Influence of a low-carbohydrate diet on endothelial microvesicles in overweight women

Low-carbohydrate diets (LCD) are increasing in popularity, but their effect on vascular health has been questioned.Endothelial microvesicles (EMV) are membrane-derived vesicles with the potential to act as a sensitive prognostic biomarker of vascular health and endothelial function. The aim of this study was to examine the influence of a LCD on EMV and other endothelial biomarkers of protein origin. Twenty-four overweight women (age, 48.4 ± 0.6 years; height, 1.60 ± 0.07 m; body mass, 76.5 ± 9.1 kg; body mass index, 28.1 ± 2.7 kg·m−2; waist circumference, 84.1 ± 7.4 cm; mean ± standard deviation) were randomisedto either 24 weeks on their normal diet (ND) or a LCD, after which they crossed over to 24 weeks on the alternative diet.Participants were assisted in reducing carbohydrate intake, but not below 40 g·day−1. Body composition and endothelial biomarkers were assessed at the crossover point and at the end of the study. Daily carbohydrate intake (87 ± 7 versus 179 ± 11 g) and the percentage of energy derived from carbohydrate (29% versus 44%) were lower (p < 0.05) on the LCD compared to the ND, but absolute fat and saturated fat intake were unchanged. Body mass and waist circumference were 3.7 ± 0.8 kg and 3.5 ± 1.0 cmlower (p < 0.05), respectively, after the LCD compared with the ND phases. CD31+CD41−EMV, soluble (s) thrombomodulin, sE-selectin, sP-selectin, serum amyloid A and C-reactive protein were lower (p < 0.05) after the LCD compared to the ND, but serum lipids and apolipoproteins were not different. EMV along with a range of endothelial and inflammatory biomarkers are reduced by a LCD that involves modest weight loss

Effects of Feeding Bt MON810 Maize to Pigs for 110 Days on Peripheral Immune Response and Digestive Fate of the cry1Ab Gene and Truncated Bt Toxin

peer-reviewedBackground: The objective of this study was to evaluate potential long-term (110 days) and age-specific effects of feeding genetically modified Bt maize on peripheral immune response in pigs and to determine the digestive fate of the cry1Ab gene and truncated Bt toxin. Methodology/Principal Findings: Forty day old pigs (n = 40) were fed one of the following treatments: 1) isogenic maize-based diet for 110 days (isogenic); 2) Bt maize-based diet (MON810) for 110 days (Bt); 3) Isogenic maize-based diet for 30 days followed by Bt maize-based diet for 80 days (isogenic/Bt); and 4) Bt maize-based diet (MON810) for 30 days followed by isogenic maize-based diet for 80 days (Bt/isogenic). Blood samples were collected during the study for haematological analysis, measurement of cytokine and Cry1Ab-specific antibody production, immune cell phenotyping and cry1Ab gene and truncated Bt toxin detection. Pigs were sacrificed on day 110 and digesta and organ samples were taken for detection of the cry1Ab gene and the truncated Bt toxin. On day 100, lymphocyte counts were higher (P<0.05) in pigs fed Bt/isogenic than pigs fed Bt or isogenic. Erythrocyte counts on day 100 were lower in pigs fed Bt or isogenic/Bt than pigs fed Bt/isogenic (P<0.05). Neither the truncated Bt toxin nor the cry1Ab gene were detected in the organs or blood of pigs fed Bt maize. The cry1Ab gene was detected in stomach digesta and at low frequency in the ileum but not in the distal gastrointestinal tract (GIT), while the Bt toxin fragments were detected at all sites in the GIT. Conclusions/Significance: Perturbations in peripheral immune response were thought not to be age-specific and were not indicative of Th 2 type allergenic or Th 1 type inflammatory responses. There was no evidence of cry1Ab gene or Bt toxin translocation to organs or blood following long-term feeding.The research leading to these results has received funding from the European Union’s Seventh Framework Programme (FP7/2007-2013) under grant agreement n° 211820 and the Teagasc Walsh Fellowship programme

Genetic correlation between amyotrophic lateral sclerosis and schizophrenia

A. Palotie on työryhmän Schizophrenia Working Grp Psychiat jäsen.We have previously shown higher-than-expected rates of schizophrenia in relatives of patients with amyotrophic lateral sclerosis (ALS), suggesting an aetiological relationship between the diseases. Here, we investigate the genetic relationship between ALS and schizophrenia using genome-wide association study data from over 100,000 unique individuals. Using linkage disequilibrium score regression, we estimate the genetic correlation between ALS and schizophrenia to be 14.3% (7.05-21.6; P = 1 x 10(-4)) with schizophrenia polygenic risk scores explaining up to 0.12% of the variance in ALS (P = 8.4 x 10(-7)). A modest increase in comorbidity of ALS and schizophrenia is expected given these findings (odds ratio 1.08-1.26) but this would require very large studies to observe epidemiologically. We identify five potential novel ALS-associated loci using conditional false discovery rate analysis. It is likely that shared neurobiological mechanisms between these two disorders will engender novel hypotheses in future preclinical and clinical studies.Peer reviewe

Analysis of miRNAs: Biomarkers for HER2-Targeted Breast Cancer Therapy

Breast cancer remains a leading lethal cancer in women globally, with the HER2+ positive subtype associated with a higher chance of therapeutic resistance. Treatments tailored specifically to this subtype, such as targeted therapies, have significantly developed over the past decade. However, the issue of drug resistance to targeted drugs underlines the necessity of better treatment approaches. Recent studies have focused on microRNAs (miRNAs), single-stranded non-coding RNAs, as critical regulators in drug resistance mechanisms. These miRNAs, capable of influencing various cellular processes, have emerged as critical modulators in numerous diseases, including different cancer types, particularly breast cancer. This article reviews current methodologies in the study of miRNAs within the context of HER2-positive breast cancer, from the selection of study models and sample extraction to comprehensive analysis methods. Our objective is to highlight the potential that miRNAs hold as biomarkers capable of regulating drug resistance in this specific cancer subtype. Moreover, we also discuss the importance of integrating advanced study models alongside the latest bioinformatics tools to enrich this research domain. Furthermore, this article evaluates the use of clinical samples and cell line models for studying miRNAs in this field, outlining the advantages and limitations of each method and proposing a refined approach to research design. The main contribution of this work is the establishment of a detailed taxonomy of research strategies that address current challenges while also outlining promising future directions, particularly focused on elucidating the regulatory mechanisms of miRNAs in therapeutic resistance in breast cancer. In addition, by underscoring the necessity of employing a diverse array of study models and capitalizing on bioinformatics advancements, this article seeks to uncover the complex interactions between miRNAs and drug resistance mechanisms in breast cancer. Ultimately, our goal is to pave the way toward overcoming therapeutic resistance, thereby improving the prognosis for patients afflicted with HER2-positive breast cancer

Distinct microbiome composition and metabolome exists across subgroups of elite Irish athletes

peer-reviewedObjectives: The gut microbiome has begun to be characterised in athlete groups, albeit, to date, only across a subset of sports. This study aimed to determine if the gut microbiome and metabolome differed across sports classification groups (SCGs) among elite Irish athletes, many of whom were participating in the 2016 Summer Olympics. Methods: Faecal and urine samples were collected from 37 international level athletes. Faecal samples were prepared for shotgun metagenomic sequencing and faecal and urine samples underwent metabolomic profiling. Results: Differences were observed in the composition and functional capacity of the gut microbiome of athletes across SCGs. The microbiomes of athletes participating in sports with a high dynamic component were the most distinct compositionally (greater differences in proportions of species), while those of athletes participating in sports with high dynamic and static components were the most functionally distinct (greater differences in functional potential). Additionally, both microbial (faecal) and human (urine) derived metabolites were found to vary between SCGs. In particular cis-aconitate, succinic acid and lactate, in urine samples, and creatinine, in faeces, were found to be significantly different between groups. These differences were evident despite the absence of significant differences in diet, as determined using food frequency questionnaires, which were translated into nutrient intake values using FETA. Conclusions: Differences in the gut microbiome and metabolome between groups, in the absence of dietary changes, indicates a role for training load or type as a contributory factor. Further exploration of this hypothesis has the potential to benefit athletes, aspiring athletes and the general public

Dexamethasone-Loaded Nanostructured Lipid Carriers for the Treatment of Dry Eye Disease

Dry eye disease (DED) or keratoconjunctivitis sicca is a chronic multifactorial disorder of the ocular surface caused by tear film dysfunction. Symptoms include dryness, irritation, discomfort and visual disturbance, and standard treatment includes the use of lubricants and topical steroids. Secondary inflammation plays a prominent role in the development and propagation of this debilitating condition. To address this we have investigated the pilot scale development of an innovative drug delivery system using a dexamethasone-encapsulated cholesterol-Labrafac™ lipophile nanostructured lipid carrier (NLC)-based ophthalmic formulation, which could be developed as an eye drop to treat DED and any associated acute exacerbations. After rapid screening of a range of laboratory scale pre-formulations, the chosen formulation was prepared at pilot scale with a particle size of 19.51 ± 0.5 nm, an encapsulation efficiency of 99.6 ± 0.5%, a PDI of 0.08, and an extended stability of 6 months at 4 °C. This potential ophthalmic formulation was observed to have high tolerability and internalization capacity for human corneal epithelial cells, with similar behavior demonstrated on ex vivo porcine cornea studies, suggesting suitable distribution on the ocular surface. Further, ELISA was used to study the impact of the pilot scale formulation on a range of inflammatory biomarkers. The most successful dexamethasone-loaded NLC showed a 5-fold reduction of TNF-α production over dexamethasone solution alone, with comparable results for MMP-9 and IL-6. The ease of formulation, scalability, performance and biomarker assays suggest that this NLC formulation could be a viable option for the topical treatment of DED

Assessment of the antioxidant and antibacterial activities of different olive processing wastewaters

<div><p>Olive processing wastewaters (OPW), namely olive mill wastewater (OMW) and table-olive wastewaters (TOW) were evaluated for their antibacterial activity against five Gram-positive and two Gram-negative bacteria using the standard disc diffusion and thin layer chromatography (TLC)-bioautography assays. Disc diffusion screening and bioautography of OMW were compared to the phenolic extracts of table-olive brines. Positive activity against <i>S</i>. <i>aureus</i> was demonstrated. The optimization of chromatographic separation revealed that hexane/acetone in the ratio of 4:6 was the most effective for phenolic compounds separation. A HPLC-MS analysis was performed showing that only two compounds, hydroxytyrosol and tyrosol, were the predominant phenolic compounds in all OPW. The phenolic extract of OMW generated by a semi-modern process showed the highest free radical-scavenging activity (DPPH assay) compared to the other phenolic extracts. It is apparent from the present study that OPW are a rich source of antioxidants suitable for use in food, cosmetic or pharmaceutical applications.</p></div

Effect of concentration of OMW and TOW phenolic extracts on their antibacterial activity against <i>S</i>. <i>aureus</i> using the disc diffusion assay.

<p>Effect of concentration of OMW and TOW phenolic extracts on their antibacterial activity against <i>S</i>. <i>aureus</i> using the disc diffusion assay.</p