Simultaneous Intake of Chlorella and Ascidian Ethanolamine Plasmalogen Accelerates Activation of BDNF-TrkB-CREB Signaling in Rats.

Brain-derived neurotrophic factor (BDNF) plays an important role in neurogenesis, synaptic plasticity, and cognition. BDNF is a neurotrophin that binds to tropomyosin receptor kinase B (TrkB), a specific receptor on target cell surfaces; it acts on neuronal formation, development, growth, and repair via transcription factors, such as cAMP response element-binding protein (CREB), and it is involved in learning and memory. BDNF expression is decreased in patients with Alzheimer's disease (AD). Exercise and the intake of several different foods or ingredients can increase BDNF expression, as confirmed with lutein, xanthophylls (polar carotenoids), and ethanolamine plasmalogen (PlsEtn), which are present at high levels in the brain. This study examined the effects of combining lutein and PlsEtn using lutein-rich Chlorella and ascidian extracts containing high levels of PlsEtn bearing docosahexaenoic acid, which is abundant in the human brain, on the activation of the BDNF-TrkB-CREB signaling pathway in the hippocampus of Sprague-Dawley rats. Although activation of the BDNF-TrkB-CREB signaling pathway in the hippocampus was not observed in Chlorella or ascidian PlsEtn monotherapy, activation was observed with combination therapy at an equal dose. The results of this study suggest that the combination of Chlorella and ascidian PlsEtn may have a preventive effect against dementia, including AD.

Hypolipidemic and Anti-Inflammatory Effects of Curcuma longa-Derived Bisacurone in High-Fat Diet-Fed Mice.

Turmeric (Curcuma longa) contains various compounds that potentially improve health. Bisacurone is a turmeric-derived compound but has been less studied compared to other compounds, such as curcumin. In this study, we aimed to evaluate the anti-inflammatory and lipid-lowering effects of bisacurone in high-fat diet (HFD)-fed mice. Mice were fed HFD to induce lipidemia and orally administered bisacurone daily for two weeks. Bisacurone reduced liver weight, serum cholesterol and triglyceride levels, and blood viscosity in mice. Splenocytes from bisacurone-treated mice produced lower levels of the pro-inflammatory cytokines IL-6 and TNF-α upon stimulation with a toll-like receptor (TLR) 4 ligand, lipopolysaccharide (LPS), and TLR1/2 ligand, Pam3CSK4, than those from untreated mice. Bisacurone also inhibited LPS-induced IL-6 and TNF-α production in the murine macrophage cell line, RAW264.7. Western blot analysis revealed that bisacurone inhibited the phosphorylation of IKKα/ß and NF-κB p65 subunit, but not of the mitogen-activated protein kinases, p38 kinase and p42/44 kinases, and c-Jun N-terminal kinase in the cells. Collectively, these results suggest that bisacurone has the potential to reduce serum lipid levels and blood viscosity in mice with high-fat diet-induced lipidemia and modulate inflammation via inhibition of NF-κB-mediated pathways.

Microgreens-A Comprehensive Review of Bioactive Molecules and Health Benefits.

Microgreens, a hypothesized term used for the emerging food product that is developed from various commercial food crops, such as vegetables, grains, and herbs, consist of developed cotyledons along with partially expanded true leaves. These immature plants are harvested between 7-21 days (depending on variety). They are treasured for their densely packed nutrients, concentrated flavors, immaculate and tender texture as well as for their vibrant colors. In recent years, microgreens are on demand from high-end restaurant chefs and nutritional researchers due to their potent flavors, appealing sensory qualities, functionality, abundance in vitamins, minerals, and other bioactive compounds, such as ascorbic acid, tocopherol, carotenoids, folate, tocotrienols, phylloquinones, anthocyanins, glucosinolates, etc. These qualities attracted research attention for use in the field of human health and nutrition. Increasing public concern regarding health has prompted humans to turn to microgreens which show potential in the prevention of malnutrition, inflammation, and other chronic ailments. This article focuses on the applications of microgreens in the prevention of the non-communicable diseases that prevails in the current generation, which emerged due to sedentary lifestyles, thus laying a theoretical foundation for the people creating awareness to switch to the recently introduced category of vegetable and providing great value for the development of health-promoting diets with microgreens.

Marine Plasmalogens: A Gift from the Sea with Benefits for Age-Associated Diseases.

Aging increases oxidative and inflammatory stress caused by a reduction in metabolism and clearance, thus leading to the development of age-associated diseases. The quality of our daily diet and exercise is important for the prevention of these diseases. Marine resources contain various valuable nutrients, and unique glycerophospholipid plasmalogens are found abundantly in some marine invertebrates, including ascidians. One of the major classes, the ethanolamine class (PlsEtn), exists in a high ratio to phospholipids in the brain and blood, while decreased levels have been reported in patients with age-associated diseases, including Alzheimer's disease. Animal studies have shown that the administration of marine PlsEtn prepared from marine invertebrates improved PlsEtn levels in the body and alleviated inflammation. Animal and human studies have reported that marine PlsEtn ameliorates cognitive impairment. In this review, we highlight the biological significance, relationships with age-associated diseases, food functions, and healthcare materials of plasmalogens based on recent knowledge and discuss the contribution of marine plasmalogens to health maintenance in aging.

Determination of intracellular ascorbic acid using tandem mass spectrometry.

Ascorbic acid is involved in a variety of biological events. Nevertheless, its detailed intracellular behavior remains unexplored due to a lack of sensitive analytical methods. Here we report a method using HPLC-ESI-MS/MS achieving the lowest detection limit ever reported (1 pg), to provide mechanistic insight into the intracellular ascorbic acid physiology.

Current Use of Fenton Reaction in Drugs and Food.

Iron is the most abundant mineral in the human body and plays essential roles in sustaining life, such as the transport of oxygen to systemic organs. The Fenton reaction is the reaction between iron and hydrogen peroxide, generating hydroxyl radical, which is highly reactive and highly toxic to living cells. "Ferroptosis", a programmed cell death in which the Fenton reaction is closely involved, has recently received much attention. Furthermore, various applications of the Fenton reaction have been reported in the medical and nutritional fields, such as cancer treatment or sterilization. Here, this review summarizes the recent growing interest in the usefulness of iron and its biological relevance through basic and practical information of the Fenton reaction and recent reports.

Removal of chlorophyll and pheophorbide from Chlorella pyrenoidosa by supercritical fluid extraction: potential of protein resource.

This study tried to quantitatively clarify the usefulness of supercritical fluid extraction for removal of chlorophyll and pheophorbide from Chlorella pyrenoidosa. C. pyrenoidosa powder was subjected to supercritical fluid extraction, and chlorophyll a and pheophorbide a in its extracted fractions were measured by HPLC-UV. Chlorophyll a and pheophorbide a in residue after supercritical fluid extraction became below of detection limit.

Vitamin E: Regulatory Redox Interactions.

Vitamin E is an essential nutrient that was discovered in the 1920s. Many of the physiological functions of vitamin E, including its antioxidative effects, have been studied for nearly 100 years. Changes in redox balance induced by both endogenously and exogenously generated reactive oxygen species (ROS) are involved in various diseases, and are also a phenomenon that is considered essential for survival. Vitamin E is known to regulate redox balance in the body due to its high concentration among the lipid soluble vitamin groups, and exists ubiquitously in the whole body, including cell membranes and lipoproteins. However, it has been reported that the beneficial properties of vitamin E, including its antioxidative effects, are only displayed in vitro, and not in vivo. Therefore, there exists an ongoing debate regarding the biological functions of vitamin E and its relationship with redox balance. In this review, we introduce the relationship between vitamin E and redox interactions with (i) absorption, distribution, metabolism, and excretion of vitamin E, (ii) oxidative stress and ROS in the body, (iii) mechanism of antioxidative effects, (iv) non-antioxidant functions of vitamin E, and (v) recent recognition of the field of oxidative stress research. Understanding the recent findings of the redox interaction of vitamin E may help to elucidate the different antioxidative phenomena observed for vitamin E in vitro and in vivo. © 2019 IUBMB Life, 71(4):430-441, 2019.

Determination of cellular vitamin C dynamics by HPLC-DAD.

A redox-sensitive inter-conversion between ascorbic acid (ASC) and its oxidized form dehydroascorbic acid (DHA) in the intracellular environment has been of exceptional interest to recent metabolomics and pharmaceutical research. We developed a chromatographic protocol to instantly determine these vitamers with each identity from cellular extracts, without any labeling and pretreatments. Owing to its simplicity, one can readily continue the assay for hours, an otherwise difficult to cover timescale at which the intracellular DHA-ASC conversion comes into play. The method was validated for the analysis of pancreatic cancer cells, to our knowledge the first-ever study on a nucleated cell type, to trace in detail their kinetics of glucose transporter-dependent DHA uptake and, simultaneously, that for the intracellular ASC conversion. The simplest of all the relevant techniques and yet with the unique ability to provide each vitamer identity on a high-throughput basis, this method should offer the most practical option for VC-involved physiological and pharmaceutical studies including high-dose VC cancer therapy.

Carbon tetrachloride-induced hepatic and renal damages in rat: inhibitory effects of cacao polyphenol.

Here, we investigated the protective effect of cacao polyphenol extract (CPE) on carbon tetrachloride (CCl4)-induced hepato-renal oxidative stress in rats. Rats were administered CPE for 7 days and then received intraperitoneal injection of CCl4. Two hours after injection, we found that CCl4 treatment significantly increased biochemical injury markers, lipid peroxides (phosphatidylcholine hydroperoxide (PCOOH) and malondialdehyde (MDA)) and decreased glutathione peroxidase activity in kidney rather than liver, suggesting that kidney is more vulnerable to oxidative stress under the present experimental conditions. CPE supplementation significantly reduced these changes, indicating that this compound has antioxidant properties against CCl4-induced oxidative stress. An inhibitory effect of CPE on CCl4-induced CYP2E1 mRNA degradation may provide an explanation for CPE antioxidant property. Together, these results provide quantitative evidence of the in vivo antioxidant properties of CPE, especially in terms of PCOOH and MDA levels in the kidneys of CCl4-treated rats.

Influence of single bout of aerobic exercise on aortic pulse pressure.

PURPOSE: Regular aerobic exercise has come to the forefront of non-pharmacological treatment for hypertension. In this line, post-exercise hypotension may have a potential tool for efficient blood pressure management. However, less is known about the influence of acute aerobic exercise on aortic pulse pressure (PP), an important property underlying the pathophysiology of cardiovascular disease. We tested the hypotheses that aortic PP would be attenuated with a single aerobic exercise and that its extent would be associated with the delayed return of reflected wave and the leg vasodilatory capacity. METHODS: In 23 apparent healthy men (22 ± 4 years), hemodynamic variables and aortic pulse wave velocity (PWV) were measured before and 20 and 50 min after a 60-min bout of cycling exercise at moderate intensity (corresponding to 65-75 % heart rate reserve). Aortic pressure was estimated from applanation tonometrically measured radial arterial pressure waveform via general transfer function. Peak calf vascular dilatory capacity was measured with the ischemic exercise-induced hyperemia (via venous occlusion plethysmography). RESULTS: Finger, brachial, and aortic PP were significantly attenuated following the exercise. At 20 min after the exercise cessation, individual changes in aortic PWV significantly correlated with corresponding changes in aortic PP (r = 0.541, P < 0.05), but this correlation was no longer significant at 50 min after the exercise cessation. Peak calf vascular dilatory capacity was not associated with change in aortic PP. CONCLUSIONS: We conclude that in young men the aortic PP would be attenuated with the moderate-intensity dynamic exercise partly due to the delayed return of reflection wave from periphery.

Comparative analysis of macro- and micro-nutrients of Perilla frutescens var. crispa f. viridis microgreens and germinated seeds.

This study aimed to conduct a comparative analysis of germinated seeds and microgreens derived from Perilla frutescens var. crispa f. viridis, hypothesizing that microgreens would exhibit higher concentrations of nutrients and bioactive compounds compared to their precursors. Perilla frutescens was chosen for its popularity and wide use in Asian cuisine. A series of analytical methods was employed to quantify and qualify various components. The findings indicate that germinated seeds exhibit significantly higher quantities of lipids, proteins, sugars, free amino acids, and minerals, whereas microgreens possess significantly high concentration of vitamins and polyphenols. These results provide valuable insights into the nutritional differences between germinated seeds and microgreens, highlighting their distinct contributions to diet. Specifically, incorporating germinated seeds can enhance macronutrient intake, while microgreens can boost antioxidant intake. These findings can inform the development of targeted dietary recommendations, promoting the inclusion of both germinated seeds and microgreens to meet specific nutritional needs and improve health outcomes.

Prevalence of Poor Sleep Quality and its Association with Lifestyle Habits, Competition-Based Activities, and Psychological Distress in Japanese Student-Athletes During the COVID-19 Pandemic.

Objectives The present study clarified the prevalence of poor sleep quality and its relation to lifestyle habits, competitive-based activities, and psychological distress among Japanese student-athletes in the initial pandemic period (2020) and 1 year later (2021). Methods In the present study, student-athletes were defined as individuals belonging to university athletic clubs. The data of two cross-sectional surveys (2020: n = 961 and 2021: n = 711) were collected from student-athletes in 6 universities in Japan. First, the prevalence of poor sleep quality (Pittsburgh sleep quality index score > 5) was investigated. Relationships between poor sleep quality and lifestyle habits, competition-based activities, and psychological distress were then explored using multivariate logistic regression analysis adjusted for age, sex, and body mass index. Results The prevalence of poor sleep quality was 33.6% in 2020 and 36.6% in 2021. Poor sleep quality in 2020 was related to late bedtime, taking supplements before bed, part-time job (no late night), stressors of expectations and pressure from others, and psychological distress, whereas that in 2021 was related to early wake-up time, skipping breakfast, taking caffeinated drinks before bed, use of smartphone/cellphone after lights out, stressors of motivation loss, and psychological distress. Conclusions In both 2020 and 2021, one-third of student-athletes had poor sleep quality and psychological distress was its common risk factor. Lifestyle habits and competition stressors associated with poor sleep quality were pandemic-specific in 2020, but similar to the prepandemic period in 2021.

Oxidative stress during development of alcoholic fatty liver: therapeutic potential of cacao polyphenol.

The lipid and antioxidative/oxidative profiles of livers from rats fed an ethanol liquid diet for 8 weeks provided evidence for an involvement of oxidative stress (e.g., phospholipid peroxidation) in the development of alcoholic fatty liver (AFL), possibly in an early stage. Cacao polyphenol supplementation produced an ameliorating effect, and may help in AFL prevention.

Skin blood flow influences cerebral oxygenation measured by near-infrared spectroscopy during dynamic exercise.

PURPOSE: Near-infrared spectroscopy (NIRS) is widely used to investigate cerebral oxygenation and/or neural activation during physiological conditions such as exercise. However, NIRS-determined cerebral oxygenated hemoglobin (O2Hb) may not necessarily correspond to intracranial blood flow during dynamic exercise. To determine the selectivity of NIRS to assess cerebral oxygenation and neural activation during exercise, we examined the influence of changes in forehead skin blood flow (SkBF(head)) on NIRS signals during dynamic exercise. METHODS: In ten healthy men (age: 20 ± 1 years), middle cerebral artery blood flow velocity (MCA V mean, via transcranial Doppler ultrasonography), SkBF(head) (via laser Doppler flowmetry), and cerebral O2Hb (via NIRS) were continuously measured. Each subject performed 60 % maximum heart rate moderate-intensity steady-state cycling exercise. To manipulate SkBF(head), facial cooling using a mist of cold water (~4 °C) was applied for 3 min during steady-state cycling. RESULTS: MCA V mean significantly increased during exercise and remained unchanged with facial cooling. O2Hb and SkBF(head) were also significantly increased during exercise; however, both of these signals were lowered with facial cooling and returned to pre-cooling values with the removal of facial cooling. The changes in O2Hb correlated significantly with the relative percent changes in SkBF(head) in each individual (r = 0.71-0.99). CONCLUSIONS: These findings suggest that during dynamic exercise NIRS-derived O2Hb signal can be influenced by thermoregulatory changes in SkBF(head) and therefore, may not be completely reflective of cerebral oxygenation or neural activation.

The Potential Use of Exosomes in Anti-Cancer Effect Induced by Polarized Macrophages.

The rapid development of aberrant cells outgrowing their normal bounds, which can subsequently infect other body parts and spread to other organs-a process known as metastasis-is one of the significant characteristics of cancer. The main reason why cancer patients die is because of widespread metastases. This abnormal cell proliferation varies in cancers of over a hundred types, and their response to treatment can vary substantially. Several anti-cancer drugs have been discovered to treat various tumors, yet they still have harmful side-effects. Finding novel, highly efficient targeted therapies based on modifications in the molecular biology of tumor cells is essential to reduce the indiscriminate destruction of healthy cells. Exosomes, an extracellular vesicle, are promising as a drug carrier for cancer therapy due to their good tolerance in the body. In addition, the tumor microenvironment is a potential target to regulate in cancer treatment. Therefore, macrophages are polarized toward M1 and M2 phenotypes, which are involved in cancer proliferation and are malignant. It is evident from recent studies that controlled macrophage polarization might contribute to cancer treatment, by the direct way of using miRNA. This review provides an insight into the potential use of exosomes to develop an 'indirect', more natural, and harmless cancer treatment through regulating macrophage polarization.

Effects of Particle Size of Curcumin Solid Dispersions on Bioavailability and Anti-Inflammatory Activities.

The delivery of curcumin (CUR) using the solid dispersion system (CUR solid dispersions; C-SDs) has been shown to improve CUR bioavailability. However, it is unclear how different particle sizes of C-SDs affect the bioavailability and biological activities of CUR. Hence, we prepared C-SDs in different sizes using food-grade excipients and evaluated their bioavailability and biological activities. By pulverizing large particle sizes of C-SDs using zirconia beads, we successfully prepared C-SDs I-IV (particle size: (I) 120, (II) 447, (III) 987, (IV) 1910 nm). When administrated orally in rats, the bioavailability of CUR was increased with decreasing C-SDs size, most likely by improving its solubility in micelles. When administrated intravenously in rats, blood concentrations of CUR were increased with increasing particle size, suggesting that larger C-SDs presumably control the metabolic conversion of CUR. In RAW264 cells, more CUR was taken up by cells as their sizes reduced, and the more potent their anti-inflammatory activities were, suggesting that smaller C-SDs were taken up through a number of cellular uptake pathways. Altogether, the present study showed an evident effect of C-SDs size on their bioavailability and anti-inflammatory activities-information that serves as a basis for improving the functionality of CUR.

Differential blood flow responses to CO2 in human internal and external carotid and vertebral arteries.

Arterial CO2 serves as a mediator of cerebral blood flow(CBF), and its relative influence on the regulation of CBF is defined as cerebral CO2 reactivity. Our previous studies have demonstrated that there are differences in CBF responses to physiological stimuli (i.e. dynamic exercise and orthostatic stress) between arteries in humans. These findings suggest that dynamic CBF regulation and cerebral CO2 reactivity may be different in the anterior and posterior cerebral circulation. The aim of this study was to identify cerebral CO2 reactivity by measuring blood flow and examine potential differences in CO2 reactivity between the internal carotid artery (ICA), external carotid artery (ECA) and vertebral artery (VA). In 10 healthy young subjects, we evaluated the ICA, ECA, and VA blood flow responses by duplex ultrasonography (Vivid-e, GE Healthcare), and mean blood flow velocity in middle cerebral artery (MCA) and basilar artery (BA) by transcranial Doppler (Vivid-7, GE healthcare) during two levels of hypercapnia (3% and 6% CO2), normocapnia and hypocapnia to estimate CO2 reactivity. To characterize cerebrovascular reactivity to CO2,we used both exponential and linear regression analysis between CBF and estimated partial pressure of arterial CO2, calculated by end-tidal partial pressure of CO2. CO2 reactivity in VA was significantly lower than in ICA (coefficient of exponential regression 0.021 ± 0.008 vs. 0.030 ± 0.008; slope of linear regression 2.11 ± 0.84 vs. 3.18 ± 1.09% mmHg−1: VA vs. ICA, P <0.01). Lower CO2 reactivity in the posterior cerebral circulation was persistent in distal intracranial arteries (exponent 0.023 ± 0.006 vs. 0.037 ± 0.009; linear 2.29 ± 0.56 vs. 3.31 ± 0.87% mmHg−1: BA vs. MCA). In contrast, CO2 reactivity in ECA was markedly lower than in the intra-cerebral circulation (exponent 0.006 ± 0.007; linear 0.63 ± 0.64% mmHg−1, P <0.01). These findings indicate that vertebro-basilar circulation has lower CO2 reactivity than internal carotid circulation, and that CO2 reactivity of the external carotid circulation is markedly diminished compared to that of the cerebral circulation, which may explain different CBF responses to physiological stress.

Kinetics of exercise-induced neural activation; interpretive dilemma of altered cerebral perfusion.

Neural activation decreases cerebral deoxyhaemoglobin (HHb(C)) and increases oxyhaemoglobin concentration (O(2)Hb(C)). In contrast, patients who present with restricted cerebral blood flow, such as those suffering from cerebral ischaemia or Alzheimer's disease, and during the course of ageing the converse occurs, in that HHb(C) increases and O(2)Hb(C) decreases during neural activation. In the present study, we examined the interpretive implications of altered exercise-induced cerebral blood flow for cortical oxygenation in healthy subjects. Both O(2)Hb(C) and HHb(C) (prefrontal cortex) were determined in 11 healthy men using near-infrared spectroscopy (NIRS). Middle cerebral artery mean blood velocity (MCA V(mean)) was determined via transcranial Doppler ultrasonography. Measurements were performed during contralateral hand-grip exercise during suprasystolic bilateral thigh-cuff occlusion (Cuff+) and within 2 s of cuff release (Cuff-) for the acute manipulation of cerebral perfusion. During Cuff+, both MCA V(mean) and O(2)Hb(C) increased during exercise, whereas HHb(C) decreased. In contrast, the opposite occurred during the Cuff- manipulation. These findings highlight the inverse relationship between cerebral blood flow and cerebral oxygenation as determined by NIRS, which has interpretive implications for the kinetics underlying exercise-induced neural activation.

Biological Functions of Antioxidant Dipeptides.

In the history of modern nutritional science, understanding antioxidants is one of the major topics. In many cases, food-derived antioxidants have π conjugate or thiol group in their molecular structures because π conjugate stabilizes radical by its delocalization and two thiol groups form a disulfide bond in its antioxidative process. In recent years, antioxidant peptides have received much attention because for their ability to scavenge free radicals, inhibition of lipid peroxidation, chelation of transition metal ions, as well as their additional nutritional value. Among them, dipeptides are attracting much interest as post-amino acids, which have residues in common with amino acids, but also have different physiological properties and functions from those of amino acids. Especially, dipeptides containing moieties of several amino acid (tryptophan, tyrosine, histidine, cysteine, and methionine) possess potent antioxidant activity. This review summarizes previous details of structural property, radical scavenging activity, and biological activity of antioxidant dipeptide. Hopefully, this review will help provide a new insight into the study of the biological functions of antioxidant dipeptides.