Induction of Cyclooxygenase-2 by Overexpression of the Human NADPH Oxidase 5 (NOX5) Gene in Aortic Endothelial Cells

Oxidative stress is a main molecular mechanism that underlies cardiovascular diseases. A close relationship between reactive oxygen species (ROS) derived from NADPH oxidase (NOX) activity and the prostaglandin (PG) biosynthesis pathway has been described. However, little information is available about the interaction between NOX5 homolog-derived ROS and the PG pathway in the cardiovascular context. Our main goal was to characterize NOX5-derived ROS effects in PG homeostasis and their potential relevance in cardiovascular pathologies. For that purpose, two experimental systems were employed: an adenoviral NOX5-β overexpression model in immortalized human aortic endothelial cells (TeloHAEC) and a chronic infarction in vivo model developed from a conditional endothelial NOX5 knock-in mouse. NOX5 increased cyclooxygenase-2 isoform (COX-2) expression and prostaglandin E2 (PGE2) production through nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) in TeloHAEC. Protein kinase C (PKC) activation and intracellular calcium level (Ca++) mobilization increased ROS production and NOX5 overexpression, which promoted a COX-2/PGE2 response in vitro. In the chronic infarction model, mice encoding endothelial NOX5 enhanced the cardiac mRNA expression of COX-2 and PGES, suggesting a COX-2/PGE2 response to NOX5 presence in an ischemic situation. Our data support that NOX5-derived ROS may modulate the COX-2/PGE2 axis in endothelial cells, which might play a relevant role in the pathophysiology of heart infarction

Selenium, iodine, omega-3 PUFA and natural antioxidant from Melissa officinalis L.: a combination of components from healthier dry fermented sausages formulation.

A new formulation of dry fermented sausage, including ingredients that improve the nutritional and health benefits of this type of product is presented. Se yeast (2g/kg), iodized salt (26g/kg), linseed:algae (3:2) emulsion (62.5g/kg), and lyophilized water extract of Melissa officinalis L. as a source of natural antioxidants (686mg/kg), yielded dry fermented sausages with technological and sensory properties similar to traditional ones. From the nutritional standpoint, a 50g portion of this product would give 100% of the recommended daily intake for Se, 70% of DRI for iodine, and 40% and 100% of the reference intake for alpha-linolenic and EPA+DHA, respectively. The omega-6/omega-3 ratio decreased from 15.7 in the control product to 1.96 in the modified one. Despite the high PUFA content, no oxidation was detected by TBARS (<0.15mgMDA/kg) and volatile compounds, showing the effectiveness of the natural antioxidants from M. officinalis. The modified formulation presented good acceptability for panelists with similar appearance, odor, taste and juiciness as the control products

Endothelial NOX5 expression modulates thermogenesis and lipolysis in mice fed with a high-fat diet and 3T3-L1 adipocytes through an interleukin-6 dependent mechanism

Obesity is a global health issue associated with the development of metabolic syndrome, which correlates with insulin resistance, altered lipid homeostasis, and other pathologies. One of the mechanisms involved in the development of these pathologies is the increased production of reactive oxygen species (ROS). One of the main producers of ROS is the family of nicotinamide adenine dinucleotide phosphate (NADPH) oxidases, among which NOX5 is the most recently discovered member. The aim of the present work is to describe the effect of endothelial NOX5 expression on neighboring adipose tissue in obesity conditions by using two systems. An in vivo model based on NOX5 conditional knock-in mice fed with a high-fat diet and an in vitro model developed with 3T3-L1 adipocytes cultured with conditioned media of endothelial NOX5-expressing bEnd.3 cells, previously treated with glucose and palmitic acid. Endothelial NOX5 expression promoted the expression and activation of specific markers of thermogenesis and lipolysis in the mesenteric and epididymal fat of those mice fed with a high-fat diet. Additionally, the activation of these processes was derived from an increase in IL-6 production as a result of NOX5 activity. Accordingly, 3T3-L1 adipocytes treated with conditioned media of endothelial NOX5-expressing cells, presented higher expression of thermogenic and lipolytic genes. Moreover, endothelial NOX5-expressing bEnd.3 cells previously treated with glucose and palmitic acid also showed interleukin (IL-6) production. Finally, it seems that the increase in IL-6 stimulated the activation of markers of thermogenesis and lipolysis through phosphorylation of STAT3 and AMPK, respectively. In conclusion, in response to obesogenic conditions, endothelial NOX5 activity could promote thermogenesis and lipolysis in the adipose tissue by regulating IL-6 production

Nanosistemas a base de poliésteres

Amplia presentacion de los: Nanosistemas a base de poliésteres, desarrollando todas las posibilidades de estos compuestos que constituyen tal vez los polímeros mas frecuentemente utilizados por estar, algunos de ellos, autorizado su empleo por las agen- cias regulatorias

Injectable alginate hydrogel loaded with GDNF promotes functional recovery in a hemisection model of spinal cord injury

We hypothesized that local delivery of GDNF in spinal cord lesion via an injectable alginate hydrogel gelifying in situ would support spinal cord plasticity and functional recovery. The GDNF release from the hydrogel was slowed by GDNF encapsulation in microspheres compared to non-formulated GDNF (free GDNF). When injected in a rat spinal cord hemisection model, more neurofilaments were observed in the lesion when the rats were treated with free GDNF-loaded hydrogels. More growing neurites were detected in the tissues surrounding the lesion when the animals were treated with GDNF microsphere-loaded hydrogels. Intense GFAP (astrocytes), low III tubulin (neural cells) and RECA-1 (endothelial cells) stainings were observed for non-treated lesions while GDNF-treated spinal cords presented less GFAP staining and more endothelial and nerve fiber infiltration in the lesion site. The animals treated with free GDNF-loaded hydrogel presented superior functional recovery compared with the animals treated with the GDNF microsphere-loaded hydrogels and non-treated animals

A lyophilized water extract of melissa officinalis L. as an effective natural antioxidant during the storage of dry fermented sausages high in alpha-linolenic acid and DHA

Abstract: A pre-emulsified mixture of linseed and algae oils (15/10) and stabilized with 686 ppm of a lyophilized water extract of Melissa officinalis, was successfully applied in dry fermented sausages to increase the ω-3 PUFA content. The objective of this work was to evaluate the stability of this modified formulation during the storage and to compare it to that of a traditional formulation. Traditional and modified products were stored during 90 days at 4 ºC in aerobic conditions. Fatty acid profiles, TBARS and volatile compounds derived from oxidation were analyzed at 0, 30 and 90 days of storage. The fatty acid profiles did not significantly change along the storage period. The stabilizing effect of the natural antioxidants of M. officinalis could contribute to detect no losses of ω-3 PUFA in Modified (30 days: 2.13 g/100 g of product, 90 days: 2.33 g/100 g of product), whereas in Control products a slightly significant reduction was detected (30 days: 0.34 g/100 g of product, 90 days: 0.29 g/100 g of product). After 90 days, the increases of TBARS and hexanal content were much higher in Control than in Modified (Control: 1.41 mg MDA/kg & 17,915 ng dodecane/kg of dry matter; Modified: 0.48 mg MDA/kg & 2,496 ng dodecane/kg of dry matter). In conclusion, the lyophilized water extract of M. officinalis protected high ω-3 PUFA of dry fermented sausages from oxidation along the storage time, guaranteeing the nutritional improvements achieved with the modified formulation

HuR/ELAVL1 drives malignant peripheral nerve sheath tumor growth and metastasis

Cancer cells can develop a strong addiction to discrete molecular regulators, which control the aberrant gene expression programs that drive and maintain the cancer phenotype. Here, we report the identification of the RNA-binding protein HuR/ELAVL1 as a central oncogenic driver for malignant peripheral nerve sheath tumors (MPNSTs), which are highly aggressive sarcomas that originate from cells of the Schwann cell lineage. HuR was found to be highly elevated and bound to a multitude of cancer-associated transcripts in human MPNST samples. Accordingly, genetic and pharmacological inhibition of HuR had potent cytostatic and cytotoxic effects on tumor growth, and strongly suppressed metastatic capacity in vivo. Importantly, we linked the profound tumorigenic function of HuR to its ability to simultaneously regulate multiple essential oncogenic pathways in MPNST cells, including the Wnt/β-catenin, YAP/TAZ, RB/E2F, and BET pathways, which converge on key transcriptional networks. Given the exceptional dependency of MPNST cells on HuR for survival, proliferation, and dissemination, we propose that HuR represents a promising therapeutic target for MPNST treatment

Post-mortem volatiles of vertebrate tissue

Volatile emission during vertebrate decay is a complex process that is understood incompletely. It depends on many factors. The main factor is the metabolism of the microbial species present inside and on the vertebrate. In this review, we combine the results from studies on volatile organic compounds (VOCs) detected during this decay process and those on the biochemical formation of VOCs in order to improve our understanding of the decay process. Micro-organisms are the main producers of VOCs, which are by- or end-products of microbial metabolism. Many microbes are already present inside and on a vertebrate, and these can initiate microbial decay. In addition, micro-organisms from the environment colonize the cadaver. The composition of microbial communities is complex, and communities of different species interact with each other in succession. In comparison to the complexity of the decay process, the resulting volatile pattern does show some consistency. Therefore, the possibility of an existence of a time-dependent core volatile pattern, which could be used for applications in areas such as forensics or food science, is discussed. Possible microbial interactions that might alter the process of decay are highlighted