Recent studies have demonstrated that the anti-diabetic drug, metformin, can exhibit direct antitumoral effects, or can indirectly decrease tumor proliferation by improving insulin sensitivity. ...Despite these recent advances, the underlying molecular mechanisms involved in decreasing tumor formation are not well understood. In this study, we examined the antiproliferative role and mechanism of action of metformin in MCF-7 cancer cells treated with 10 mM of metformin for 24, 48, and 72 hours. Using BrdU and the MTT assay, it was found that metformin demonstrated an antiproliferative effect in MCF-7 cells that occurred in a time- and concentration-dependent manner. Flow cytometry was used to analyze markers of cell cycle, apoptosis, necrosis and oxidative stress. Exposure to metformin induced cell cycle arrest in G0-G1 phase and increased cell apoptosis and necrosis, which were associated with increased oxidative stress. Gene and protein expression were determined in MCF-7 cells by real time RT-PCR and western blotting, respectively. In MCF-7 cells metformin decreased the activation of IRβ, Akt and ERK1/2, increased p-AMPK, FOXO3a, p27, Bax and cleaved caspase-3, and decreased phosphorylation of p70S6K and Bcl-2 protein expression. Co-treatment with metformin and H2O2 increased oxidative stress which was associated with reduced cell number. In the presence of metformin, treating with SOD and catalase improved cell viability. Treatment with metformin resulted in an increase in p-p38 MAPK, catalase, MnSOD and Cu/Zn SOD protein expression. These results show that metformin has an antiproliferative effect associated with cell cycle arrest and apoptosis, which is mediated by oxidative stress, as well as AMPK and FOXO3a activation. Our study further reinforces the potential benefit of metformin in cancer treatment and provides novel mechanistic insight into its antiproliferative role.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Facing the ever-growing demand for data storage will most probably require a new paradigm. Nanoscale magnetic skyrmions are anticipated to solve this issue as they are arguably the smallest spin ...textures in magnetic thin films in nature. We designed cobalt-based multilayered thin films in which the cobalt layer is sandwiched between two heavy metals and so provides additive interfacial Dzyaloshinskii-Moriya interactions (DMIs), which reach a value close to 2 mJ m(-2) in the case of the Ir|Co|Pt asymmetric multilayers. Using a magnetization-sensitive scanning X-ray transmission microscopy technique, we imaged small magnetic domains at very low fields in these multilayers. The study of their behaviour in a perpendicular magnetic field allows us to conclude that they are actually magnetic skyrmions stabilized by the large DMI. This discovery of stable sub-100 nm individual skyrmions at room temperature in a technologically relevant material opens the way for device applications in the near future.
In this review we have focused on the preparation of cross-linked enzyme aggregates (CLEAs) from lipases, as these are among the most used enzyme in bioprocesses. This immobilization method is ...considered very attractive due to preparation simplicity, non-use of supports and the possibility of using crude enzyme extracts. CLEAs provide lipase stabilization under extreme temperature or pH conditions or in the presence of organic solvents, in addition to preventing enzyme leaching in aqueous medium. However, it presents some problems in the preparation and limitations in their use. The problems in preparation refer mainly to the crosslinking step, and may be solved using an aminated feeder. The problems in handling have been tackled designing magnetic-CLEAs or trapping the CLEAs in particles with better mechanical properties, the substrate diffusion problems has been reduced by producing more porous-CLEAs, etc. The enzyme co-immobilization using combi-CLEAs is also a new tendency. Therefore, this review explores the CLEAs methodology aimed at lipase immobilization and its applications.
•Lipase CLEAs permit enzyme immobilization and stabilization, useful for many processes•Substrate diffusion problems may be solved using porogenic agents•The use of feeders or amination of enzyme solve the problem of CLEA crosslinking•The trapping of CLEAs in rigid structures solve the problem of CLEAs mechanical fragility•Magnetic CLEAs may simplify CLEAs handing and activity/stability
► Antioxidants tested would be beneficial for reducing the velocity of lipid oxidation. ► Herbs and honey exhibited great efficacy on preventing formation of hexanal. ► The sensory evaluation ...indicated that herbs and honey resulted in a pleasant flavour.
The effect of combinations of sage, oregano and honey on lipid oxidation in cooked chicken meat during refrigeration at 4°C for 96h was determined. Chicken samples (thigh and breast) were then separated into five groups: control; butylated hydroxytoluene; oregano+sage; oregano+sage+5%honey and oregano+sage+10%honey. Quantitative measurements of thiobarbituric acid reactive substances, conjugated dienes, hexanal, fatty acids, cholesterol and cholesterol oxides were used as indicators of lipid oxidation. Acceptability and preference were also evaluated. The effectiveness of the natural antioxidants for reducing the velocity of lipid oxidation in cooked chicken thigh and breast was demonstrated after 48 and 96h of refrigeration at 4°C. The treatments that presented the lowest hexanal values after 96h of refrigeration were oregano+sage+5%honey and oregano+sage+10%honey. Only traces of free cholesterol oxides were found (25-OH, 7-k, 7α-OH and 7β-OH). The natural antioxidants protected cooked chicken meat from oxidation processes and resulted in great acceptability.
•Digested guaraná inhibited carbohydrate enzymes activity.•Guaraná may be useful to modulate postprandial hyperglycemia.•The polyphenols of guaraná are unstable throughout the in vitro digestion ...process.
Guaraná (Paullinia cupana) is a typical product from Amazon biota that exerts antioxidant capacity due to the presence of phenolic compounds, such as catechin, epicatechin and proanthocyanidins. The objective of this study was to evaluate the potential inhibitory activity of guaraná extracts, after digestion in vitro, on carbohydrates-metabolism enzymes and to assess the bioacessibility of guaraná polyphenols. The guaraná samples before and after enzymatic digestion, were compared for total phenolic content and phenolic profile. Furthermore, we investigated the uptake of polyphenols from guarana, using Caco-2 cells, and the effect of digested guaraná on carbohydrate metabolism enzymes. The amount of total phenolic compounds extracted from guaraná decreased after digestion in vitro, and native phenolics were not identified after cell permeation. On the other hand, polyphenols from guaraná were able to inhibit α-glucosidase and α-amylase activities. In conclusion, guaraná can be considered as a dietary source with anti-hyperglycemic potential.
Purpose
This study aims to explore the nature of the relationship between market orientation and business performance in the Portuguese hotel industry and to evaluate the mediating role of service ...quality in this relationship.
Design/methodology/approach
A literature analysis on market orientation, service quality and hotel business performance was conducted. The structural model was developed, and the measurement scales’ items were generated. Working data were obtained by sending a survey to Portuguese hotel managers. A purification process was conducted, and the convergent and discriminant validity, as well the reliability, of the measurement models were assessed. The structural model was tested by conducting a path analysis, as well by evaluating the coefficient of determination (R2) and the predictive relevance indicator (Q2).
Findings
Research results show that market orientation has a positive direct effect on business performance. Moreover, results indicate that market orientation effects on business performance are mediated throughout the hotels’ ability to provide service quality.
Originality/value
Despite the large amount of research on market orientation, research on the hospitality sector has been conducted mainly using tools developed for the manufacturing and consumer goods sectors. On the other hand, little has been done to explore the nature of the mediating effect of service quality on the relationship between market orientation and business performance in the hotel industry. Moreover, despite the contribution of the tourism industry to the Portuguese gross domestic product, research on the hotel industry is scarce.
Polycyclic aromatic hydrocarbons (PAHs) are chemical compounds comprised of carbon and hydrogen molecules in a cyclic arrangement. PAHs are associated with risks to human health, especially ...carcinogenesis. One form of exposure to these compounds is through ingestion of contaminated food, which can occur during preparation and processing involving high temperatures (e.g., grilling, smoking, toasting, roasting, and frying) as well as through PAHs present in the soil, air, and water (i.e., environmental pollution). Differently from changes caused by microbiological characteristics and lipid oxidation, consumers cannot sensorially perceive PAH contamination in food products, thereby hindering their ability to reject these foods. Herein, the occurrence and biological effects of PAHs were comprehensively explored, as well as analytical methods to monitor their levels, legislations, and strategies to reduce their generation in food products. This review updates the current knowledge and addresses recent regulation changes concerning the widespread PAHs contamination in several types of food, often surpassing the concentration limits deemed acceptable by current legislations. Therefore, effective measures involving different food processing strategies are needed to prevent and reduce PAHs contamination, thereby decreasing human exposure and detrimental health effects. Furthermore, gaps in literature have been addressed to provide a basis for future studies.
This paper presents new rotational and longitudinal symmetric self-clinching fasteners to fabricate reliable connections in busbars with low electrical resistance for energy distribution systems. ...Connections consist of form-closed joints that are hidden inside regions where two busbars overlap. The investigation into the fabrication and performance of the new self-clinched joints involved finite element modelling and experimentation to determine the required forces and to evaluate the electric current flow and the electrical resistance at different service temperatures. The original design of the joints that was proposed in a previous work was modified to account for busbar strips of copper and/or aluminum with similar or dissimilar thicknesses, connected by means of self-clinching fasteners made from the same materials of the busbars, instead of steel. The effectiveness of the new self-clinched joints was compared to that of conventional bolted joints that are included in the paper for reference purposes. The results show that rotational symmetric self-clinching fasteners yield lighter fabrication and more compact joints with a similar electrical resistance to that of bolted joints. They also show that longitudinal symmetric self-clinching fasteners aimed at replicating the resistance-seam-welding contact conditions yield a reduction in electrical resistance to values close to that of ideal joints, consisting of two strips in perfect contact and without contaminant or oxide films along their overlapped surfaces.
Gut Microbiome and Organ Fibrosis Costa, Carolina F F A; Sampaio-Maia, Benedita; Araujo, Ricardo ...
Nutrients,
01/2022, Letnik:
14, Številka:
2
Journal Article
Recenzirano
Odprti dostop
Fibrosis is a pathological process associated with most chronic inflammatory diseases. It is defined by an excessive deposition of extracellular matrix proteins and can affect nearly every tissue and ...organ system in the body. Fibroproliferative diseases, such as intestinal fibrosis, liver cirrhosis, progressive kidney disease and cardiovascular disease, often lead to severe organ damage and are a leading cause of morbidity and mortality worldwide, for which there are currently no effective therapies available. In the past decade, a growing body of evidence has highlighted the gut microbiome as a major player in the regulation of the innate and adaptive immune system, with severe implications in the pathogenesis of multiple immune-mediated disorders. Gut microbiota dysbiosis has been associated with the development and progression of fibrotic processes in various organs and is predicted to be a potential therapeutic target for fibrosis management. In this review we summarize the state of the art concerning the crosstalk between intestinal microbiota and organ fibrosis, address the relevance of diet in different fibrotic diseases and discuss gut microbiome-targeted therapeutic approaches that are current being explored.
Chronic kidney disease (CKD) is a relevant disease in feline clinic. The tubulointerstitial damage, with collagen deposition and fibrosis, is an important result of this process. The aim of this ...study was to quantify and correlate the deposition of collagen and severity of interstitial fibrosis (IF) in the kidney from cats in different stages of CKD. Kidney fragments from 10 adult cats with CKD were analyzed and stained by Masson's trichrome (MT) and Picrosirius red (PSR) for circular polarized microscopy. Random quantitative analysis was performed on MT sections to classify the degree of IF, per field area, with and without circular polarization. Statistics correlations were performed by Spearman's (ρ; p < .05). There was a significant correlation of IF quantification with the area of interstitial collagen deposition by polarized PSR (PSRp) (r = .7939, p = .0098) and nonpolarized PSR (PSRn) (r = .7781, p = .0080). There was a positive correlation of serum creatinine (sCr) at different stages of CKD with PSRp (r = .7939, p = .0098), PSRn (r = .8667, p = .0027) and MT (r = .7818, p = .0117). Correlations between the percentage of quantified area was also positive from PSRp to PSRn (r = .9030, p = .0009) and PSRp to MT (r = .7939, p = .0098). The PSRN was also correlated with MT (r = .9273, p = .0001). The correlation with IF and sCr follows the disease evolution and the quantification of collagen by PSR is an excellent tool for analyzing the disease severity at different stages.
The quantification of interstitial collagen is an excellent tool to analyze tubulointerstitial damage in cats with CKD
Circular polarization microscopy is a good apparatus for the analysis of collagen deposition in kidneys of cats with CKD.
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