Assessment of bioelectrical phase angle as a predictor of nutritional status in patients with Crohn's disease: A cross sectional study

Background & aims: The assessment of body composition (BC) can be used to identify malnutrition in patients with Crohn's disease (CD). The aim of this study was to evaluate the nutritional status of CD patients by assessing BC, phase angle (PhA) and muscle strength. Differences in disease duration and medications were also considered. Methods: Consecutive adult CD patients aged 18–65 years were enrolled in this cross-sectional study. Disease activity was clinically defined by the Crohn's Disease Activity Index (CDAI) in the active and quiescent phases. All participants underwent anthropometry, BC and handgrip-strength (HGS) measurements; additionally, blood samples were taken. Data from CD patients were also compared with age-, sex- and BMI-matched healthy people. Results: A total of 140 CD patients with a mean age of 38.8 ± 13.9 years and a mean body weight of 64.9 ± 12 kg were recruited and compared to controls. The findings showed that all nutritional parameters, especially PhA and HGS, were lower in CD patients than in controls, and these parameters were substantially impaired as disease activity increased. Active CD patients had a lower body weight and fat mass than both the quiescent and control groups. PhA was negatively correlated with age (r = −0.362; p = 0.000) and CDAI (r = −0.135; p = 0.001) but was positively associated with fat free mass (FFM) (r = 0.443; p = 0.000) and HGS (r = 0.539; p = 0.000). Similarly, serum protein markers were lower in the active CD group than in the quiescent group (p < 0.05). Disease duration and medications did not significantly affect nutritional status. Conclusions: BIA-derived PhA is a valid indicator of nutritional status in CD patients, and its values decreased with increasing disease activity. Additionally, small alterations in BC, such as low FFM, and reduced HGS values can be considered markers of nutritional deficiency. Therefore, the assessment of BC should be recommended in clinical practice for screening and monitoring the nutritional status of CD patients

The Effects of Ceric Ammonium Nitrate in the Oxidation of 2-Benzyl-1,4-dimethoxybenzene Derivatives

The one- or two-electron reduction in quinone compounds gives rise to semiquinones and hydroquinones, respectively, which, in turn, can be oxidized back to quinones, generating a cyclic redox system with the production of reactive oxygen species (ROS). For these reasons, quinone derivatives participate in various biological processes in metabolic pathways, such as oxidative reactions and electron transport. In addition, natural quinone compounds as well as their semisynthetic and/or synthetically produced derivatives are of great pharmacological interest for the discovery and design of new drugs. As a result, their chemical reactivity as well as new methods for their synthesis are being investigated on an ongoing basis. Herein, a mild and efficient synthesis to obtain 2-(4-benzyl substituted)-1,4-dimethoxybenzene derivatives is reported. In addition, an evaluation of the effects on the quinone/diquinone ratio in the reaction product in relation to different ways of adding the oxidant CAN to the arene solution is discussed

Natural Bioactive Compounds from Marine Invertebrates That Modulate Key Targets Implicated in the Onset of Type 2 Diabetes Mellitus (T2DM) and Its Complications

Background: Type 2 diabetes mellitus (T2DM) is an ongoing, risky, and costly health problem that therefore always requires new treatment options. Moreover, although several drugs are available, only 36% of patients achieve glycaemic control, and patient adherence is a major obstacle. With monotherapy, T2DM and its comorbidities/complications often cannot be managed, and the concurrent administration of several hypoglycaemic drugs is required, which increases the risk of side effects. In fact, despite the efficacy of the drugs currently on the market, they generally come with serious side effects. Therefore, scientific research must always be active in the discovery of new therapeutic agents. Discussion: The present review highlights some of the recent discoveries regarding marine natural products that can modulate the various targets that have been identified as crucial in the establishment of T2DM disease and its complications, with a focus on the compounds isolated from marine invertebrates. The activities of these metabolites are illustrated and discussed. Objectives. The paper aims to capture the relevant evidence of the great chemical diversity of marine natural products as a key tool that can advance understanding in the T2DM research field, as well as in antidiabetic drug discovery. The variety of chemical scaffolds highlighted by the natural hits provides not only a source of chemical probes for the study of specific targets involved in the onset of T2DM, but is also a helpful tool for the development of drugs that are capable of acting via novel mechanisms. Thus, it lays the foundation for the design of multiple ligands that can overcome the drawbacks of polypharmacology

Independent associations of physical activity and cardiorespiratory fitness with metabolic risk factors in children: the European youth heart study

Udgivelsesdato: septemberAIMS/HYPOTHESIS: High levels of cardiorespiratory fitness (CRF) and physical activity (PA) are associated with a favourable metabolic risk profile. However, there has been no thorough exploration of the independent contributions of cardiorespiratory fitness and subcomponents of activity (total PA, time spent sedentary, and time spent in light, moderate and vigorous intensity PA) to metabolic risk factors in children and the relative importance of these factors. METHODS: We performed a population-based, cross-sectional study in 9- to 10- and 15- to 16-year-old boys and girls from three regions of Europe (n = 1709). We examined the independent associations of subcomponents of PA and CRF with metabolic risk factors (waist circumference, BP, fasting glucose, insulin, triacylglycerol and HDL-cholesterol levels). Clustered metabolic risk was expressed as a continuously distributed score calculated as the average of the standardised values of the six subcomponents. RESULTS: CRF (standardised beta = -0.09, 95% CI -0.12, -0.06), total PA (standardised beta = -0.08, 95% CI -0.10, -0.05) and all other subcomponents of PA were significantly associated with clustered metabolic risk. After excluding waist circumference from the summary score and further adjustment for waist circumference as a confounding factor, the magnitude of the association between CRF and clustered metabolic risk was attenuated (standardised beta = -0.05, 95% CI -0.08, -0.02), whereas the association with total PA was unchanged (standardised beta = -0.08 95% CI -0.10, -0.05). CONCLUSIONS/INTERPRETATION: PA and CRF are separately and independently associated with individual and clustered metabolic risk factors in children. The association between CRF and clustered risk is partly mediated or confounded by adiposity, whereas the association between activity and clustered risk is independent of adiposity. Our results suggest that fitness and activity affect metabolic risk through different pathways

Comparative Study of Condensed and Hydrolysable Tannins during the Early Stages of Zebrafish Development

In this study, we present data on the effects of condensed tannins (CTs) and hydrolysable tannins (HTs), polyphenols extracted from plants, at different concentrations on zebrafish development to identify the range of concentrations with toxic effects. Zebrafish embryos were exposed to CTs and HTs at two different concentration ranges (5.0–20.0 μgL−1 and 5.0–20.0 mgL−1) for 72 h. The toxicity parameters were observed up to 72 h of treatment. The uptake of CTs and HTs by the zebrafish larvae was assessed via HPLC analysis. A qRT-PCR analysis was performed to evaluate the expressions of genes cd63, zhe1, and klf4, involved in the hatching process of zebrafish. CTs and HTs at 5.0, 10.0, and 20.0 μgL−1 were not toxic. On the contrary, at 5.0, 10.0, and 20.0 mgL−1, HTs induced a delay in hatching starting from 48 h of treatment, while CTs showed a delay in hatching mainly at 48 h. The analysis of gene expression showed a downregulation in the group exposed to HTs, confirming the hatching data. We believe that this study is important for defining the optimal doses of CTs and HTs to be employed in different application fields such as the chemical industry, the animal feed industry, and medical science

Meta-analysis of four new genome scans for lipid parameters and analysis of positional candidates in positive linkage regions

Lipid levels in plasma strongly influence the risk for coronary heart disease. To localise and subsequently identify genes affecting lipid levels, we performed four genome-wide linkage scans followed by combined linkage/association analysis. Genome-scans were performed in 701 dizygotic twin pairs from four samples with data on plasma levels of HDL- and LDL-cholesterol and their major protein constituents, apolipoprotein AI (ApoAI) and Apolipoprotein B (ApoB). To maximise power, the genome scans were analysed simultaneously using a well-established meta-analysis method that was newly applied to linkage analysis. Overall LOD scores were estimated using the means of the sample-specific quantitative trait locus (QTL) effects inversely weighted by the standard errors obtained using an inverse regression method. Possible heterogeneity was accounted for with a random effects model. Suggestive linkage for HDL-C was observed on 8p23.1 and 12q21.2 and for ApoAI on 1q21.3. For LDL-C and ApoB, linkage regions frequently coincided (2p24.1, 2q32.1, 19p13.2 and 19q13.31). Six of the putative QTLs replicated previous findings. After fine mapping, three maximum LOD scores mapped within 1cM of major candidate genes, namely APOB (LOD =2.1), LDLR (LOD =1.9) and APOE (LOD =1.7). APOB haplotypes explained 27% of the QTL effect observed for LDL-C on 2p24.1 and reduced the LOD-score by 0.82. Accounting for the effect of the LDLR and APOE haplotypes did not change the LOD score close to the LDLR gene but abolished the linkage signal at the APOE gene. In conclusion, application of a new meta-analysis approach maximised the power to detect QTLs for lipid levels and improved the precision of their location estimate. © 2005 Nature Publishing Group. All rights reserved

Dual targeting of ptp1b and aldose reductase with marine drug phosphoeleganin: A promising strategy for treatment of type 2 diabetes

An in-depth study on the inhibitory mechanism on protein tyrosine phosphatase 1B (PTP1B) and aldose reductase (AR) enzymes, including analysis of the insulin signalling pathway, of phosphoeleganin, a marine-derived phosphorylated polyketide, was achieved. Phosphoeleganin was demonstrated to inhibit both enzymes, acting respectively as a pure non-competitive inhibitor of PTP1B and a mixed-type inhibitor of AR. In addition, in silico docking analyses to evaluate the interaction mode of phosphoeleganin with both enzymes were performed. Interestingly, this study showed that phosphoeleganin is the first example of a dual inhibitor polyketide extracted from a marine invertebrate, and it could be used as a versatile scaffold structure for the synthesis of new designed multiple ligands

“The crackers challenge”: A reassuring low-dose gluten challenge in adults on gluten-free diet without proper diagnosis of coeliac disease

Background: Gluten-free diet (GFD) is the one therapy in coeliac disease (CeD). Unfortunately, some patients adopt GFD before the diagnostic work-up. The guidelines suggest a 14-day gluten intake > 3 gr to get CeD diagnosis, although many subjects refuse this approach. Other evidence showed that the intake of 50 mg/day of gluten for 3 months could be useful for CeD diagnosis. Aims: We performed a dietary study, administering a low dose of gluten in form of “crackers” (about 60–120 mg of gluten/day) for 3 months, to get a final diagnosis of CeD in subjects already on GFD. Methods: We enrolled adult patients with a suspicion of CeD on self-prescribed GFD. All subjects performed the crackers challenge for 3 months. At the end, all patients were analysed for CeD serology and if positive underwent endoscopy/histology. Also, we recorded the grade of satisfaction for the gluten challenge and the onset of adverse events. Results: We enrolled 120 patients. All patients concluded the challenge without relevant adverse events. Serological positivity was detected in 54 patients (45%). Histology showed atrophy in 87% and Marsh 1–2 grade in 13% of patients. Ninety-nine patients (83%) were satisfied by this challenge. Conclusions: The “crackers challenge” is a useful and safe diagnostic approach in people on self-administered GFD

The FHP01 DDX3X helicase inhibitor exerts potent anti-tumor activity in vivo in breast cancer pre-clinical models

Inhibition of DDX3X expression or activity reduces proliferation in cells from various tumor tissues, in particular in breast cancer, and its expression often correlates to tumor aggressiveness. This makes DDX3X a prominent candidate for the design of drugs for novel personalized therapeutic strategies. Starting from an in silico drug discovery approach, a group of molecules has been selected by molecular docking at the RNA binding site of DDX3X. Here, the most promising among them, FHP01, was evaluated in breast cancer preclinical models. Specifically, FHP01 exhibited very effective antiproliferative and killing activity against different breast cancer cell types, among which those from triple-negative breast cancer (TNBC). Interestingly, FHP01 also inhibited WNT signaling, a key tumorigenic pathway already correlated to DDX3X functions in breast cancer model cell lines. Ultimately, FHP01 also caused a significant reduction, in vivo, in the growth of MDA MB 231- derived TNBC xenograft models. Importantly, FHP01 showed good bioavailability and no toxicity on normal peripheral blood mononuclear cells in vitro and on several mouse tissues in vivo. Overall, our data suggest that the use of FHP01 and its related compounds may represent a novel therapeutic approach with high potential against breast cancer, including the triple-negative subtype usually correlated to the most unfavorable outcomes because of the lack of available targeted therapies

Abdominal Adiposity Is Associated With Elevated C-Reactive Protein Independent of BMI in Healthy Nonobese People

Objective: There is debate over the most appropriate adiposity markers of obesityassociated health risks. We evaluated the relationship between fat distribution and highsensitivity C-reactive protein (hs-CRP), independent of total adiposity. Research design and methods : We studied 350 people with abdominal adiposity (waist-to-hip ratio (WHR) ≥0.9 in male and ≥0.85 in female subjects) and 199 control subjects (WHR< 0.9 in male and <0.85 in female subjects) matched for BMI and age. We measured hs-CRP and major cardiovascular risk factors. Results Participants with abdominal adiposity had BMI similar to that in control subjects (24.8 ±2.5 vs. 24.7 ±2.2 kg/m2, respectively), but significantly higher waist circumference (96.4 6.±0 vs. 83.3 ±6.7 cm; p < 0.01) and WHR (1.07 ± 0.08 vs. 0.85 ±0.05; p<0.001). Compared with the control subjects, participants with abdominal adiposity had an adverse cardiovascular risk factor profile, significantly higher hs-CRP (1.96 ±2.60 vs. 1.53 ± 1.74 mg/dl; p< 0.01), and a twofold prevalence of elevated CRP values (≥3 mg/dl). Conclusions In non obese people, moderate abdominal adiposity is associated with markers of subclinical inflammation independent of BMI