Search results for " effects"
showing 10 items of 2364 documents
Use of deep learning methods to translate drug-induced gene expression changes from rat to human primary hepatocytes
2020
In clinical trials, animal and cell line models are often used to evaluate the potential toxic effects of a novel compound or candidate drug before progressing to human trials. However, relating the results of animal and in vitro model exposures to relevant clinical outcomes in the human in vivo system still proves challenging, relying on often putative orthologs. In recent years, multiple studies have demonstrated that the repeated dose rodent bioassay, the current gold standard in the field, lacks sufficient sensitivity and specificity in predicting toxic effects of pharmaceuticals in humans. In this study, we evaluate the potential of deep learning techniques to translate the pattern of …
Apoptosis induced by a HIPK2 full-length-specific siRNA is due to off-target effects rather than prevalence of HIPK2-Δe8 isoform
2017
Small interfering RNAs (siRNAs) are widely used to study gene function and extensively exploited for their potential therapeutic applications. HIPK2 is an evolutionary conserved kinase that binds and phosphorylates several proteins directly or indirectly related to apoptosis. Recently, an alternatively spliced isoform skipping 81 nucleotides of exon 8 (Hipk2-Δe8) has been described. Selective depletion of Hipk2 full-length (Hipk2-FL) with a specific siRNA that spares the Hipk2-Δe8 isoform has been shown to strongly induce apoptosis, suggesting an unpredicted dominant-negative effect of Hipk2-FL over the Δe8 isoform. From this observation, we sought to take advantage and assessed the therape…
Production Conditions Affect the In Vitro Anti-Tumoral Effects of a High Concentration Multi-Strain Probiotic Preparation.
2016
A careful selection of the probiotic agent, standardization of the dose and detailed characterization of the beneficial effects are essential when considering use of a probiotic for the dietary management of serious diseases. However, changes in the manufacturing processes, equipment or facilities can result in differences in the product itself due to the live nature of probiotics. The need to reconfirm safety and/or efficacy for any probiotic product made at a different factory is therefore mandatory. Recently, under the brand VSL#3®, a formulation produced by a manufacturer different from the previous one, has been commercialized in some European countries (the UK and Holland). VSL#3 is a…
Biology of frailty: Modulation of ageing genes and its importance to prevent age-associated loss of function
2016
Frailty is associated with loss of functional reserve as well as with the prediction of adverse events in the old population. The traditional criteria of frailty are based on five physical determinations described in the Cardiovascular Health Study. We propose that biological and genetic markers of frailty should be used to increase the predictive capacity of the established clinical indeces. In recent times, research for biological markers of frailty has gained impetus. Finding a biological markers with diagnostic and prognostic capacity would be a major milestone to identify frailty risk, and also pre-frailty status. In the first section of the manuscript, we review the available biomarke…
What drives athletes toward dietary supplement use: objective knowledge or self-perceived competence? Cross-sectional analysis of professional team-s…
2019
Background Issues related to knowledge of nutrition and dietary supplementation (DS) are understudied in professional athletes. This study aimed to examine the possible association between knowledge of nutrition and DS (KN&DS) and dietary supplement use (DSU) among professional athletes involved in team sports. Methods The sample comprised professional team-sport athletes (N = 912, age: 22.11 ± 3.37 years, 356 females) involved in four Olympic sports: basketball (N = 228), soccer (N = 324), volleyball (N = 154), and handball (N = 206). The participants were tested by previously validated questionnaires to examine their self-perceived competence on nutrition and DS (S/KN&DS), their objective…
Biofilms of Lactobacillus plantarum and Lactobacillus fermentum: Effect on stress responses, antagonistic effects on pathogen growth and immunomodula…
2016
IF 3.682; International audience; Few studies have extensively investigated probiotic functions associated with biofilms. Here, we show that strains of Lactobacillus plantarum and Lactobacillus fermentum are able to grow as biofilm on abiotic surfaces, but the biomass density differs between strains. We performed microtiter plate biofilm assays under growth conditions mimicking to the gastrointestinal environment. Osmolarity and low concentrations of bile significantly enhanced Lactobacillus spatial organization. Two L. plantarum strains were able to form biofilms under high concentrations of bile and mucus. We used the agar well-diffusion method to show that supernatants from all Lactobaci…
Dietary components modulate the risk of hepatocellular carcinoma in cirrhotic patients.
2018
Abstract Eighty percent of hepatocellular carcinoma (HCC) cases occur after cirrhosis from various etiologies. The association between diet and cancer is well accepted, but the links with cirrhosis progression and HCC risk have been poorly investigated. However, we hypothesized that diet could be a modifiable preventive factor for HCC. Thus, the aim of our study was to explore the relationships between dietary factors and the risk of HCC in a population of cirrhotic patients. A total of 582 cirrhotic patients were studied: 401 without HCC (controls) and 181 with HCC (cases). These patients were recruited between 2008 and 2012 for the “CiRCE” case-control study conducted in six French univer…
The Effect of Lutein on Eye and Extra-Eye Health
2018
Lutein is a carotenoid with reported anti-inflammatory properties. A large body of evidence shows that lutein has several beneficial effects, especially on eye health. In particular, lutein is known to improve or even prevent age-related macular disease which is the leading cause of blindness and vision impairment. Furthermore, many studies have reported that lutein may also have positive effects in different clinical conditions, thus ameliorating cognitive function, decreasing the risk of cancer, and improving measures of cardiovascular health. At present, the available data have been obtained from both observational studies investigating lutein intake with food, and a few intervention tri…
Safety and effectiveness of regorafenib in patients with metastatic colorectal cancer in routine clinical practice in the prospective, observational …
2019
Abstract Background Regorafenib prolonged overall survival (OS) versus placebo in patients with treatment-refractory metastatic colorectal cancer (mCRC) in phase III trials. We conducted an observational study of regorafenib for patients with mCRC in real-world clinical practice. Methods The international, prospective, CORRELATE study recruited patients with mCRC previously treated with approved therapies, for whom the decision to treat with regorafenib was made by the treating physician according to the local health authority approved label. The primary objective was safety, assessed by treatment-emergent adverse events (TEAEs; National Cancer Institute Common Terminology Criteria for Adve…
A phase I dose-escalation study of IMAB362 (Zolbetuximab) in patients with advanced gastric and gastro-oesophageal junction cancer
2018
Introduction IMAB362 (Zolbetuximab) is a chimeric monoclonal antibody that binds to Claudin-18.2, a target antigen specific to cancer cells. In vitro, IMAB362 mediates cell death through antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity; thus, IMAB362 may serve as a potent, targeted immunotherapeutic agent. Methods This first-in-human phase I study enroled adult patients (N = 15) with advanced gastric or gastro-oesophageal junction cancer into five sequential single dose-escalation cohorts (33, 100, 300, 600, and 1000 mg/m2) following a 3 + 3 design. Safety/tolerability, including determination of maximum tolerated dose and recommended phase II dose, were the pr…