Search

The sympathetic nervous system and the immune system are responsible for producing neurotransmitters and cytokines that interact by binding to receptors; due to this, there is communication between these systems. Liver immune cells and nerve fibres are systematically distributed in the liver, and the partial overlap of both patterns may favour interactions between certain elements. Dendritic cells are attached to fibroblasts, and nerve fibres are connected via the dendritic cell-fibroblast complex. Receptors for most neuroactive substances, such as catecholamines, have been discovered on dendritic cells. The sympathetic nervous system regulates hepatic fibrosis through sympathetic fibres and adrenaline from the adrenal glands through the blood. When there is liver damage, the sympathetic nervous system is activated locally and systemically through proinflammatory cytokines that induce the production of epinephrine and norepinephrine. These neurotransmitters bind to cells through α-adrenergic receptors, triggering a cellular response that secretes inflammatory factors that stimulate and activate hepatic stellate cells. Hepatic stellate cells are key in the fibrotic process. They initiate the overproduction of extracellular matrix components in an active state that progresses from fibrosis to liver cirrhosis. It has also been shown that they can be directly activated by norepinephrine. Alpha and beta adrenoblockers, such as carvedilol, prazosin, and doxazosin, have recently been used to reverse CCl4-induced liver cirrhosis in rodent and murine models. Neurotransmitters from the sympathetic nervous system activate and increase the proliferation of hepatic stellate cells. Hepatic fibrosis and cirrhosis treatment might depend on neurotransmitter and hepatic nervous system regulation. Strategies to reduce hepatic stellate cell activation and fibrosis are based on experimentation with α-adrenoblockers. [ABSTRACT FROM AUTHOR]

The endoplasmic reticulum (ER) is a key organelle in cell homeostasis and cell health through antigen presentation to immune cells. Thus, the ER has become a therapeutic target to induce cellular immune responses. We previously reported the antitumor effect of a DNA vaccine that expresses the E7 antigen fused to the cyclooxygenase-2 (COX-2) protein. This inflammation-related enzyme contains a degradation cassette associated with the endoplasmic reticulum-associated degradation (ERAD) pathway. To avoid the use of full-length COX-2 and any risk of adverse effects due to the activity of its catalytic site, we designed new versions of the fusion protein. These new constructs encode the E7 antigen fused to the signal peptide and the ERAD sequence of COX-2 with or without the membrane-binding domain (MBD) as well as deletion of the catalytic site. We evaluated the antigen-specific antitumor effect of these DNA constructs in murine prophylactic and therapeutic cancer models. These assays showed that the ERAD cassette is the minimum sequence in the COX-2 protein that induces an antitumor effect when fused to the E7 antigen with the advantage of eliminating any potential adverse effects from the use of full-length COX-2. [ABSTRACT FROM AUTHOR]

Introduction: The use of probiotics has been broadly popularized due to positive effects in the attenuation of aberrant immune responses such as asthma. Allergic asthma is a chronic respiratory disease characterized by airway inflammation and remodelling. Objective: This study was aimed to evaluate the effect of oral administration of Lactococcus lactis NZ9000 on asthmatic airway inflammation and lung tissue remodelling in rats and its relation to the maintenance of an adequate intestinal barrier. Methods: Wistar rats were ovalbumin (OVA) sensitized and challenged and orally treated with L. lactis. Lung inflammatory infiltrates and cytokines were measured, and remodelling was evaluated. Serum OVA-specific immunoglobulin (Ig) E levels were assessed. We also evaluated changes on intestinal environment and on systemic immune response. Results:L. lactis diminished the infiltration of proinflammatory leucocytes, mainly eosinophils, in the bronchoalveolar compartment, decreased lung IL-4 and IL-5 expression, and reduced the level of serum allergen-specific IgE. Furthermore, L. lactis prevented eosinophil influx, collagen deposition, and goblet cell hyperplasia in lung tissue. In the intestine, L. lactis-treated asthmatic rats increased Peyer's patch and goblet cell quantity and mRNA expression of IgA, MUC-2, and claudin. Additionally, intestinal morphological alterations were normalized by L. lactis administration. Splenocyte proliferative response to OVA was abolished, and serum levels of transforming growth factor (TGF)-β were increased by L. lactis treatment. Conclusions: These findings suggest that L. lactis is a potential candidate for asthma prevention, and the effect is mediated by the improvement of intestinal barrier function and systemic TGF-β production. [ABSTRACT FROM AUTHOR]

Chronic diseases are a worldwide health problem directly related to society, lifestyle, and the development of unhealthy habits over time. Cardiovascular disease, cancer, chronic respiratory disease, and diabetes are the main causes of death. Environmental factors, such as air pollutants, poor diet, genetic predisposition, or a combination of these, are related to the development of these diseases. These factors activate cell mechanisms, such as DNA damage, oxidative stress, endoplasmic reticulum stress, autophagy, inflammation, and cell death. Depending on the dose and duration of exposure to causative agents, this cell damage can be acute or chronic. Activating these cell mechanisms can rescue normal cell function and cause permanent damage, unleashing the degeneration of tissues and organs over time. A wide variety of treatments help control chronic diseases; however, they cannot be cured completely. This fact leads to complications, dysfunctions, and disabilities. Herein, we discuss some of the principal mechanisms involved and how cellular stress can lead to these diseases when they persist for a long time.

The aim of this study was to characterize and compare the morphological and histomorphometric characteristics of the pectoral fascia, fascia lata and ventral rectus sheath. Twenty cadaveric samples of these fascias were analyzed and stained with hematoxylin and eosin, orcein, Van Gieson, Masson's trichrome and Verhoeff¨s stain (1200 slides in total). Morphological evaluation, semiquantitative, morphometric and microdensitometric analysis of elastic fibers present in each of the tissues and a morphometrical analysis of tissue thickness were performed. The mean value of the pectoral fascia thickness was 612±68.13 μm; 84±246 μm for the fascia lata and 584±92 μm for the ventral rectus sheath. The area occupied by the elastic fibers in the pectoral fascia was 12.24±5.84%; 6,54±3.85% for the fascia lata and 11.11±5.26% for the ventral rectus sheath. There were no statistically significant differences when comparing the mean values between the pectoral fascia and the ventral rectus sheath (p=0.07). There were statistically significant differences when comparing the fascia lata to the pectoral fascia and the ventral rectus sheath (p≤0.001). This study reports other morphological characteristics not described in previous histological studies of the analyzed tissues. The results of the morphometric and densitometric analysis in this study reveal that the fascia lata has the fewest elastic fibers of all the tissues analyzed, and the pectoral fascia has the most. These results will be useful for the beginning of a morphological information bank of human fascias.