The dietary recommendation encourages reducing saturated fatty acids (SFA) in diet and replacing them with polyunsaturated fatty acids (PUFAs) n–3 (omega–3) and n–6 (omega–6) to decrease the risk of ...metabolic disturbances. Consequently, excessive n–6 PUFAs content and high n–6/n–3 ratio are found in Western-type diet. The importance of a dietary n–6/n–3 ratio to prevent chronic diseases is linked with anti-inflammatory functions of linolenic acid (ALA, 18:3n–3) and longer-chain n–3 PUFAs. Thus, this review provides an overview of the role of oxylipins derived from n–3 PUFAs and oxylipins formed from n–6 PUFAs on inflammation. Evidence of PUFAs’ role in carcinogenesis was also discussed. In vitro studies, animal cancer models and epidemiological studies demonstrate that these two PUFA groups have different effects on the cell growth, proliferation and progression of neoplastic lesions.
•Evalute Cutpoints is a user friendly suite of algorithms used for survival determination and hazard ratio calculations with estimation of significant cut point regarding any variable of continuous ...type. It offers Kaplan-Meier plot with calculation of hazard ratio as well as receiver operating characteristic (ROC) method.•The advantage of Evaluate Cutpoints over similar interfaces such as Cutoff Finder or X-Tile is a possibility of classification of data into three groups. Moreover, using Evaluate Cutpoints researcher can manually adapt cut point within values of statistical significance that may better fits medical and biological parameters than mathematically determined.•This software allows user to perform survival analysis and generate corresponding figures that may be downloaded and published along with the results.
Growing evidence of transcriptional and metabolomic differentiation induced many studies which analyze such differentiation in context of outcome of disease progression, treatment or influence of many different factors affecting cellular and tissue metabolism. Particularly, cancer researchers are looking for new biomarkers that can serve as a diagnostic/prognostic factor and its further corresponding relationship regarding clinical effects. As a result of the increasing interest in use of dichotomization of continuous variables involving clinical or epidemiological data (gene expression, biomarkers, biochemical parameters, etc.) there is a large demand for cutoff point determination tools with simultaneous lack of software offering stratification of patients based on continuous and binary variables. Therefore, we developed “Evaluate Cutpoints” application offering wide set of statistical and graphical methods for cutpoint optimization enabling stratification of population into two or three groups.
Application is based on R language including algorithms of packages such as survival, survMisc, OptimalCutpoints, maxstat, Rolr, ggplot2, GGally and plotly offering Kaplan-Meier plots and ROC curves with cutoff point determination.
All capabilities of Evaluate Cutpoints were illustrated with example analysis of estrogen, progesterone and human epidermal growth factor 2 receptors in breast cancer cohort. Through ROC curve the cutoff points were established for expression of ESR1, PGR and ERBB2 in correlation with their immunohistochemical status (cutoff: 1301.253, 243.35, 11,434.438, respectively; sensitivity: 94%, 85%, 64%, respectively; specificity: 93%, 86%, 91%, respectively). Through disease-free survival analysis we divided patients into two and three groups regarding expression of ESR1, PGR and ERBB2. Example algorithm cutp showed that lowered expression of ESR1 and ERBB2 was more favorable (HR = 2.07, p = 0.0412; HR = 2.79, p = 0.0777, respectively), whereas heightened PGR expression was correlated with better prognosis (HR = 0.192, p = 0.0115).
This work presents application Evaluate Cutpoints that is freely available to download at http://wnbikp.umed.lodz.pl/Evaluate-Cutpoints/. Currently, many softwares are used to split continuous variables such as Cutoff Finder and X-Tile, which offer distinct algorithms. Unlike them, Evaluate Cutpoints allows not only dichotomization of populations into groups according to continuous variables and binary variables, but also stratification into three groups as well as manual selection of cutoff point thus preventing potential loss of information.
Telomeres are complexes consisting of tandem repeat DNA combined with associated proteins that play a key role in protecting the ends of chromosomes and maintaining genome stability. They are ...considered a biological clock, as they shorten in parallel with aging. Furthermore, short telomeres are associated with several age-related diseases. However, the variability in telomere shortening independent of chronological age suggests that it is a modifiable factor. In fact, it is regulated inter alia by genetic damage, cell division, aging, oxidative stress, and inflammation. A key question remains: how can we prevent accelerated telomere attrition and subsequent premature replicative senescence? A number of studies have explored the possible impact of omega-3 fatty acids on telomere shortening. This review summarizes published cross-sectional studies, randomized controlled trials, and rodent studies investigating the role of omega-3 fatty acids in telomere biology. It also covers a broad overview of the mechanism, currently favored in the field, that explains the impact of omega-3 fatty acids on telomeres—the food compound’s ability to modulate oxidative stress and inflammation. Although the results of the studies performed to date are not consistent, the vast majority indicate a beneficial effect of omega-3 fatty acids on telomere length.
Iron is an essential micronutrient for almost all living organisms. It plays an important role in DNA, RNA, and protein synthesis and takes part in electron transport, cellular respiration, cell ...proliferation and differentiation, and gene expression regulation. However, there is a fine line between excessive and insufficient body iron content. Iron overload is biochemically dangerous. It causes serious toxicities and generates reactive oxygen species via the Fenton reaction, leading to damage to cellular membranes, proteins, and DNA. Omega-3 fatty acids play an essential role in many physiological processes, including energy metabolism and signal transduction, as well as acting as structural components of cell membranes. Omega-3 fatty acids also help to maintain homeostasis and combat diseases. Recent studies using model organisms as well as clinical studies have revealed a link between omega-3 fatty acids and iron metabolism. Moreover, various iron-related disorders are significantly affected by omega-3 fatty acids. There is a clear relationship between iron and omega-3 fatty acid metabolisms; however, the underlying mechanisms are unknown. Therefore, in-depth research is needed to determine the exact nature of the metabolic interactions of these nutrients. Here, we focus on iron and omega-3 fatty acid metabolisms at their crossroads in the liver and brain.
Equine sarcoid is the most common skin tumor of horses. Clinically, it occurs as a locally invasive, fibroblastic, wart-like lesion of equine skin, which has 6 clinical classes: occult, verrucose, ...nodular, fibroblastic, mixed, and malignant. Sarcoids may be single but multiple lesions are more frequent. The typical histological feature is increased density of dermal fibroblasts which form interlacing bundles and whorls within the dermis. Lesions are mostly persistent, resist therapy, and tend to recur following treatment. In general, sarcoids are not fatal but their location, size, and progression to the more aggressive form may lead to the withdrawal of a horse from use and serious infringement of their welfare leading to the loss of valuable animals. Bovine papillomavirus (BPV) type 1 and less commonly type 2 contribute to the development of equine sarcoid. The viral genome and proteins are detected in a high percentage of cases. Furthermore, viral oncoprotein activity leads to changes in the fibroblastic tissue similar to changes seen in other types of tumors. Equine sarcoids are characterized by a loss of tumor suppressor activity and changes allowing abnormal formation of the affected tissue, as well as y immune defense abnormalities that weaken the host’s immune response. This impaired immune response to BPV infection appears to be crucial for the development of lesions that do not spontaneously regress, as occurs in BPV-infected cows.
The critically low hepatic iron stores of newborn piglets are considered to be a major cause of neonatal iron deficiency in modern breeds of domestic pig (Sus domestica). The main factor believed to ...contribute to this phenomenon is large litter size, which has been an objective of selective breeding of pigs for decades. As consequence, iron transferred from the pregnant sow has to be distributed among a greater number of fetuses.
Here, we investigated whether litter size influences red blood cell (RBC) indices and iron parameters in Polish Large White (PLW) piglets and gilts. Small and large litters were produced by the transfer of different numbers of embryos, derived from the same superovulated donor females, to recipient gilts. Piglets from large litters obtained following routine artificial insemination were also examined. Our results clearly demonstrated that varying the number of piglets in a litter did not affect the RBC and iron status of 1-day-old piglets, with all showing iron deficiency anemia. In contrast, gilts with small litters displayed higher RBC and iron parameters compared to mothers with large litters. A comparative analysis of the RBC status of wild boars (having less than half as many piglets per litter as domestic pigs) and PLW pigs, demonstrated higher RBC count, hemoglobin level and hematocrit value of both wild boar sows and piglets, even compared to small-litter PLW animals.
These findings provide evidence that RBC and iron status in newborn PLW piglets are not primarily determined by litter size, and indicate the need to study the efficiency of iron transport across the placenta in domestic pig and wild boar females.
The aim of the study was to evaluate the effect of different types of high-fat diets (HFDs) on the proteomic profile of mouse liver. The analysis included four dietary groups of mice fed a standard ...diet (STD group), a high-fat diet rich in SFAs (SFA group), and high-fat diets dominated by PUFAs with linoleic acid (LA, C18:2n-6) to α-linolenic acid (ALA, C18:3n-3) ratios of 14:1 (14:1 group) and 5:1 (5:1 group). After three months of diets, liver proteins were resolved by two-dimensional gel electrophoresis (2DE) using 17 cm non-linear 3-10 pH gradient strips. Protein spots with different expression were identified by MALDI-TOF/TOF. The expression of 13 liver proteins was changed in the SFA group compared to the STD group (↓: ALB, APOA1, IVD, MAT1A, OAT and PHB; ↑: ALDH1L1, UniProtKB-Q91V76, GALK1, GPD1, HMGCS2, KHK and TKFC). Eleven proteins with altered expression were recorded in the 14:1 group compared to the SFA group (↓: ARG1, FTL1, GPD1, HGD, HMGCS2 and MAT1A; ↑: APOA1, CA3, GLO1, HDHD3 and IVD). The expression of 11 proteins was altered in the 5:1 group compared to the SFA group (↓: ATP5F1B, FTL1, GALK1, HGD, HSPA9, HSPD1, PC and TKFC; ↑: ACAT2, CA3 and GSTP1). High-PUFA diets significantly affected the expression of proteins involved in, e.g., carbohydrate metabolism, and had varying effects on plasma total cholesterol and glucose levels. The outcomes of this study revealed crucial liver proteins affected by different high-fat diets.
•Persistent avoidance of humans would confirm de-domestication in semi-feral horses.•Forest-born (FB) foals withdraw more from approaching human than stable (SB) foals.•At each age of testing, FB ...foals were physiologically more aroused.•The fearfulness had not changed either in stable or in forest born group.•De-domestication may be induced in horses by the relaxation of contact with humans.
In the present study, we hypothesise that persistent avoidance of human would confirm de-domestication process in semi-feral horses.
Fifty-three Konik polski horses (stable-born: SB, N1=27 and forest-born: FB, N2=26), additionally handled for 5 or 15days after weaning, were evaluated. Human (stationary, approaching and touching the foals when 6, 9, 12, 15 and 18 months old) and handling (approaching, leg-lifting, leading, and handling the foals when startled at 12 and 18 months old) tests were conducted. During handling test heart rate (HR) and heart rate variability (RMSSD) were measured.
Compared to FB foals, a greater number of SB foals approached (P<0.05) and touched (P<0.05) the experimenter when tested at 6, 9, 15 and 18 months old. The latency to approach the experimenter and flight distance were longer in FB foals than in SB foals (P<0.01). FB foals withdraw more from approaching human as compared to SB foals (P<0.05) and this response was consistent across ages in the human and handling tests.
The time to raise the fore legs was not different between groups at both tested ages, however FB foals slightly decreased their performance with time (P<0.01). They also performed less well than SBs in a hand-leading task at 12 months old (P<0.01) while they improved their performance when older (P<0.01). SB foals when older were easier than FB horses to halt (P<0.05). When tested at 12 and 18 months old FB foals were physiologically more aroused than SB foals (greater mean HR, P<0.01, HRmax, P<0.01 and lower RMSSD P<0.01). Extensively handled foals presented greater HR than the control group (P<0.05). However, FB and SB groups did not differ in overall fearfulness, since they reacted similarly to a startling novel object, but, when frightened stable foals showed better manageability to calm down when older. It is concluded that de-domestication is very easy to induce in horses only by the relaxation of every-day contact with humans. This suggests that Konik horses underwent little genetic selection for fearfulness, but like their wild ancestors, adapt relatively easy to man-made conditions and are capable of being domesticated.
Omega-3 fatty acids are health-promoting nutrients that contribute to the amelioration of age-related diseases. Recent studies have reported the role of these fatty acids in the aging process, ...explicitly impacting telomere biology. The shelterin protein complex, located at the extremities of chromosomes, ensures telomere protection and length regulation. Here, we analyzed the impact of dietary omega-3 alpha-linolenic fatty acid from linseed oil on skeletal muscle telomere biology using an animal model of female pigs. Fifteen animals were supplemented with linseed oil for nine weeks and an equal number of individuals were fed with a control diet. Linseed-oil-supplemented animals showed an increased level of alpha-linolenic acid in skeletal muscles compared to control animals. There was no difference between groups in the telomere length measured in leukocytes and muscles. However, muscles of the linseed-oil-supplemented pigs showed lower levels of the shelterin TRF1 protein compared to the control group. Our results suggest that omega-3 linolenic acid counteracts the elevation of TRF1 levels, which increase with age and due to the presence of reactive oxygen species in muscle. The observed effect may be due to attenuation of oxidative stress.
Abstract Introduction Some health disorders, such as obesity and type 2 diabetes, are associated with a poor diet and low quality of the fat in it. The type and duration of the diet have an impact on ...the liver. This investigation uses the proteomic approach to identify changes in the mouse liver protein profile in adaptation to high-fat diets with different saturated fatty acid contents and linoleic acid (18:2 n -6) to α-linolenic acid (18:3 n -3) fatty acid ratios. Material and Methods Four groups of male mice were fed different diets: one standard diet and three high-fat diets were investigated. After six months on these diets, the animals were sacrificed for liver dissection. Two-dimensional electrophoresis was used to separate the complex liver protein mixture, which enabled the separation of proteins against a wide, 3–10 range of pH and molecular weights of 15–250 kDa. Protein profiles were analysed in the PDQuest Advanced 8.0.1 program. Differentially expressed spots were identified using matrix-assisted laser desorption/ionisation–time-of-flight tandem mass spectrometry and peptide mass fingerprinting. The levels of identified proteins were validated using Western blotting. Transcript levels were evaluated using a real-time quantitative PCR. Results The analysis of mouse liver protein profiles enabled the identification of 32 protein spots differing between nutritional groups. Conclusion A diet high in polyunsaturated fatty acids modulated the levels of liver proteins involved in critical metabolic pathways, including amino acid metabolism, carbohydrate metabolism and cellular response to oxidative stress.
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