Nutrient Profiling of Japanese Dishes: The Development of a Novel Ajinomoto Group Nutrient Profiling System.

Government agencies and private companies have supported the development of nutrient profiling (NP) systems to facilitate the selection of nutrient-dense foods by consumers, promote nutritious food development, and limit excessive advertising of products with low nutritional value. While most NP models were developed to assess individual foods, the Ajinomoto Group Nutrient Profiling System (ANPS) was developed to assess the overall nutritional value of cooked dishes that are culturally specific to Japan. Based on the national dietary recommendations and nutritional surveys, target values were created for 13 dish categories, while considering the combinations of meal units. For the ANPS, the four evaluating elements were protein and vegetables, which should be encouraged, and sodium and saturated fatty acids, which should be limited. The ANPS algorithm for dishes was the sum of the scores of individual elements, with a maximum of 10 points per serving. The sum of scores was then multiplied by 2.5 to convert to the 100-point scale. Convergent validity was tested using the nutrient-rich food index (NRF) score of 6.3. In total, 1,089 popular Japanese dishes were evaluated using the ANPS, and the median score of ANPS was 70.0 points (interquartile range, 55-78.8), and the average score was 67.7 (standard deviation, 16.5) points. Since salt intake is a major health risk in Japan, this tool was designed to evaluate sodium content with high sensitivity, and low-salt dishes significantly improved sodium and ANPS scores compared with regular dishes. The Pearson's correlation coefficient between the total score of NRF 6.3 and ANPS in 1,089 dishes was r = 0.452 (p < 0.0001). This newly developed ANPS could be used to evaluate culture-specific cooked dishes per serving size. It can determine the nutritional values of dishes, with a high sensitivity to sodium content, a major Japanese nutritional issue. Further research is needed to determine the accuracy and usefulness of the ANPS as a system that would lead to changes in eating behavior nationwide.

Modulation of Self-Assembly Enhances the Catalytic Activity of Iron Porphyrin for CO2 Reduction.

Electrochemical reduction of CO2 in aqueous media is an important reaction to produce value-added carbon products in an environmentally and economically friendly manner. Various molecule-based catalytic systems for the reaction have been reported thus far. The key features of state-of-the-art catalytic systems in this field can be summarized as follows: 1) an iron-porphyrin-based scaffold as a catalytic center, 2) a dinuclear active center for the efficient activation of a CO2 molecule, and 3) a hydrophobic channel for the accumulation of CO2 . This article reports a novel approach to construct a catalytic system for CO2 reduction with the aforementioned three key substructures. The self-assembly of a newly designed iron-porphyrin complex bearing bulky substituents with noncovalent interaction ability forms a highly ordered crystalline solid with adjacent catalytically active sites and hydrophobic pores. The obtained crystalline solid serves as an electrocatalyst for CO2 reduction in aqueous media. Note that a relevant iron-porphyrin complex without bulky substituents cannot form a porous structure with adjacent active sites, and the catalytic performance of the crystals of this relevant iron-porphyrin complex is substantially lower than that of the newly developed catalytic system. The present study provides a novel strategy for constructing porous crystalline solids for small-molecule conversions.

Association of olfactory impairment with indexes of sarcopenia and frailty in community-dwelling older adults.

AIM: Individuals with olfactory or gustatory impairment often have associated difficulties with food-related activities. As both functions decline in older adults, we investigated the association of these impairments with sarcopenia/frailty indexes in community-dwelling older adults. METHODS: A total of 141 participants (69 men and 72 women, mean age 73.0 years) were enrolled. Odor identification was examined using the Open Essence test. Salty and sweet tastes were assessed using a whole-mouth gustatory test. Participants underwent evaluation of the appendicular skeletal muscle mass index (ASMI) by InBody720 and grip strength, and determination of the Study of Osteoporotic Fractures frailty index. RESULTS: Participants with olfactory impairment (Open Essence ≤7), but not with gustatory impairment, showed a significantly higher prevalence of ASMI and grip strength less than the cut-off values recommended by the Asian Working Group for Sarcopenia, and Study of Osteoporotic Fractures frailty and/or pre-frailty status, compared with those without impairment. Multivariate logistic regression analysis showed a significant association of olfactory impairment with ASMI less than the cut-off value, grip strength less than the cut-off value, Asian Working Group for Sarcopenia sarcopenia and pre-frailty/frailty in the Study of Osteoporotic Fractures index in the whole population, and with ASMI less than the cut-off value and Asian Working Group for Sarcopenia sarcopenia in women, after adjustment. Three (Japanese cypress, wood and roasted garlic) and four (Japanese orange, India ink, menthol and curry) Open Essence odorants were elucidated as the "sarcopenia subset" and "frailty subset," respectively, and showed higher ability to identify sarcopenia and frailty status, compared with the remaining five odorants. CONCLUSIONS: These findings suggest that olfactory impairment is closely associated with sarcopenia and/or frailty in community-dwelling older adults. Geriatr Gerontol Int 2019; 19: 384-391.

Validation of Energy and Nutrition Intake in Japanese Elderly Individuals Estimated Based on a Short Food Frequency Questionnaire Compared against a 7-day Dietary Record: The Kyoto-Kameoka Study.

To determine the association between geriatric disorders and dietary intake, validation of a food frequency questionnaire (FFQ) for elderly individuals is needed. We compared energy and nutrient intakes derived from dietary records (DR) and FFQ in an elderly population and compared the data against results from middle-aged individuals (30⁻68 years) from a previous study. Current participants included 65 women and 78 men (65⁻88 years) who completed FFQ and 7-day DR in a subpopulation of the Kyoto-Kameoka study. Our FFQ was created for middle-aged individuals. To validate the FFQ, we investigated equivalent precision by comparing the correlation coefficients between the present and previous study. Median correlations for energy and nutrient intake between the DR and FFQ in the current and previous studies were 0.24 and 0.30 (p = 0.329) in women and 0.24 and 0.28 (p = 0.399) in men, respectively. The median ratio of FFQ to DR for these intakes were also similar. The accuracy and precision of the FFQ for energy and nutrient intake in elderly individuals did not differ compared with previous findings in a middle-aged population. A validation study evaluating energy and nutrient intake using recovery biomarkers is further needed.

Crystal structure of the complex between venom toxin and serum inhibitor from Viperidae snake.

Venomous snakes have endogenous proteins that neutralize the toxicity of their venom components. We previously identified five small serum proteins (SSP-1-SSP-5) from a highly venomous snake belonging to the family Viperidae as inhibitors of various toxins from snake venom. The endogenous inhibitors belong to the prostate secretory protein of 94 amino acids (PSP94) family. SSP-2 interacts with triflin, which is a member of the cysteine-rich secretory protein (CRISP) family that blocks smooth muscle contraction. However, the structural basis for the interaction and the biological roles of these inhibitors are largely unknown. Here, we determined the crystal structure of the SSP-2-triflin complex at 2.3 Å resolution. A concave region centrally located in the N-terminal domain of triflin is fully occupied by the terminal ß-strands of SSP-2. SSP-2 does not bind tightly to the C-terminal cysteine-rich domain of triflin; this domain is thought to be responsible for its channel-blocker function. Instead, the cysteine-rich domain is tilted 7.7° upon binding to SSP-2, and the inhibitor appears to sterically hinder triflin binding to calcium channels. These results help explain how an endogenous inhibitor prevents the venomous protein from maintaining homeostasis in the host. Furthermore, this interaction also sheds light on the binding interface between the human homologues PSP94 and CRISP-3, which are up-regulated in prostate and ovarian cancers.

Structure of MHC class I-like MILL2 reveals heparan-sulfate binding and interdomain flexibility.

The MILL family, composed of MILL1 and MILL2, is a group of nonclassical MHC class I molecules that occur in some orders of mammals. It has been reported that mouse MILL2 is involved in wound healing; however, the molecular mechanisms remain unknown. Here, we determine the crystal structure of MILL2 at 2.15 Å resolution, revealing an organization similar to classical MHC class I. However, the α1-α2 domains are not tightly fixed on the α3-ß2m domains, indicating unusual interdomain flexibility. The groove between the two helices in the α1-α2 domains is too narrow to permit ligand binding. Notably, an unusual basic patch on the α3 domain is involved in the binding to heparan sulfate which is essential for MILL2 interactions with fibroblasts. These findings suggest that MILL2 has a unique structural architecture and physiological role, with binding to heparan sulfate proteoglycans on fibroblasts possibly regulating cellular recruitment in biological events.

Sex Difference in the Association Between Protein Intake and Frailty: Assessed Using the Kihon Checklist Indexes Among Older Adults.

BACKGROUND: Dietary protein intake is inversely associated with physical frailty risk. However, it is unknown whether an association exists between dietary protein intake and comprehensive frailty. OBJECTIVE: To evaluate the association between protein intake and comprehensive frailty in older Japanese adults. DESIGN, SETTING AND PARTICIPANTS: This cross-sectional study included 5638 Japanese participants (2707 men and 2931 women) aged ≥65 years from Kameoka City, Kyoto, Japan. MEASUREMENTS: Dietary intake was estimated using a validated self-administered food frequency questionnaire. Comprehensive frailty was assessed using a 25-item Kihon Checklist (KCL), which comprised instrumental activities of daily living, mobility disability, malnutrition, oral or eating function, socialization and housebound, cognitive function, and depression domains. A KCL score of 4 to 6 was defined as prefrailty, and ≥7 as frailty. RESULTS: In women, but not in men, protein intake showed a lower prevalence for prefrailty (Q1-Q4, 40.2%, 34.3%, 34.3%, and 36.0%). Higher protein intake was associated with lower prevalence of frailty both in men (32.5%, 28.4%, 28.3%, and 27.3%) and women (35.7%, 31.4%, 27.6%, and 28.2%). Moreover, higher dietary protein intake decreased the odds ratio (OR) for frailty after adjustment for potential confounding factors in both men (OR for highest vs lowest quartile, 0.62; 95% CI, 0.43-0.89; P for trend = 0.016) and women (OR 0.64; 95% CI, 0.45-0.91; P for trend = 0.017). CONCLUSIONS/IMPLICATIONS: The higher dietary protein intake may be inversely associated with the prevalence of comprehensive frailty in Japanese men and women. Future studies are needed to examine associations of dietary protein intake within KCL domains.

Low plasma tryptophan is associated with olfactory function in healthy elderly community dwellers in Japan.

BACKGROUND: Decreased circulating tryptophan (Trp) levels are frequently observed in elderly patients with neurodegenerative disease including Alzheimer's disease. Trp may serve as a potential biomarker for monitoring disease risk in elderly people. We aimed to investigate the association between low plasma Trp levels and olfactory function, which is known to predict age-related diseases including dementia in elderly people. METHODS: A total of 144 healthy elderly Japanese community (≥ 65 years old) dwellers from the Health, Aging and Nutritional Improvement study (HANI study) were the subjects of our analysis. Low Trp levels were classified using the lower limit values of the reference interval according to a previous report. Olfactory function was assessed using a card-type test called Open Essence, which includes 12 odour items that are familiar to Japanese people. The elderly subjects with low circulating Trp levels were compared to a control group with normal plasma Trp levels. RESULTS: We conducted the analyses using 144 people aged 65 years or older (mean age 73.7 ± 5.5 years; 36.1% men). The subjects showed normal serum albumin levels (4.4 ± 0.2 g/dL) and no daily living disabilities. Low plasma Trp levels (low Trp group) were found in 11.1% of the study population. The low Trp group showed a significantly lower correct-answer rate for the items india ink, perfume, curry and sweaty smelling socks than control group (P < 0.05). There was also a significant association between low Trp levels and low olfactory ability, after adjusting for age and sex. CONCLUSIONS: Lower plasma Trp levels were associated with a decrease in olfactory function in functionally competent older individuals. Because olfactory dysfunction predicts age-related diseases, low plasma Trp levels may represent a clinical sign of disease risk in elderly people.

Syntheses and CO2 reduction activities of π-expanded/extended iron porphyrin complexes.

The construction of molecular catalysts that are active toward CO2 reduction is of great significance for designing sustainable energy conversion systems. In this study, we aimed to develop catalysts for CO2 reduction by introducing aromatic substituents to the meso-positions of iron porphyrin complexes. Three novel iron porphyrin complexes with π-expanded substituents (5,10,15,20-tetrakis(pyren-1-yl)porphyrinato iron(III) chloride (Fe-Py)), π-extended substituents (5,10,15,20-tetrakis((1,1'-biphenyl)-4-yl)porphyrinato iron(III) chloride (Fe-PPh)) and π-expanded and extended substituents (5,10,15,20-tetrakis(4-(pyren-1-yl)phenyl)porphyrinato iron(III) chloride (Fe-PPy)) were successfully synthesized, and their physical properties were investigated by UV-vis absorption spectroscopy and electrochemical measurements under Ar in comparison with an iron complex with a basic framework, 5,10,15,20-tetrakis(phenyl)porphyrinato iron(III) chloride (Fe-Ph). Moreover, the catalytic activity of the complexes was studied by electrochemical measurements under CO2, and it is found that the complex with the π-expanded substituents exhibits the highest activity among these complexes.

The immunosuppressive effect of domain-deleted dimer of HLA-G2 isoform in collagen-induced arthritis mice.

HLA-G is involved in maternal-fetal immune tolerance and is reported to be a natural tolerogenic molecule. Seven-spliced isoforms including dimeric and ß2m-free forms have been identified. The major isoform, HLA-G1 (and its soluble type HLA-G5), binds to the inhibitory immune receptors, leukocyte immunoglobulin (Ig)-like receptor (LILR) B1 and LILRB2. We previously reported that HLA-G1 also binds to paired Ig-like receptor (PIR)-B, a mouse homolog of LILRBs, and had a significant immunosuppressive effect in collagen-induced arthritis (CIA) mice. Although HLA-G2 and its soluble form HLA-G6 bind specifically to LILRB2, its functional characteristics are largely unknown. In this study, we report the significant immunosuppressive effect of HLA-G2 dimer in CIA mice. Surface plasmon resonance analysis revealed a specific interaction of HLA-G2 with PIR-B. CIA mice were administered HLA-G2 protein subcutaneously once in the left footpad and clinical severity was evaluated in a double-blind study. A single administration of HLA-G2 maintained a suppressive effect for over 1month. These results suggested that the HLA-G2 protein might be a useful biopharmaceutical for the treatment of rheumatoid arthritis by binding to inhibitory PIR-B.

Crystal structure of extracellular domain of human lectin-like transcript 1 (LLT1), the ligand for natural killer receptor-P1A.

Emerging evidence has revealed the pivotal roles of C-type lectin-like receptors (CTLRs) in the regulation of a wide range of immune responses. Human natural killer cell receptor-P1A (NKRP1A) is one of the CTLRs and recognizes another CTLR, lectin-like transcript 1 (LLT1) on target cells to control NK, NKT and Th17 cells. The structural basis for the NKRP1A-LLT1 interaction was limitedly understood. Here, we report the crystal structure of the ectodomain of LLT1. The plausible receptor-binding face of the C-type lectin-like domain is flat, and forms an extended ß-sheet. The residues of this face are relatively conserved with another CTLR, keratinocyte-associated C-type lectin, which binds to the CTLR member, NKp65. A LLT1-NKRP1A complex model, prepared using the crystal structures of LLT1 and the keratinocyte-associated C-type lectin-NKp65 complex, reasonably satisfies the charge consistency and the conformational complementarity to explain a previous mutagenesis study. Furthermore, crystal packing and analytical ultracentrifugation revealed dimer formation, which supports a complex model. Our results provide structural insights for understanding the binding modes and signal transduction mechanisms, which are likely to be conserved in the CTLR family, and for further rational drug design towards regulating the LLT1 function.

Charge transfer (CT) mechanochromism: dramatic CT absorption change of crystalline π-conjugated oligomers containing TCNQ upon mechanical grinding.

New π-conjugated oligomers with high crystallinity were prepared from the simple solvothermal reaction of squaric acid and diaminopyrenes. The oligomers were bonded at the 1,3- and 1,6-positions of the pyrene units, oligo(sq-alt-1,3py) and oligo(sq-alt-1,6py), which greatly affected their planar configuration and resulting mechanochromic properties. Oligomers containing a charge transfer (CT) complex were selectively synthesized in one step. Upon mechanical grinding in the solid state, the color changed from orange to deep metallic green.

Structural analysis for glycolipid recognition by the C-type lectins Mincle and MCL.

Mincle [macrophage inducible Ca(2+)-dependent (C-type) lectin; CLEC4E] and MCL (macrophage C-type lectin; CLEC4D) are receptors for the cord factor TDM (trehalose-6,6'-dimycolate), a unique glycolipid of mycobacterial cell-surface components, and activate immune cells to confer adjuvant activity. Although it is known that receptor-TDM interactions require both sugar and lipid moieties of TDM, the mechanisms of glycolipid recognition by Mincle and MCL remain unclear. We here report the crystal structures of Mincle, MCL, and the Mincle-citric acid complex. The structures revealed that these receptors are capable of interacting with sugar in a Ca(2+)-dependent manner, as observed in other C-type lectins. However, Mincle and MCL uniquely possess shallow hydrophobic regions found adjacent to their putative sugar binding sites, which reasonably locate for recognition of fatty acid moieties of glycolipids. Functional studies using mutant receptors as well as glycolipid ligands support this deduced binding mode. These results give insight into the molecular mechanism of glycolipid recognition through C-type lectin receptors, which may provide clues to rational design for effective adjuvants.

The long-term immunosuppressive effects of disulfide-linked HLA-G dimer in mice with collagen-induced arthritis.

HLA-G, a natural immunosuppressant present in the human placenta during pregnancy, prevents fetal destruction by the maternal immune system. The immunosuppressive effect of HLA-G is mediated by the immune cell inhibitory receptors, LILRB1 and LILRB2. HLA-G forms disulfide-linked dimers by natural oxidation, and the dimer associates with LILRB1/B2 much more strongly than the monomer. Furthermore, the dimer formation remarkably enhanced the LILRB-mediated signaling. In this report, we studied the in vivo immunosuppressive effect of the HLA-G dimer, using the collagen-induced arthritis model mouse. Mice were treated with the HLA-G monomer or dimer intracutaneously at the left foot joint, once or for 5 days, and the clinical severity was evaluated daily in a double-blind study. The HLA-G monomer and dimer both produced excellent anti-inflammatory effects with a single, local administration. Notably, as compared to the monomer, the dimer exhibited significant immunosuppressive effects at lower concentrations, which persisted for about two months. In accordance with this result, a binding study revealed that the HLA-G dimer binds PIR-B, the mouse homolog of the LILRBs, with higher affinity and avidity than the monomer. The HLA-G dimer is expected to be quite useful as an anti-rheumatoid arthritis agent, in small amounts with minimal side effects.

Molecular basis for LLT1 protein recognition by human CD161 protein (NKRP1A/KLRB1).

Human Th17 cells express high levels of CD161, a member of the killer cell lectin-like receptor (KLR) family (also referred to as NK receptor-P1A (NKRP1A) or KLRB1), as a representative marker. CD161 is also expressed on natural killer (NK) cells and NKT cells. Lectin-like transcript 1 (LLT1), another KLR family member, was recently identified as a ligand for CD161. This interaction may play pivotal roles in the immunomodulatory functions of Th17 cells as well as those of NK and NKT cells. However, the molecular basis for the interaction is poorly understood. Here we show that the extracellular domain of CD161 bound directly to LLT1 with a K(d) of 48 µM and with the fast kinetics typical of cell-cell recognition receptors. Mutagenesis revealed that the similar membrane-distal ß-sheet and loop regions of both CD161 and LLT1 were utilized for the binding, and notably, these regions correspond to the ligand-binding sites for major histocompatibility complex (MHC)-recognizing KLRs. Furthermore, we found a pair of detrimental mutations for both molecules that restored the binding. These results reveal a new template model for the recognition mode between the KLR family members and provide insights into the molecular mechanism underlying Th17/NK/NKT-mediated immune responses.

Intragastric administration of capsiate, a transient receptor potential channel agonist, triggers thermogenic sympathetic responses.

The sympathetic thermoregulatory system controls the magnitude of adaptive thermogenesis in correspondence with the environmental temperature or the state of energy intake and plays a key role in determining the resultant energy storage. However, the nature of the trigger initiating this reflex arc remains to be determined. Here, using capsiate, a digestion-vulnerable capsaicin analog, we examined the involvement of specific activation of transient receptor potential (TRP) channels within the gastrointestinal tract in the thermogenic sympathetic system by measuring the efferent activity of the postganglionic sympathetic nerve innervating brown adipose tissue (BAT) in anesthetized rats. Intragastric administration of capsiate resulted in a time- and dose-dependent increase in integrated BAT sympathetic nerve activity (SNA) over 180 min, which was characterized by an emergence of sporadic high-activity phases composed of low-frequency bursts. This increase in BAT SNA was abolished by blockade of TRP channels as well as of sympathetic ganglionic transmission and was inhibited by ablation of the gastrointestinal vagus nerve. The activation of SNA was delimited to BAT and did not occur in the heart or pancreas. These results point to a neural pathway enabling the selective activation of the central network regulating the BAT SNA in response to a specific stimulation of gastrointestinal TRP channels and offer important implications for understanding the dietary-dependent regulation of energy metabolism and control of obesity.

Higher bioavailability of isoflavones after a single ingestion of aglycone-rich fermented soybeans compared with glucoside-rich non-fermented soybeans in Japanese postmenopausal women.

BACKGROUND: There have been conflicting study results concerning how the food matrix affects the bioavailability of isoflavone aglycone and glucoside. In this study the bioavailability of isoflavones after a single ingestion of aglycone-rich fermented soybeans (Fsoy) and glucoside-rich non-fermented soybeans (Soy) was compared. Eleven healthy postmenopausal Japanese women were recruited for a randomised, double-blind, crossover trial and consumed Fsoy or Soy powder dissolved in hot water. Blood samples were collected 0, 1, 2, 3, 4, 6, 8, 12 and 24 h and urine samples from 0 to 48 h after ingestion of the powders. The Fsoy and Soy powders ingested had the same total isoflavone content (95 µmol), but the former was rich in aglycone (90.6 µmol) while the latter was rich in glucoside (81.9 µmol). RESULTS: Serum concentrations of total isoflavones after 1-4 h were significantly higher in the Fsoy group than in the Soy group. The Fsoy group showed significantly higher maximum concentration (Cmax: 2.79 ± 0.13 vs 1.74 ± 0.13 µmol L(-1) ) and area under the curve (AUC(0-24 h) : 23.78 ± 2.41 vs 19.95 ± 2.03 µmol day L(-1) ) and lower maximum concentration time (Tmax: 1.00 ± 0.00 vs 5.00 ± 0.67 h) compared with the Soy group. The cumulative urinary excretion of total isoflavones after 2 h was significantly higher in the Fsoy group than in the Soy group. Individual isoflavones (daidzein, genistein and glycitein) showed similar trends to total isoflavones. Equol (a metabolite from daidzein) did not differ between the two groups. CONCLUSION: The results of this study demonstrated that the isoflavones of aglycone-rich Fsoy were absorbed faster and in greater amounts than those of glucoside-rich Soy in postmenopausal Japanese women.

The anti-fatigue effects of the low-molecular-weight fraction of bonito extract in mice.

Bonito extract (BE), a hot-water extract of bonito muscle, has traditionally been considered as a folk remedy for fatigue. In this study we investigated the effects of BE on physical fatigue. BE was divided into, high, mid, and low-molecular-weight fractions (LMF), to explore the effectiveness of BE compounds. The swimming times to exhaustion of mice administered 0.86 g/kg BE and those administered 0.86 g/kg LMF were significantly longer than those of the vehicle-treated mice in a forced swimming model, indicating that BE possesses an anti-fatigue effect and that the LMF contributes to this effect. The LMF was also confirmed to aid the recovery of locomotor activity after physical fatigue in a forced walking model. We also examined respiratory gas levels and found that oxygen consumption and lipid oxidation were significantly greater in the group administered LMF than in the vehicle group, indicating that LMF promotes the utilization of fatty acids as an energy source. To elucidate why the mice administered LMF showed an anti-fatigue effect, we evaluated metabolic variables during exercise. The concentrations of nonesterified fatty acids and ketone bodies were higher, whereas serum and muscle lactic acid levels were lower in the mice administered LMF than in those in the vehicle group after the start of swimming. When the results were taken as a group they indicated that the effect of BE administration on improving endurance capacity was mediated, at least partly, by an increased utilization of lipids as a source of energy during exercise.