, driving the activation of a newly described ROS/AMPK/EP300 axis that enhances Wnt/b-catenin signaling. Increased EP300 leads to increased acetylation of β-catenin at K354, a requirement for nuclear accumulation and transcriptional activation of WNT target genes (5,6). The critical role driven by ROS suggest a possible involvement of the NADPH oxidases (NOX family, as a source of ROS. Specifically, NOX 1 and NOX 4 are expressed in colon epithelial cells, and their overexpression in CRC cells promotes cell proliferation and invasiveness (7,8,9,10). Our results indicate that hyperglycemia significantly increases NOX1 levels, in correlation with increased ROS production in CRC cells, suggesting a possible regulation of the ROS/ AMPK/EP300 axis by NOX1. Antioxidant mechanisms dealing with NOX1-induced ROS should be effective against CRC. Vitamin D (1α, 25-dihydroxyvitamin D3) is a powerful antioxidant that inhibits proliferation and promotes differentiation of CRC cells at least partially through inhibition of Wnt/β-catenin signalling. Consequently, vitamin D deficiency is associated with poor survival to CRC (11,12). Our results indicate that vitamin D causes a reduction in the levels and / or activity of some members of the NOX family by turning off the ROS/AMPK/EP300/β-catenin axis and its proliferative and tumorigenic effects. The data suggest a new antitumor mechanism of vitamin D linked to its anti-oxidant action. Our results integrate independent epidemiological links between vitamin D deficiency, diabetes and cancer in one overarching and unifying mechanism

Aedes aegypti mosquitoes at nonresidential sites might be related to transmission of dengue virus in Monterrey, Northeastern Mexico

has been assumed to be households. In Mexico, dengue outbreaks continue year after year despite intense control efforts. Nonresidential sites (public and private spaces) infested with Aedes aegypti (L.) were evaluated. In total, 141 nonresidential sites were sampled for the presence of potential and active oviposition sites and adult mosquitoes. Eighty percent of the sites were oviposition sites; Ae. aegypti adults were recovered at 94.7% of nonresidential sites. Most female Ae. aegypti, 21.6 and 10.4, were at schools and recreational sites, respectively. Chi-squared indicated no significant differences in the dengue vector to categories of sample site

HER2-signaling pathway, JNK and ERKs kinases, and cancer stem-like cells are targets of Bozepinib

Identification of novel anticancer drugs presenting more than one molecular target and efficacy against cancer stem-like cells (CSCs) subpopulations represents a therapeutic need to combat the resistance and the high risk of relapse in patients. In the present work we show how Bozepinib [(RS)-2,6-dichloro-9-[1-(p-nitrobenzenesulfonyl)-1,2,3,5-tetrahydro-4,1-benzoxazepin-3-yl]-9H-purine], a small anti-tumor compound, demonstrated selectivity on cancer cells and showed an inhibitory effect over kinases involved in carcinogenesis, proliferation and angiogenesis. The cytotoxic effects of Bozepinib were observed in both breast and colon cancer cells expressing different receptor patterns. Bozepinib inhibited HER-2 signaling pathway and JNK and ERKs kinases. In addition, Bozepinib has an inhibitory effect on AKT and VEGF together with anti-angiogenic and anti-migratory activities. Moreover, the modulation of pathways involved in tumorigenesis by Bozepinib was also evident in microarrays analysis. Interestingly, Bozepinib inhibited both mamo- and colono-spheres formation and eliminated ALDH+ CSCs subpopulations at a low micromolar range similar to Salinomycin. Bozepinib induced the down-regulation of c-MYC, β-CATENIN and SOX2 proteins and the up-regulation of the GLI-3 hedgehog-signaling repressor. Finally, Bozepinib shows in vivo anti-tumor and anti-metastatic efficacy in xenotransplanted nude mice without presenting sub-acute toxicity. These findings support further studies on the therapeutic potential of Bozepinib in cancer patients.This work was supported in part by grants from the Instituto de Salud Carlos III (Fondo de Investigación Sanitaria, projects nº. PI10/02295, CP08/00063 and PI10/00592) and the ERDF (European Regional Development Fund)

Describing Complexity in Palliative Home Care Through HexCom : A Cross-Sectional, Multicenter Study

Complexity has become a core issue in caring for patients with advanced disease and/or at the end-of-life. The Hexagon of Complexity (HexCom) is a complexity assessment model in the process of validation in health-care settings. Our objective is to use the instrument to describe differences in complexity across disease groups in specific home care for advanced disease and/or at the end-of-life patients, both in general and as relates to each domain and subdomain. Cross-sectional study of home care was conducted in Catalonia. The instrument includes 6 domains of needs (clinical, psychological/emotional, social/family, spiritual, ethical, and death-related), 4 domains of resources (intrapersonal, interpersonal, transpersonal, and practical), and 3 levels of complexity (High (H), Moderate (M), and Low (L)). Interdisciplinary home care teams assessed and agreed on the level of complexity for each patient. Forty-three teams participated (74.1% of those invited). A total of 832 patients were assessed, 61.4% of which were cancer patients. Moderate complexity was observed in 385 (47.0%) cases and high complexity in 347 (42.4%). The median complexity score was 51 for cancer patients and 23 for patients with dementia (p<0.001). We observed the highest level of complexity in the social/family domain. Patients/families most frequently used interpersonal resources (80.5%). This study sheds light on the high-intensity work of support teams, the importance of the social/family domain and planning the place of death, substantial differences in needs and resources across disease groups, and the importance of relationship wellbeing at the end-of-life

Metabolic syndrome, adiposity, diet, and emotional eating are associated with oxidative stress in adolescents

Background: Metabolic syndrome (MS), a condition related to adiposity and oxidative stress, can develop in adolescence, a critical stage in life that impacts health in adulthood. However, there is scarce scientific research about the relationship between lifestyle factors, emotion management, and oxidative stress in this phase of life.Aim: To analyze whether nutritional parameters, lifestyle factors, emotion management, and MS in adolescents are associated with oxidative stress measured by the biomarker 8-isoprostane.Methods: A cross-sectional study was carried out in 132 adolescents (48.5% girls, aged 12 ± 0.48 years) and data were collected on nutritional parameters (anthropometric measurements, biochemical analyzes, and blood pressure), lifestyle factors (physical activity, sleep, and diet), and emotion management (self-esteem, emotional eating, and mood). 8-isoprostane was analyzed in spot urine samples. The study population was categorized in three groups (healthy, at-risk, and with MS) using the International Diabetes Federation definition of MS in adolescents. To capture more complex interactions, a multiple linear regression was used to analyze the association between 8-isoprostane and the aforementioned variables.Results: Urinary 8-isoprostane levels were significantly higher in the MS group compared to the healthy group (1,280 ± 543 pg./mg vs. 950 ± 416 pg./mg respectively). In addition, univariable analysis revealed positive significant associations between 8-isoprostane and body mass index, waist circumference, waist-to-height ratio, body fat percentage, blood lipid profile and glucose, emotional eating, and refined cereal intake. Conversely, a negative significant association was found between 8-isoprostane and sleep duration and fish intake. The multiple linear regression analysis revealed associations between 8-isoprostane and LDL-c (β = 0.173 value of p = 0.049), emotional eating (low β = 0.443, value of p = 0.036; high β = 0.152, value of p = 0.470), refined cereal intake (β =0.191, value of p = 0.024), and fish intake (β = -0.187, value of p = 0.050).Conclusion: The MS group, LDL-c, emotional eating, and high refined cereals and low fish intakes were associated with higher levels of oxidative stress in an adolescent population.</p

Total urinary polyphenols and ideal cardiovascular health metrics in Spanish adolescents enrolled in the SI Program: a cross-sectional study.

To study the relationship between urinary total polyphenol excretion (TPE) in adolescents and ideal cardiovascular (CVH) metrics. 1151 adolescents aged 12.04 (0.46) years participating in the SI! Program for Secondary Schools were selected based on the availability of urine samples and information required to assess CVH metrics. Data on health behaviours (smoking status, body mass index, physical activity, and healthy diet) and health factors (blood pressure, total cholesterol, and blood glucose) were used to calculate the CVH metrics. TPE in urine was analysed by a Folin-Ciocalteu method after solid-phase extraction. Associations between TPE (categorized into tertiles) and CVH metrics (total and separate scores) were assessed using multilevel mixed-effect regression models. Higher TPE levels were associated with higher (healthier) CVH scores and ideal smoking status (OR 1.54, 95% CI 1.10; 1.87, p value = 0.007), physical activity (OR 1.12, 95% CI 1.02; 1.23, p value = 0.022) and total cholesterol (OR 1.78, 95% CI 1.16; 2.73, p value = 0.009) after multivariate adjustment. An association between TPE and total CVH scores was observed only in boys. Girls with higher TPE had higher rates of ideal total cholesterol and blood pressure. According to our findings, higher urinary TPE is related to better CVH scores, with relevant differences in this association by gender.The authors wish to thank all the volunteers and their families, teachers, and schools for their contribution to the SI! Program for Secondary Schools. The SI! Program for Secondary Schools trial was supported by the SHE Foundation, the “la Caixa” Foundation (grant numbers LCF/PR/CE16//10700001 and LCF/PR/MS19/12220001), and the Fundació la Marató de TV3 (grant number 369/C/2016). Support was also provided by the Ministerio de Ciencia, Innovación y Universidades (grant number AGL2016–75329-R), and Generalitat de Catalunya. Rodrigo Fernández-Jiménez is a recipient of grant PI19/01704 funded by the Fondo de Investigación Sanitaria- Instituto de Salud Carlos III (ISCIII) and co-funded by the European Regional Development Fund/European Social Fund "A way to make Europe"/"Investi ng in your future". The Centro Nacional de Investigaciones Cardiovasculares is supported by the ISCIII, the Ministerio de Ciencia e Innovación, and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (CEX2020-001041-S). Anna Tresserra-Rimbau was supported by a Serra Húnter Fellowship. Emily P. Laveriano-Santos is thankful for the FI-SDUR (EMC/3345/2020) fellowship from the Generalitat de Catalunya. Isabella Parilli-Moser thanks the FI-SDUR (EMC/2703/2019) fellowship.S

Polyphenols in Urine and Cardiovascular Risk Factors: A Cross-Sectional Analysis Reveals Gender Differences in Spanish Adolescents from the SI! Program

Abstract: (1) Background: Epidemiological studies have shown an inverse association between polyphenol intake and cardiovascular risk factors (CVRFs) in adults, but few have provided information about adolescents. The aim of this study was to evaluate the relationship between urinary total polyphenol excretion (TPE) and CVRFs in adolescents. (2) Methods: A cross-sectional study was performed in 1194 Spanish adolescents from the SI! (Salud Integral) program. TPE in urine samples was determined by the Folin-Ciocalteu method, after solid-phase extraction, and categorized into quartiles. The association between TPE and CVRFs was estimated using mixed-effect linear regression and a structural equation model (SEM). (3) Results: Linear regression showed negative associations among the highest quartile of TPE and body fat percentage (B = −1.75, p-value = <0.001), triglycerides (TG) (B = −17.68, p-value = <0.001), total cholesterol (TC) (B = −8.66, p-value = 0.002), and low-density lipoprotein (LDL)-cholesterol (LDL-C) (B = −4.09, p-value = 0.008) in boys, after adjusting for all confounder variables. Negative associations between TPE quartiles and systolic blood pressure (SBP), diastolic blood pressure (DBP), and TC were also found in girls. Moreover, a structural equation model revealed that TPE was directly associated with body composition and blood glucose and indirectly associated with blood pressure, TG, LDL-C, and high-density lipoprotein-cholesterol (HDL-C) in boys. Conclusions: Higher concentrations of TPE were associated with a better profile of cardiovascular health, especially in boys, while in girls, the association was not as strong. Keywords: antioxidants; pediatric; body composition; cardiovascular; lipid profile; Folin-Ciocalte

Gender and observed complexity in palliative home care : A prospective multicentre study using the hexcom model

This study analyses gender differences in the complexity observed in palliative home care through a multicentre longitudinal observational study of patients with advanced disease treated by palliative home care teams in Catalonia (Spain). We used the HexCom model, which includes six dimensions and measures three levels of complexity: high (non-modifiable situation), medium (difficult) and low. Results: N = 1677 people, 44% women. In contrast with men, in women, cancer was less prevalent (64.4% vs. 73.9%) (p < 0.001), cognitive impairment was more prevalent (34.1% vs. 26.6%; p = 0.001) and professional caregivers were much more common (40.3% vs. 24.3%; p < 0.001). Women over 80 showed less complexity in the following subareas: symptom management (41.7% vs. 51,1%; p = 0.011), emotional distress (24.5% vs. 32.8%; p = 0.015), spiritual distress (16.4% vs. 26.4%; p = 0.001), socio-familial distress (62.7% vs. 70.1%; p = 0.036) and location of death (36.0% vs. 49.6%; p < 0.000). Men were more complex in the subareas of "practice" OR = 1.544 (1.25-1.90 p = 0.000) and "transcendence" OR = 1.52 (1.16-1.98 p = 0.002). Observed complexity is related to male gender in people over 80 years of age. Women over the age of 80 are remarkably different from their male counterparts, showing less complexity regarding care for their physical, psycho-emotional, spiritual and socio-familial needs