Some Molecular and Cellular Stress Mechanisms Associated with Neurodegenerative Diseases and Atherosclerosis

Chronic stress is a combination of nonspecific adaptive reactions of the body to the influence of various adverse stress factors which disrupt its homeostasis, and it is also a corresponding state of the organism’s nervous system (or the body in general). We hypothesized that chronic stress may be one of the causes occurence of several molecular and cellular types of stress. We analyzed literary sources and considered most of these types of stress in our review article. We examined genes and mutations of nuclear and mitochondrial genomes and also molecular variants which lead to various types of stress. The end result of chronic stress can be metabolic disturbance in humans and animals, leading to accumulation of reactive oxygen species (ROS), oxidative stress, energy deficiency in cells (due to a decrease in ATP synthesis) and mitochondrial dysfunction. These changes can last for the lifetime and lead to severe pathologies, including neurodegenerative diseases and atherosclerosis. The analysis of literature allowed us to conclude that under the influence of chronic stress, metabolism in the human body can be disrupted, mutations of the mitochondrial and nuclear genome and dysfunction of cells and their compartments can occur. As a result of these processes, oxidative, genotoxic, and cellular stress can occur. Therefore, chronic stress can be one of the causes forthe occurrence and development of neurodegenerative diseases and atherosclerosis. In particular, chronic stress can play a large role in the occurrence and development of oxidative, genotoxic, and cellular types of stress.     

The Multifaceted Mas-Related G Protein-Coupled Receptor Member X2 in Allergic Diseases and Beyond

Recent research on mast cell biology has turned its focus on MRGPRX2, a new member of the Mas-related G protein-coupled subfamily of receptors (Mrgprs), originally described in nociceptive neurons of the dorsal root ganglia. MRGPRX2, a member of this group, is present not only in neurons but also in mast cells (MCs), specifically, and potentially in other cells of the immune system, such as basophils and eosinophils. As emerging new functions for this receptor are studied, a variety of both natural and pharmacologic ligands are being uncovered, linked to the ability to induce receptor-mediated MC activation and degranulation. The diversity of these ligands, characterized in their human, mice, or rat homologues, seems to match that of the receptor’s interactions. Natural ligands include host defense peptides, basic molecules, and key neuropeptides such as substance P and vasointestinal peptide (known for their role in the transmission of pain and itch) as well as eosinophil granule-derived proteins. Exogenous ligands include MC secretagogues such as compound 48/80 and mastoparan, a component of bee wasp venom, and several peptidergic drugs, among which are members of the quinolone family, neuromuscular blocking agents, morphine, and vancomycin. These discoveries shed light on its capacity as a multifaceted participant in naturally occurring responses within immunity and neural stimulus perception, as in responses at the center of immune pathology. In host defense, the mice Mrgprb2 has been proven to aid mast cells in the detection of peptidic molecules from bacteria and in the release of peptides with antimicrobial activities and other immune mediators. There are several potential actions described for it in tissue homeostasis and repair. In the realm of pathologic response, there is evidence to suggest that this receptor is also involved in chronic inflammation. Furthermore, MRGPRX2 has been linked to the pathophysiology of non-IgE-mediated immediate hypersensitivity drug reactions. Different studies have shown its possible role in other allergic diseases as well, such as asthma, atopic dermatitis, contact dermatitis, and chronic spontaneous urticaria. In this review, we sought to cover its function in physiologic processes and responses, as well as in allergic and nonallergic immune disease.     

Development and in vivo response of hydroxyapatite/whitlockite from chicken bones as bone substitute using a chitosan membrane for guided bone regeneration

Biomaterials that meet the requirements to stimulate bone tissue formation play a vital role in orthopedics and dentistry. In this work, chitosan and a biphasic, non-cytotoxic material hydroxyapatite/whitlockite were obtained from natural sources, which are available as organic waste. The osteogenic activity was assessed using a rabbit model animal with a chitosan barrier membrane in combination with a bone-filling graft substitute composed of hydroxyapatite/whitlockite. FT-IR results showed the typical absorption bands of the chitosan and hydroxyapatite. Moreover, the X-ray diffraction pattern revealed a typical hexagonal phase of hydroxyapatite and rhombohedral structures related to whitlockite. Masson's trichrome stain showed an early formation of extracellular matrix mineralized, in accord with the surface morphology of a cortical mature bond observed by Scanning Electron Microscopy. The immunocytochemistry results showed a significant increase of positive immunoreactive cells to osteonectin in the treated defects in comparison with the control defects 6 and 8 weeks postoperatively. Overall, the results confirm that the use of this low-cost and versatile biomaterial as a barrier membrane and a bone substitute graft are useful for bone tissue engineering.     

BMP9-Induced Survival Effect in Liver Tumor Cells Requires p38MAPK Activation

The study of bone morphogenetic proteins (BMPs) role in tumorigenic processes, and specifically in the liver, has gathered importance in the last few years. Previous studies have shown that BMP9 is overexpressed in about 40% of hepatocellular carcinoma (HCC) patients. In vitro data have also shown evidence that BMP9 has a pro-tumorigenic action, not only by inducing epithelial to mesenchymal transition (EMT) and migration, but also by promoting proliferation and survival in liver cancer cells. However, the precise mechanisms driving these effects have not yet been established. In the present work, we deepened our studies into the intracellular mechanisms implicated in the BMP9 proliferative and pro-survival effect on liver tumor cells. In HepG2 cells, BMP9 induces both Smad and non-Smad signaling cascades, specifically PI3K/AKT and p38MAPK. However, only the p38MAPK pathway contributes to the BMP9 growth-promoting effect on these cells. Using genetic and pharmacological approaches, we demonstrate that p38MAPK activation, although dispensable for the BMP9 proliferative activity, is required for the BMP9 protective effect on serum withdrawal-induced apoptosis. These findings contribute to a better understanding of the signaling pathways involved in the BMP9 pro-tumorigenic role in liver tumor cells.     

Use of photodegradable inhibitors in UV-curable compositions to form polymeric 2D-structures by visible light

The process of two-wave photopolymerization of a UV-curable composition with an optically degrading inhibitor is considered. By numerical simulation, it is shown that in the composition layer uniformly exposed to UV-radiation, such systems allow getting segments with different conversion under the action of inhomogeneous visible light. Based on the data on the photopolymerization kinetics of the compositions from triethylene glycol dimethacrylate (TEGDMA) and bisphenol-A glycidyl dimethacrylate (bis-GMA) with the UV-initiator 2,2-dimethoxy-2-phenylacetophenone (DMPA), it was shown that 3,5-di-tert-butyl-o-benzoquinone (35Q) with N,N-dimethylaniline (DMA, “Aldrich”, 99%) can serve as an inhibitor that degrades under action of visible radiation. Combining inhomogeneous visible light generated with a conventional DLP-projector and uniform UV-radiation of LED (365 nm) the two-wave lithographic process was implemented to create polymeric 2D-structures in 20 μm layer of the compositions from TEGDMA (70)/bis-GMA (30)/DMPA (0.05 wt%)/35Q (0.5 wt%)/DMA (1 wt%).     

A Feature Selection Strategy to Optimize Retinal Vasculature Segmentation

Diabetic retinopathy (DR) is a complication of diabetes mellitus that appears in the retina. Clinitians use retina images to detect DR pathological signs related to the occlusion of tiny blood vessels. Such occlusion brings a degenerative cycle between the breaking off and the new generation of thinner and weaker blood vessels. This research aims to develop a suitable retinal vasculature segmentation method for improving retinal screening procedures by means of computer-aided diagnosis systems. The blood vessel segmentation methodology relies on an effective feature selection based on Sequential Forward Selection, using the error rate of a decision tree classifier in the evaluation function. Subsequently, the classification process is performed by three alternative approaches: artificial neural networks, decision trees and support vector machines. The proposed methodology is validated on three publicly accessible datasets and a private one provided by Hospital Sant Joan of Reus. In all cases we obtain an average accuracy above 96% with a sensitivity of 72% in the blood vessel segmentation process. Compared with the state-of-the-art, our approach achieves the same performance as other methods that need more computational power. Our method significantly reduces the number of features used in the segmentation process from 20 to 5 dimensions. The implementation of the three classifiers confirmed that the five selected features have a good effectiveness, independently of the classification algorithm.     

Performance Evaluation of Two High‐Shear Impellers in an Unbaffled Stirred Tank

High‐shear impellers (HSIs) are mixers used in industrial stirred tanks to incorporate powders into liquids and break down particle agglomerates. A detailed numerical study of two commercial ring‐style HSIs of laboratory scale was carried out and their performance was compared with the Rushton turbine (RT). It was found that power and pumping numbers or their ratio cannot be simply connected for properly selecting an impeller in applications where highly localized viscous dissipation is desirable. The ratio of the average viscous dissipation in the impeller swept volume to the mean in the entire volume at two constant values of power input turned out to be lower for HSIs compared to that evaluated for RT. However, at higher power input, the dimensionless average viscous dissipation in the blade swept volume was found to be similar for the HSI of two rings and the RT, corroborating the high local viscous dissipation of this HSI when operated at higher speeds.     

Laser‐induced surface structures on gold‐coated polymers: Influence of morphology on surface‐enhanced Raman scattering enhancement

The fabrication of highly sensitive and reproducible substrates for Surface‐Enhanced Raman Scattering (SERS) remains a challenging scientific and technological issue. In this work, laser‐induced periodic surface structures are generated on poly(trimethylen terephthalate) films upon laser irradiation with the linearly polarized beams of a Nd:YAG laser (4th harmonic, 266 nm), an ArF excimer laser (193 nm), and a Titanium:sapphire laser (795 nm), resulting in periods close to the laser wavelength when irradiating at normal incidence, and larger periods for different angles of incidence. Additional irradiation with a circularly polarized beam at 266 nm produces superficial circular structures. The nanostructured polymers are coated with a nanoparticle assembled gold layer by pulsed laser deposition at 213 nm. The capabilities of these substrates for SERS are evaluated using benzenethiol as a test molecule and different degrees of Raman signal enhancement are observed depending on the nanostructure type. The highest enhancement factor is obtained by for nanostructured substrates with the highest values of period, depth, and roughness. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 42770.