The stimulation with LPS increased the production of IL-6 and IL-1β while PM decreased the production of IL-6 in WT macrophages. In KO macrophages, LPS increased the production of TNF-α and IL-6 and PM decreased the production of TNFα.The expression of inflammatory markers such NFκB and IL1β were increased by LPS and decreased by PM in both WT and KO macrophages. PM reduced the expression of MyD88 and caspase-1 in KO macrophages, and the expression of TLR4 and HIF-1αin both WT and KO macrophages, although LPS had not effect. CD86, an inflammatory macrophage marker, was reduced by PM independently of genotype. PM increased PPARγ and reduced PPARβ gene expression in macrophages of both genotypes, and increased ACOX-1 expression in KO macrophages. In conclusion, PM promotes anti-inflammatory effects in macrophages exposed to LPS through inhibition of inflammasome pathway, which was independent of PPARα, PPARϒ and AMPK, thus the molecular mechanisms of anti-inflammatory response caused by PM is still unclear.

In mice fed with a high-fat diet, palmitoleic acid supplementation stimulated the uptake of glucose in liver through activation of AMPK and FGF-21, dependent on PPARα. J. Cell. Physiol. 232: 2168-2177, 2017. © 2016 Wiley Periodicals, Inc.

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Thimet oligopeptidase (EC 3.4.24.15; EP24.15; THOP1) is a potential therapeutic target, as it plays key biological functions in processing biologically functional peptides. The structural conformation of THOP1 provides a unique restriction regarding substrate size, in that it only hydrolyzes peptides (optimally, those ranging from eight to 12 amino acids) and not proteins. The proteasome activity of hydrolyzing proteins releases a large number of intracellular peptides, providing THOP1 substrates within cells. The present study aimed to investigate the possible function of THOP1 in the development of diet-induced obesity (DIO) and insulin resistance by utilizing a murine model of hyperlipidic DIO with both C57BL6 wild-type (WT) and THOP1 null (THOP1−/−) mice. After 24 weeks of being fed a hyperlipidic diet (HD), THOP1−/− and WT mice ingested similar chow and calories; however, the THOP1−/− mice gained 75% less body weight and showed neither insulin resistance nor non-alcoholic fatty liver steatosis when compared to WT mice. THOP1−/− mice had increased adrenergic-stimulated adipose tissue lipolysis as well as a balanced level of expression of genes and microRNAs associated with energy metabolism, adipogenesis, or inflammation. Altogether, these differences converge to a healthy phenotype of THOP1−/− fed a HD. The molecular mechanism that links THOP1 to energy metabolism is suggested herein to involve intracellular peptides, of which the relative levels were identified to change in the adipose tissue of WT and THOP1−/− mice. Intracellular peptides were observed by molecular modeling to interact with both pre-miR-143 and pre-miR-222, suggesting a possible novel regulatory mechanism for gene expression. Therefore, we successfully demonstrated the previously anticipated relevance of THOP1 in energy metabolism regulation. It was suggested that intracellular peptides were responsible for mediating the phenotypic differences that are described herein by a yet unknown mechanism of action.

Nonalcoholic fatty liver disease (NAFLD) is one of the main liver diseases today, and may progress to steatohepatitis, cirrhosis, and hepatocellular carcinoma. Some studies have shown the beneficial effects of aerobic exercise on reversing NAFLD. To verify whether chronic aerobic exercise improves the insulin resistance, liver inflammation, and steatohepatitis caused by a high fat diet (HF) and whether PPARα is involved in these actions. C57BL6 wild type (WT) and PPAR-α knockout (KO) mice were fed with a standard diet (SD) or HF during 12 weeks; the HF mice were trained on a treadmill during the last 8 weeks. Serum glucose and insulin tolerances, serum levels of aspartate aminotransferase, hepatic content of triacylglycerol, cytokines, gene expression, and protein expression were evaluated in all animals. Chronic exposure to HF diet increased triacylglycerol accumulation in the liver, leading to NAFLD, increased aminotransferase in the serum, increased peripheral insulin resistance, and higher adiposity index. Exercise reduced all these parameters in both animal genotypes. The liver lipid accumulation was not associated with inflammation; trained KO mice, however, presented a huge inflammatory response that was probably caused by a decrease in PPAR-γ expression. We conclude that exercise improved the damage caused by a HF independently of PPARα, apparently by a peripheral fatty acid oxidation in the skeletal muscle. We also found that the absence of PPARα together with exercise leads to a decrease in PPAR-γ and a huge inflammatory response. J. Cell. Physiol. 232: 1008-1019, 2017. © 2016 Wiley Periodicals, Inc.

Purpose:The aim of this study was to analyse the changes in transfusion requirements, in patients submitted to orthotopic liver transpantation from cadaveric donors, with the use of intraoperative red blood cell salvage (Cell Saver). Methods: Data from 41 transplants were analysed. Intraoperative blood loss was calculated from the cell salvage, suction and the swabs. The autologous and heterologous transfusions were recorded The red blood salvage was performed using the Cell Saver 5 System (Haemonetics).. For analysis the patients were divided in two groups: one that used the Cell Saver and another that didn´t. Results: The median age of the patients was 50 years and the main indication for liver transplantation was cirrhosis (35 cases -85.3%). The median blood loss was 8362 + 3994 ml (with the Cell Saver) and 10824 + 7002 ml (without the Cell Saver) and the median transfusion of heterologous packed red blood cells was 9,6 + 8 units (with the Cell Saver) compared to 22,3 + 21 units (without the Cell Saver). Conclusions: The Cells Saver has the potential to reduce the need for heterologous blood transfusion reducing the risks of transmissible diseases. Key words: Liver Transplantation. Cell Saver. Blood Transfusion. Liver Surgery. RESUMO Objetivo: O objetivo desse estudo foi analisar as mundanças na quantidade de transfusão necessária com uso doIntraoperative red blood cell salvage (Cell saver), em pacientes submetidos a transplante ortotópico de fígado, doador cadáver. Métodos: Foram avaliados dados de 41 pacientes submetidos a transplante de fígado. O sangramento foi calculado de acordo com débito do aspirador, compressas e captação do Cell saver. A reposição necessária foi avaliada de acordo com a quantidade de transfusão heteróloga e autóloga. Para análise dos dados os pacientes foram dividos em dois grupos: com e sem uso de Cell saver. Resultados: A mediana de idade foi 50 anos e principal indicação de transplante foi cirrose hepática com 35 casos (85,3%). A mediana de sangramento durante o procedimento cirúrgico 8362 + 3994 ml (com cell saver) e 10824 + 7002 ml (sem cell saver) e a mediana de transfusão de concentrado de hemácias heterólogo, durante o período de internação hospitalar 9,6 + 8 unidades (com cell saver) compar 22,3 + 21 unidades (sem cell saver). Conclusão: Uso de Cell Saver tem um potential para reduzir a quantidade de transfusão heteróloga, dimuindo o risco de transmissão de doenças.

High proportions of HBV-infected subjects with an HBeAg-negative pattern were observed, with a higher risk of vertical/intrafamily transmission. Alcohol abuse was associated with male subjects and with cirrhosis of the liver in this group. A tendency toward an increase in the number of HBeAg-negative cases was observed over time.