Proteoma y vías de señalización inducidas por AAS en células que expresan el VHC

RESUMEN El AAS disminuye la expresión del VHC por mecanismos aún desconocidos. Se compararon perfiles de expresión proteómica en células de hepatocarcinoma (Huh7) y células que expresan proteínas no estructuradas del VHC (Huh7-VHC) tratadas con AAS 4mM. Los perfiles obtenidos mediante electroforesis bidimensional fueron analizados por pI y PM. Se identificaron diferentes patrones entre células Huh7- VHC tratadas y no tratadas con AAS. Entre las proteínas diferencialmente expresadas encontramos proteínas relacionadas con proliferación celular (MTMR6, FAM22, HDGF y HCF-1) y sobreexpresión de angiotensina, PI4KA y STAT-1. A las 72h, identificamos sobreexpresión de adenil-succinato sintasa, 2’-3’-di-deoxiadenosina, proteína ligasa de ubiquitina E6A, adenilsuccinato-liasa y nibrina. El AAS induce diferentes patrones proteicos en células Huh7- VHC, promoviendo la activación de proteínas relacionadas con progresión celular, reparación de DNA, inhibición de apoptosis y estimulación del crecimiento. ABSTRACT ASA has been shown to downregulate HCV expression; however, the involved mechanisms are unknown. We used proteomic analysis to compare protein expression profiles between human hepatocarcinome cells (Huh7) and Huh7-HCV cells harboring expression of non-structural HCV proteins to elucidate the mechanisms involved in ASAmediated downregulation of HCV replication. Cell lines were treated with 4 mM ASA and harvested to isolate total proteins, which were resolved by 2-DE. Gels were analyzed and proteins elucidated by pI and MW patterns. Different protein patterns among hepatocytes expressing HCV-proteins in ASA treated and untreated cells were found. Among proteins differentially expressed we found proteins related to cellular proliferation (MTMR6, FAM22, HDGF y HCF-1) and overexpression of angiotensin (PI4KA y STAT-1). We found that ASA induces different protein patterns in Huh7-HCV cells promoting activation of proteins involved in cell progression, repair of double strand breaks, proliferation, inhibition of apoptosis and growth stimulation at the same time that it decreased HCV expression

Antioxidants benefits in hepatitis C infection in the new DAAs era

Some of the evidence on whether antioxidant supplements are effective in treatment of liver diseases is contradictory. Here we perform a descriptive analysis of the available data in vivo and in vitro of the possible antiviral action and controversy of several antioxidant molecules against HCV

Symptoms associated with reading from a smartphone in conditions of light and dark

Asthenopia symptoms were investigated in visually-normal subjects without computer-related vision symptoms after prolonged reading from: smartphone versus hardcopy under photopic conditions, and smartphone in conditions of ambient versus dark room illumination. After reading from the smartphone, total symptom scores and nine out of ten questionnaire symptoms were significantly worse than for the hardcopy (“blurred vision while viewing the text, “blurred distance vision after the task”, “difficulty in refocusing from one distance to another”, “irritated or burning eyes”, “dry eyes”, “eyestrain”, “tired eyes”, “sensitivity to bright lights” and “eye discomfort”). Mean total symptom scores and scores for “irritated or burning eyes” and “dry eyes” were significantly higher for the dark versus photopic conditions. In conclusion, prolonged smartphone reading could cause worse asthenopic symptoms than reading from a hardcopy under similar conditions. Symptoms could be even worse when reading from a smartphone in the dark

Natural Dietary Pigments:Potential Mediators against Hepatic Damage Induced by Over-The-Counter Non-Steroidal Anti-Inflammatory and Analgesic Drugs

Over-the-counter (OTC) analgesics are among the most widely prescribed and purchased drugs around the world. Most analgesics, including non-steroidal anti-inflammatory drugs (NSAIDs) and acetaminophen, are metabolized in the liver. The hepatocytes are responsible for drug metabolism and detoxification. Cytochrome P450 enzymes are phase I enzymes expressed mainly in hepatocytes and they account for ≈75% of the metabolism of clinically used drugs and other xenobiotics. These metabolic reactions eliminate potentially toxic compounds but, paradoxically, also result in the generation of toxic or carcinogenic metabolites. Cumulative or overdoses of OTC analgesic drugs can induce acute liver failure (ALF) either directly or indirectly after their biotransformation. ALF is the result of massive death of hepatocytes induced by oxidative stress. There is an increased interest in the use of natural dietary products as nutritional supplements and/or medications to prevent or cure many diseases. The therapeutic activity of natural products may be associated with their antioxidant capacity, although additional mechanisms may also play a role (e.g., anti-inflammatory actions). Dietary antioxidants such as flavonoids, betalains and carotenoids play a preventive role against OTC analgesics-induced ALF. In this review, we will summarize the pathobiology of OTC analgesic-induced ALF and the use of natural pigments in its prevention and therapy

The Importance of Autophagy and Proteostasis in Metabolic Cardiomyopathy

Metabolic cardiomyopathy and other heart disorders are associated with proteostasis derailment and subsequent autophagy. Proteostasis is a process of protein homeostasis, and autophagy is a mechanism of self-degradation for surviving cells facing stressful conditions. Metabolic challenges have been linked to excess reactive oxygen species. Cardiomyocyte proteotoxicity, an important underlying pathologic mechanism in cardiac disease, is characterized by chronic accumulation of misfolded or unfolded proteins that can lead to proteotoxic formation or aggregation of soluble peptides. Autophagic processes are mediated by the ubiquitin-proteasome and autophagy-lysosome systems, fundamental for cardiac adaptation to physiological and pathological stress. Cellular proteostasis alterations in cardiomyopathy are represented by myocardial remodeling and interstitial fibrosis with reduced diastolic function and arrhythmias. Autophagy regulation may be a potential therapeutic strategy for metabolic cardiomyopathy necessary for the treatment of fibrosis and cardiac tissue remodeling alterations. Furthermore, autophagy has been shown to be active in the perimeter of cardiovascular fibrotic tissue as mechanism of fibrosis recovery and scarring secondary to cell apoptosis. In the present work, we review the current knowledge on the role of autophagy and proteostasis in the pathogenesis of heart failure to resolve the ever-expanding epidemic of metabolic cardiomyopathy and heart failure associated with substantial morbidity and mortality

Approximation to the Consumption of Healthcare Resources and the Economic Cost of SARS-CoV-2 Patient Management: A Retrospective Study

Spain has become one of the countries most affected by coronavirus disease 2019 (COVID-19), with the highest testing rates, and one of the worst-performing countries in the fight against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. There are no studies related to the consumption of health resources and the economic cost of the SARS-CoV-2 virus. We present a retrospective analysis of 9,811 (Primary Care and Hospital) patients which aimed to estimate public health expenditure by the consumption of health resources due to COVID-19. According to the results, the gender distribution of patients has a similar rate in both groups, with slightly higher rates in women. Similarly, age is the same in both groups, with a median of 62 years in the case of hospitalizations and 61 years in the case of primary care; using a weighted average of these rates and costs, we can estimate that the average cost of care per patient infected with the SARS-CoV-2 virus, regardless of the course is €2373.24. We conclude that a patient with COVID-19 without hospitalization costs €729.79, while the expenses of a hospitalized patient are between €4294.36 and €14440.68, if there is ICU admission

Development and Validation of a Mobile Application as an Adjuvant Treatment for People Diagnosed with Long COVID-19: Protocol for a Co-Creation Study of a Health Asset and an Analysis of Its Effectiveness and Cost-Effectiveness

Objective: To analyse the overall effectiveness and cost-efficiency of a mobile application (APP) as a community health asset (HA) with recommendations and recovery exercises created bearing in mind the main symptoms presented by patients in order to improve their quality of life, as well as other secondary variables, such as the number and severity of ongoing symptoms, physical and cognitive functions, affective state, and sleep quality. Methods: The first step was to design and develop the technologic community resource, the APP, following the steps involved in the process of recommending health assets (RHA). After this, a protocol of a randomised clinical trial for analysing its effectiveness and cost-efficiency as a HA was developed. The participants will be assigned to: (1st) usual treatment by the primary care practitioner (TAU), as a control group; and (2nd) TAU + use of the APP as a HA and adjuvant treatment in their recovery + three motivational interviews (MI), as an interventional group. An evaluation will be carried out at baseline with further assessments three and six months following the end of the intervention. Discussion: Although research and care for these patients are still in their initial stages, it is necessary to equip patients and health care practitioners with tools to assist in their recovery. Furthermore, enhanced motivation can be achieved through telerehabilitation (TR)