Role and Dysregulation of miRNA in Patients with Parkinson’s Disease

Parkinson’s disease (PD) is a neurodegenerative synucleinopathy that has a not yet fully understood molecular pathomechanism behind it. The role of risk genes regulated by small non-coding RNAs, or microRNAs (miRNAs), has also been highlighted in PD, where they may influence disease progression and comorbidities. In this case-control study, we analyzed miRNAs on peripheral blood mononuclear cells by means of RNA-seq in 30 participants, with the aim of identifying miRNAs differentially expressed in PD compared to age-matched healthy controls. Additionally, we investigated the pathways influenced by differentially expressed miRNAs and assessed whether a specific pathway could potentially be associated with PD susceptibility (enrichment analyses performed using the Ingenuity Pathway Analysis tools). Overall, considering that the upregulation of miRNAs might be related with the downregulation of their messenger RNA targets, and vice versa, we found several putative targets of dysregulated miRNAs (i.e., upregulated: hsa-miR-1275, hsa-miR-23a-5p, hsa-miR-432-5p, hsa-miR-4433b-3p, and hsa-miR-4443; downregulated: hsa-miR-142-5p, hsa-miR-143-3p, hsa-miR-374a-3p, hsa-miR-542-3p, and hsa-miR-99a-5p). An inverse connection between cancer and neurodegeneration, called “inverse comorbidity”, has also been noted, showing that some genes or miRNAs may be expressed oppositely in neurodegenerative disorders and in some cancers. Therefore, it may be reasonable to consider these miRNAs as potential diagnostic markers and outcome measures.     

Interplay of Cellular mRNA,miRNA and Viral miRNA during Infection of a Cell

The understanding of the kinetics of gene expression in cells infected by viruses is currently limited. As a rule, the corresponding models do not take viral microRNAs (miRNAs) into account. Such RNAs are, however, operative during the replication of some viruses, including, e.g., herpesvirus. To clarify the kinetics of this category (with emphasis on the information available for herpesvirus), I introduce a generic model describing the transient interplay of cellular mRNA, protein, miRNA and viral miRNA. In the absence of viral miRNA, the cellular miRNA is considered to suppress the populations of mRNA and protein due to association with mRNA and subsequent degradation. During infection, the viral miRNA suppresses the population of cellular miRNA and via this pathway makes the mRNA and protein populations larger. This effect becomes appreciable with the progress of intracellular viral replication. Using biologically reasonable parameters, I investigate the corresponding mean-field kinetics and show the scale of the effect of viral miRNAs on cellular miRNA and mRNA. The scale of fluctuations of the populations of these species is illustrated as well by employing Monte Carlo simulations.     

A Focus on Enterochromaffin Cells among the Enteroendocrine Cells: Localization,Morphology, and Role

The intestinal epithelium plays a key role in managing the relationship with the environment, the internal and external inputs, and their changes. One percent of the gut epithelium is represented by the enteroendocrine cells. Among the enteroendocrine cells, a group of specific cells characterized by the presence of yellow granules, the enterochromaffin cells, has been identified. These granules contain many secretion products. Studies showed that these cells are involved in gastrointestinal inflammatory conditions and hyperalgesia; their number increases in these conditions both in affected and not-affected zones of the gut. Moreover, they are involved in the preservation and modulation of the intestinal function and motility, and they sense metabolic–nutritional alterations. Sometimes, they are confused or mixed with other enteroendocrine cells, and it is difficult to define their activity. However, it is known that they change their functions during diseases; they increased in number, but their involvement is related mainly to some secretion products (serotonin, melatonin, substance P). The mechanisms linked to these alterations are not well investigated. Herein, we provide an up-to-date highlight of the main findings about these cells, from their discovery to today. We emphasized their origin, morphology, and their link with diet to better evaluate their role for preventing or treating metabolic disorders considering that these diseases are currently a public health burden.     

Ternary nanocomposites based on epoxy,modified silica,and tetrabutyl titanate: Morphology,characteristics, and kinetics of the curing process

In this study, the effects of unmodified nanosilica and nanosilica modified by an isopropyl tri[di(octyl) phosphate] titanate coupling agent (KR-12; m-nanosilica) on the structure, morphology, thermomechanical properties, and kinetics of the curing process of epoxy–tetrabutyl titanate (TBuT) nanocomposites were investigated. The viscosity, tensile strength, and flexural strength of the cured epoxy and cured epoxy–m-silica–TBuT nanocomposites were determined with a Brookfield viscometer and an Instron 5582-100KN universal machine. The morphology and gel fraction content of the nanocomposites were analyzed with transmission electron microscopy and scanning electron microscopy methods and Soxhlet extraction. The viscosity, mechanical properties, gel fraction content, and morphology results of the cured epoxy–m-silica–TBuT nanocomposites confirm that 5 wt % m-nanosilica was the most suitable for improving the dispersion of m-nanosilica in the epoxy matrix and the properties of these materials. The thermal behavior of the nanocomposites was determined by thermogravimetric analysis and differential scanning calorimetry (DSC) methods. On the basis of DSC data, the average value of the activation energy of the cured epoxy–TBuT system, calculated according to Flynn–Wall–Ozawa and Kissinger equations, was 67.893 kJ/mol. The calculation according to the Crane equation showed that the first-order kinetics complied with the curing reaction for the neat epoxy. When we introduced the unmodified nanosilica and modified nanosilica into the epoxy matrix, the order kinetics of the curing reaction for the nanocomposites also followed first-order kinetics, but the activation energy of their curing reaction decreased significantly. Some other properties were also investigated with dynamic mechanical analysis and Fourier transform infrared analysis and are discussed. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019 , 136, 47412.     

Evaluation of Phase Morphology,Rheological, and Mechanical Properties Based on Polypropylene Toughened with Poly(ethylene-co-octene)

The influence of blend composition on phase morphology, rheological, and mechanical properties of polypropylene/poly(ethylene-co-octene) blends was studied. Phase morphology of the blends in the whole range of composition was examined using scanning electron microscope. The rheological data were analyzed to yield the variations of rheological properties and insight into the microstructure of PP/POE blends. The finite element code ANSYS was used for the analysis of the interfacial stress and its distribution between dispersed phase and matrix phase.     

A Comparative Study on Curing Characteristics,Mechanical Properties,Swelling Behavior,Thermal Stability,and Morphology of Feldspar and Silica in SMR L Vulcanizates

Abstract

Comparison studies on effects of feldspar and silica (Vulcasil C) as a filler in (SMR L grade natural rubber) vulcanizates on curing characteristics, mechanical properties, swelling behavior, thermal analysis, and morphology were examined. The incorporation of both fillers increases the scorch time, t ₂, and cure time, t ₉₀, of SMR L vulcanizates. At a similar filler loading, feldspar exhibited longer t ₂ and t ₉₀ but lower values of maximum torque, M_HR, and torque difference, M_HR–M_L than did silica-filled SMR L vulcanizates. For mechanical properties, both fillers were found to be effective in enhancing the tensile strength (up to 10 phr), tensile modulus, and hardness of the vulcanizates. However, feldspar-filled SMR L vulcanizates showed lower values of mechanical properties than did silica-filled SMR L vulcanizates. Swelling measurement indicates that swelling percentages of both fillers-filled SMR L vulcanizates decrease with increasing filler loading whereas silica shows a lower swelling percentage than feldspar-filled SMR L vulcanizates. Scanning electron microscopy (SEM) on fracture surface of tensile samples showed poor filler–matrix adhesion for both fillers with increasing filler loading in the vulcanizates. However, feldspar-filled SMR L vulcanizates showed poorer filler–matrix adhesion than did silica-filled SMR L vulcanizates. Thermogravimetric analysis (TGA) results indicate that the feldspar-filled SMR L vulcanizates have higher thermal stability than do silica-filled SMR L vulcanizates.     

Next-Generation Grade and Survival Expression Biomarkers of Human Gliomas Based on Algorithmically Reconstructed Molecular Pathways

In gliomas, expression of certain marker genes is strongly associated with survival and tumor type and often exceeds histological assessments. Using a human interactome model, we algorithmically reconstructed 7494 new-type molecular pathways that are centered each on an individual protein. Each single-gene expression and gene-centric pathway activation was tested as a survival and tumor grade biomarker in gliomas and their diagnostic subgroups (IDH mutant or wild type, IDH mutant with 1p/19q co-deletion, MGMT promoter methylated or unmethylated), including the three major molecular subtypes of glioblastoma (proneural, mesenchymal, classical). We used three datasets from The Cancer Genome Atlas and the Chinese Glioma Genome Atlas, which in total include 527 glioblastoma and 1097 low grade glioma profiles. We identified 2724 such gene and 2418 pathway survival biomarkers out of total 17,717 genes and 7494 pathways analyzed. We then assessed tumor grade and molecular subtype biomarkers and with the threshold of AUC > 0.7 identified 1322/982 gene biomarkers and 472/537 pathway biomarkers. This suggests roughly two times greater efficacy of the reconstructed pathway approach compared to gene biomarkers. Thus, we conclude that activation levels of algorithmically reconstructed gene-centric pathways are a potent class of new-generation diagnostic and prognostic biomarkers for gliomas.