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Docosahexaenoic acid (DHA) is present in high concentrations in salmon, herring, and trout. Epidemiologic studies have shown that high dietary consumption of these and other oily fish is associated with reduced rates of myocardial infarction, atherosclerosis, and other ischemic pathologies. Atherosclerosis is induced by inflammation and can lead to acute cardiovascular events and extensive plaque. DHA inhibits the development of inflammation in endothelial cells, alters the function and regulation of vascular biomarkers, and reduces cardiovascular risk. It also affects vascular relaxation and constriction by controlling nitric oxide and endothelin 1 production in endothelial cells. DHA also contributes to the prevention of arteriosclerosis by regulating the expression of oxidized low density lipoprotein receptor 1, plasminogen activator inhibitor 1, thromboxane A2 receptor, and adhesion molecules such as vascular cell adhesion molecule-1, monocyte chemoattractant protein-1, and intercellular adhesion molecule 1 in endothelial cells. Recent research showed that DHA reduces the increase in adhesion factor expression induced by lipopolysaccharide by suppressing toll-like receptor 4. A new mechanism of action of DHA has been described that is mediated through endothelial free fatty acid receptor 4, associated with heme oxygenase 1 induction by Nrf2. However, the efficacy and mechanisms of action of DHA in cardiovascular disease prevention are not yet completely understood. The aim of this paper was to review the effects of DHA on vascular endothelial cells and recent findings on their potential for the prevention of circulatory diseases.

Epidemiologic studies from several countries have found that mortality rates associated with the metabolic syndrome are inversely associated with coffee consumption. Metabolic syndrome can lead to arteriosclerosis by endothelial dysfunction, and increases the risk for myocardial and cerebral infarction. Accordingly, it is important to understand the possible protective effects of coffee against components of the metabolic syndrome, including vascular endothelial function impairment, obesity and diabetes. Coffee contains many components, including caffeine, chlorogenic acid, diterpenes and trigonelline. Studies have found that coffee polyphenols, such as chlorogenic acids, have many health-promoting properties, such as antioxidant, anti-inflammatory, anti-cancer, anti-diabetes, and antihypertensive properties. Chlorogenic acids may exert protective effects against metabolic syndrome risk through their antioxidant properties, in particular toward vascular endothelial cells, in which nitric oxide production may be enhanced, by promoting endothelial nitric oxide synthase expression. These effects indicate that coffee components may support the maintenance of normal endothelial function and play an important role in the prevention of metabolic syndrome. However, results related to coffee consumption and the metabolic syndrome are heterogeneous among studies, and the mechanisms of its functions and corresponding molecular targets remain largely elusive. This review describes the results of studies exploring the putative effects of coffee components, especially in protecting vascular endothelial function and preventing metabolic syndrome.

Isoflavones are polyphenols primarily contained in soybean. As phytoestrogens, isoflavones exert beneficial effects on various chronic diseases. Metabolic syndrome increases the risk of death due to arteriosclerosis in individuals with various pathological conditions, including obesity, hypertension, hyperglycemia, and dyslipidemia. Although the health benefits of soybean-derived isoflavones are widely known, their beneficial effects on the pathogenesis of metabolic syndrome are incompletely understood. This review aims to describe the association between soybean-derived isoflavone intake and the risk of metabolic syndrome development. We reviewed studies on soy isoflavones, particularly daidzein and genistein, and metabolic syndrome, using PubMed, ScienceDirect, and Web of Science. We describe the pathological characteristics of metabolic syndrome, including those contributing to multiple pathological conditions. Furthermore, we summarize the effects of soybean-derived daidzein and genistein on metabolic syndrome reported in human epidemiological studies and experiments using in vitro and in vivo models. In particular, we emphasize the role of soy isoflavones in metabolic syndrome-induced cardiovascular diseases. In conclusion, this review focuses on the potential of soy isoflavones to prevent metabolic syndrome by influencing the onset of hypertension, hyperglycemia, dyslipidemia, and arteriosclerosis and discusses the anti-inflammatory effects of isoflavones.

Previous studies indicated that chlorogenic acid, a compound present in many fruits and vegetables, has anti-cancer activities. We report that chlorogenic acid regulates the expression of apoptosis-related genes and self-renewal-related stem cell markers in cancer cells. The lung cancer cell line A549 was cultured with or without chlorogenic acid. The presence of chlorogenic acid decreased cell proliferation as measured by MTT activity. Polymerase chain reaction (PCR) showed that treatment of cells with chlorogenic acid reduced the expression of BCL2 but increased that of both BAX and CASP3. Chlorogenic acid enhanced annexin V expression as measured using fluorescently labeled annexin V. Chlorogenic acid also induced p38 MAPK and JNK gene expression. Meanwhile, several agents, including SB203580 (p38 MAP kinase inhibitor), N-acetylcysteine (antioxidant inhibitor), dipyridamole (phosphodiesterase inhibitor), and apocynin (NADPH-oxidase inhibitor) blocked chlorogenic acid-induced BAX gene expression. Chlorogenic acid reduced gene expression levels of stem cell-associated markers NANOG, POU5F1, and SOX2 . Together these results indicate that chlorogenic acid affects the expression of apoptosis-related genes that are part of oxidative stress and p38 MAP-dependent pathways, as well as genes encoding stem cell markers. In conclusion, chlorogenic acid may contribute to the polyphenolic anti-cancer effect associated with consumption of vegetables and fruits.

Vascular endothelial cell (EC) dysfunction strongly induces development of cardiovascular and cerebrovascular diseases. Epidemiologic studies demonstrated a preventative effect of dietary polyphenols toward cardiovascular disease. In studies using cultured vascular ECs, polyphenols were recognized to regulate nitric oxide and endothelin-1 (ET-1) production. Furthermore, epigallocatechin-3-gallate inhibited the expression of adhesion molecules by a signaling pathway that is similar to that of high-density lipoprotein and involves induction of Ca2+/calmodulin-dependent kinase II, liver kinase B, and phosphatidylinositol 3-kinase expression. The effects of polyphenols on ECs include antioxidant activity and enhancement of the expression of several protective proteins, including endothelial nitric oxide synthase and paraoxonase 1. However, the observed effects of dietary polyphenols in vitro do not always translate to an in vivo setting. As such, there are many questions concerning their physiological mode of action. In this review, we discuss research on the effect of dietary polyphenols on cardiovascular disease and their protective effect on EC dysfunction.

Chromosome segregation defects in cancer cells lead to encapsulation of chromosomes in micronuclei (MN), small nucleus-like structures within which dangerous DNA rearrangements termed chromothripsis can occur. Here we uncover a strikingly different consequence of MN formation in preimplantation development. We find that chromosomes from within MN become damaged and fail to support a functional kinetochore. MN are therefore not segregated, but are instead inherited by one of the two daughter cells. We find that the same MN can be inherited several times without rejoining the principal nucleus and without altering the kinetics of cell divisions. MN motion is passive, resulting in an even distribution of MN across the first two cell lineages. We propose that perpetual unilateral MN inheritance constitutes an unexpected mode of chromosome missegregation, which could contribute to the high frequency of aneuploid cells in mammalian embryos, but simultaneously may serve to insulate the early embryonic genome from chromothripsis.

In the pre-implantation embryo, aneuploidy resulting from chromosome segregation error is considered responsible for pregnancy loss. However, only a few studies have examined the relationship between chromosome segregation errors during early cleavage and development. Here, we evaluated this relationship by live-cell imaging using the histone H2B-mCherry probe and subsequent single blastocyst transfer using mouse embryos obtained by in vitro fertilization. We showed that some embryos exhibiting early chromosomal segregation error and formation of micronuclei retained their developmental potential; however, the error affected the blastocyst/arrest ratio. Further, single-cell sequencing after live-cell imaging revealed that all embryos exhibiting micronuclei formation during 1 st mitosis showed aneuploidy at the 2-cell stage. These results suggest that early chromosome segregation error causing micronuclei formation affects ploidy and development to blastocyst but does not necessarily cause developmental failure after the blastocyst stage. Our result suggests the importance of the selection of embryos that have reached blastocysts.

Totipotency emerges in early embryogenesis, but its molecular underpinnings remain poorly characterized. In the present study, we employed DNA fiber analysis to investigate how pluripotent stem cells are reprogrammed into totipotent-like 2-cell-like cells (2CLCs). We show that totipotent cells of the early mouse embryo have slow DNA replication fork speed and that 2CLCs recapitulate this feature, suggesting that fork speed underlies the transition to a totipotent-like state. 2CLCs emerge concomitant with DNA replication and display changes in replication timing (RT), particularly during the early S-phase. RT changes occur prior to 2CLC emergence, suggesting that RT may predispose to gene expression changes and consequent reprogramming of cell fate. Slowing down replication fork speed experimentally induces 2CLCs. In vivo, slowing fork speed improves the reprogramming efficiency of somatic cell nuclear transfer. Our data suggest that fork speed regulates cellular plasticity and that remodeling of replication features leads to changes in cell fate and reprogramming. Totipotent cells in mouse embryos and 2-cell-like cells have slow DNA replication fork speed. Perturbations that slow replication fork speed promote 2-cell-like cell emergence and improve somatic cell nuclear transfer reprogramming and formation of induced pluripotent stem cell colonies.

In female eutherian mammal development, X-chromosome inactivation (XCI) of one of the two X chromosomes is initiated early. Understanding the relationship between the initiation of XCI and cell fate is critical for understanding early female development and requires a system that can monitor XCI in single living cells. Traditional embryonic stem cells (ESCs) used for XCI studies often lose X chromosomes spontaneously during culture and differentiation, making accurate monitoring difficult. Additionally, most XCI assessment methods necessitate cell disruption, hindering cell fate tracking. We developed the Momiji (version 2) ESC line to address these difficulties, enabling real-time monitoring of X-chromosome activity via fluorescence. We inserted green and red fluorescent reporter genes and neomycin and puromycin resistance genes into the two X chromosomes of PGK12.1 ESCs, creating a female ESC line that retains two X chromosomes more faithfully during differentiation. Momiji (version 2) ESCs exhibit a more stable XX karyotype than other ESC lines, including the parental PGK12.1 line. This new tool offers valuable insights into the relationship between XCI and cell fate, improving our understanding of early female development.

Onion consumption has been reported to be associated with a lower incidence of myocardial infarction and stroke. Quercetin found in onions may contribute to this effect. This review aimed to describe the role of quercetin in vascular endothelial dysfunction-related hypertension. It also described the effects of quercetin on blood pressure (BP) regulation, vascular endothelial cell health associated with cardiovascular disease (CVD), and possible mechanisms underlying these effects. To this end, several epidemiological, in vivo, and in vitro studies published in PubMed, ScienceDirect, and Web of Science were analyzed. Epidemiological studies have shown that onions and quercetin can lower BP level and improve vascular dysfunction. The antioxidant and anti-inflammatory effects of quercetin may contribute to antihypertensive effect and endothelial cell health. In particular, in vivo studies have demonstrated that quercetin and its metabolites inhibit the renin–angiotensin (RA) system and increase nitric oxide (NO) production, reactive oxygen species production, and vascular endothelial cell inflammation, thereby possibly contributing to the improvement of endothelial dysfunction. Thus, quercetin acts directly on vascular endothelial cells to block hypertension and potentially contributes to CVD prevention.