Plant Metabolites in Plant Defense Against Pathogens

Medicinal plants are widely used worldwide to treat various diseases. Its widespread use is due in part to the cultural acceptance of traditional medicine in different regions of the world, as well as its effectiveness in treating various diseases. Many of its active substances or secondary metabolites are formed to a response of various situations that generate stress in their habitat, such as sudden changes in environmental temperature, humidity, rain, drought, and infections by phytopathogens (fungi, bacteria, viruses, nematodes, protozoa). The production of these secondary metabolites is a mechanism of defense of plants. In this context, the objective of this chapter is to study the secondary metabolites of medicinal plants that could have a promising application in the control of different phytopathogens in crops of agricultural and economic interest

Clinical Relevance of Medicinal Plants and Foods of Vegetal Origin on the Activity of Cytochrome P450

Drug metabolism is a pharmacokinetic process whose main objective is to modify the chemical structure of drugs to easily excretable compounds. This process is carried out through phase I and phase II reactions. The enzymes of cytochrome P450 (CYP450) participate in phase I reactions, and their activity can be inhibited or induced by xenobiotics. The aim of this chapter is to study the clinical relevance of the induction and inhibition of CYP450, by describing the effect that some bioactive compounds present in medicinal plants or foods can modify, either increasing or decreasing the activity of CYP450 enzymes and with it modify the bioavailability and depuration of drugs. Examples will be described on the interaction of medicinal plants and foods of vegetal origin that when combined with some drugs can generate toxicity or therapeutic failure; this will allow gathering relevant information on the adequate pharmacological management in different clinical situations

Central relaxin-3 receptor (RXFP3) activation increases ERK phosphorylation in septal cholinergic neurons and impairs spatial working memory.

The medial septum/diagonal band (MS/DB) is a relay region connecting the hypothalamus and brainstem with the hippocampus, and both the MS/DB and dorsal/ventral hippocampus receive strong topographic GABA/peptidergic projections from the nucleus incertus of the pontine tegmentum. The neuropeptide relaxin-3, released by these neurons, is the cognate ligand for a Gi/o-protein-coupled receptor, RXFP3, which is highly expressed within the MS/DB, and both cholinergic and GABAergic neurons in this region of rat brain receive relaxin-3 positive terminals/boutons. Comprehensive in vitro studies have demonstrated that a range of cell signaling pathways can be altered by RXFP3 stimulation, including inhibition of forskolin-activated cAMP levels and activation of ERK phosphorylation. In this study we investigated whether intracerebroventricular (icv) injection of RXFP3-A2, a selective relaxin-3 receptor agonist, altered ERK phosphorylation levels in the MS/DB of adult male rats. In addition, we assessed the neurochemical phenotype of phosphorylated (p) ERK-positive neurons in MS/DB after RXFP3-A2 administration by dual-label immunostaining for pERK and key neuronal markers. RXFP3-A2 injection significantly increased pERK levels in MS/DB, compared to vehicle at 20 and 90 min post-injection. In addition, icv injection of RXFP3-A2 increased the number of cells expressing pERK in the MS/DB after 90 min, with increases detected in cholinergic, but not GABAergic neurons. Moreover, we found that septal cholinergic neurons express RXFP3 and that icv infusions of RXFP3-A2 impaired alternation in a spatial working memory behavioral paradigm. The presence of the receptor and the specific RXFP3-related activation of the MAPK/ERK pathway in MS/DB cholinergic neurons identifies them as a key target of ascending relaxin-3 projections with implications for the acute and chronic inhibition of cholinergic neuron activity/function by relaxin-3/RXFP3 signaling.This research was supported by a predoctoral fellowship (FPI-UJI: PREDOC/2014/35) to HAG; a traineeship fellowship (UJI P1·1A2014-06) to AGA; the FP7-PEOPLE-IRSES PIRSES-GA-2012-318997 NEUREN project to ALG and FEO-B; NHMRC (Australia) project grants (1027522, 1026939) and a Brain and Behavior Research Foundation (USA) NARSAD Independent Investigator Award to ALG; Generalitat Valenciana (AICO/2015/042) project grant and Universitat Jaume I (P1·1A2014-06) project grant to AMS

The effect of abscisic acid chronic treatment on neuroinflammatory markers and memory in a rat model of high-fat diet induced neuroinflammation

Background Western diet and lifestyle are associated with overweight, obesity, and type 2 diabetes, which, in turn, are correlated with neuroinflammation processes. Exercise and a healthy diet are important in the prevention of these disorders. However, molecules inhibiting neuroinflammation might also be efficacious in the prevention and/or treatment of neurological disorders of inflammatory etiology. The abscisic acid (ABA) is a phytohormone involved in hydric-stress responses. This compound is not only found in plants but also in other organisms, including mammals. In rodents, ABA can play a beneficial role in the regulation of peripheral immune response and insulin action. Thus, we hypothesized that chronic ABA administration might exert a protective effect in a model of neuroinflammation induced by high-fat diet (HFD). Methods Male Wistar rats were fed with standard diet or HFD with or without ABA in the drinking water for 12 weeks. Glucose tolerance test and behavioral paradigms were performed to evaluate the peripheral and central effects of treatments. One-Way ANOVA was performed analyzed statistical differences between groups. Results The HFD induced insulin resistance peripherally and increased the levels of proinflammatory markers in in the brain. We observed that ABA restored glucose tolerance in HFD-fed rats, as expected. In addition, chronic ABA treatment rescued cognitive performance in these animals, while not affecting control diet fed animals. Moreover, it counteracted the changes induced by HFD in the hypothalamus; microglia activations and TNFα mRNA levels. Conclusion These results suggest that ABA might become a new therapeutic molecule improving the neuroinflammatory status and insulin resistance.This work was supported by Plan Propi Universitat Jaume I P1.1A2014-06 and GVA AICO/2015/042 to AMSP

Changes in membrane sphingolipid composition modulate dynamics and adhesion of integrin nanoclusters

Sphingolipids are essential constituents of the plasma membrane (PM) and play an important role in signal transduction by modulating clustering and dynamics of membrane receptors. Changes in lipid composition are therefore likely to influence receptor organisation and function, but how this precisely occurs is difficult to address given the intricacy of the PM lipid-network. Here, we combined biochemical assays and single molecule dynamic approaches to demonstrate that the local lipid environment regulates adhesion of integrin receptors by impacting on their lateral mobility. Induction of sphingomyelinase (SMase) activity reduced sphingomyelin (SM) levels by conversion to ceramide (Cer), resulting in impaired integrin adhesion and reduced integrin mobility. Dual-colour imaging of cortical actin in combination with single molecule tracking of integrins showed that this reduced mobility results from increased coupling to the actin cytoskeleton brought about by Cer formation. As such, our data emphasizes a critical role for the PM local lipid composition in regulating the lateral mobility of integrins and their ability to dynamically increase receptor density for efficient ligand binding in the process of cell adhesion

Surgical treatment of Verneuil disease or severe hidradenitis

La hidrosadenitis supurativa es una enfermedad que afecta a las glándulas apocrinas de la piel. La incidencia exacta de esta enfermedad no se conoce debido a la falta de notificaciones de esta enfermedad. Se estima en 1 caso/300-600 habitantes-año. Existen una serie de enfermedades asociadas y otras con las que hay que realizar un diagnóstico diferencial, debido a su similitud clínica. El diagnóstico de la enfermedad es fundamentalmente clínico y su tratamiento dependerá del estadio de la misma, desde el tratamiento médico tópico o sistémico hasta el abordaje quirúrgico. Debido a la baja prevalencia y a la discordancia en cuanto al tratamiento de esta enfermedad, se expone aquí un caso diagnosticado y tratado en nuestro servicio, en el cual hubo que hacer un tratamiento quirúrgico muy agresivo por la gravedad de la enfermedad.Suppurative hidradenitis is a disease that affects the apocrine glands of the skin. The precise incidence is not known due to the lack of notification of this disease. The incidence is estimated at 1 case/ 300-600 habitants/ year. Is necessary to make a differencial diagnosis with other diseases which have a similar clinical. The disease diagnosis is essentially clinical and treatment depend on the stage of the same, from the topical or systemic medical treatment to the surgical approach. Due to the low prevalence and discordance in the treatment of this disease, is published here a case diagnosed and treated in our department that needed surgical treatment due to his agressivemness

Resistance to Bleomycin-Induced Lung Fibrosis in MMP-8 Deficient Mice Is Mediated by Interleukin-10

BACKGROUND: Matrix metalloproteinases (MMPs) may have pro and antifibrotic roles within the lungs, due to its ability to modulate collagen turnover and immune mediators. MMP-8 is a collagenase that also cleaves a number of cytokines and chemokines. METHODOLOGY AND PRINCIPAL FINDINGS: To evaluate its relevance in lung fibrosis, wildtype and Mmp8(-/-) mice were treated with either intratracheal bleomycin or saline, and lungs were harvested at different time points. Fibrosis, collagen, collagenases, gelatinases, TGFβ and IL-10 were measured in lung tissue. Mmp8(-/-) mice developed less fibrosis than their wildtype counterparts. This was related to an increase in lung inflammatory cells, MMP-9 and IL-10 levels in these mutant animals. In vitro experiments showed that MMP-8 cleaves murine and human IL-10, and tissue from knockout animals showed decreased IL-10 processing. Additionally, lung fibroblasts from these mice were cultured in the presence of bleomycin and collagen, IL-10 and STAT3 activation (downstream signal in response to IL-10) measured by western blotting. In cell cultures, bleomycin increased collagen synthesis only in wildtype mice. Fibroblasts from knockout mice did not show increased collagen synthesis, but increased levels of unprocessed IL-10 and STAT3 phosphorylation. Blockade of IL-10 reverted this phenotype, increasing collagen in cultures. CONCLUSIONS: According to these results, we conclude that the absence of MMP-8 has an antifibrotic effect by increasing IL-10 and propose that this metalloprotease could be a relevant modulator of IL-10 metabolism in vivo

Modeling discards in Trawling Mediterranean Northern Alboran Sea Fishery

Target and Bycatch species metrics estimated from fishery-dependent data were explored to assess their use in governance of habitat conservation in respect to fisheries. Fishing data collected by onboard observers in otter-trawl boats between 2011 and 2012 at monthly sampling frequency in the Alboran Sea (Western Mediterranean) were used to build maps of sensitivity to fishing stress. Maps were drawn by means kriging interpolation techniques of biomass and abundance (Catch Per Unit of Effort, CPUE) in kilogram and number per fishing hour of blue whiting (Micromesistius poutassou), European hake (Merluccius merluccius), and red mullets (Mullus barbatus and Mullus surmuletus) target species, seabreams (Pagellus acarne, Pagellus bogaraveo, and Pagellus erythrinus), and mackerels (Trachurus mediterraneus, Trachurus trachurus, and Trachurus picturatus) bycatch species and Bogue (Boops boops) bycatch discarded species. Modelling discards by means Generalised Additive Models (GAMs) use environmental (sea surface temperature and chlorophyll-a from satellite data and NAO climatic index); spatial (latitude, longitude, depth and port) and temporal (season, haul duration, moon phase), as well as technical (boat length and power) explanatory variables. The main causes of discards, for both target and bycatch species, are associated to the seasonality of the recruitment and the changes on the spatial distribution of habitat preferences along their ontogeny. Environmental variables did not reveal significant effects, showing that operational oceanography standard products must be not enough to assess discards, and therefore products providing information on specific ecological processes to discards must be designed with this purpose. In Bycatch species, such as sea breams, mackerels and bogue, discards were also highly dependent of the port and boat (fleet/boat strategies, power, etc, and market preferences). The higher discards corresponded to these bycatch pelagic or bentho-pelagic species. Keywords: Discards, Otter-trawl fisheries, fishery conservation, operational oceanography, spatial modelin