Vitamin D Compounds PRI-2191 and PRI-2205 Enhance Anastrozole Activity in Human Breast Cancer Models

1,25-Dihydroxycholecalciferol, the hormonally active vitamin D₃ metabolite, is known to exhibit therapeutic effects against breast cancer, mainly by lowering the expression of estrogen receptors and aromatase activity. Previously, the safety of the vitamin D active metabolite (24R)-1,24-dihydroxycholecalciferol (PRI-2191) and 1,25(OH)₂D₃ analog PRI-2205 was tested, and the in vitro activity of these analogs against different cancer cell lines was studied. We determined the effect of the two vitamin D compounds on anastrozole (An) activity against breast cancer based on antiproliferative activity, ELISA, flow cytometry, enzyme inhibition potency, PCR, and xenograft study. Both the vitamin D active metabolite and synthetic analog regulated the growth of not only estrogen receptor-positive cells (T47D and MCF-7, in vitro and in vivo), but also hormone-independent cancer cells such as SKBR-3 (HER-2-positive) and MDA-MB-231 (triple-negative), despite their relatively low VDR expression. Combined with An, PRI-2191 and PRI-2205 significantly inhibited the tumor growth of MCF-7 cells. Potentiation of the antitumor activity in combined treatment of MCF-7 tumor-bearing mice is related to the reduced activity of aromatase by both An (enzyme inhibition) and vitamin D compounds (switched off/decreased aromatase gene expression, decreased expression of other genes related to estrogen signaling) and by regulation of the expression of the estrogen receptor ERα and VDR.     

Thermo-protective properties of polymer composites with nano-titanium dioxide

International Journal of Mechanics and Materials in Design - The present work investigates the ablative and thermal properties of an epoxy resin which was modified with titanium dioxide...     

Influence of some lysosomotropic compounds on calcium ion desorption process from liposome membrane

The effect of a group of model lysosomotropic compounds on the process of Ca2+ ion desorption from lecithin liposome membranes was studied. The compounds studied were: hydrochlorides of fatty acids 2-dimethylaminoethyl esters (DM-n) for n = 9, 11, 13 and 15 carbon atoms in the fatty acid alkyl chain and methochloride of 2-dimethylaminoethyl laurate (DMS-11). It was found that all the compounds studied caused increased desorption with increasing concentration of the compound. Most effective was the quaternary ammonium salt, DMS-11. Moreover, it was found that the process of Ca2+ desorption from the membrane depended on pH of the medium. Compound DM-11 was more active at pH 8 than at pH 5. The action of DM-n compounds depended on the alkyl chain length, DM-11 and DM-13 being the most active. Apparently free amines penetrate the phospholipid membranes and incorporate into its hydrophobic core causing structural deformations. Hydrochlorides of fatty acids and the quaternary ammonium salt induce desorption of calcium ions mostly as a result of competitive electrostatic interactions. By quantum chemistry, PM3 method, and methods of molecular modelling we established the higher hydrophilicity of the polar head of DM-n series with respect to the polar head of the DMS-n compounds. DM-n compounds possess both acceptor and donor properties for hydrogen bonding while DMS-n are instrumental as acceptors only. It should be noted, that the results obtained in this paper for model membranes are in accordance with those for biological ones.     

The Effect of Hypoxia on the Expression of CXC Chemokines and CXC Chemokine Receptors—A Review of Literature

Hypoxia is an integral component of the tumor microenvironment. Either as chronic or cycling hypoxia, it exerts a similar effect on cancer processes by activating hypoxia-inducible factor-1 (HIF-1) and nuclear factor (NF-κB), with cycling hypoxia showing a stronger proinflammatory influence. One of the systems affected by hypoxia is the CXC chemokine system. This paper reviews all available information on hypoxia-induced changes in the expression of all CXC chemokines (CXCL1, CXCL2, CXCL3, CXCL4, CXCL5, CXCL6, CXCL7, CXCL8 (IL-8), CXCL9, CXCL10, CXCL11, CXCL12 (SDF-1), CXCL13, CXCL14, CXCL15, CXCL16, CXCL17) as well as CXC chemokine receptors—CXCR1, CXCR2, CXCR3, CXCR4, CXCR5, CXCR6, CXCR7 and CXCR8. First, we present basic information on the effect of these chemoattractant cytokines on cancer processes. We then discuss the effect of hypoxia-induced changes on CXC chemokine expression on the angiogenesis, lymphangiogenesis and recruitment of various cells to the tumor niche, including myeloid-derived suppressor cells (MDSCs), tumor-associated macrophages (TAMs), tumor-associated neutrophils (TANs), regulatory T cells (T_regs) and tumor-infiltrating lymphocytes (TILs). Finally, the review summarizes data on the use of drugs targeting the CXC chemokine system in cancer therapies.     

Poly(chitosan-ester-ether-urethane) Hydrogels as Highly Controlled Genistein Release Systems

Polymeric hydrogels play an increasingly important role in medicine, pharmacy and cosmetology. They appear to be one of the most promising groups of biomaterials due to their favorable physicochemical properties and biocompatibility. The objective of the presented study was to synthesize new poly(chitosan-ester-ether-urethane) hydrogels and to study the kinetic release of genistein (GEN) from these biomaterials. In view of the above, six non-toxic hydrogels were synthesized via the Ring-Opening Polymerization (ROP) and polyaddition processes. The poly(ester-ether) components of the hydrogels have been produced in the presence of the enzyme as a biocatalyst. In some cases, the in vitro release rate of GEN from the obtained hydrogels was characterized by near-zero-order kinetics, without “burst release” and with non-Fickian transport. It is important to note that developed hydrogels have been shown to possess the desired safety profile due to lack of cytotoxicity to skin cells (keratinocytes and fibroblasts). Taking into account the non-toxicity of hydrogels and the relatively highly controlled release profile of GEN, these results may provide fresh insight into polymeric hydrogels as an effective dermatological and/or cosmetological tool.     

Analysis of polymer foil heaters as infrared radiation sources

Infrared radiation as a heat source is used in many fields. In particular, the positive effect of far-infrared radiation on living organisms has been observed. This paper presents two technological solutions for infrared heater production using polymer-silver and polymer-carbon pastes screenprinted on foil substrates. The purpose of this work was the identification of polymer layers as a specific frequency range IR radiation sources. The characterization of the heaters was determined mainly by measurement of the surface temperature distribution using a thermovision camera and the spectral characteristics were determined using a special measuring system. Basic parameters obtained for both, polymer silver and polymer carbon heaters were similar and were as follows: power rating of 10–12 W/dm², continuous working surface temperature of 80–90 °C, temperature coefficient of resistance (TCR) about +900 ppm/K for polymer-carbon heater and about +2000 ppm/K for polymer-silver, maximum radiation intensity in the wavelength range of 6–14 μm with top intensity at 8.5 μm and heating time about 20 min. For comparison purposes, commercial panel heater was tested. The results show that the characteristics of infrared polymer heaters are similar to the characteristics of the commercial heater, so they can be taken into consideration as the alternative infrared radiation sources.     

Rheological characteristics of oligomeric semiproducts gained via chemical degradation of polyurethane foam using crude glycerin in the presence of different catalysts

Polyurethane (PU) recycling is a topic of growing interest due to the increasing amount of polyurethane waste. The main purpose of polyurethane chemical recycling is to recover the starting polyol. In this study, a method of polyurethane thermochemical recycling, glycerolysis by means of crude glycerin, is proposed. This work presents a comparative study of commercial catalysts used in order to accelerate the decomposition process, namely triethylamine (TEA), potassium acetate (KAc), 1,4‐diazabicyclo[2.2.2]octane (DABCO), sodium hydroxide (NaOH), dibutyltin dilaurate (DbDl), and stannous octoate (StOc).The effect of used catalyst on the chemical structure and rheological properties was studied. The type of catalyst does not have significant influence on the chemical structure, but causes different course of reaction: split‐ and single‐phase in applied conditions. Glycerolysates were measured by Brookfield Rheometer. It was found that repolyols can be described by the Herschel–Bulkely mathematical model in the best accuracy. The investigation showed that the rheological behavior of glycerolysates depended on the catalyst used in glycerolysis process. POLYM. ENG. SCI., 57:891–900, 2017. © 2016 Society of Plastics Engineers     

Long-Term Changes in Ovarian Follicles of Gilts Exposed Neonatally to Methoxychlor: Effects on Oocyte-Derived Factors,Anti-Müllerian Hormone,Follicle-Stimulating Hormone,and Cognate Receptors

In this paper, we investigated the effects of neonatal exposure to methoxychlor (MXC), a synthetic organochlorine used as an insecticide with estrogenic, antiestrogenic, and antiandrogenic activities on ovarian follicles of adult pigs. Piglets were injected with MXC (20 μg/kg body weight) or corn oil (controls) from postnatal Day 1 to Day 10 (n = 5 per group). Then, mRNA expression, protein abundance and immunolocalization of growth and differentiation factor 9 (GDF9), bone morphogenetic protein 15 (BMP15), anti-Müllerian hormone (AMH) and cognate receptors (ACVR1, BMPR1A, BMPR1B, TGFBR1, BMPR2, and AMHR2), as well as FSH receptor (FSHR) were examined in preantral and small antral ovarian follicles of sexually mature gilts. The plasma AMH and FSH levels were also assessed. In preantral follicles, neonatal exposure to MXC increased GDF9, BMPR1B, TGFBR1, and BMPR2 mRNAs, while the levels of AMH and BMP15 mRNAs decreased. In addition, MXC also decreased BMP15 and BMPR1B protein abundance. Regarding small antral follicles, neonatal exposure to MXC upregulated mRNAs for BMPR1B, BMPR2, and AMHR2 and downregulated mRNAs for AMH, BMPR1A, and FSHR. MXC decreased the protein abundance of AMH, and all examined receptors in small antral follicles. GDF9 and BMP15 were immunolocalized in oocytes and granulosa cells of preantral follicles of control and treated ovaries. All analyzed receptors were detected in the oocytes and granulosa cells of preantral follicles, and in the granulosa and theca cells of small antral follicles. The exception, however, was FSHR, which was detected only in the granulosa cells of small antral follicles. In addition, MXC decreased the plasma AMH and FSH concentrations. In conclusion, the present study may indicate long-term effects of neonatal MXC exposure on GDF9, BMP15, AMH, and FSH signaling in ovaries of adult pigs. However, the MXC effects varied at different stages of follicular development. It seems that neonatal MXC exposure may result in accelerated initial recruitment of ovarian follicles and impaired cyclic recruitment of antral follicles.     

Cannabidiol Downregulates Myocardial de Novo Ceramide Synthesis Pathway in a Rat Model of High-Fat Diet-Induced Obesity

It is known that metabolic disturbances, including obesity, predispose to an increased incidence of cardiovascular diseases. Elevated consumption of dietary fat results in intramyocardial accumulation of lipids and their biologically active derivatives, which can disrupt the contractile function of the heart, its metabolism, and intracellular signaling pathways. Therefore, alternative methods, such as phytocannabinoids, are being sought for the treatment of obesity-related effects. In a model of rodent obesity (seven weeks of high-fat-diet (HFD) regime), we used cannabidiol—CBD therapy (intraperitoneal injections for 14 days; 10 mg/kg). High-performance and gas-liquid chromatographies were applied in order to determine sphingolipids in the heart and plasma as well as Western blotting for protein expression. Two-week CBD administration significantly inhibited the de novo ceramide synthesis pathway in the heart of HFD fed rats by lowering sphinganine and sphinganine-1-phosphate contents. The above reductions were accompanied by markedly diminished expressions of myocardial serine palmitoyltransferase 1 and 2 as well as ceramide synthase 5 and 6 in the HFD group with 2-week CBD treatment. To our knowledge, this research is the first that reveals unknown effects of CBD treatment on the heart, i.e., amelioration of de novo ceramide synthesis pathway in obese rats.     

Investigation of the Sharkskin melt instability using optical Fourier analysis

An optical method allowing the characterization of melt flow instabilities typically occurring during an extrusion process of polymers and polymer compounds is presented. It is based on a camera-acquired image of the extruded compound with a reference length scale. Application of image processing and transformation of the calibrated image to the frequency domain yields the magnitude spectrum of the instability. The effectiveness of the before mentioned approach is shown on Styrene-butadiene rubber (SBR) compounds, covering a wide range of silica filler content, extruded through a Göttfert capillary rheometer. The results of the image-based analysis are compared with the results from the sharkskin option, a series of highly sensitive pressure transducers installed inside the rheometer. A simplified version of the code used to produce the optical analysis results is included as supplementary material. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2020 , 137, 48806.