Examinando por Autor "Cabrera, D."
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Ítem Andrographolide Ameliorates Inflammation and Fibrogenesis and Attenuates Inflammasome Activation in Experimental Non-Alcoholic Steatohepatitis(Nature Publishing Group, 2017-06) Cabrera, D.; Wree, A.; Povero, D.; Solís, N.; Hernandez, A.; Pizarro, M.; Moshage, H.; Torres, J.; Feldstein, A.E.; Cabello-Verrugio, C.; Brandan, E.; Barrera, F.; Arab, J.P.; Arrese, M.Therapy for nonalcoholic steatohepatitis (NASH) is limited. Andrographolide (ANDRO), a botanical compound, has a potent anti-inflammatory activity due to its ability to inhibit NF-κB. ANDRO has been also shown to inhibit the NLRP3 inflammasome, a relevant pathway in NASH. Our aim was to evaluate the effects of ANDRO in NASH and its influence on inflammasome activation in this setting. Thus, mice were fed a choline-deficient-Amino-Acid-defined (CDAA) diet with/without concomitant ANDRO administration (1 mg/kg, 3-Times/week). Also, we assessed serum levels of alanine-Aminotransferase (ALT), liver histology, hepatic triglyceride content (HTC) and hepatic expression of pro-inflammatory, pro-fibrotic and inflammasome genes. Inflammasome activation was also evaluated in fat-laden HepG2 cells. Our results showed that ANDRO administration decreased HTC and attenuated hepatic inflammation and fibrosis in CDAA-fed mice. ANDRO treatment determined a strong reduction in hepatic macrophage infiltration and reduced hepatic mRNA levels of both pro-inflammatory and pro-fibrotic genes. In addition, mice treated with ANDRO showed reduced expression of inflammasome genes. Finally, ANDRO inhibited LPS-induced interleukin-1β expression through NF-κB inhibition in fat-laden HepG2 cells and inflammasome disassembly. In conclusion, ANDRO administration reduces inflammation and fibrosis in experimental NASH. Inflammasome modulation by a NF-κB-dependent mechanism may be involved in the therapeutic effects of ANDRO.Ítem Angiotensin-(1-7) attenuates disuse skeletal muscle atrophy in mice via its receptor, Mas(Universidad Andrés Bello, 2016-04) Morales, M.G.; Abrigo, J.; Acuna, M.J.; Santos, R.A.; Bader, M.; Brandan, E.; Simon, F.; Olguin, H.; Cabrera, D.; Cabello-Verrugio, C.Immobilization is a form of disuse characterized by a loss of strength and muscle mass. Among the main features are decreased IGF-1/Akt signalling and increased ubiquitin-proteasome pathway signalling, which induce greater myosin heavy chain degradation. Activation of the classical renin-angiotensin system (RAS) causes deleterious effects in skeletal muscle, including muscle wasting. In contrast, angiotensin-(1-7) [Ang-(1-7)], a peptide of the non-classical RAS, produces beneficial effects in skeletal muscle. However, the role of Ang-(1-7) in skeletal muscle disuse atrophy and independent of classical RAS activation has not been evaluated. Therefore, we assessed the functions of Ang-(1-7) and the Mas receptor in disuse muscle atrophy in vivo using unilateral cast immobilization of the hind limb in male, 12-week-old wild-type (WT) and Mas-knockout (Mas KO) mice for 1 and 14 days. Additionally, we evaluated the participation of IGF-1/IGFR-1/Akt signalling and ubiquitin-proteasome pathway expression on the effects of Ang-(1-7) immobilization-induced muscle atrophy. Our results found that Ang-(1-7) prevented decreased muscle strength and reduced myofiber diameter, myosin heavy chain levels, and the induction of atrogin-1 and MuRF-1 expressions, all of which normally occur during immobilization. Analyses indicated that Ang-(1-7) increases IGF-1/IGFR-1/Akt pathway signalling through IGFR-1 and Akt phosphorylation, and the concomitant activation of two downstream targets of Akt, p70S6K and FoxO3. These anti-atrophic effects of Ang-(1-7) were not observed in Mas KO mice, indicating crucial participation of the Mas receptor. This report is the first to propose anti-atrophic effects of Ang-(1-7) via the Mas receptor and the participation of the IGF-1/IGFR-1/Akt/p70S6K/FoxO3 mechanism in disuse skeletal muscle atrophy.Ítem Obfuscation-based malware update: A comparison of manual and automated methods(Agora University, 2017) Barría, C.; Cordero, D.; Cubillos, C.; Palma, M.; Cabrera, D.This research presents a proposal of malware classification and its update based on capacity and obfuscation. This article is an extension of [4]a, and describes the procedure for malware updating, that is, to take obsolete malware that is already detectable by antiviruses, update it through obfuscation techniques and thus making it undetectable again. As the updating of malware is generally performed manually, an automatic solution is presented together with a comparison from the standpoint of cost and processing time. The automated method proved to be more reliable, fast and less intensive in the use of resources, specially in terms of antivirus analysis and malware functionality checking times.Ítem Somatotropic axis dysfunction in non-alcoholic fatty liver disease: Beneficial hepatic and systemic effects of hormone supplementation(MDPI AG, 2018-05) Cabrera, D.; Cabello-Verrugio, C.; Solís, N.; Martín, D.S.; Cofré, C.; Pizarro, M.; Arab, J.P.; Abrigo, J.; Campos, F.; Irigoyen, B.; Carrasco-Avino, G.; Bezares, K.; Riquelme, V.; Riquelme, A.; Arrese, M.; Barrera, F.Background: Somatotropic axis dysfunction associated with non-alcoholic fatty liver disease (NAFLD) has potential multisystemic detrimental effects. Here, we analysed the effects of growth hormone (GH) and insulin-like growth factor-1 (IGF-1) supplementation on liver histology, adipokine profile and muscle function in an NAFLD model. Methods: C57BL/6 mice were fed with a high fat diet (HFD) for 12 weeks and were separated into three groups treated for 4 weeks with: (1) High fat diet (HFD) (n = 10); (2) HFD + GH 9 μg/g/d (n = 10); (3) HFD + IGF-1 0.02 μg/g/d (n = 9). A control group fed a chow diet was included (n = 6). Liver histology, liver triglycerides content, serum alanine aminotransferase (ALT) activity, adiponectin and leptin serum levels, in vivo muscle strength, tetanic force and muscle fibre cross-sectional area (CSA) were measured. Results: HFD + GH and HFD + IGF-1 groups showed significantly lower ALT activity compared to HFD (p < 0.01). Liver triglyceride content in HFD + GH was decreased compared to HFD (p < 0.01). Histologic steatosis score was increased in HFD and HFD + GH group (p < 0.01), whereas HFD + IGF-1 presented no difference compared to the chow group (p = 0.3). HFD + GH group presented lower serum leptin and adiponectin levels compared to HFD. GH and IGF-1 supplementation therapy reverted HFD-induced reduction in muscle strength and CSA (sarcopenia). Conclusions: GH and IGF-1 supplementation induced significant improvement in liver steatosis, aminotransferases and sarcopenia in a diet-induced NAFLD model. © 2018 by the authors. Licensee MDPI, Basel, Switzerland.