Search results for "inform"
showing 10 items of 20464 documents
AISF position paper on nonalcoholic fatty liver disease (NAFLD): Updates and future directions
2017
Abstract This review summarizes our current understanding of nonalcoholic fatty liver disease (NAFLD), a multi-factorial systemic disease resulting from a complex interaction between a specific genetic background and multiple environmental/metabolic “hits”. The role of gut microbiota, lipotoxicity, inflammation and their molecular pathways is reviewed in-depth. We also discuss the epidemiology and natural history of NAFLD by pinpointing the remarkably high prevalence of NAFLD worldwide and its inherent systemic complications: hepatic (steatohepatitis, advanced fibrosis and cirrhosis), cardio-metabolic (cardiovascular disease, cardiomyopathy, arrhythmias and type 2 diabetes) and neoplastic (…
Circadian rhythms in the pathogenesis of gastrointestinal diseases
2018
The etiology of digestive pathologies such as irritable bowel syndrome (IBS), inflammatory bowel diseases (IBD) and cancer is not yet fully understood. In recent years, several studies have evidenced circadian variations in mechanisms involved in digestive health. In situations of disturbed circadian rhythms (chronodisruption) where the central clock and the peripheral clocks receive incoherent signals, the synchronicity is lost producing implications for health. This lack of coordination could alter the tissue function and cause long term damage to the organs. Life habits such as sleep, physical exercise, social interaction, and feeding times are determinants for stability and integrity of…
Measuring spectrally-resolved information transfer.
2020
Information transfer, measured by transfer entropy, is a key component of distributed computation. It is therefore important to understand the pattern of information transfer in order to unravel the distributed computational algorithms of a system. Since in many natural systems distributed computation is thought to rely on rhythmic processes a frequency resolved measure of information transfer is highly desirable. Here, we present a novel algorithm, and its efficient implementation, to identify separately frequencies sending and receiving information in a network. Our approach relies on the invertible maximum overlap discrete wavelet transform (MODWT) for the creation of surrogate data in t…
The emergence of drug resistance to targeted cancer therapies: Clinical evidence.
2019
For many decades classical anti-tumor therapies included chemotherapy, radiation and surgery; however, in the last two decades, following the identification of the genomic drivers and main hallmarks of cancer, the introduction of therapies that target specific tumor-promoting oncogenic or non-oncogenic pathways, has revolutionized cancer therapeutics. Despite the significant progress in cancer therapy, clinical oncologists are often facing the primary impediment of anticancer drug resistance, as many cancer patients display either intrinsic chemoresistance from the very beginning of the therapy or after initial responses and upon repeated drug treatment cycles, acquired drug resistance deve…
Need for Deprescribing in Hospital Elderly Patients Discharged with a Limited Life Expectancy: The REPOSI Study
2019
<b><i>Objective:</i></b> Older people approaching the end of life are at a high risk for adverse drug reactions. Approaching the end of life should change the therapeutic aims, triggering a reduction in the number of drugs.<b><i></i></b>The main aim of this study is to describe the preventive and symptomatic drug treatments prescribed to patients discharged with a limited life expectancy from internal medicine and geriatric wards. The secondary aim was to describe the potentially severe drug-drug interactions (DDI). <b><i>Materials and Methods:</i></b> We analyzed Registry of Polytherapies Societa Italiana di Medicina I…
Kinase Inhibitors in Multitargeted Cancer Therapy
2017
The old-fashioned anticancer approaches, aiming in arresting cancer cell proliferation interfering with non-specific targets (e.g. DNA), have been replaced, in the last decades, by more specific target oriented ones. Nonetheless, single-target approaches have not always led to optimal outcomes because, for its complexity, cancer needs to be tackled at various levels by modulation of several targets. Although at present, combinations of individual single-target drugs represent the most clinically practiced therapeutic approaches, the modulation of multiple proteins by a single drug, in accordance with the polypharmacological strategy, has become more and more appealing. In the perspective of…
Drugs Polypharmacology by in Silico Methods: New Opportunities in Drug Discovery
2016
Background Polypharmacology, defined as the modulation of multiple proteins rather than a single target to achieve a desired therapeutic effect, has been gaining increasing attention since 1990s, when industries had to withdraw several drugs due to their adverse effects, leading to permanent injuries or death, with multi-billiondollar legal damages. Therefore, if up to then the "one drug one target" paradigm had seen many researchers interest focused on the identification of selective drugs, with the strong expectation to avoid adverse drug reactions (ADRs), very recently new research strategies resulted more appealing even as attempts to overcome the decline in productivity of the drug dis…
Towards patient stratification and treatment in the autoimmune disease lupus erythematosus using a systems pharmacology approach
2015
Drug development in Systemic Lupus Erythematosus (SLE) has been hindered by poor translation from successful preclinical experiments to clinical efficacy. This lack of success has been attributed to the high heterogeneity of SLE patients and to the lack of understanding of disease physiopathology. Modelling approaches could be useful for supporting the identification of targets, biomarkers and patient subpopulations with differential response to drugs. However, the use of traditional quantitative models based on differential equations is not justifiable in a sparse data situation. Boolean networks models are less demanding on the required data to be implemented and can provide insights into…
Cardiovascular toxicity of abacavir: a clinical controversy in need of a pharmacological explanation.
2017
: There is a long-lasting controversy surrounding an association between abacavir (ABC) and an increased risk of cardiovascular disease in HIV-positive patients. Although differing in their specifics, a number of published cohort studies and clinical trials support such an association, usually relating it to recent exposure to the drug, independently of traditional predisposing factors. However, other clinical trials have failed to reveal such a relation and have pointed to methodological differences to explain discrepancies. Significantly, the controversy has been fueled by the lack of a credible mechanism of action to justify the putative detrimental actions of ABC. There is a myriad of c…
Overview of key molecular and pharmacological targets for diabetes and associated diseases
2021
Diabetes epidemiological quantities are demonstrating one of the most important communities' health worries. The essential diabetic difficulties are including cardiomyopathy, nephropathy, inflammation, and retinopathy. Despite developments in glucose decreasing treatments and drugs, these diabetic complications are still ineffectively reversed or prohibited. Several signaling and molecular pathways are vital targets in the new therapies of diabetes. This review assesses the newest researches about the key molecules and signaling pathways as targets of molecular pharmacology in diabetes and diseases related to it for better treatment based on molecular sciences. The disease is not cured by c…