Caffeic Acid-Zinc Basic Salt/Chitosan Nanohybrid Possesses Controlled Release Properties and Exhibits In Vivo Anti-Inflammatory Activities.

Caffeic acid (CA) exhibits a myriad of biological activities including cardioprotective action, antioxidant, antitumor, anti-inflammatory, and antimicrobial properties. On the other hand, CA presents low water solubility and poor bioavailability, which have limited its use for therapeutic applications. The objective of this study was to develop a nanohybrid of zinc basic salts (ZBS) and chitosan (Ch) containing CA (ZBS-CA/Ch) and evaluate its anti-edematogenic and antioxidant activity in dextran and carrageenan-induced paw edema model. The samples were obtained by coprecipitation method and characterized by X-ray diffraction, Fourier transform infrared (FT-IR), scanning electron microscope (SEM) and UV-visible spectroscopy. The release of caffeate anions from ZBS-CA and ZBS-CA/Ch is pH-dependent and is explained by a pseudo-second order kinetics model, with a linear correlation coefficient of R2 ≥ 0.99 at pH 4.8 and 7.4. The in vivo pharmacological assays showed excellent anti-edematogenic and antioxidant action of the ZBS-CA/Ch nanoparticle with slowly releases of caffeate anions in the tissue, leading to a prolongation of CA-induced anti-edematogenic and anti-inflammatory activities, as well as improving its inhibition or sequestration antioxidant action toward reactive species. Overall, this study highlighted the importance of ZBS-CA/Ch as an optimal drug carrier.

The angiotensin-(1-7)/Mas axis reduces myonuclear apoptosis during recovery from angiotensin II-induced skeletal muscle atrophy in mice.

Angiotensin-(1-7) [Ang (1-7)] is a peptide belonging to the non-classical renin-angiotensin system (RAS). Ang (1-7), through its receptor Mas, has an opposite action to angiotensin II (Ang II), the typical peptide of the classical RAS axis. Ang II produces skeletal muscle atrophy, a pathological condition characterised by the loss of strength and muscle mass. A feature of muscle atrophy is the decrease of the myofibrillar proteins produced by the activation of the ubiquitin-proteasome pathway (UPP), evidenced by the increase in the expression of two muscle-specific ubiquitin ligases: atrogin-1 and MuRF-1. In addition, it has been described that Ang II also induces myonuclear apoptosis during muscle atrophy. We assessed the effects of Ang (1-7) and Mas participation on myonuclear apoptosis during skeletal muscle atrophy induced by Ang II. Our results show that Ang (1-7), through Mas, prevents the effects induced by Ang II in the diaphragm muscles and decreases several events associated with apoptosis in the diaphragm (increased apoptotic nuclei, increased expression of caspase-8 and caspase-9, increased caspase-3 activity and increased Bax/Bcl-2 ratio). Concomitantly, Ang (1-7) also attenuates the decrease in fibre diameter and muscle strength, and prevents the increase in atrogin-1 and MuRF-1 during the muscle wasting induced by Ang II. Interestingly, these effects of Ang (1-7) are dependent on the Mas receptor. Thus, we demonstrated for the first time that Ang (1-7) prevents myonuclear apoptosis during the recovery of skeletal muscle atrophy induced by Ang II.

Expression of the Mas receptor is upregulated in skeletal muscle wasting.

Skeletal muscle atrophy during sepsis, immobilization, and chronic diseases is characterized by an increase in expression and activity of the muscle-specific ubiquitin 3 ligases atrogin-1 and MuRF-1. The classical renin-angiotensin system (RAS), by high level of circulating angiotensin II (AngII) is directly involved in skeletal muscle wasting associated with cardiac and renal failure. Ang (1-7), a peptide belonging to the non-classical RAS system, produces effects that are opposite to AngII. The actions of Ang (1-7) are mediated by its binding and signalling through the Mas receptor. Our purpose is to assess the effects of atrophic stimuli AngII, lipopolysaccharide (LPS), and immobilization on the expression of the Mas receptor in skeletal muscle. For that we used gastrocnemius and tibialis anterior muscles of C57BL10 mice treated with AngII, LPS or subjected to unilateral hindlimb immobilization by casting. In addition, we used C2C12 myotubes incubated with AngII or LPS. We evaluated Mas expression by quantitative real-time PCR, Western blot immunohistochemical analysis. Skeletal muscle atrophy was corroborated by the expression of atrogin-1 and MuRF-1 and the fibre diameter. Our results show that Mas receptor expression was increased by AngII or LPS in vitro and in vivo, and upregulated by immobilization. The increase of the Mas expression was concomitantly with the upregulation of atrogin-1 and MuRF-1 and the reduction of the fibre diameter. These results from studies in vitro and in vivo demonstrate for the first time that the Mas receptor is increased under atrophic stimulus and suggest that the non-classical RAS system could have an important role in muscle wasting.

Angiotensin-(1-7) decreases skeletal muscle atrophy induced by angiotensin II through a Mas receptor-dependent mechanism.

Skeletal muscle atrophy is a pathological condition characterized by the loss of strength and muscle mass, an increase in myosin heavy chain (MHC) degradation and increase in the expression of two muscle-specific ubiquitin ligases: atrogin-1 and MuRF-1. Angiotensin II (AngII) induces muscle atrophy. Angiotensin-(1-7) [Ang-(1-7)], through its receptor Mas, produces the opposite effects than AngII. We assessed the effects of Ang-(1-7) on the skeletal muscle atrophy induced by AngII. Our results show that Ang-(1-7), through Mas, prevents the effects induced by AngII in muscle gastrocnemius: the decrease in the fibre diameter, muscle strength and MHC levels and the increase in atrogin-1 and MuRF-1. Ang-(1-7) also induces AKT phosphorylation. In addition, our analysis in vitro using C2C12 myotubes shows that Ang-(1-7), through a mechanism dependent on Mas, prevents the decrease in the levels of MHC and the increase in the expression of the atrogin-1 and MuRF-1, both induced by AngII. Ang-(1-7) induces AKT phosphorylation in myotubes; additionally, we demonstrated that the inhibition of AKT with MK-2206 decreases the anti-atrophic effects of Ang-(1-7). Thus, we demonstrate for the first time that Ang-(1-7) counteracts the skeletal muscle atrophy induced by AngII through a mechanism dependent on the Mas receptor, which involves AKT activity. Our study indicates that Ang-(1-7) is novel molecule with a potential therapeutical use to improve muscle wasting associated, at least, with pathologies that present high levels of AngII.

The Ang-(1-7)/Mas-1 axis attenuates the expression and signalling of TGF-ß1 induced by AngII in mouse skeletal muscle.

AngII (angiotensin II) induces pathological conditions such as fibrosis in skeletal muscle. In this process, AngII increases ROS (reactive oxygen species) and induces a biphasic phosphorylation of p38 MAPK (mitogen-activated protein kinase). In addition, AngII stimulates the expression and production of TGF (transforming growth factor)-ß1 via a mechanism dependent on ROS production mediated by NADPH oxidase (NOX) and p38 MAPK activation. In the present study, we investigated whether Ang-(1-7) [angiotensin-(1-7)], through the Mas-1 receptor, can counteract the signalling induced by AngII in mouse skeletal muscle and cause a decrease in the expression and further activity of TGF-ß1 in skeletal muscle cells. Our results show that Ang-(1-7) decreased the expression of TGF-ß1 induced by AngII in a dose-dependent manner. In addition, we observed that Ang-(1-7) prevented the increase in TGF-ß1 expression induced by AngII, ROS production dependent on NOX and the early phase of p38 MAPK phosphorylation. Interestingly, Ang-(1-7) also prevented the late phase of p38 MAPK phosphorylation, Smad-2 phosphorylation and Smad-4 nuclear translocation, an increase in transcriptional activity, as determined using the p3TP-lux reporter, and fibronectin levels, all of which are dependent on the TGF-ß1 levels induced by AngII. We also demonstrated that Ang-(1-7) prevented the increase in TGF-ß1, fibronectin and collagen content in the diaphragm of mice infused with AngII. All of these effects were reversed by the administration of A779, indicating the participation of Mas-1. In conclusion, our findings support the hypothesis that Ang-(1-7) decreases the expression and further biological activity of TGF-ß1 induced by AngII in vitro and in vivo.

Synthesis, antimalarial activity in vitro, and docking studies of novel neolignan derivatives.

The absence of effective vaccines against malaria and the difficulties associated with controlling mosquito vectors have left chemotherapy as the primary control measure against malaria. However, the emergence and spread of parasite resistance to conventional antimalarial drugs result in a worrisome scenario making the search for new drugs a priority. In the present study, the activities of nine neolignan derivatives were evaluated as follows: (i) against blood forms of chloroquine-resistant Plasmodium falciparum (clone W2), using the tritiated hypoxanthine incorporation and anti-HRPII assays; (ii) for cytotoxic activity against cultured human hepatoma cells (HepG2); and (iii) for intermolecular interaction with the P. falciparum cysteine protease of falcipain-2 (F2) by molecular docking. The neolignan derivatives 9 and 10 showed activity against the blood form of the chloroquine-resistant P. falciparum clone W2 and were not cytotoxic against cultured human hepatoma cells. A molecular docking study of these two neolignans with FP2 revealed several intermolecular interactions that should guide the design of future analogs.

Functional performance, nutritional status and level of physical activity of elderly

The elderly is a risk group for changes in health conditions and as well as in functional performance related to the decline in grip strength and reduced walking speed, which can compromise the performance of activities of daily living. Based on this, the objective was to analyze the factors associated with functional performance in the elderly. For that, a cross-sectional study was developed involving a group of 179 elderly people who received medical care at an outpatient clinic of the public health network. Muscle strength and gait speed were measured. Nutritional status was determined by Body Mass Index (BMI), calf circumference (CC), waist circumference (WC) and waist-to-hip ratio (WHR). Level of physical activity was measured by the adapted version of the Minnesota Leisure Activities Questionnaire. Low muscle strength was found in 20.7% of the elderly and slow gait in 20.1%. Increased risk of cardiovascular disease was found in 40.8% considering WC, and 35.2% by WHR. Most of the elderly had low weight and no loss of muscle mass. Loss of muscle strength was associated with sex and CC and gait speed were associated with sex, age, and presence of a partner (p < 0.05). The chance of loss of muscle strength and lower gait speed was higher in elderly women. Loss of muscle mass due to CC was associated with the chance of loss of strength, and the chance of reduced walking speed was greater among the elderly individuals aged 75 years and over.

Representações sociais sobre fragilidade: concepções de idosos na atenção básica de saúde / Social representations of frailty: conceptions of elder in health primary

O objetivo geral desta pesquisa é identificar as representações sociais dos idosos sobre fragilidade, desvelando sua visão e o significado de como vivenciam essa condição. Trata-se de um estudo transversal envolvendo 179 idosos de ambos os sexos e com idades entre 65 e 91 anos. Os dados foram coletados pela Técnica de Associação Livre de Palavras com os estímulos-indutores: idoso frágil, fragilidade e fraqueza muscular, sendo que os indivíduos deveriam evocar 5 palavras em um tempo de 3 minutos e, em seguida, hierarquizá-las. O material coletado na entrevista foi categorizado e analisado pela técnica de redes semânticas: tamanho da rede (TR), núcleo da rede (NR), peso semântico (PS) e distância semântica quantitativa (DSQ). Os termos mais mencionados foram: ajuda, dependente e cansaço. Constatou-se, que os idosos tinham pouco conhecimento sobre fragilidade, apesar de apresentarem elevado percentual de pré-frágil e frágil. Evidenciou-se que os estímulos-indutores relacionados aos termos idoso frágil, fragilidade e fraqueza muscular foram representados como ajuda, incapacidade, dependente, cansaço e má alimentação. Espera-se que estes dados possam contribuir com informações esclarecedoras sobre a fragilidade no intuito de promover um envelhecimento saudável. (AU)

The objective of this research is to identify the social representations of the elderly about fragility, unveiling its vision and the significance of how they experience this condition. It is a cross-sectional study involving 179 elderly men and women, aged between 65 and 91 years. Data were collected by the Technical Words of Free Association with the inducing stimulus: "frail elderly", "weak" and "weakness", and individuals should evoke 5 words in a time of 3 minutes and then hierarchize them. The material collected in the interview was categorized and analyzed by the technique of semantic networks: network size (TR), core network (NR), semantic weight (PS) and quantitative semantic distance (DSQ). The most mentioned terms were: help, dependent and fatigue. It was found that these people had little knowledge about fragility, despite having a high percentage of pre-frail and frail. It was demonstrated that inducing stimuli related to the terms: frail elderly, weakness and muscle weakness were represented as: aid, disability, dependent, fatigue and poor diet. It is expected that these data can contribute to clarifying information about the fragility in order to promote healthy aging. (AU)