Flavonoids are polyphenolic compounds produced by plants and delivered to the human body through food. Although the epidemiological analyses of large human populations did not reveal a simple ...correlation between flavonoid consumption and health, laboratory investigations and clinical trials clearly demonstrate the effectiveness of flavonoids in the prevention of cardiovascular, carcinogenic, neurodegenerative and immune diseases, as well as other diseases. At present, the abilities of flavonoids in the regulation of cell metabolism, gene expression, and protection against oxidative stress are well-known, although certain biophysical aspects of their functioning are not yet clear. Most flavonoids are poorly soluble in water and, similar to lipophilic compounds, have a tendency to accumulate in biological membranes, particularly in lipid rafts, where they can interact with different receptors and signal transducers and influence their functioning through modulation of the lipid-phase behavior. In this study, we discuss the enhancement in the lipophilicity and antioxidative activity of flavonoids after their complexation with transient metal cations. We hypothesize that flavonoid–metal complexes are involved in the formation of molecular assemblies due to the facilitation of membrane adhesion and fusion, protein–protein and protein–membrane binding, and other processes responsible for the regulation of cell metabolism and protection against environmental hazards.
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•Flavonoids are plant polyphenols delivered to the human body from food.•Flavonoids may prevent cardiovascular, carcinogenic, and other diseases.•Flavonoids interact with receptors and signal transducers of lipid rafts.•Complexation with iron enhances flavonoid interaction with proteins and membranes.•Flavonoid–iron may control cell signaling by fastening molecular assemblies.
BACKGROUND/OBJECTIVES Brain aging is a major risk factor for severe neurodegenerative diseases. Conversely, L-histidine and L-carnosine are known to exhibit neuroprotective effects. The aim of this ...study was to examine the potential for L-histidine, L-carnosine, and their combination to mediate anti-brain aging effects in neuronal cells subjected to D-galactose-induced aging. MATERIALS/METHODS The neuroprotective potential of L-histidine, L-carnosine, and their combination was examined in a retinoic acid-induced neuronal differentiated SH-SY5Y cell line exposed to D-galactose (200 mM) for 48 h. Neuronal cell proliferation, differentiation, and expression of anti-oxidant enzymes and apoptosis markers were subsequently evaluated. RESULTS Treatment with L-histidine (1 mM), L-carnosine (10 mM), or both for 48 h efficiently improved the proliferation, neurogenesis, and senescence of D-galactose-treated SH-SY5Y cells. In addition, protein expression levels of both neuronal markers (β tubulin-III and neurofilament heavy protein) and anti-oxidant enzymes, glutathione peroxidase-1 and superoxide dismutase-1 were up-regulated. Conversely, protein expression levels of amyloid β (1-42) and cleaved caspase-3 were down-regulated. Levels of mRNA for the pro-inflammatory cytokines, interleukin (IL)-8, IL-1β, and tumor necrosis factor-α were also down-regulated. CONCLUSIONS To the best of our knowledge, we provide the first evidence that L-histidine, L-carnosine, and their combination mediate anti-aging effects in a neuronal cell line subjected to D-galactose-induced aging. These results suggest the potential benefits of L-histidine and L-carnosine as anti-brain aging agents and they support further research of these amino acid molecules.
Abstract The blood–brain barrier (BBB) is a structural and functional barrier that regulates the passage of molecules into and out of the brain to maintain the neural microenvironment. We have ...previously developed the in vitro BBB model with human brain microvascular endothelial cells (HBMEC). However, in vivo HBMEC are shown to interact with astrocytes and also exposed to shear stress through blood flow. In an attempt to develop the BBB model to mimic the in vivo condition we constructed the flow-based in vitro BBB model using HBMEC and human fetal astrocytes (HFA). We also examined the effect of astrocyte-conditioned medium (ACM) in lieu of HFA to study the role of secreted factor(s) on the BBB properties. The tightness of HBMEC monolayer was assessed by the permeability of dextran and propidium iodide as well as by measuring the transendothelial electrical resistance (TEER). We showed that the HBMEC permeability was reduced and TEER was increased by non-contact, co-cultivation with HFA and ACM. The exposure of HBMEC to shear stress also exhibited decreased permeability. Moreover, HFA/ACM and shear flow exhibited additive effect of decreasing the permeability of HBMEC monolayer. In addition, we showed that the HBMEC expression of ZO-1 (tight junction protein) was increased by co-cultivation with ACM and in response to shear stress. These findings suggest that the non-contact co-cultivation with HFA helps maintain the barrier properties of HBMEC by secreting factor(s) into the medium. Our in vitro flow model system with the cells of human origin should be useful for studying the interactions between endothelial cells, glial cells, and secreted factor(s) as well as the role of shear stress in the barrier property of HBMEC.
Despite the ongoing spread of MERS, there is limited knowledge of the factors affecting its severity and outcomes. We analyzed clinical data and specimens from fourteen MERS patients treated in a ...hospital who collectively represent a wide spectrum of disease severity, ranging from mild febrile illness to fatal pneumonia, and classified the patients into four groups based on severity and mortality. Comparative and kinetic analyses revealed that high viral loads, weak antibody responses, and lymphopenia accompanying thrombocytopenia were associated with disease mortality, whereas persistent and gradual increases in lymphocyte responses might be required for effective immunity against MERS-CoV infection. Leukocytosis, primarily due to increased neutrophils and monocytes, was generally observed in more severe and fatal cases. The blood levels of cytokines such as IL-10, IL-15, TGF-β, and EGF were either positively or negatively correlated with disease mortality. Robust induction of various chemokines with differential kinetics was more prominent in patients that recovered from pneumonia than in patients with mild febrile illness or deceased patients. The correlation of the virological and immunological responses with disease severity and mortality, as well as their responses to current antiviral therapy, may have prognostic significance during the early phase of MERS.
•Imitation was reflected in neural patterns in the affective empathy system.•After imitation, a response was exhibited in the cognitive empathy system.•Affective empathic responses induced by ...imitation support cognitive empathy.•Imitation encourages cognitive and affective empathy toward hemiplegia.
Many people have difficulty empathizing with others who have dissimilar characteristics, such as physical disabilities. We hypothesized that people with no disabilities imitating the movements of individuals with disabilities could improve the empathic capacity toward their difficulties. To evaluate this hypothesis, we used functional magnetic resonance imaging to measure the neural activity patterns of 26 healthy participants while they felt the difficulties of individuals with hemiplegia by adopting their perspective. The participants initially either imitated or observed hemiplegic hand movements shown in video clips. Subsequently, the videos were rewatched and their difficulties were rated. Analysis of the subjective rating scores indicated that after imitating the hemiplegic movements, the participants felt into the difficulties of hemiplegia better than if they simply observed them. The cross-validation approach of multivoxel pattern analyses demonstrated that the information regarding the effect of imitation on empathizing with the difficulties was represented in specific activation patterns of brain regions involved in the mirror neuron system and cognitive empathy by comparing to other conditions that did not contain the information. The cross-classification approach detected distinct activation patterns in the brain regions involved in affective and cognitive empathy, commonly while imitating the hemiplegic movements and subsequently feeling them. This indicated that the common representation related to these two types of empathy existed between imitating and feeling the hemiplegic movements. Furthermore, representational similarity analysis revealed that activity patterns in the anterior cingulate cortex linked to affective empathy tuned to the subjective assessment of hemiplegic movements. Our findings indicate that imitating the movements of individuals with hemiplegia triggered the affective empathic response and improved the cognitive empathic response toward them. The affective empathic response also linked the subjective assessment to the difficulties of hemiplegia, which was especially modulated by the experience of imitation. Imitating the movements of individuals with disabilities likely encourages empathic capacity from both affective and cognitive aspects, resulting in people with no disabilities precisely feeling what they are feeling.
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•l-histidine and l-carnosine inhibited d-galactose-induced skin aging.•l-histidine and l-carnosine improved skin proliferation and migration in d-galactose-induced skin aging ...models.•l-histidine and l-carnosine improved collagen and wound healing in d-galactose-induced skin aging.•l-histidine and l-carnosine regulated the levels of corticosterone and PI3K/Akt phosphorylation in skin wound.
Impaired skin wound healing in the elderly can lead to medical issues and increased mortality. Although l-histidine and l-carnosine are potent anti-aging amino acids, the wound healing effects of these amino acids in aging remain to be elucidated. Here, we investigated the regenerative potential of l-histidine and l-carnosine in in vitro and in vivo aging models. l-histidine (1 mM), l-carnosine (10 mM), or a combination improved proliferation, migration, senescence, and epithelial-mesenchymal transition (EMT) in d-galactose-induced aged keratinocytes. An in vivo mouse aging model was established with injection of d-galactose (s.c. 500 mg/kg) daily for eight weeks. Supplementation with l-histidine (2 g/L), l-carnosine (2 g/L), or a combination improved collagen and wound healing with EMT markers, E-cadherin, N-cadherin, and MMP-2. These effects were concomitant with reduced circulating levels of corticosterone and increased PI3K/Akt phosphorylation. These results suggest that l-histidine and l-carnosine have the potential to facilitate wound healing in aging skin.
The adult mammalian heart has limited potential for regeneration. Thus, after injury, cardiomyocytes are permanently lost, and contractility is diminished. In contrast, the neonatal heart can ...regenerate owing to sustained cardiomyocyte proliferation. Identification of critical regulators of cardiomyocyte proliferation and quiescence represents an important step toward potential regenerative therapies. Yes-associated protein (Yap), a transcriptional cofactor in the Hippo signaling pathway, promotes proliferation of embryonic cardiomyocytes by activating the insulin-like growth factor and Wnt signaling pathways. Here we report that mice bearing mutant alleles of Yap and its paralog WW domain containing transcription regulator 1 (Taz) exhibit gene dosage-dependent cardiac phenotypes, suggesting redundant roles of these Hippo pathway effectors in establishing proper myocyte number and maintaining cardiac function. Cardiac-specific deletion of Yap impedes neonatal heart regeneration, resulting in a default fibrotic response. Conversely, forced expression of a constitutively active form of Yap in the adult heart stimulates cardiac regeneration and improves contractility after myocardial infarction. The regenerative activity of Yap is correlated with its activation of embryonic and proliferative gene programs in cardiomyocytes. These findings identify Yap as an important regulator of cardiac regeneration and provide an experimental entry point to enhance this process.
BACKGROUND/OBJECTIVESExcess intake of dietary sodium, either directly or indirectly, increases the risk of several diseases, including cardio-cerebral vascular diseases such as stroke and ...hypertension. Excessive sodium intake and increased prevalence of hypertension have emerged as major issues worldwide. Therefore, the present study evaluated the recent trends in dietary sodium intake and the food sources of sodium intake in the Korean population using the Korea National Health and Nutrition Examination Survey (KNHANES, 2013-2017) data.SUBJECTS/METHODSThis study used the one-day 24-h recall dietary intake survey data from the 2013-2017 KNHANES to determine the average daily sodium intake by sex and age and the main dishes and food groups contributing to the dietary sodium intake.RESULTSThe mean sodium intake range was 3,477.2-3,889.6 mg/day during 2013-2017. The major food groups contributing to sodium intake were seasonings (1,597.5-1,870.5 mg/day), vegetables (680.4-756.7 mg/day), and cereal and grains (573.2-609.4 mg/day). Noodles and dumplings (536.7-573.2 mg/day), kimchi (487.3-539.6 mg/day), and soups (367.6-428.9 mg/day) were the top three dish groups that contributed to the sodium intake. In these dishes, the major sources of sodium intake were ramyeon (age groups 10-18 and 19-29 yrs), baechukimchi (age groups 40-49 and 50-59 yrs) and doenjang-kuk (age groups 60-69 and ≥ 70 yrs), respectively.CONCLUSIONSIn summary, reducing the consumption of soups and kimchi is an effective way to reduce sodium intake. Personalized nutrition education on dietary sodium intake management is required because of the different food sources contributing to the sodium intake according to the subjects' age.
Ingroup favoritism and fairness are two potentially competing motives guiding intergroup behaviors in human. Here, we investigate if and how limited resources can modulate the way these two motives ...affect individuals' decisions in intergroup situation. In the present study, participants (N = 58) were asked to accept or reject three types of resource allocation proposals generated by a computer: the ingroup advantageous condition, outgroup advantageous condition, and neutral condition. In general, participants were more willing to accept the proposals in the ingroup advantageous condition than the outgroup advantageous or the neutral conditions, and also in the moderate inequality than the extreme inequality condition. This may indicate that people sought a careful balance between ingroup favoritism and fairness, although we also found marked individual differences in their preferences for ingroup favoritism or fairness. Importantly, as predicted, participants were more likely to show ingroup favoritism only when limited resources affect the well-being of ingroup members. The present study provides novel insights into the situational and personality factors affecting human intergroup behaviors, shedding light on motives underlying intergroup conflicts prevalent in human societies.
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