Flavonoids in Skin Senescence Prevention and Treatment

Skin aging is associated with the accumulation of senescent cells and is related to many pathological changes, including decreased protection against pathogens, increased susceptibility to irritation, delayed wound healing, and increased cancer susceptibility. Senescent cells secrete a specific set of pro-inflammatory mediators, referred to as a senescence-associated secretory phenotype (SASP), which can cause profound changes in tissue structure and function. Thus, drugs that selectively eliminate senescent cells (senolytics) or neutralize SASP (senostatics) represent an attractive therapeutic strategy for age-associated skin deterioration. There is growing evidence that plant-derived compounds (flavonoids) can slow down or even prevent aging-associated deterioration of skin appearance and function by targeting cellular pathways crucial for regulating cellular senescence and SASP. This review summarizes the senostatic and senolytic potential of flavonoids in the context of preventing skin aging.     

Synthetic adipic complex tetraesters as eco‐friendly lubricants

The paper presents results concerning the synthesis and characterisation as lubricants with biodegradability potential of some complex tetraesters realised on the basis of adipic acid and different glycols such as (mono) ethylene, 1,3‐propylene, 1,4‐butylene, 1,5‐pentamethylene, 1,6‐hexamethylene, diethylene and triethylene glycol, respectively, along with oleic acid used, considered as an end, final segment or as a capping element. On the basis of a regular alternation or successive distribution principle of the polar and nonpolar chemical functions equally distributed, shared out on the length of a sufficient, satisfactorily long, large molecule, valuable synthetic complex tetraester lubricants considered as eco‐friendly base oils with biodegradability potential were performed. These products showed very good tribological properties, such as high viscosity indices and high flash points, and also very good lubricity features. Copyright © 2013 John Wiley & Sons, Ltd.     

Acetylcholinesterase voltammetric biosensors based on carbon nanostructure-chitosan composite material for organophosphate pesticides

A sensitive biosensor for chloropyrifos (CPF), an organophosphorus pesticide, was developed by immobilizing acetylcholinesterase (AChE) through covalent bonding to an oxidized exfoliated graphite nanoplatelet (xGnPs)–chitosan cross-linked composite. Because of the increased surface area and the conductive properties of the nanomaterial, AChE developed a high affinity for acetylthiocholine (ATCI) and formed thiocholine with a fast response. The response of the sensor was a linear function of ATCI concentration in two segments, one from 0.005 to 0.039 mM and the second from 0.064 mM to 0.258 mM. The corresponding equation for the first range was i_p(A) = 2.26 × 10^? 5c + 4.39 × 10^? 7 (R² = 0.992) and the equation for the second was i_p(A) = 6.80 × 10^? 6c + 1.30 × 10^? 6 (R² = 1.000), with a detection limit of 1.58 × 10^? 10 M. The fabrication of the sensor was simple, the response was fast and the stability acceptable. This sensor has many potential applications, the foremost being in organophosphorus pesticides.     

Silica Nanoparticles Inhibit Responses to ATP in Human Airway Epithelial 16HBE Cells

Because of their low cost and easy production, silica nanoparticles (SiNPs) are widely used in multiple manufacturing applications as anti-caking, densifying and hydrophobic agents. However, this has increased the exposure levels of the general population and has raised concerns about the toxicity of this nanomaterial. SiNPs affect the function of the airway epithelium, but the biochemical pathways targeted by these particles remain largely unknown. Here we investigated the effects of SiNPs on the responses of 16HBE14o- cultured human bronchial epithelial (16HBE) cells to the damage-associated molecular pattern ATP, using fluorometric measurements of intracellular Ca²⁺ concentration. Upon stimulation with extracellular ATP, these cells displayed a concentration-dependent increase in intracellular Ca²⁺, which was mediated by release from intracellular stores. SiNPs inhibited the Ca²⁺ responses to ATP within minutes of application and at low micromolar concentrations, which are significantly faster and more potent than those previously reported for the induction of cellular toxicity and pro-inflammatory responses. SiNPs-induced inhibition is independent from the increase in intracellular Ca²⁺ they produce, is largely irreversible and occurs via a non-competitive mechanism. These findings suggest that SiNPs reduce the ability of airway epithelial cells to mount ATP-dependent protective responses.     

Prognostic Analysis of Human Pluripotent Stem Cells Based on Their Morphological Portrait and Expression of Pluripotent Markers

The ability of human pluripotent stem cells for unlimited proliferation and self-renewal promotes their application in the fields of regenerative medicine. The morphological assessment of growing colonies and cells, as a non-invasive method, allows the best clones for further clinical applications to be safely selected. For this purpose, we analyzed seven morphological parameters of both colonies and cells extracted from the phase-contrast images of human embryonic stem cell line H9, control human induced pluripotent stem cell (hiPSC) line AD3, and hiPSC line HPCASRi002-A (CaSR) in various passages during their growth for 120 h. The morphological phenotype of each colony was classified using a visual analysis and associated with its potential for pluripotency and clonality maintenance, thus defining the colony phenotype as the control parameter. Using the analysis of variance for the morphological parameters of each line, we showed that selected parameters carried information about different cell lines and different phenotypes within each line. We demonstrated that a model of classification of colonies and cells by phenotype, built on the selected parameters as predictors, recognized the phenotype with an accuracy of 70–75%. In addition, we performed a qRT-PCR analysis of eleven pluripotency markers genes. By analyzing the variance of their expression in samples from different lines and with different phenotypes, we identified group-specific sets of genes that could be used as the most informative ones for the separation of the best clones. Our results indicated the fundamental possibility of constructing a morphological portrait of a colony informative for the automatic identification of the phenotype and for linking this portrait to the expression of pluripotency markers.     

Replacing the Burden of the Gluten Free Diet: Then,Now, and the Future

Without a doubt, a majority of diseases are food-pattern-related. However, one disease stands out as an increasingly more common autoimmune-mediated enteropathy triggered by the ingestion of gluten. Celiac disease (CD) is an old disease, with changing clinical patterns, affecting any age, including infancy and adolescence, and becoming more frequent among the elderly. The gluten-free diet (GFD) has been the sole provider of clinical, serological, and histological improvement for patients with CD for more than seven decades. Nowadays, complete avoidance of dietary gluten is rarely possible because of the wide availability of wheat and other processed foods that contain even more gluten, to the detriment of gluten-free products. Undeniably, there is a definite need for replacing the burdensome GFD. An add-on therapy that could control the dietary transgressions and inadvertent gluten consumption that can possibly lead to overt CD should be considered while on GFD. Nevertheless, future drugs should be able to provide patients some freedom to self-manage CD and increase food independence, while actively reducing exposure and mucosal damage and alleviating GI symptoms. Numerous clinical trials assessing different molecules have already been performed with favorable outcomes, and hopefully they will soon be available for patient use.     

Mitochondrial DNA Together with miR-142-3p in Plasma Can Predict Unfavorable Outcomes in Patients after Acute Myocardial Infarction

Myocardial infarction is one of the leading causes of death worldwide, despite numerous efforts to find efficient prognostic biomarkers and treatment targets. In the present study, we aimed to assess the potential of six microRNAs known to be involved in cardiovascular diseases, cell-free DNA (cfDNA), and mitochondrial DNA (mtDNA) circulating in plasma to be used as prognostic tools for the occurrence of unfavorable outcomes such as major adverse cardiovascular events (MACE) after acute ST-segment elevation myocardial infarction (STEMI). Fifty STEMI patients were enrolled and monitored for 6 months for the occurrence of MACE. Plasma was collected at three time points: upon admission to hospital (T₀), at discharge from hospital (T₁), and 6 months post-STEMI (T₆). Plasma levels of miR-223-3p, miR-142-3p, miR-155-5p, miR-486-5p, miR-125a-5p, and miR-146a-5p, as well as of cfDNA and mtDNA, were measured by RT-qPCR. Results showed that the levels of all measured miRNAs, as well as of cfDNA and mtDNA, were the most increased at T₁, compared to the other two time points. In the plasma of STEMI patients with MACE compared to those without MACE, we determined increased levels of miRNAs, cfDNA, and mtDNA at T_1. Hence, we used the levels of all measured parameters at T₁ for further statistical analysis. Statistical analysis demonstrated that all six miRNAs and cfDNA plus mtDNA levels, respectively, were associated with MACE. The minimal statistical model that could predict MACE in STEMI patients was the combination of mtDNA and miR-142-3p levels, as evidenced by ROC analysis (AUC = 0.97, p < 0.001). In conclusion, the increased plasma levels of mtDNA, along with miR-142-3p, could be used to predict unfavorable outcomes in STEMI patients.     

Brain Neurons during Physiological Aging: Morphological Features,Autophagic and Mitochondrial Contribution

Accumulating data suggest that the brain undergoes various changes during aging. Among them are loss of both white and gray matter, neurons and synapses degeneration, as well as oxidative, inflammatory, and biochemical changes. The above-mentioned age-related features are closely related to autophagy and mitochondria. Therefore, we aimed to reveal the most peculiar morphological features of brain nervous tissue and to characterize the expression of autophagy and mitochondrial immunohistochemical biomarkers in neurons of different human brain zones during aging. Counting the number of neurons as well as Microtubule-associated proteins 1A/1B light chain 3B (LC3B), Heat shock protein 70 (HSP70), Lysosome-associated membrane protein type 2A (LAMP2A), Alpha subunit of ATP synthase (ATP5A), and Parkinson disease protein 7 (DJ1) immunohistochemical staining were performed on FFPE samples of human prefrontal cortex, corpus striatum, and hippocampus obtained from autopsy. Statistical analysis revealed a loss of neurons in the studied elderly group in comparison to the young group. When the expression of macroautophagy (LC3B), chaperon-mediated autophagy (HSP70, LAMP2A), and mitochondrial respiratory chain complex V (ATP5A) markers for the young and elderly groups were compared, the latter was found to have a significantly higher rate of optical density, whilst there was no significance in DJ1 expression. These findings, while preliminary, suggest that both autophagy and mitochondria are involved in neuronal maintenance during aging and could indicate their potential role in adaptive mechanisms that occur in aging.     

Magnetic composites based on bovine serum albumin and poly(aspartic acid)

In this investigation, magnetic polymer composites were developed by using a magnetic field‐assisted strategy. To create the composite, an interpolymeric complex based on bovine serum albumin and poly(aspartic acid) used as a polymer matrix was mixed with pre‐synthesized magnetite nanoparticles and then exposed to a high‐frequency magnetic field. The formation of such composite was confirmed by FTIR‐spectra, scanning electron micrographs, dynamic light scattering measurements, and magnetic susceptibility analysis. The results revealed that the materials have a superparamagnetic behavior and an average hydrodynamic size ranging from 220 to 580 nm. The polymer matrix improved the colloidal stability of the magnetic filler. The proposed composites are expected to be promising candidates for biomedical applications, such as drug delivery systems. POLYM. ENG. SCI., 59:1409–1415 2019. © 2019 Society of Plastics Engineers