cis9, trans11-Conjugated Linoleic Acid Differentiates Mouse 3T3-L1 Preadipocytes into Mature Small Adipocytes through Induction of Peroxisome Proliferator-activated Receptor γ

Dietary conjugated linoleic acid (CLA) has been reported to exhibit a number of therapeutic effects in animal models and patients, such as anti-hypertensive, anti-hyperlipidemic, anti-arteriosclerotic, anti-carcinogenic, and anti-diabetic effects. However, the underlying mechanism is not well-characterized. In the present study, the effects of cis(c)9, trans(t)11-CLA on the differentiation of mouse 3T3-L1 preadipocytes into mature adipocytes were examined. Treatment with c9, t11-CLA in the presence of insulin, dexamethasone, and 3-isobutyl-1-methyl-xanthine (differentiation cocktail) significantly stimulated the accumulation of triacylglycerol. The microscopic observation of cells stained by Oil Red O demonstrated that c9, t11-CLA increases the amount and proportion of small mature adipocytes secreting adiponectin, a benign adipocytokine, when compared to the differentiation cocktail alone. Furthermore, c9, t11-CLA increased bioactive peroxisome proliferator-activated receptor γ (PPARγ) levels in a nuclear extract of 3T3-L1 cells, suggesting the enhancing effect of this fatty acid on the nuclear transmission of PPARγ, a master regulator of adipocyte differentiation, in 3T3-L1 cells. These results suggest that the therapeutic effects of c9, t11-CLA on lifestyle-related diseases are partially due to the enhanced formation of small adipocytes from preadipocytes via PPARγ stimulation

Correlation between mass and percentage of fat according to the age in duchenne muscular Dystrophy

INTRODUÇÃO: A Distrofia Muscular de Duchenne (DMD) é uma desordem genética, caracterizada pela perda progressiva e irreversível da musculatura esquelética. OBJETIVO: Este estudo objetiva correlacionar a porcentagem e a massa de gordura com a idade em pacientes com DMD. METODOLOGIA: Foram selecionados 68 indivíduos com idades entre 5 e 20 anos, com diagnóstico molecular de certeza para DMD, residentes na cidade de São Paulo. Todos foram submetidos à mensuração do peso e altura e também ao teste de análise de composição corporal com o uso da bioimpedância, no período da manhã, todas no mesmo dia. RESULTADOS E DISCUSSÃO: Os resultados foram analisados agrupando os indivíduos em quartis de idade e mostraram um índice de massa corpóreo (IMC) de 21 ± 8 kg/m². Assim, observou-se que, com a idade e o grau de sedentarismo imposto pela doença, houve um acúmulo de gordura corporal e perda de massa magra. CONCLUSÃO: São necessários mais estudos relacionados às características nutricionais desses indivíduos, para que se esclareçam melhor os efeitos da doença e da alimentação no ganho de porcentagem e massa de gordura.INTRODUCTION: The Duchenne Muscular Dystrophy (DMD) is a genetic disorder, characterized by the progressive and irreversible loss of skeletal muscle. PURPOSE: This study aims to correlate the percentage and mass of fat to the age of patients with DMD. METHODS: It was selected 68 individuals aged between 5 and 20 years, with molecular diagnosis of certainty for DMD, residents in the city of São Paulo. All the them were submitted to weight and height measurement and also to the test of body composition analysis with the use of bioelectrical impedance, in the morning period, all the same day. RESULTS AND DISCUSSION: The results were analyzed by grouping individuals into quartiles of age and showed a body mass index (BMI) of 21 ± 8 kg / m². Thus, it was observed that with the age and the degree of inactivity imposed by the disease, there was an accumulation of body fat and loss of lean mass. CONCLUSION: Further studies related to the nutritional characteristics of these individuals are necessary to clarify the effects of disease and food in the gain on the percentage of body and mass fat

The phenology of epiphytic diatoms and epifauna observed on Zostera marina of Arikawa Bay, Nagasaki Prefecture, Japan

We present a descriptive account of the dynamics of epiphytic diatoms, epifauna, and the leaf surface area of Zostera marina in a shallow water ecosystem. We hypothesized that the growth stage of the host macrophyte (i.e., leaf surface area) influenced the presence of epiflora and epifauna, as well as that the leaf surface area and epifaunal population density affected the cell density and species composition of epiphytic diatoms. To evaluate this hypothesis, we quantified the leaf surface area of a host macrophyte (Zostera marina), the presence of epifauna, and the community of epiphytic diatoms that could be observed on the leaves of Z. marina during the period from May 2017 to December 2018. We conducted a descriptive analysis of the time-series observations of leaf surface area, epiphytic diatom density, and epifauna population density. Epiphytic diatom density was low and epifauna density was high during the growing season of Z. marina. Epiphytic diatom density was high and epifauna density was low during the maturation and senescence periods of Z. marina. Our analysis shows that epifauna densities lagged epiflora densities by at least four months, and that epiflora densities lagged leaf area by four months. Therefore, we hypothesized that herbivorous gastropods and amphipods could alter species composition via their preference of food items (active choice) or by ingesting more of the species that were structurally more available (passive preference)

Discovery of soticlestat, a potent and selective inhibitor for cholesterol 24-hydroxylase (CH24H)

Cholesterol 24-hydroxylase (CH24H, CYP46A1), a brain-specific cytochrome P450 (CYP) family enzyme, plays a role in the homeostasis of brain cholesterol by converting cholesterol to 24S-hydroxycholesterol (24HC). Despite a wide range of potential of CH24H as a drug target, no potent and selective inhibitors have been identified. Here, we report on the structure-based drug design (SBDD) of novel 4-arylpyridine derivatives based on the X-ray co-crystal structure of hit derivative 1b. Optimization of 4-arylpyridine derivatives led us to identify 3v ((4-benzyl-4-hydroxypiperidin-1-yl)­(2,4′-bipyridin-3-yl)­methanone, IC50 = 7.4 nM) as a highly potent, selective, and brain-penetrant CH24H inhibitor. Following oral administration to mice, 3v resulted in a dose-dependent reduction of 24HC levels in the brain (1, 3, and 10 mg/kg). Compound 3v (soticlestat, also known as TAK-935) is currently under clinical investigation for the treatment of Dravet syndrome and Lennox-Gastaut syndrome as a novel drug class for epilepsies

The effects of nitroxyl (HNO) on soluble guanylate cyclase activity: interactions at ferrous heme and cysteine thiols

It has been previously proposed that nitric oxide (NO) is the only biologically relevant nitrogen oxide capable of activating the enzyme soluble guanylate cyclase (sGC). However, recent reports implicate HNO as another possible activator of sGC. Herein, we examine the affect of HNO donors on the activity of purified bovine lung sGC and find that, indeed, HNO is capable of activating this enzyme. Like NO, HNO activation appears to occur via interaction with the regulatory ferrous heme on sGC. Somewhat unexpectedly, HNO does not activate the ferric form of the enzyme. Finally, HNO-mediated cysteine thiol modification appears to also affect enzyme activity leading to inhibition. Thus, sGC activity can be regulated by HNO via interactions at both the regulatory heme and cysteine thiols