The effects of dark chocolate on cognitive performance during cognitively demanding tasks: A randomized, single-blinded, crossover, dose-comparison study.

Dark chocolate, rich in polyphenols, increases cerebral blood flow and improves cognitive function. This study aimed to determine whether the consumption of chocolate with a high concentration of polyphenols helps to maintain cognitive performance during cognitively demanding tasks. In this randomized, single-blinded, crossover, dose-comparison study, 18 middle-aged adults consumed two types of chocolate (25 g each), one with a high concentration (635.0 mg) and the other with a low concentration (211.7 mg) of cacao polyphenols, and performed a cognitive task requiring response inhibition and selective attention over two time periods (15-30 min and 40-55 min after consumption, respectively). Autonomic nerve function and subjective feelings, such as fatigue and concentration, were measured before food intake and after the second task to assess the participant's state. The results showed that the average reaction time between the first and second sessions was not significantly different for either high- or low-concentration chocolate consumption. However, the percentage of correct responses was similar in the first (96.7 %) and second (96.8 %) sessions for high-concentration chocolate consumption and significantly lower for low-concentration chocolate consumption in the second (96.4 %) session than in the first session (97.3 %). Autonomic nerve function showed a significant increase in sympathetic nerve activity after the second task with high-concentration chocolate consumption, while subjective feelings showed an increase in mental fatigue for both chocolate types but a significant decrease in concentration only after the second task with low-concentration chocolate consumption. These findings suggest that dark chocolate consumption contributes to the maintenance of performance and concentration in continuous and demanding cognitive tasks.

Effects of Pawpaw (Asimina triloba) Seed Extract on the Differentiation and Fat Accumulation of 3T3-L1 Cells under Different Glucose Conditions.

Asimina triloba (pawpaw) contains various bioactive alkaloids and acetogenins. In the present study, the effects of pawpaw seed extract (PSE) on adipocyte differentiation and fat accumulation were investigated in 3T3-L1 cells under different glucose conditions. Treatment of undifferentiated cells with 10 ng/mL PSE increased lactic acid production, suggesting enhanced anaerobic glycolysis. PSE treatment also suppressed cell proliferation and decreased the nicotinamide adenine dinucleotide (NAD)+/NADH ratio in low-glucose medium; however, this effect was not observed in high-glucose medium. Additionally, PSE treatment under low-glucose conditions resulted in reduced accumulation of triglycerides and decreased expression of peroxisome proliferator-activated receptor (PPAR)-γ, CAAT/enhancer-binding protein (C/EBP)-α, and sterol regulatory element binding protein (SREBP)-1c in adipocyte-differentiated cells. PSE exerted greater effects on adipocyte differentiation and triglyceride content in 3T3-L1 cells under low-glucose conditions than under high-glucose conditions. These findings indicate that PSE enhances anaerobic glycolysis and inhibits adipocyte differentiation and fat accumulation in 3T3-L1 cells under glucose-restricted conditions.

Cacao Polyphenol-Rich Dark Chocolate Intake Contributes to Efficient Brain Activity during Cognitive Tasks: A Randomized, Single-Blinded, Crossover, and Dose-Comparison fMRI Study.

Cacao polyphenol-enriched dark chocolate may have beneficial effects on human health, such as facilitating maintaining good performance in long-lasting cognitive tasks. This study examined the effects of dark chocolate intake on improving brain function during cognitive tasks using functional magnetic resonance imaging (fMRI). In this randomized, single-blinded, crossover, and dose-comparison study, 26 healthy middle-aged participants ingested dark chocolate (25 g) either with a low concentration (LC) (211.7 mg) or a high concentration (HC) (635 mg) of cacao polyphenols. Thereafter, their brain activities were analyzed during continuous and effortful cognitive tasks relevant to executive functioning using fMRI in two consecutive 15 min sessions (25 and 50 min after ingestion). We observed significant interaction effects between chocolate consumption and brain activity measurement sessions in the left dorsolateral prefrontal cortex and left inferior parietal lobule. After HC chocolate ingestion, these areas showed lower brain activity in the second session than in the first session; however, these areas showed higher activity in the second session after LC chocolate ingestion. These results suggest that cacao polyphenol-enriched dark chocolate enhances the efficient use of cognitive resources by reducing the effort of brain activity.

Usefulness of a new DUV-LED device for the control of infection by Escherichia coli, Staphylococcus aureus, mycobacteria and spore-forming bacteria.

Reliable disinfection and sterilization technologies are needed to deal with the various infectious diseases spreading around the world. Furthermore, bacteria that are difficult to eliminate by ordinary disinfection are also a problem in the medical environment. We examined the germicidal effect of a newly developed deep-ultraviolet light-emitting diode (DUV-LED) prototype device (wavelength of 280 ± 5 nm; power of 0.9 to 1.4 mW/cm2) for floor sterilization against Escherichia coli (E. coli), Staphylococcus aureus (S. aureus), Mycobacterium gordonae (M. gordonae), and Bacillus subtilis (B. subtilis). This prototype device is equipped with highly practical DUV-LEDs with a high output efficiency and a long life, and was designed with consideration of the irradiation distance and the angle of the DUV-LEDs to provide a uniform irradiation rate. We found a statistically significant reduction of ≥90% in the infectious titers of both E. coli and S. aureus after irradiation for 2 s. Although acid-fast bacilli and spore-type bacilli are generally thought to be resistant to UV light irradiation compared to general bacteria, the acid-fast bacillus M. gordonae was inactivated after irradiation for 10 s, and spore-type cells of the bacillus B. subtilis were inactivated by ≥90% after irradiation for 30 s. We also found that the effects were cumulative when irradiation was performed at intervals. In the future, the usefulness of this device as an infection control measure will be evaluated in daily medical practice.

Antioxidant effects of continuous intake of electrolyzed hydrogen water in healthy adults.

Chronic oxidative stress induces deterioration of health and a risk for the onset of various diseases. Previous clinical studies revealed that electrolyzed hydrogen water (EHW) is effective to reduce oxidative stress during hemodialysis in patients with chronic dialysis. In the present observational study, we investigated the antioxidant effects of a daily continuous intake of EHW in healthy adults. The concentrations of serum reactive oxygen metabolites-derived compounds (d-ROMs) and blood urea nitrogen in healthy volunteers (n = 64) who had a habit of intake over 500 mL/day of EHW at least 5 days a week for longer than 6 months were lower than those of age- and sex-matched controls (n = 470) without the habit of EHW intake. Oxidation stress index which the ratio between concentrations in d-ROMs and biological antioxidant potential was correlated with the serum concentration of high-sensitivity C-reactive protein or low-density lipoprotein cholesterol in the EHW group. These results suggest that the continuous intake of EHW induces antioxidant effects and may contribute to alleviate the risk of various oxidative stress-related dysfunctions and diseases in healthy adults.

The Expression Level of HIV-1 Vif Is Optimized by Nucleotide Changes in the Genomic SA1D2prox Region during the Viral Adaptation Process.

HIV-1 Vif plays an essential role in viral replication by antagonizing anti-viral cellular restriction factors, a family of APOBEC3 proteins. We have previously shown that naturally-occurring single-nucleotide mutations in the SA1D2prox region, which surrounds the splicing acceptor 1 and splicing donor 2 sites of the HIV-1 genome, dramatically alter the Vif expression level, resulting in variants with low or excessive Vif expression. In this study, we investigated how these HIV-1 variants with poor replication ability adapt and evolve under the pressure of APOBEC3 proteins. Adapted clones obtained through adaptation experiments exhibited an altered replication ability and Vif expression level compared to each parental clone. While various mutations were present throughout the viral genome, all replication-competent adapted clones with altered Vif expression levels were found to bear them within SA1D2prox, without exception. Indeed, the mutations identified within SA1D2prox were responsible for changes in the Vif expression levels and altered the splicing pattern. Moreover, for samples collected from HIV-1-infected patients, we showed that the nucleotide sequences of SA1D2prox can be chronologically changed and concomitantly affect the Vif expression levels. Taken together, these results demonstrated the importance of the SA1D2prox nucleotide sequence for modulating the Vif expression level during HIV-1 replication and adaptation.

Developmental dysregulation of excitatory-to-inhibitory GABA-polarity switch may underlie schizophrenia pathology: A monozygotic-twin discordant case analysis in human iPS cell-derived neurons.

Schizophrenia is a major psychiatric disorder, but the molecular mechanisms leading to its initiation or progression remain unclear. To elucidate the pathophysiology of schizophrenia, we used an in vitro neuronal cell culture model involving human induced pluripotent stem cells (hiPSCs) derived from a monozygotic-twin discordant schizophrenia pair. The cultured neurons differentiated from hiPSCs were composed of a mixture of glutamatergic excitatory neurons and gamma aminobutyric acid (GABA)ergic inhibitory neurons. In the electrophysiological analysis, a different pattern of spontaneous neuronal activity was observed under the condition without any stimulants. The frequency of spontaneous excitatory post-synaptic currents (sEPSCs) was significantly higher in the hiPSC-derived neurons of the patient with schizophrenia than in the control sibling at day-in-vitro 30. However, the synaptic formation was not different between the patient with schizophrenia and the control sibling during the same culture period. To explain underlying mechanisms of higher excitability of presynaptic cells, we focused on the potassium-chloride co-transporter KCC2, which contributes to excitatory-to-inhibitory GABA polarity switch in developing neurons. We also revealed the altered expression pattern of KCC2 in hiPSC-derived neurons from the patient with schizophrenia, which could contribute to understanding the pathology of schizophrenia in the developing nervous system.

Effects of Collagen Peptide Administration on Visceral Fat Content in High-Fat Diet-Induced Obese Mice.

Collagen peptides (CPs) are bioactive molecules that have beneficial effects on bone metabolism and against joint disorders. In the present study, we investigated the effect of CP supplementation on visceral fat mass and plasma lipid concentrations in high-fat diet (HFD)-induced obese mice. Male ddY mice were fed a normal diet or HFD for 3 wk, and assigned to N or NCP groups and to F or FCP groups, respectively. The NCP and FCP group mice were administered experimental diets containing 25 mg/g CPs for 3 wk further. During the experimental period, CP supplementation affected neither the food consumption nor the body weight of the mice. No significant differences in the plasma triglyceride, non-esterified fatty acid, and cholesterol concentrations were observed among all the groups. In contrast, the weight of testicular fat mass was significantly decreased in the FCP group as compared with that in the F group. The expression levels of leptin and tumor necrosis factor (TNF)-α genes in the adipose tissue correlated with the visceral fat mass, although these differences were not significant. These findings indicate that CPs may have a reducing effect on visceral fat content but are less effective in reducing body weight.

Ubiquinol-10 Intake Is Effective in Relieving Mild Fatigue in Healthy Individuals.

Our double-blind, placebo-controlled study evaluated effects of ubiquinol, the reduced form of coenzyme Q10, on mild fatigue in healthy individuals experiencing fatigue in daily life that had continued for more than 1 and less than 6 months. The participants received 100-mg/day (Ubq100; age 44.0 ± 9.8 years; 14 females and 6 males) or 150-mg/day ubiquinol (Ubq150; age 40.4 ± 11.8 years; 14 females and 8 males) or placebo (Plc; age 41.3 ± 13.4 years; 13 females and 7 males) daily for 12 weeks. Measurements of subjective and objective fatigue were conducted by using questionnaires-based fatigue scales/visual analogue scales and autonomic nerve function/biological oxidation index, respectively, prior to the first dosing and every 4 weeks thereafter. Serum ubiquinol level increased three- to four-fold after 4 weeks and remained significantly higher than that after Plc administration throughout the intake period. Although a higher blood level of ubiquinol was observed with Ubq150 than with Ubq100, the difference was not statistically significant. In both Ubq100 and Ubq150 groups, subjective levels of fatigue sensation and sleepiness after cognitive tasks, which consisted of the modified Advanced Trail Making Test, the modified Stroop Color-Word Test, and the Digit Symbol Substitution Test, improved significantly compared with those in the placebo group, suggesting an anti-fatigue effect. The Ubq150 group demonstrated significant improvement compared with the Plc group regarding subjective level of relaxation after task, sleepiness before and after task, motivation for task, and serum level of oxidative stress. Correlation analysis between blood level of ubiquinol and each evaluated effect suggested a positive relationship with relaxation after task, motivation for cognitive task, and parasympathetic activity. The results of the study suggest that ubiquinol intake relieves mild fatigue in healthy individuals.

Mental fatigue is linked with attentional bias for sad stimuli.

Previous studies have revealed that patients with chronic fatigue syndrome and affective disorders (such as depression and anxiety disorders) exhibit a vigilant attentional bias toward negative emotional stimuli. However, it remains unclear whether the change in an attentional bias for negative emotional stimuli can be induced by mental fatigue in healthy individuals. To address this question, we examined healthy participants' (n = 27) performance in a visual probe task and emotional Stroop task before and after the mental-fatigue-inducing task. We demonstrated that acute mental fatigue induced by the long-lasting working memory task led to the alteration of cognitive processing of negative emotional information in the healthy volunteers.

PET imaging of 11C-labeled coenzyme Q10: Comparison of biodistribution between [11C]ubiquinol-10 and [11C]ubiquinone-10.

Coenzyme Q10 (CoQ10) plays a key role not only as an essential electron carrier in the mitochondrial electron transport chain, but also as an antioxidant to protect cells from oxidative stress. CoQ10 supplementation is expected to be effective for a variety of diseases. The predominant forms of CoQ10 are the ubiquinol-10 (reduced form) and ubiquinone-10 (oxidized form). Both forms of CoQ10 supplements are commercially available, however, their kinetic difference is still unclear. In order to conduct in vivo analysis of the kinetics of ubiquinol-10 and ubiquinone-10, we succeeded in synthesizing 11C-labeled ubiquinol-10 ([11C]UQL) and ubiquinone-10 ([11C]UQN), respectively. In the present study, we aimed to investigate the kinetics of [11C]UQL and [11C]UQN, both of which were administered via the tail vein of 8-week-old male Sprague-Dawley rats. Whole-body positron emission tomography (PET) imaging was performed to follow the time course of accumulation in the liver, spleen, brain, and other organs. Then, at the two typical time points at 20 or 90 min after injection, we conducted the biodistribution study. Various organs/tissues and blood were collected, weighed and counted with a gamma counter. Percent injected dose per gram of tissue (%ID/g) was calculated as the indicator of the accumulation of each compound. As the results, at both time points, %ID/g of [11C]UQL in the cerebrum, cerebellum, white adipose tissue, muscle, kidney, and testis were higher (P < 0.05) than that of [11C]UQN: at 90-min time point, %ID/g of [11C]UQL in the brown adipose tissue was higher (P < 0.05) than that of [11C]UQN: on the contrary, %ID/g of [11C]UQL in the spleen was lower (P < 0.05) than that of [11C]UQN at 90 min. In a separate study of the metabolite analysis in the plasma, UQL injected into the tail vein of rats was almost unchanged during the PET scanning time, but UQN was gradually converted to the reduced form UQL. Therefore, the uptake values of UQL into the tissues and organs were rather accurate but those of UQN might be the sum of UQN uptake and partly converted UQL uptake. These studies suggested that the accumulation level of administered CoQ10 differs depending on its redox state, and that CoQ10 redox state could be crucial for optimization of the effective supplementation.

Synthesis of 11 C-labeled ubiquinone and ubiquinol via Pd0 -mediated rapid C-[11 C]methylation using [11 C]methyl iodide and 39-demethyl-39-(pinacolboryl)ubiquinone.

To enable positron emission tomography (PET) imaging of the in vivo kinetics of ubiquinone and ubiquinol, which is referred to as coenzyme Q10 , their 11 C-radiolabeled counterparts were synthesized herein. 11 C-Labeled ubiquinone [11 C]-1 was realized by Pd-mediated rapid C-[11 C]methylation of [11 C]CH3 I with 39-demethyl-39-(pinacolboryl)ubiquinone, prepared by Ru-catalyzed olefin metathesis of unradiolabeled ubiquinone with 2-(pinacolboryl)propene. Subsequent reduction of [11 C]-1 using Na2 S2 O4 yielded 11 C-labeled ubiquinol [11 C]-2. The synthesis time and [11 C]CH3 I-based radiochemical yield of [11 C]-1 were within 36 minutes and up to 53%, while those of [11 C]-2 were within 38 minutes and up to 39%, respectively. After radiopharmaceutical formulation, the qualities of [11 C]-1 and [11 C]-2 were confirmed to be applicable for animal PET studies. The analytical values of [11 C]-1 and [11 C]-2 are as follows: radioactivity of up to 3.5 and 1.4 GBq, molar activity of 21 to 78 and 48 to 76 GBq/µmol, radiochemical purity of greater than 99% and greater than 95%, and chemical purity of greater than 99% and 77%, respectively. The concept behind this radiolabeling procedure is that unradiolabeled natural ubiquinone can be converted to 11 C-radiolabeled ubiquinone and ubiquinol via a pinacolborane-substituted ubiquinone derivative. Each PET probe was used for molecular imaging using rats to investigate the in vivo kinetics and biodistribution of the coenzyme Q10 .

Imaging the passionate stage of romantic love by dopamine dynamics.

Using [(11)C]raclopride, a dopamine D2/D3 receptor antagonist, we undertook a positron emission tomography (PET) study to investigate the involvement of the dopaminergic neurotransmitter system when subjects viewed the pictures of partners to whom they were romantically attached. Ten subjects viewed pictures of their romantic partners and, as a control, of friends of the same sex for whom they had neutral feelings during the PET study. We administered [(11)C]raclopride to subjects using a timing for injecting the antagonist which had been determined in previous studies to be optimal for detecting increases in the amount of dopamine released by stimulation. The results demonstrated statistically significant activation of the dopaminergic system in two regions, the medial orbitofrontal cortex (mOFC) and medial prefrontal cortex, the former of which has been strongly implicated in a variety of rewarding experiences, including that of beauty and love. A positive correlation was obtained in mOFC between excitement levels and dopaminergic activation only in the love but not in the control condition.