Partialsynthesen von Cardenoliden und Cardenolid-Analogen. IX. Cardenolidderivate mit einer ungesättigten Aldehydfunktion am Lactonring

Partial Syntheses of Cardenolides and Cardenolide Analogues. IX. Cardenolide Derivatives with an Unsaturated Aldehyde Function at the Lactone Ring Oxidation of 22-allyl-digitoxigenin-3-acetate [ 1 ] and 22-allyl-digitoxin ( 4 ) with selenium dioxide resulted in the introduction of an oxygen function into the unsaturated C-22 substituent of the cardenolide molecule. The isolated compounds were the 22-(3′-oxo-prop-1′-en-1′-yl)-derivatives 3 and 6 of 1 and 4 , respectively. The molecular biological activity of 3 was estimated to be about six times higher than that of the parent compound 1 .     

Micro-RNA and Proteomic Profiles of Plasma-Derived Exosomes from Irradiated Mice Reveal Molecular Changes Preventing Apoptosis in Neonatal Cerebellum

Cell communication via exosomes is capable of influencing cell fate in stress situations such as exposure to ionizing radiation. In vitro and in vivo studies have shown that exosomes might play a role in out-of-target radiation effects by carrying molecular signaling mediators of radiation damage, as well as opposite protective functions resulting in resistance to radiotherapy. However, a global understanding of exosomes and their radiation-induced regulation, especially within the context of an intact mammalian organism, has been lacking. In this in vivo study, we demonstrate that, compared to sham-irradiated (SI) mice, a distinct pattern of proteins and miRNAs is found packaged into circulating plasma exosomes after whole-body and partial-body irradiation (WBI and PBI) with 2 Gy X-rays. A high number of deregulated proteins (59% of WBI and 67% of PBI) was found in the exosomes of irradiated mice. In total, 57 and 13 miRNAs were deregulated in WBI and PBI groups, respectively, suggesting that the miRNA cargo is influenced by the tissue volume exposed to radiation. In addition, five miRNAs (miR-99b-3p, miR-200a-3p, miR-200a, miR-182-5p, miR-182) were commonly overexpressed in the exosomes from the WBI and PBI groups. In this study, particular emphasis was also given to the determination of the in vivo effect of exosome transfer by intracranial injection in the highly radiosensitive neonatal cerebellum at postnatal day 3. In accordance with a major overall anti-apoptotic function of the commonly deregulated miRNAs, here, we report that exosomes from the plasma of irradiated mice, especially in the case of WBI, prevent radiation-induced apoptosis, thus holding promise for exosome-based future therapeutic applications against radiation injury.     

Acrylamide Neurotoxicity as a Possible Factor Responsible for Inflammation in the Cholinergic Nervous System

Acrylamide (ACR) is a chemical compound that exhibits neurotoxic and genotoxic effects. It causes neurological symptoms such as tremors, general weakness, numbness, tingling in the limbs or ataxia. Numerous scientific studies show the effect of ACR on nerve endings and its close connection with the cholinergic system. The cholinergic system is part of the autonomic nervous system that regulates higher cortical functions related to memory, learning, concentration and attention. Within the cholinergic system, there are cholinergic neurons, anatomical cholinergic structures, the neurotransmitter acetylcholine (ACh) and cholinergic receptors. Some scientific reports suggest a negative effect of ACR on the cholinergic system and inflammatory reactions within the body. The aim of the study was to review the current state of knowledge on the influence of acrylamide on the cholinergic system and to evaluate its possible effect on inflammatory processes. The cholinergic anti-inflammatory pathway (CAP) is a neuroimmunomodulatory pathway that is located in the blood and mucous membranes. The role of CAP is to stop the inflammatory response in the appropriate moment. It prevents the synthesis and the release of pro-inflammatory cytokines and ultimately regulates the local and systemic immune response. The cellular molecular mechanism for inhibiting cytokine synthesis is attributed to acetylcholine (ACh), the major vagal neurotransmitter, and the α7 nicotinic receptor (α7nAChR) subunit is a key receptor for the cholinergic anti-inflammatory pathway. The combination of ACh with α7nAChR results in inhibition of the synthesis and release of pro-inflammatory cytokines. The blood AChE is able to terminate the stimulation of the cholinergic anti-inflammatory pathway due to splitting ACh. Accordingly, cytokine production is essential for pathogen protection and tissue repair, but over-release of cytokines can lead to systemic inflammation, organ failure, and death. Inflammatory responses are precisely regulated to effectively protect against harmful stimuli. The central nervous system dynamically interacts with the immune system, modulating inflammation through the humoral and nervous pathways. The stress-induced rise in acetylcholine (ACh) level acts to ease the inflammatory response and restore homeostasis. This signaling process ends when ACh is hydrolyzed by acetylcholinesterase (AChE). There are many scientific reports indicating the harmful effects of ACR on AChE. Most of them indicate that ACR reduces the concentration and activity of AChE. Due to the neurotoxic effect of acrylamide, which is related to the disturbance of the secretion of neurotransmitters, and its influence on the disturbance of acetylcholinesterase activity, it can be concluded that it disturbs the normal inflammatory response.     

The Influence of Betulin and Its Derivatives EB5 and ECH147 on the Antioxidant Status of Human Renal Proximal Tubule Epithelial Cells

Betulin and its derivatives, 28-propyne derivative EB5 and 29-diethyl phosphonate analog ECH147, are promising compounds in anti-tumor activity studies. However, their effect on kidney cells has not yet been studied. The study aimed to determine whether betulin and its derivatives—EB5 and ECH147—influence the viability and oxidative status of human renal proximal tubule epithelial cells (RPTECs). The total antioxidant capacity of cells (TEAC), lipid peroxidation product malondialdehyde (MDA) level, and activity of antioxidant enzymes (SOD, CAT, and GPX) were evaluated. Additionally, the mRNA level of genes encoding antioxidant enzymes was assessed. Cisplatin and 5-fluorouracil were used as reference substances. Betulin and its derivatives affected the viability and antioxidant systems of RPTECs. Betulin strongly reduced TEAC in a concentration-dependent manner. All tested compounds caused an increase in MDA levels. The activity of SOD, CAT, and GPX, and the mRNA profiles of genes encoding antioxidant enzymes depended on the tested compound and its concentration. Betulin showed an cisplatin-like effect, indicating its nephrotoxic potential. Betulin derivatives EB5 and ECH147 showed different impacts on the antioxidant system, which gives hope that these compounds will not cause severe consequences for the kidneys in vivo.     

Reaktionen des 2,6-Di-tert.-butyl-4-(N-tert.-butylnitrono)-phenoxyradikals

Reactions of the 2,6-Di-tert.-butyl-4-(N-tert.-butylnitrono)-phenoxyl Radical The title compound, a phenoxyl radical containing a nitrono group, reacts with alcohols and tert.-butylhydroperoxide yielding phenol and products of secondary radical solvent reactions. The reactions with lead tetraacetate, tert.-butoxy and 2-cyanoisopropyl radicals give high yields of cyclohexadienone adducts ( 6, 7 and 10 ) containing unchanged nitrono function. The reaction with dibenzoylperoxide, however, leads to the modification of the nitrono group yielding the N-benzoyloxycarboxamide ( 8 ). In the acidic decomposition of the tert.-butoxy radical adduct we suggest a nitrenium ion ( 16 ) as an intermediate.     

Field determination of total dissolved inorganic carbon (TDIC) in natural waters using an IR analyzer: I. Preliminary laboratory tests

Preliminary laboratory tests carried out on 20 mineral waters indicate that the infrared (IR) method for the determination of total dissolved inorganic carbon (TDIC) is more accurate than the pH-alkalinity method, especially for high-TDIC, naturally sparkling waters and low-TDIC waters. The results of the two analytical methods are similar for mineral waters whose TDIC ranges from 100 to 500 mg/L as HCO₃, suggesting a relative accuracy of 0.3–2.9%. The limit of detection (LOD) of the IR method is close to 10 mg HCO₃/L and independent of pH. This value is comparable with the LOD of the pH-alkalinity method in the pH range 6.5–9 whereas the LOD of the latter increases strongly with decreasing pH below pH 6.5. The IR method is quick, since a run takes a few minutes and, on average, 10 analyses are carried out in an hour, including the time spent for clean up and preparation between samples. It constitutes a sound alternative to the pH-alkalinity technique for the field measurement of TDIC in geothermal and other natural waters.     

The Reciprocal Influences among Motivation,Personality Traits,and Game Habits for Playing Pokémon GO

This article reports a study exploring motivations of Pokémon Game use, individual differences related to personality traits, and game habits. First, it analyzed Pokémon GO motivations through exploratory factor analysis (EFA) by administering online the Pokémon GO Motivational Scale to a group of Italian gamers (N = 560). Successively, a Confirmatory Factor Analysis (CFA) was conducted testing three factorial models of Pokémon Game motivations on a selected random sample (N = 310). Results showed a three-factor model of Pokémon GO Game motivations (i.e. Personal Needs, Social Needs and Recreation), accounting for 68.9% of total variance plus a general higher order factor that best fits the data. Individual differences in Pokémon GO motivations and personality traits have been explored showing that high involved Pokémon GO players are introverted, low agreeableness, and conscientiousness people, driven by personal social and recreational needs. Reciprocal influences on motivational involvement, personality, and game habits were discussed.     

The Use of Grey Systems Theory to Analyze the Water Supply Systems Safety

Water Resources Management - New requirements for water supply companies enforce the implementation of risk analysis and assessment methods on many levels of their operation. The approach...