Maresin-1 (MaR1) is a specialized pro-resolving mediator, derived from omega-3 fatty acids, whose functions are to decrease the pro-inflammatory and oxidative mediators, and also to stimulate cell division. We investigated the hepatoprotective actions of MaR1 in a rat model of liver ischemia-reperfusion (IR) injury. MaR1 (4 ng/gr body weight) was administered prior to ischemia (1 h) and reperfusion (3 h), and controls received isovolumetric vehicle solution. To analyze liver function, transaminases levels and tissue architecture were assayed, and serum cytokines TNF-α, IL-6, and IL-10, mitotic activity index, and differential levels of NF-κB and Nrf-2 transcription factors, were analyzed. Transaminase, TNF-α levels, and cytoarchitecture were normalized with the administration of MaR1 and associated with changes in NF-κB. IL-6, mitotic activity index, and nuclear translocation of Nrf-2 increased in the MaR1-IR group, which would be associated with hepatoprotection and cell proliferation. Taken together, these results suggest that MaR1 alleviated IR liver injury, facilitated by the activation of hepatocyte cell division, increased IL-6 cytokine levels, and the nuclear localization of Nrf-2, with a decrease of NF-κB activity. All of them were related to an improvement of liver injury parameters. These results open the possibility of MaR1 as a potential therapeutic tool in IR and other hepatic pathologies.

Objective. Diabetic foot wounds are a relevant diabetes complication and a major health problem. It has been described that propolis has health benefits due to its anti-inflammatory, antioxidant, and support in the healing process. The current study assessed the effect of propolis as an adjuvant in the healing of human diabetic foot ulcers. This was evaluated in a randomized placebo-controlled study of subjects receiving care in the Diagnostic and Treatment Centre from the Regional Hospital of Talca, Chile. Research Design and Methods. Randomized subjects received ambulatory healing treatment for diabetes foot wounds with propolis spray (3%), which was applied to cover the entire wound surface each time it was dressed from week 0 until cicatrization or 8 weeks as a maximum. Two serum samples were taken (day 0 and end of the study) for cytokine and oxidative stress analyses. Also, macro- and microscopy were analyzed in the process of wound healing. Results. The study comprised 31 subjects with type 2 diabetes in treatment for diabetic foot wounds in the Diagnostic and Treatment Centre from the Regional Hospital of Talca. Propolis promotes a reduction of the wound’s area by an average of 4 cm2, related to an increase in the connective tissue deposit compared to the control. Also, propolis increased the glutathione (GSH) and GSH/glutathione disulfide (GSSG) ratio (p<0.02), depleted tumor necrosis factor- (TNF-) α, and increased interleukin- (IL-) 10 levels. Topical propolis did not modify the biochemical parameters in the serum of the studied subjects. Conclusions. The topical use of propolis turned out to be an interesting therapeutic strategy as an adjuvant in the care of diabetes foot wounds due to its ability to improve and promote healing based on its anti-inflammatory and antioxidant profile. This trial is registered with NCT03649243.

Cardiac aging is characterized by alterations in contractility and intracellular calcium ([Ca2+]i) homeostasis. It has been suggested that oxidative stress may be involved in this process. We and others have reported that in cardiomyopathies the NADPH oxidase (NOX)-derived superoxide is increased, with a negative impact on [Ca2+]i and contractility. We tested the hypothesis that in the aged heart, [Ca2+]i handling and contractility are disturbed by NOX-derived superoxide. For this we used adults (≈5 month-old) and aged (20–24 month-old) rats. Contractility was evaluated in isolated hearts, challenged with isoproterenol. To assess [Ca2+]i, isolated cardiac myocytes were field-stimulated and [Ca2+]i was monitored with fura-2. Cardiac concentration-response to isoproterenol was depressed in aged compared to adults hearts (p < 0.005), but was restored by NOX inhibitors apocynin and VAS2870. In isolated cardiomyocytes, apocynin increased the amplitude of [Ca2+]i in aged myocytes (p < 0.05). Time-50 [Ca2+]i decay was increased in aged myocytes (p < 0.05) and reduced towards normal by NOX inhibition. In addition, we found that myofilaments Ca2+ sensitivity was reduced in aged myocytes (p < 0.05), and was further reduced by apocynin. NOX2 expression along with NADPH oxidase activity was increased in aged hearts. Phospholamban phosphorylation (Ser16/Thr17) after isoproterenol treatment was reduced in aged hearts compared to adults and was restored by apocynin treatment (p < 0.05). In conclusion, β-adrenergic-induced contractility was depressed in aged hearts, and NOX inhibition restored back to normal. Moreover, altered Ca2+ handling in aged myocytes was also improved by NOX inhibition. These results suggest a NOX-dependent effect in aged myocytes at the level of Ca2+ handling proteins and myofilaments.

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PCSK 9, un nuevo blanco terapéutico para el control de la hipercolesterolemia.PCSK 9, a new therapeutic target for the control of hypercholesterolemia. Roberto ResumenLa hipercolesterolemia es un importante factor de riesgo cardiovascular (ECV), que puede ser causada por factores genéticos, por llevar una vida sedentaria y malos hábitos alimenticios, teniendo como resultado elevados niveles de lípidos séricos, principalmente colesterol asociado a lipoproteínas de baja densidad (LDL-C). La dieta terapéutica, fármacos como ezetimiba y las estatinas son la principal estrategia utilizada para disminuir los niveles de LDL-C. Sin embargo, en un porcentaje de pacientes, estas medidas no logran una reducción de los niveles séricos LDL-C, principalmente por intolerancia a las estatinas o por causas genéticas de la hipercolesterolemia. La proproteína convertasa subtilisina/kexina tipo 9 (PCSK9), una serina proteasa recientemente caracterizada, ha surgido como un importante regulador del metabolismo del LDL-C, favoreciendo la degradación de su receptor (LDLR) en el lisosoma del hepatocito. Esto la convierte en un buen blanco terapéutico para controlar los niveles de LDL-C en pacientes hipercolesterolémicos, disminuyendo así el riesgo de desarrollar ECV. La estrategia en la que más se ha avanzado para controlar PCSK9 es a través de anticuerpos monoclonales anti-PCSK9. Se han realizado varios ensayos clínicos que muestran hasta el momento su efectividad en el control de LDL-C y bajo nivel de efectos adversos. Esta revisión muestra parte de esos estudios y los resultados que se han obtenido con el uso de este nuevo fármaco aún en desarrollo y que muestra un enorme potencial.Palabras clave: Enfermedades Cardiovasculares; Proproteína Convertasa 9; anticuerpos; Receptores de LDL. (Fuente: DeCS BIREME) AbstractHypercholesterolemia is produced not only by a sedentary lifestyle and nutritional disorders but also due to genetic factors that result in elevated serum lipids, mainly low-density lipoproteins associated cholesterol (LDL-C), contributing as a risk factor for the development of cardiovascular diseases. A therapeutic diet and statins are the first line strategies aimed to reduce the levels of LDL-C in hypercholesterolemic patients. Nevertheless, statins are not devoid of side effects, or a lack of efficiency in some patients. The proprotein convertase subtilisin/kexin type 9 (PCSK9), a serine protease has been described recently to play an important role in the metabolism of LDL-C, favoring the degradation of its membrane receptor (LDLR) in the hepatocyte. This makes PCSK9 an excellent therapeutic target for the control of LDL-C in hypercholesterolemic patients, reducing their cardiovascular risks. The best-characterized approach so far to control the activity PCSK9 has been the use of monoclonal antibodies. There have been several clinical trials that tested the use of anti-PCSK antibodies showing high effectivity in the control of serum LDL-C and minimal side effects. This review describes part of those studies and their...