Oncogenic Mutation BRAF V600E Changes Phenotypic Behavior of THLE-2 Liver Cells through Alteration of Gene Expression

The accumulation of mutations in cancer driver genes, such as tumor suppressors or proto-oncogenes, affects cellular homeostasis. Disturbances in the mechanism controlling proliferation cause significant augmentation of cell growth and division due to the loss of sensitivity to the regulatory signals. Nowadays, an increasing number of cases of liver cancer are observed worldwide. Data provided by the International Cancer Genome Consortium (ICGC) have indicated many alterations within gene sequences, whose roles in tumor development are not well understood. A comprehensive analysis of liver cancer (virus-associated hepatocellular carcinoma) samples has identified new and rare mutations in B-Raf proto-oncogene (BRAF) in Japanese HCC patients, as well as BRAF V600E mutations in French HCC patients. However, their function in liver cancer has never been investigated. Here, using functional analysis and next generation sequencing, we demonstrate the tumorigenic effect of BRAF V600E on hepatocytes (THLE-2 cell line). Moreover, we identified genes such as BMP6, CXCL11, IL1B, TBX21, RSAD2, MMP10, and SERPIND1, which are possibly regulated by the BRAF V600E-mediated, mitogen-activated protein kinases/extracellular signal-regulated kinases (MAPK/ERK) signaling pathway. Through several functional assays, we demonstrate that BRAF L537M, D594A, and E648G mutations alone are not pathogenic in liver cancer. The investigation of genome mutations and the determination of their impact on cellular processes and functions is crucial to unraveling the molecular mechanisms of liver cancer development.     

Effect of Acute Sprint Exercise on Myokines and Food Intake Hormones in Young Healthy Men

Physical exercise is known to influence hormonal mediators of appetite, but the effect of short-term maximal intensity exercise on plasma levels of appetite hormones and cytokines has been little studied. We investigated the effect of a 30 s Wingate Test, followed by a postprandial period, on appetite sensations, food intake, and appetite hormones. Twenty-six physically active young males rated their subjective feelings of hunger, prospective food consumption, and fatigue on visual analogue scales at baseline, after exercise was completed, and during the postprandial period. Blood samples were obtained for the measurement of nesfatin-1, ghrelin, leptin, insulin, pancreatic polypeptide (PP), human growth factor (hGH) and cytokine interleukin-6 (IL-6), irisin and plasma lactate concentrations, at 30 min before exercise, immediately (210 s) after exercise, and 30 min following a meal and at corresponding times in control sedentary males without ad libitum meal intake, respectively. Appetite perceptions and food intake were decreased in response to exercise. Plasma levels of irisin, IL-6, lactate, nesfatin-1 and ghrelin was increased after exercise and then it was returned to postprandial/control period in both groups. A significant rise in plasma insulin, hGH and PP levels after exercise was observed while meal intake potentiated this response. In conclusion, an acute short-term fatiguing exercise can transiently suppress hunger sensations and food intake in humans. We postulate that this physiological response involves exercise-induced alterations in plasma hormones and the release of myokines such as irisin and IL-6, and supports the notion of existence of the skeletal muscle–brain–gut axis. Nevertheless, the detailed relationship between acute exercise releasing myokines, appetite sensations and impairment of this axis leading to several diseases should be further examined.     

Associations between Oil Yield and Profile of Fatty Acids,Sterols, Squalene,Carotenoids, and Tocopherols in Seed Oil of Selected Japanese Quince Genotypes during Fruit Development

Tocopherols, phytosterols, carotenoids, and squalene are present in mature seeds of Japanese quince. Yet, little is known about the relationship between these compounds and oil yield during fruit and seed development. The profile change of lipophilic compounds during fruit and seed development in Japanese quince cultivars “Darius,” “Rondo,” and “Rasa” is investigated. It is shown here that during fruit and seed development, there is a significant reduction, three‐ to over tenfold, in the concentration of minor bioactive compounds in seed oil. It is recorded that delay between synthesis of tocopherols and oil in Japanese quince seeds during the fruit development results in a logarithmic relationship between the oil content and tocopherols concentration in the seed oil (R² = 0.980). Similar trends are observed between oil yield and phytosterols, and carotenoids (R² = 0.927 and R² = 0.959, respectively). The profile of fatty acids during the development of the seeds significantly is changed. The reduction of linoleic, palmitic, and gondoic acids levels and increment of oleic acid is noted. The oil content, profile of fatty acids, and concentration of bioactive compounds in all three genotypes of Japanese quince do not change significantly statistically during the last month of fruit development. Practical Applications: Some fruits are harvested at different degrees of maturity mainly due to a logistic issue and uneven ripening of fruits, which affects the chemical composition of whole fruit including seeds. Therefore, it would be good to know how the chemical composition is changing in plant material during development especially in the last month before harvest. Production of Japanese quince continues to rise year to year and with it the volume of generated by‐products such as seeds. This study demonstrates how it changes the oil content, profile of fatty acid, and concentration of tocopherols, squalene, phytosterols, and carotenoids in the seeds and seed oil of three Japanese quince cultivars “Rondo,” “Darius,” and “Rasa” during plant development. The provided information can be very useful for the manufactories oriented on the processing of by‐products, mainly seeds, generated by other branches of industry, for instance, fruit‐processing.     

α-Triazolylboronic Acids: A Promising Scaffold for Effective Inhibitors of KPCs

Boronic acids are known reversible covalent inhibitors of serine β-lactamases. The selectivity and high potency of specific boronates bearing an amide side chain that mimics the β-lactam's amide side chain have been advanced in several studies. Herein, we describe a new class of boronic acids in which the amide group is replaced by a bioisostere triazole. The boronic acids were obtained in a two-step synthesis that relies on the solid and versatile copper-catalyzed azide–alkyne cycloaddition (CuAAC) followed by boronate deprotection. All of the compounds show very good inhibition of the Klebsiella pneumoniae carbapenemase KPC-2, with K_i values ranging from 1 nM to 1 μM, and most of them are able to restore cefepime activity against K. pneumoniae harboring bla_KPC-2. In particular, compound 1 e , bearing a sulfonamide substituted by a thiophene ring, proved to be an excellent KPC-2 inhibitor (K_i=30 nM); it restored cefepime susceptibility in KPC-Kpn cells (MIC=0.5 μg/mL) with values similar to that of vaborbactam (K_i=20 nM, MIC in KPC-Kpn 0.5 μg/mL). Our findings suggest that α-triazolylboronates might represent an effective scaffold for the treatment of KPC-mediated infections.     

Chemical Composition of Seed Oils Recovered from Different Pear (Pyrus communis L.) Cultivars

Lipophilic bioactive compounds in oils recovered from the seeds of eight pear (Pyrus communis L.) cultivars were studied. Oil yield in pear seeds ranged between 16.3 and 31.5 % (w/w) dw. The main fatty acids were palmitic acid (6.13–8.52 %), oleic acid (27.39–38.17 %) and linoleic acid (50.73–63.78 %), all three representing 96–99 % of the total detected fatty acids. The range of total tocochromanols was between 120.5 and 216.1 mg/100 g of oil. Independent of the cultivar, the γ‐tocopherol was the main tocochromanol and constituted approximately 88 %. The contents of the carotenoids and squalene were between 0.69–2.99 and 25.5–40.8 mg/100 g of oil, respectively. The β‐sitosterol constituted 83.4–87.6 % of total sterols contents, which ranged between 276.4 and 600.1 mg/100 g of oil. Three significant correlations were found between oil yield and total contents of sterols (r = ?0.893), tocochromanols (r = ?0.955) and carotenoids (r = ?0.685) in pear seed oils.     

Characterization of Fenugreek (<Emphasis Type="Italic">Trigonella foenum-graecum</Emphasis>) Seed Lipids

The composition and content of lipids, fatty acids, triacylglycerols, tocopherols and sterols in nine fenugreek genotypes were analyzed. Lipid content in fenugreek seeds ranged from 5.8 to 15.2%. Major fatty acids were: linoleic acid (45.1–47.5%), α-linolenic (18.3–22.8%), oleic (12.4–17.0%), palmitic (9.8–11.2%) and stearic (3.8–4.2%) acids. The ratios of n-6 to n-3 fatty acids were between 2.1 and 2.7. Similar fatty acid distribution was observed in all analyzed samples with some deviations. α-Tocopherol was the predominant component found in the fenugreek lipid antioxidants, and it constituted over 84% of the total amounts of tocopherols. It amounts ranged from 620 to 910 mg/kg lipids. β-Sitosterol was the major sterol in all samples, varying from 14,203 to 18,833 mg/kg of lipids. Campesterol and cycloartenol were other major sterols, and these compounds including β-sitosterol constituted 56–72% of all sterols. Fenugreek seed lipids consisted predominantly triunsaturated (56.9–66.5%) and diunsaturated (32.2–41.6%) triacylglycerides. Among these components trilinolein (LLL; 12.9–20.5%) dominated followed by PLL (14.0–20.4%), LnLnO (7.8–17.7%), PLO (5.7–11.6%), OLL (6.9–10.6%), LLLn (3.2–9.6%), and LnLnL (3.5–7.6%). Results of the study show that fenugreek seed lipids may be a source of a nutraceutical ingredient for food applications.     

Novel conventional and chelating anion exchange resins with amino ligands for sorption of silver

ABSTRACT

The polymeric resins containing diethylenetriamine, tetraethylenepentamine, 2-(diethylamino)ethanol, 1-methylimidazole, and 1,2-dimethylimidazole ligands have been synthesized from vinylbenzyl chloride-divinylbenzene copolymers and used in the removal of Ag(I) from chloride solution. The best Ag(I) sorption was reached in the case of 1-methylimidazole resin. Resins retain their capacity towards Ag(I) in five consecutive sorption/desorption cycles. The resins with imidazole ligands were highly selective for Ag(I) from synthetic chloride solution and they did not sorb chloride complexes of Cu(II). Additionally, the recovery of Ag(I) was tested from real chloride solution coming from leaching of the copper concentrate from Lubin Concentrator (KGHM Polska Mied? S.A.).     

Synthesis of Novel Phosphonic‐Type Activity‐Based Probes for Neutrophil Serine Proteases and Their Application in Spleen Lysates of Different Organisms

Neutrophils are a type of granulocyte important in the “first line of defense” of the innate immune system. Upon activation, they facilitate the destruction of invading microorganisms by the production of superoxide radicals, as well as the release of the enzymatic contents of their lysozymes. These enzymes include specific serine proteases: cathepsin G, neutrophil elastase, proteinase 3, as well as the recently discovered neutrophil serine protease 4 (NSP4). Under normal conditions, the proteolytic activity of neutrophil proteases is tightly regulated by endogenous serpins; however, this mechanism can be subverted during tissue stress, thereby resulting in the uncontrolled activity of serine proteases, which induce chronic inflammation and subsequent pathology. Herein, we describe the development of low‐molecular‐weight activity‐based probes that specifically target the active sites of neutrophil proteases.     

Environmental applications of biosurfactants: recent advances

Increasing public awareness of environmental pollution influences the search and development of technologies that help in clean up of organic and inorganic contaminants such as hydrocarbons and metals. An alternative and eco-friendly method of remediation technology of environments contaminated with these pollutants is the use of biosurfactants and biosurfactant-producing microorganisms. The diversity of biosurfactants makes them an attractive group of compounds for potential use in a wide variety of industrial and biotechnological applications. The purpose of this review is to provide a comprehensive overview of advances in the applications of biosurfactants and biosurfactant-producing microorganisms in hydrocarbon and metal remediation technologies.     

Ozonation reduces sludge production and improves denitrification

The effectiveness of partial ozonation of return activated sludge for enhancing denitrification and waste sludge minimization were examined. A pair of nitrifying sequencing batch reactors was operated in either aerobic or alternating anoxic/aerobic conditions, with one control and one ozonated reactor in each set. The amount of solids produced decreased with the ozone dose. Biomass in the anoxic/aerobic reactor was easier to destroy (up to 25% of the initial excess sludge) than in the aerobic (10%) one, generating approximately twice as much soluble COD by cell lysis. Denitrification rate improved up to 60% due to additional carbon released by ozonation. Nitrification rates deteriorated much more in the aerobic than in the alternating reactor, possibly as a result of direct destruction of nitrifying autotrophs as well as competition created by growth of heterotrophs receiving the additional COD. Overall, ozonation provided the expected benefits in denitrification and had less impact on nitrification in the alternating reactors.