Epigenetic Modulation of Vasopressin Expression in Health and Disease

Vasopressin is a ubiquitous molecule playing an important role in a wide range of physiological processes thereby implicated in the pathomechanism of many disorders. Its effect is well characterized through V2 receptors, which regulates the water resorption in kidney, while its vasoconstrictory effect through V1a receptor also received a lot of attention in the maintenance of blood pressure during shock. However, the most striking is its central effect both through the V1b receptors in stress-axis regulation as well as through V1a receptors regulating many aspects of our behavior (e.g., social behavior, learning and memory). Vasopressin has been implicated in the development of depression, due to its connection with chronic stress, as well as schizophrenia because of its involvement in social interactions and memory processes. Epigenetic changes may also play a role in the development of these disorders. The possible mechanism includes DNA methylation, histone modification and/or micro RNAs, and these possible regulations will be in the focus of our present review.     

TRPM8 as an Anti–Tumoral Target in Prostate Cancer Growth and Metastasis Dissemination

In the fight against prostate cancer (PCa), TRPM8 is one of the most promising clinical targets. Indeed, several studies have highlighted that TRPM8 involvement is key in PCa progression because of its impact on cell proliferation, viability, and migration. However, data from the literature are somewhat contradictory regarding the precise role of TRPM8 in prostatic carcinogenesis and are mostly based on in vitro studies. The purpose of this study was to clarify the role played by TRPM8 in PCa progression. We used a prostate orthotopic xenograft mouse model to show that TRPM8 overexpression dramatically limited tumor growth and metastasis dissemination in vivo. Mechanistically, our in vitro data revealed that TRPM8 inhibited tumor growth by affecting the cell proliferation and clonogenic properties of PCa cells. Moreover, TRPM8 impacted metastatic dissemination mainly by impairing cytoskeleton dynamics and focal adhesion formation through the inhibition of the Cdc42, Rac1, ERK, and FAK pathways. Lastly, we proved the in vivo efficiency of a new tool based on lipid nanocapsules containing WS12 in limiting the TRPM8–positive cells’ dissemination at metastatic sites. Our work strongly supports the protective role of TRPM8 on PCa progression, providing new insights into the potential application of TRPM8 as a therapeutic target in PCa treatment.     

Investigation of Anxiety- and Depressive-like Symptoms in 4- and 8-Month-Old Male Triple Transgenic Mouse Models of Alzheimer’s Disease

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder and the most common form of dementia. Approximately 50% of AD patients show anxiety and depressive symptoms, which may contribute to cognitive decline. We aimed to investigate whether the triple-transgenic mouse (3xTg-AD) is a good preclinical model of this co-morbidity. The characteristic histological hallmarks are known to appear around 6-month; thus, 4- and 8-month-old male mice were compared with age-matched controls. A behavioral test battery was used to examine anxiety- (open field (OF), elevated plus maze, light-dark box, novelty suppressed feeding, and social interaction (SI) tests), and depression-like symptoms (forced swim test, tail suspension test, sucrose preference test, splash test, and learned helplessness) as well as the cognitive decline (Morris water maze (MWM) and social discrimination (SD) tests). Acetylcholinesterase histochemistry visualized cholinergic fibers in the cortex. Dexamethasone-test evaluated the glucocorticoid non-suppression. In the MWM, the 3xTg-AD mice found the platform later than controls in the 8-month-old cohort. The SD abilities of the 3xTg-AD mice were missing at both ages. In OF, both age groups of 3xTg-AD mice moved significantly less than the controls. During SI, 8-month-old 3xTg-AD animals spent less time with friendly social behavior than the controls. In the splash test, 3xTg-AD mice groomed themselves significantly less than controls of both ages. Cortical fiber density was lower in 8-month-old 3xTg-AD mice compared to the control. Dexamethasone non-suppression was detectable in the 4-month-old group. All in all, some anxiety- and depressive-like symptoms were present in 3xTg-AD mice. Although this strain was not generally more anxious or depressed, some aspects of comorbidity might be studied in selected tests, which may help to develop new possible treatments.     

Targeting the Surface of the Protein 14-3-3 by Ultrasmall (1.5 nm) Gold Nanoparticles Carrying the Specific Peptide CRaf

The surface of ultrasmall gold nanoparticles with an average diameter of 1.55 nm was conjugated with a 14-3-3 protein-binding peptide derived from CRaf. Each particle carries 18 CRaf peptides, leading to an overall stoichiometry of Au(115)Craf(18). The binding to the protein 14-3-3 was probed by isothermal titration calorimetry (ITC) and fluorescence polarization spectroscopy (FP). The dissociation constant (K_D) was measured as 5.0 μM by ITC and 0.9 μM by FP, which was close to the affinity of dissolved CRaf to 14-3-3σ. In contrast to dissolved CRaf, which alone did not enter HeLa cells, CRAF-conjugated gold nanoparticles were well taken up by HeLa cells, opening the opportunity to target the protein inside a cell.     

Analysis of Biomechanical Parameters of Muscle Soleus Contraction and Blood Biochemical Parameters in Rat with Chronic Glyphosate Intoxication and Therapeutic Use of C60 Fullerene

The widespread use of glyphosate as a herbicide in agriculture can lead to the presence of its residues and metabolites in food for human consumption and thus pose a threat to human health. It has been found that glyphosate reduces energy metabolism in the brain, its amount increases in white muscle fibers. At the same time, the effect of chronic use of glyphosate on the dynamic properties of skeletal muscles remains practically unexplored. The selected biomechanical parameters (the integrated power of muscle contraction, the time of reaching the muscle contraction force its maximum value and the reduction of the force response by 50% and 25% of the initial values during stimulation) of muscle soleus contraction in rats, as well as blood biochemical parameters (the levels of creatinine, creatine phosphokinase, lactate, lactate dehydrogenase, thiobarbituric acid reactive substances, hydrogen peroxide, reduced glutathione and catalase) were analyzed after chronic glyphosate intoxication (oral administration at a dose of 10 μg/kg of animal weight) for 30 days. Water-soluble C₆₀ fullerene, as a poweful antioxidant, was used as a therapeutic nanoagent throughout the entire period of intoxication with the above herbicide (oral administration at doses of 0.5 or 1 mg/kg). The data obtained show that the introduction of C₆₀ fullerene at a dose of 0.5 mg/kg reduces the degree of pathological changes by 40–45%. Increasing the dose of C₆₀ fullerene to 1 mg/kg increases the therapeutic effect by 55–65%, normalizing the studied biomechanical and biochemical parameters. Thus, C₆₀ fullerenes can be effective nanotherapeutics in the treatment of glyphosate-based herbicide poisoning.     

Optimisation of the synthesis of vancomycin-selective molecularly imprinted polymer nanoparticles using automatic photoreactor

A novel optimized protocol for solid-state synthesis of molecularly imprinted polymer nanoparticles (nanoMIPs) with specificity for antibiotic vancomycin is described. The experimental objective was optimization of the synthesis parameters (factors) affecting the yield of obtained nanoparticles which have been synthesized using the first prototype of an automated solid-phase synthesizer. Applications of experimental design (or design of experiments) in optimization of nanoMIP yield were carried out using MODDE 9.0 software. The factors chosen in the model were the amount of functional monomers in the polymerization mixture, irradiation time, temperature during polymerization, and elution temperature. In general, it could be concluded that the irradiation time is the most important and the temperature was the least important factor which influences the yield of nanoparticles. Overall, the response surface methodology proved to be an effective tool in reducing time required for optimization of complex experimental conditions.     

Printing Inks＇ Characteristics

Hybrid inks are often used for the advertising products because a variety of effects can serve as an added value. Much attention is paid to the inks application settings, using the hybrid inks at the hi-tech offset equipment and color features of images. The thorough research of the different printing settings with the use of modern inks and efficient equipment, is an urgent problem. Work reveals some new facts about characteristics for printability such as emulsification and influences of ink＇s additives on color characteristics of imprints. The experimental inks were developed to define the technological settings of offset printing. The result of research showed that conventional inks have the considerably high degree of emulsification comparing to experimental hybrid inks. Also it was discovered that the UV components influence the emulsification. An optimal water-ink balance and stable printing process can be achieved with adding of 2%-10% of the UV-component to the hybrid inks. Inks application and drying settings as well as color features of the imprints are analyzed in the context of offset printing.     

Ultrastructural study of mouse adipose‐derived stromal cells induced towards osteogenic direction

We investigated the ultrastructural characteristics of mouse adipose‐derived stem/stromal cells (ASCs) induced towards osteogenic lineage. ASCs were isolated from adipose tissue of FVB‐Cg‐Tg(GFPU)5Nagy/J mice and expanded in monolayer culture. Flow cytometry, histochemical staining, and electron microscopy techniques were used to characterize the ASCs with respect to their ability for osteogenic differentiation capacity. Immunophenotypically, ASCs were characterized by high expression of the CD44 and CD90 markers, while the relative content of cells expressing CD45, CD34 and CD117 markers was <2%. In assays of differentiation, the positive response to osteogenic differentiation factors was observed and characterized by deposition of calcium in the extracellular matrix and alkaline phosphatase production. Electron microscopy analysis revealed that undifferentiated ASCs had a rough endoplasmic reticulum with dilated cisterns and elongated mitochondria. At the end of the osteogenic differentiation, the ASCs transformed from their original fibroblast‐like appearance to having a polygonal osteoblast‐like morphology. Ultrastructurally, these cells were characterized by large euchromatic nucleus and numerous cytoplasm containing elongated mitochondria, a very prominent rough endoplasmic reticulum, Golgi apparatus and intermediate filament bundles. Extracellular matrix vesicles of variable size similar to the calcification nodules were observed among collagen fibrils. Our data provide the ultrastructural basis for further studies on the cellular mechanisms involved in osteogenic differentiation of mouse adipose‐derived stem/stromal cells. Microsc. Res. Tech. 79:557–564, 2016. © 2016 Wiley Periodicals, Inc.     

Fabrication of new antifungal polyamide‐12 material

Water‐resistant polymeric biocide poly(hexamethylene guanidine) dodecylbenzenesulfonate (PHMG‐DBS) was synthesized by anion metathesis between poly(hexamethylene guanidine) hydrochloride and sodium dodecylbenzenesulfonate and subsequently characterized using elemental analysis, Raman spectroscopy and thermogravimetric analysis. It is found that PHMG‐DBS is thermally stable to at least 350 °C, which makes it suitable for melt blending with polyamide (PA) resins. An antifungal PA‐12 composition was prepared by compression moulding of PA‐12 and PHMG‐DBS powder mixture at 240 °C. The characteristics of the prepared films were investigated: surface roughness and hydrophobicity using atomic force microscopy and contact angle measurements, respectively. No significant change in the material characteristics is observed compared to pure PA‐12 films. PA‐12 films containing 2 wt% of the PHMG‐DBS biocide are found to be highly resistant against Trychophyton mentagrophytes fungus. Copyright © 2012 Society of Chemical Industry     

Modified bentonites as adsorbents of hydrogen sulfide gases

Carbonate-rich bentonite was modified by iron and copper chlorides in order to synthesize effective and cheap adsorbents for neutralization of H₂S in low-concentrated exhaust gases. Bentonite and modified bentonite were analysed using atomic absorption spectroscopy (AAS), X-ray diffraction (XRD), scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR) and BET surface area analysis. In addition, bentonite and modified bentonite were tested as hydrogen sulfide adsorbents. Iron-containing material showed a significant improvement in the capacity for H₂S removal. The longest time of effective protective action (before H₂S appears on the outlet of the column) was obtained for the bentonite modified with copper hydroxide. The results indicated that on the surface of modified samples hydrogen sulfide reacts with metal hydroxide forming sulfides. Sulfided iron-containing sample could be regenerated by exposing it to the air.