Trans isomeric fatty acids in human milk and their role in infant health and development.

It is well known that long chain polyunsaturated fatty acids (LCPUFAs) play an important role in neurodevelopment in the perinatal life. The most important source of these fatty acids is the diet, however, they can also be formed in the human body from their shorter chain precursors, the essential fatty acids. Since the WHO recommends exclusive breastfeeding for the first six months after birth, the exclusive source of these fatty acids for breastfed infants is human milk, which can be influenced by the mother's diet. Unsaturated fatty acids can have either cis or trans configuration double bond in their chain with distinct physiological effects. Cis isomeric unsaturated fatty acids have several beneficial effects, while trans isomers are mostly detrimental, because of their similar structure to saturated fatty acids. Trans fatty acids (TFAs) can be further subdivided into industrial (iTFA) and ruminant-derived trans fatty acids (rTFA). However, the physiological effects of these two TFA subgroups may differ. In adults, dietary intake of iTFA has been linked to atherosclerosis, insulin resistance, obesity, chronic inflammation, and increased development of certain cancers, among other diseases. However, iTFAs can have a negative impact on health not only in adulthood but in childhood too. Results from previous studies have shown that iTFAs have a significant negative effect on LCPUFA levels in the blood of newborns and infants. In addition, iTFAs can affect the growth and development of infants, and animal studies suggest that they might even have lasting negative effects later in life. Since the only source of TFAs in the human body is the diet, the TFA content of breast milk may determine the TFA supply of breastfed infants and thus affect the levels of LCPUFAs important for neurodevelopment and the health of infants. In this review, we aim to provide an overview of the TFA content in human milk available in the literature and their potential effects on infant health and development.

A comparative study to optimize experimental conditions of pentylenetetrazol and pilocarpine-induced epilepsy in zebrafish larvae.

A common way to investigate epilepsy and the effect of antiepileptic pharmaceuticals is to analyze the movement patterns of zebrafish larvae treated with different convulsants like pentylenetetrazol (PTZ), pilocarpine, etc. Many articles have been written on this topic, but the research methods and exact settings are not sufficiently defined in most. Here we designed and executed a series of experiments to optimize and standardize the zebrafish epilepsy model. We found that during the light and the dark trials, the zebrafish larvae moved significantly more in the light, independent of the treatment, both in PTZ and pilocarpine-treated and the control groups. As expected, zebrafish larvae treated with convulsants moved significantly more than the ones in the control group, although this difference was higher between the individuals treated with PTZ than pilocarpine. When examining the optimal observation time, we divided the half-hour period into 5-minute time intervals, and between these, the first 5 minutes were found to be the most different from the others. There were fewer significant differences in the total movement of larvae between the other time intervals. We also performed a linear regression analysis with the cumulative values of the distance moved during the time intervals that fit the straight line. In conclusion, we recommend 30 minutes of drug pretreatment followed by a 10-minute test in light conditions with a 5-minute accommodation time. Our result paves the way toward improved experimental designs using zebrafish to develop novel pharmaceutical approaches to treat epilepsy.

Higher Availability of Long-Chain Monounsaturated Fatty Acids in Preterm than in Full-Term Human Milk.

While the role of n-3 and n-6 long-chain polyunsaturated fatty acids (LCPUFAs) in the maturation of the infantile nervous system is extensively studied and relatively well-characterized, data on the potential developmental importance of the n-9 long-chain monounsaturated fatty acid (LCMUFA), nervonic acid (NA, C24:1n-9) are scarce and ambiguous. Therefore, the aim of the present study was to reanalyze our available data on the contribution of NA and its LCMUFA precursors, gondoic acid (C20:1n-9) and erucic acid (EA, C22:1n-9) to the fatty acid composition of human milk (HM) during the first month of lactation in mothers of both preterm (PT) and full-term (FT) infants. HM samples were obtained daily during the first week of lactation, and then on the 14th, 21st, and 28th days. Values of the LCMUFAs, C20:1n-9, EA, and NA were significantly higher in colostrum than in transient and mature HM. Consequently, there were highly significant inverse associations between LCMUFA values and the duration of lactation. Moreover, C20:1n-9, EA, and NA values were monotonously, considerably, and at many timepoints significantly higher in PT than in FT HM samples. By the 28th day of lactation, summarized LCMUFA values in PT HM samples declined to the level measured in FT HM samples on the first day of lactation; however, EA and NA values were still significantly higher in PT than in FT HM on the 28th day. Significantly higher availability of LCMUFAs in PT than in FT HM underpins the potential biological role of this hitherto somewhat neglected group of fatty acids.

Lipid Changes in the Peri-Implantation Period with Mass Spectrometry Imaging: A Systematic Review.

Mass spectrometry imaging is a sensitive method for detecting molecules in tissues in their native form. Lipids mainly act as energy stores and membrane constituents, but they also play a role in lipid signaling. Previous studies have suggested an important role of lipids in implantation; therefore, our aim was to investigate the lipid changes during this period based on the available literature. The systematic literature search was performed on Ovid MEDLINE, Cochrane Library, Embase, and LILACS. We included studies about lipid changes in the early embryonal stage of healthy mammalian development published as mass spectrometry imaging. The search retrieved 917 articles without duplicates, and five articles were included in the narrative synthesis of the results. Two articles found a different spatial distribution of lipids in the early bovine embryo and receptive uterus. Three articles investigated lipids in mice in the peri-implantation period and found a different spatial distribution of several glycerophospholipids in both embryonic and maternal tissues. Although only five studies from three different research groups were included in this systematic review, it is clear that the spatial distribution of lipids is diverse in different tissues and their distribution varies from day to day. This may be a key factor in successful implantation, but further studies are needed to elucidate the exact mechanism.

The Utilization of Physiologically Active Molecular Components of Grape Seeds and Grape Marc.

Nutritional interventions may highly contribute to the maintenance or restoration of human health. Grapes (Vitis vinifera) are one of the oldest known beneficial nutritional components of the human diet. Their high polyphenol content has been proven to enhance human health beyond doubt in statistics-based public health studies, especially in the prevention of cardiovascular disease and cancer. The current review concentrates on presenting and classifying polyphenol bioactive molecules (resveratrol, quercetin, catechin/epicatechin, etc.) available in high quantities in Vitis vinifera grapes or their byproducts. The molecular pathways and cellular signaling cascades involved in the effects of these polyphenol molecules are also presented in this review, which summarizes currently available in vitro and in vivo experimental literature data on their biological activities mostly in easily accessible tabular form. New molecules for different therapeutic purposes can also be synthesized based on existing polyphenol compound classes available in high quantities in grape, wine, and grape marc. Therefore an overview of these molecular structures is provided. Novel possibilities as dendrimer nanobioconjugates are reviewed, too. Currently available in vitro and in vivo experimental literature data on polyphenol biological activities are presented in easily accessible tabular form. The scope of the review details the antidiabetic, anticarcinogenic, antiviral, vasoprotective, and neuroprotective roles of grape-origin flavonoids. The novelty of the study lies in the description of the processing of agricultural by-products (grape seeds and skins) of industrial relevance, and the detailed description of the molecular mechanisms of action. In addition, the review of the clinical therapeutic applications of polyphenols is unique as no summary study has yet been done.

The Chemopreventive Effects of Polyphenols and Coffee, Based upon a DMBA Mouse Model with microRNA and mTOR Gene Expression Biomarkers.

Polyphenols are capable of decreasing cancer risk. We examined the chemopreventive effects of a green tea (Camellia sinensis) extract, polyphenol extract (a mixture of blackberry (Rubus fruticosus), blackcurrants (Ribes nigrum), and added resveratrol phytoalexin), Chinese bayberry (Myrica rubra) extract, and a coffee (Coffea arabica) extract on 7,12-dimethylbenz[a]anthracene (DMBA) carcinogen-increased miR-134, miR-132, miR-124-1, miR-9-3, and mTOR gene expressions in the liver, spleen, and kidneys of CBA/Ca mice. The elevation was quenched significantly in the organs, except for miR-132 in the liver of the Chinese bayberry extract-consuming group, and miR-132 in the kidneys of the polyphenol-fed group. In the coffee extract-consuming group, only miR-9-3 and mTOR decreased significantly in the liver; also, miR-134 decreased significantly in the spleen, and, additionally, miR-124-1 decreased significantly in the kidney. Our results are supported by literature data, particularly the DMBA generated ROS-induced inflammatory and proliferative signal transducers, such as TNF, IL1, IL6, and NF-κB; as well as oncogenes, namely RAS and MYC. The examined chemopreventive agents, besides the obvious antioxidant and anti-inflammatory effects, mainly blocked the mentioned DMBA-activated factors and the mitogen-activated protein kinase (MAPK) as well, and, at the same time, induced PTEN as well as SIRT tumor suppressor genes.

Changes in miR-124-1, miR-212, miR-132, miR-134, and miR-155 Expression Patterns after 7,12-Dimethylbenz(a)anthracene Treatment in CBA/Ca Mice.

Specific gene and miRNA expression patterns are potential early biomarkers of harmful environmental carcinogen exposures. The aim of our research was to develop an assay panel by using several miRNAs for the rapid screening of potential carcinogens. The expression changes of miR-124-1, miR-212, miR-132, miR-134, and miR-155 were examined in the spleen, liver, and kidneys of CBA/Ca mice, following the 20 mg/bwkg intraperitoneal 7,12-dimethylbenz(a)anthracene (DMBA) treatment. After 24 h RNA was isolated, the miRNA expressions were analyzed by a real-time polymerase chain reaction and compared to a non-treated control. DMBA induced significant changes in the expression of miR-134, miR-132, and miR-124-1 in all examined organs in female mice. Thus, miR-134, miR-132, and miR-124-1 were found to be suitable biomarkers for the rapid screening of potential chemical carcinogens and presumably to monitor the protective effects of chemopreventive agents.

Olive Oil Improves While Trans Fatty Acids Further Aggravate the Hypomethylation of LINE-1 Retrotransposon DNA in an Environmental Carcinogen Model.

DNA methylation is an epigenetic mechanism that is crucial for mammalian development and genomic stability. Aberrant DNA methylation changes have been detected not only in malignant tumor tissues; the decrease of global DNA methylation levels is also characteristic for aging. The consumption of extra virgin olive oil (EVOO) as part of a balanced diet shows preventive effects against age-related diseases and cancer. On the other hand, consuming trans fatty acids (TFA) increases the risk of cardiovascular diseases as well as cancer. The aim of the study was to investigate the LINE-1 retrotransposon (L1-RTP) DNA methylation pattern in liver, kidney, and spleen of mice as a marker of genetic instability. For that, mice were fed with EVOO or TFA and were pretreated with environmental carcinogen 7,12-dimethylbenz[a]anthracene (DMBA)-a harmful substance known to cause L1-RTP DNA hypomethylation. Our results show that DMBA and its combination with TFA caused significant L1-RTP DNA hypomethylation compared to the control group via inhibition of DNA methyltransferase (DNMT) enzymes. EVOO had the opposite effect by significantly decreasing DMBA and DMBA + TFA-induced hypomethylation, thereby counteracting their effects.