Flaxseed supplementation improved insulin resistance in obese glucose intolerant people: a randomized crossover design

<p>Abstract</p> <p>Background</p> <p>Obesity leads to an increase in inflammation and insulin resistance. This study determined antioxidant activity of flaxseed and its role in inflammation and insulin resistance in obese glucose intolerant people.</p> <p>Methods</p> <p>Using a randomized crossover design, nine obese glucose intolerant people consumed 40 g ground flaxseed or 40 g wheat bran daily for 12 weeks with a 4-week washout period. Plasma inflammation biomarkers (CRP, TNF-α, and IL-6), glucose, insulin, and thiobaribituric acid reactive substance (TBARS) were measured before and after of each supplementation.</p> <p>Results</p> <p>Flaxseed supplementation decreased TBARS (p = 0.0215) and HOMA-IR (p = 0.0382). Flaxseed or wheat bran supplementation did not change plasma inflammatory biomarkers. A positive relationship was found between TBARS and HOMA-IR (r = 0.62, p = 0.0003).</p> <p>Conclusions</p> <p>The results of the study weakly support that decreased insulin resistance might have been secondary to antioxidant activity of flaxseed. However, the mechanism(s) of decreased insulin resistance by flaxseed should be further determined using flaxseed lignan.</p

Maslinic Acid, a Natural Triterpene, Induces a Death Receptor-Mediated Apoptotic Mechanism in Caco-2 p53-Deficient Colon Adenocarcinoma Cells

Maslinic acid (MA) is a natural triterpene present in high concentrations in the waxy skin of olives. We have previously reported that MA induces apoptotic cell death via the mitochondrial apoptotic pathway in HT29 colon cancer cells. Here, we show that MA induces apoptosis in Caco-2 colon cancer cells via the extrinsic apoptotic pathway in a dose-dependent manner. MA triggered a series of effects associated with apoptosis, including the cleavage of caspases -8 and -3, and increased the levels of t-Bid within a few hours of its addition to the culture medium. MA had no effect on the expression of the Bax protein, release of cytochrome-c or on the mitochondrial membrane potential. This suggests that MA triggered the extrinsic apoptotic pathway in this cell type, as opposed to the intrinsic pathway found in the HT29 colon-cancer cell line. Our results suggest that the apoptotic mechanism induced in Caco-2 may be different from that found in HT29 colon-cancer cells, and that in Caco-2 cells MA seems to work independently of p53. Natural antitumoral agents capable of activating both the extrinsic and intrinsic apoptotic pathways could be of great use in treating colon-cancer of whatever origin.This study was supported by grants Group BIO 157 from the Technology and Innovation Council of the Andalucian regional government and AGL2006-12210-C03-02/ALI, SAF2005-01627, ISCIII-RTICC (RD06/0020/0046) from the Spanish government and European Union FEDER funds

Genetics of human hydrocephalus

Human hydrocephalus is a common medical condition that is characterized by abnormalities in the flow or resorption of cerebrospinal fluid (CSF), resulting in ventricular dilatation. Human hydrocephalus can be classified into two clinical forms, congenital and acquired. Hydrocephalus is one of the complex and multifactorial neurological disorders. A growing body of evidence indicates that genetic factors play a major role in the pathogenesis of hydrocephalus. An understanding of the genetic components and mechanism of this complex disorder may offer us significant insights into the molecular etiology of impaired brain development and an accumulation of the cerebrospinal fluid in cerebral compartments during the pathogenesis of hydrocephalus. Genetic studies in animal models have started to open the way for understanding the underlying pathology of hydrocephalus. At least 43 mutants/loci linked to hereditary hydrocephalus have been identified in animal models and humans. Up to date, 9 genes associated with hydrocephalus have been identified in animal models. In contrast, only one such gene has been identified in humans. Most of known hydrocephalus gene products are the important cytokines, growth factors or related molecules in the cellular signal pathways during early brain development. The current molecular genetic evidence from animal models indicate that in the early development stage, impaired and abnormal brain development caused by abnormal cellular signaling and functioning, all these cellular and developmental events would eventually lead to the congenital hydrocephalus. Owing to our very primitive knowledge of the genetics and molecular pathogenesis of human hydrocephalus, it is difficult to evaluate whether data gained from animal models can be extrapolated to humans. Initiation of a large population genetics study in humans will certainly provide invaluable information about the molecular and cellular etiology and the developmental mechanisms of human hydrocephalus. This review summarizes the recent findings on this issue among human and animal models, especially with reference to the molecular genetics, pathological, physiological and cellular studies, and identifies future research directions

Besides Purkinje cells and granule neurons: an appraisal of the cell biology of the interneurons of the cerebellar cortex

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Mesenchymal stem/stromal cell therapy for pulmonary arterial hypertension: Comprehensive review of preclinical studies.

Pulmonary arterial hypertension (PAH) is a disease characterized by progressive pulmonary vascular remodeling, resulting in right-sided heart failure and premature death. Current available therapies for PAH have limited efficacy, and new therapeutic strategies need to be developed. Mesenchymal stem/stromal cells (MSCs) may offer a novel therapeutic approach to PAH. Since the first report in 2006, a number of preclinical studies have demonstrated a potential therapeutic effect of this approach, with attenuated hemodynamic and histological progression of PAH, in animal models of PAH. However, there remain several issues that should be addressed for this approach to be clinically successful. With the aim to highlight such issues, this review clarifies existing knowledge on MSC therapy for PAH in preclinical studies, including types of PAH animal models used for MSC therapy, MSC sources, and administration protocol (route, cell dose, and timing of administration). This review thereafter summarizes thoroughly and discusses the mechanism underpinning MSC therapy for PAH. For clinical success of MSC therapy, insufficient evidence of safety (e.g. critical risk of pulmonary embolism) and therapeutic efficacy of MSCs on established PAH with severe vascular remodeling, as well as further optimization of the MSC administration protocol, are considered as remaining issues to be addressed. In terms of the efficacy, it is controversial whether angiogenic cytokines, which are considered as one of the therapeutic mechanisms of MSC, have beneficial effect for human PAH. To address these issues, further preclinical data using more clinically-relevant animal models of PAH, such as SU5416 model, should be accumulated, whereas most preclinical studies have been conducted using monocrotaline-induced PAH model. While MSC therapy has a great potential to become a novel therapy in PAH, continuing careful preclinical research is warranted for clinical success in PAH