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Abstract Background The purpose of this study was to examine the correlation between fasting blood glucose and new-onset hypertension and examine any synergistically effect modification with multiple risk factors. Methods We conducted post-hoc analyses of repeated-measures data in the original Dongzhi osteoporosis cohort study. In total, 3985 participants without hypertension aged 25–64 years were included in the current analyses. Generalized estimating equation models were used to assess the relationship between fasting blood glucose and risk of new-onset hypertension after adjusting for pertinent covariates and autocorrelations among siblings. Results 393 men (19.4%) and 398 women (20.3%) without hypertension at the baseline developed hypertension by the end of the study period. Compared to lower baseline fasting blood glucose levels (Q1–Q3:

Preventing the decrease in bone mineral density (BMD) is significant for postmenopausal women. We previously discovered that rhamnose, a deoxy monosaccharide used as a food additive, could suppress bone resorption; however, studies confirming this effect in postmenopausal women are lacking. Therefore, this pilot study aimed to explore whether rhamnose could help maintain BMD via bone resorption suppression in postmenopausal women. The participants consumed either 1.0 or 0.5 g/day of rhamnose or placebo for 24 weeks, and BMD (lumbar spine and femur) and bone turnover markers were measured. After 24 weeks, the group consuming rhamnose 1.0 g/day exhibited a significantly higher BMD of the lumbar spine than the placebo group. Furthermore, the levels of tartrate-resistant acid phosphatase 5b, a bone resorption marker, were significantly lower in both rhamnose groups. These results indicated that rhamnose might contribute to the maintenance of BMD by suppressing bone resorption in healthy postmenopausal women (UMIN000046570).

The high prevalence of autoimmune hypothyroidism (AIHT) - more than 5% in human populations - provides a unique opportunity to unlock the most complete picture to date of genetic loci that underlie systemic and organ-specific autoimmunity. Using a meta-analysis of 81,718 AIHT cases in FinnGen and the UK Biobank, we dissect associations along axes of thyroid dysfunction and autoimmunity. This largest-to-date scan of hypothyroidism identifies 418 independent associations (p < 5×10 - 8 ), more than half of which have not previously been documented in thyroid disease. In 48 of these, a protein-coding variant is the lead SNP or is highly correlated (r 2 > 0.95) with the lead SNP at the locus, including low-frequency coding variants at LAG3, ZAP70, TG, TNFSF11, IRF3, S1PR4, HABP2, ZNF429 as well as established variants at ADCY7, IFIH1 and TYK2 . The variants at LAG3 (P67T), ZAP70 (T155M), and TG (Q655X) are highly enriched in Finland and functional experiments in T-cells demonstrate that the ZAP70 :T155M allele reduces T-cell activation. By employing a large-scale scan of non-thyroid autoimmunity and a published meta-analysis of TSH levels, we use a Bayesian classifier to dissect the associated loci into distinct groupings and from this estimate, a significant proportion are involved in systemic (i.e., general to multiple autoimmune conditions) autoimmunity (34%) and another subset in thyroid-specific dysfunction (17%). By comparing these association results further to other common disease endpoints, we identify a noteworthy overlap with skin cancer, with 10% of AIHT loci showing a consistent but opposite pattern of association where alleles that increase the risk of hypothyroidism have protective effects for skin cancer. The association results, including genes encoding checkpoint inhibitors and other genes affecting protein levels of PD1, bolster the causal role of natural variation in autoimmunity influencing cancer outcomes., Competing Interests: Additional Declarations: Yes there is potential Competing Interest. M.J.D. is a founder of Maze Therapeutics C.A., Z.K. and M.M. are employees of Genentech

Background: Incidental gall bladder cancer (IGBC) is often discovered unexpectedly in patients after cholecystectomy. Currently, magnetic resonance imaging (MRI) has been widely applied in the pre-operative diagnosis of gall bladder diseases as laparoscopic cholecystectomy developed into the preferred method., Aims and Objectives: This study aimed to evaluate the pre-operative MRI application and laparoscopic management in the IGBCs., Materials and Methods: Between January 2011 and January 2020, a total of 7917 patients with gall bladder diseases treated by laparoscopy were enrolled in this study., Results: Amongst 49 patients diagnosed with IGBCs, the incidence of IGBCs in polypoid lesions, biliary pancreatitis, cholecystitis, cholecystocholedocholithiasis and gall bladder stones was 0.42%, 1.19%, 0.62%, 1.20% and 0.49%, respectively. MRI evaluation showed more remarkable pre-operative imaging as compared to ultrasonographic evaluation (40.8 vs. 26.5, P < 0.05). Furthermore, 14 patients were diagnosed with gall bladder cancer through intraoperative histological examination and 11 received laparoscopic extensive resection after cholecystectomy. MRI findings with diffuse thickening of the gall bladder detected IGBCs with 6.1% sensitivity, 96.02 specificity, 0.95% positive predictive values and 99.4% negative predictive values; diffuse thickening of the gall bladder with suspicion of malignancy detected IGBCs with 12.2% sensitivity, 99.1% specificity, 7.6% positive predictive values and 99.5% negative predictive values; focal thickening of the gall bladder detected IGBCs with 16% sensitivity, 99.8% specificity, 32% positive predictive values and 99.5% negative predictive values; moreover, suspicious lesion detected IGBCs with 6.1% sensitivity, 99.6% specificity, 8.8% positive predictive values and 99.4% negative predictive values., Conclusions: Patients with biliary pancreatitis and cholecystocholedocholithiasis have a higher incidence of IGBC. MRI evaluation could provide more accurate information for the IGBCs, which should be recommended for patients accepting cholecystectomy. MRI findings exhibited an unsatisfactory sensitivity when detecting IGBCs, but they represented high specificity. Pre-operative MRI evaluation and intraoperative histological examination may help some IGBCs to achieve one-stage laparoscopic extensive resection., (Copyright © 2023 Copyright: © 2023 Journal of Minimal Access Surgery.)

Curcumin (CUR), a polyphenol, is an attractive component of functional foods, owing to various physiological activities. However, CUR is highly hydrophobic, insoluble in water, and difficult to absorb in the body. Here, we report an amorphous CUR formulation containing the dispersant polyglycerol fatty acid ester (PGFE), demonstrating high and stable water solubility. Improved water solubility enhanced the absorbability of CUR in our amorphous formulation along with enhanced triglyceride inhibition, compared to that in a commercial formulation. Nuclear Overhauser effect spectroscopy (NOESY) analysis revealed that PGFE reduced CUR-CUR interaction, resulting in higher dispersion and improved solubility of CUR. Taylor dispersion analysis showed a lower diffusion coefficient of CUR in the highly water-soluble formulation (with PGFE) than that in the low water-soluble formulation (without PGFE), which prevents recontact and recrystallization of CUR, which is trapped by PGFE. Overall, the amorphous CUR with high solubility could be used as a promising functional food., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: There is no clear objective indicator for selecting soft foods that are required for food bolus formation in older people with impaired oral function., Objective: This study aimed to investigate the relationship between maximal isometric tongue pressure (MITP) and the mechanical properties of gels that can be crushed by the tongue., Methods: This study included 65 healthy participants aged 22-96 (young group; 15 males, 15 females; older dentate group; 7 males, 8 females; older edentulous group; 10 males, 10 females). MITP was measured by the balloon-probe device. Agar gel with 10 different kinds of fracture force from 10N to 100N was used. The limit of fracture force of gels (LFFG) that were crushed by the tongue was measured by the up-and-down method. In the older edentulous group, two items were measured with and without dentures. Spearman's rank correlation coefficient was used to evaluate the relationship between MITP and LFFG in each group (p < .05)., Results: There were positive correlations between MITP and LFFG in all groups (overall groups: r s  = .66, young group: r s  = .46, older dentate group: r s  = .61, older edentulous group with dentures: r s  = .60, older edentulous group without dentures: r s  = .47)., Conclusion: MITP and LFFG were positively correlated in young, older dentate and older edentulous groups, suggesting that MITP has the potential to be an objective indicator of the range of mechanical properties of soft food that can be crushed by the tongue., (© 2023 John Wiley & Sons Ltd.)

Background: The color of endopleura is a vital factor in determining the economic value and aesthetics appeal of nut. Walnuts (Juglans) are a key source of edible nuts, high in proteins, amino acids, lipids, carbohydrates. Walnut had a variety endopleura color as yellow, red, and purple. However, the regulation of walnut endopleura color remains little known., Results: To understand the process of coloration in endopleura, we performed the integrative analysis of transcriptomes and metabolomes at two developmental stages of walnut endopleura. We obtained total of 4,950 differentially expressed genes (DEGs) and 794 metabolites from walnut endopleura, which are involved in flavonoid and phenolic biosynthesis pathways. The enrichment analysis revealed that the cinnamic acid, coniferyl alcohol, naringenin, and naringenin-7-O-glucoside were important metabolites in the development process of walnut endopleura. Transcriptome and metabolome analyses revealed that the DEGs and differentially regulated metabolites (DRMs) were significantly enriched in flavonoid biosynthesis and phenolic metabolic pathways. Through co-expression analysis, CHS (chalcone synthase), CHI (chalcone isomerase), CCR (cinnamoyl CoA reductase), CAD (cinnamyl alcohol dehydrogenase), COMT (catechol-Omethyl transferase), and 4CL (4-coumaroyl: CoA-ligase) may be the key genes that potentially regulate walnut endopleura color in flavonoid biosynthesis and phenolic metabolic pathways., Conclusions: This study illuminates the metabolic pathways and candidate genes that underlie the endopleura coloration in walnuts, lay the foundation for further study and provides insights into controlling nut's colour., (© 2024. The Author(s).)

Toxicity assessment of the food colorant Gardenia jasminoides Ellis at dietary exposures of 0.0%, 0.1%, 0.5%, 1.5%, 3.0% and 5.0% included measures of T-cell- dependent antibody response, neurotoxicity, and clinical and anatomic pathology in Sprague Dawley rats during mating, gestation, lactation, postnatal development, and following weaning for up to 12 months including 3- and 6-month interim evaluations. Blue coloration of the gastrointestinal tract, mesenteric lymph nodes and kidneys was present in treated rats only at necropsy with minimal blue coloration at the lowest dose and without histopathological correlates in any of the tissues. There was good survival with no consistent treatment-related changes in hematology, clinical chemistry, enhanced evaluation of lymphoid tissues, or tissue histopathology at interim and final time points. T-cell dependent antibody response and neurotoxicity screening were negative in treated rats. The no-observed-adverse-effect level (NOAEL) was determined to be 5.0% gardenia blue (2,854.5 and 3,465.4 mg/kg/day in parental males and females, respectively, prior to mating; 3,113.5 and 4,049.6 mg/kg/day in male and female offspring, respectively, following up to 12 months of exposure., (©2023 The Japanese Society of Toxicologic Pathology.)

Background: Subjective-physiological emotional coherence is thought to be associated with enhanced well-being, and a relationship between subjective-physiological emotional coherence and superior nutritional status has been suggested in older populations. However, no study has examined subjective-physiological emotional coherence among older adults while tasting food. Accordingly, the present study compared subjective-physiological emotional coherence during food consumption among older and younger adults., Methods: Participants consumed bite-sized gel-type foods with different flavors and provided their subjective ratings of the foods while their physiological responses (facial electromyography (EMG) of the corrugator supercilia, masseter, and suprahyoid, and other autonomic nervous system signals) were simultaneously measured., Results: Our primary findings were that (1) the ratings of liking, wanting, and valence were negatively correlated with corrugator EMG activity in older and young adult participants; (2) the positive association between masseter EMG activity and ratings of wanting/valence was weaker in the older than in the young adult group; and (3) arousal ratings were negatively correlated with corrugator EMG activity in the older group only., Conclusions: These results demonstrate commonalities and differences in subjective-physiological emotional coherence during food intake between older and young adults.

Nonalcoholic fatty liver disease is a hepatic disorder with deposition of fat droplets and has a high risk of progression to steatosis-related hepatitis and irreversible hepatic cancer. Metronidazole (MNZ) is an antiprotozoal and antimicrobial agent widely used to treat patients infected with anaerobic bacteria and intestinal parasites; however, MNZ has also been shown to induce liver tumors in rodents. To investigate the effects of MNZ on steatosis-related early-stage hepatocarcinogenesis, male rats treated with N-nitrosodiethylamine following 2/3 hepatectomy at week 3 were received a control basal diet, high fat diet (HFD), or HFD containing 0.5% MNZ. The HFD induced obesity and steatosis in the liver, accompanied by altered expression of Pparg and Fasn, genes related to lipid metabolism. MNZ increased nuclear translocation of lipid metabolism-related transcription factor peroxisome proliferator-activated receptor gamma in hepatocytes, together with altered liver expression of lipid metabolism genes (Srebf1, Srebf2, Pnpla2). Furthermore, MNZ significantly increased the number of preneoplastic liver foci, accompanied by DNA double-strand breaks and late-stage autophagy inhibition, as reflected by increased levels of γ-H2AX, LC3, and p62. Therefore, MNZ could induce steatosis-related hepatocarcinogenesis by inducing DNA double-strand breaks and modulating autophagy in HFD-fed rats., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Sensing subjective hedonic or emotional experiences during eating using physiological activity is practically and theoretically important. A recent psychophysiological study has reported that facial electromyography (EMG) measured from the corrugator supercilii muscles was negatively associated with hedonic ratings, including liking, wanting, and valence, during the consumption of solid foods. However, the study protocol prevented participants from natural mastication (crushing of food between the teeth) during physiological data acquisition, which could hide associations between hedonic experiences and masticatory muscle activity during natural eating. We investigated this issue by assessing participants' subjective ratings (liking, wanting, valence, and arousal) and recording physiological measures, including EMG of the corrugator supercilii, zygomatic major, masseter, and suprahyoid muscles while they consumed gel-type solid foods (water-based gellan gum jellies) of diverse flavors. Ratings of liking, wanting, and valence were negatively correlated with corrugator supercilii EMG and positively correlated with masseter and suprahyoid EMG. These findings imply that subjective hedonic experiences during food consumption can be sensed using EMG signals from the brow and masticatory muscles.

In this study, we used meta-analysis to comprehensively evaluate the clinical efficacy of Kangfuxin Liquid in the treatment of diabetic patients with skin ulcers. Literature search was performed through PubMed, Web of Science, Embase, China National Knowledge Infrastructure, and Wanfang Data. The retrieval was not limited by language, and the search period was from 2010 to October 12, 2020. Diabetic patients with skin ulcers were treated with Kangfuxin Liquid combined with basic treatment as the treatment group and only basic treatment as the control group. Stata16.0 software was used for system evaluation. A total of 11 studies and 874 patients were included. Meta-analysis showed that 11 studies compared the treatment efficacy between the two groups, and the results showed that the treatment efficacy in the treatment group was significantly higher than that in the control group [OR = 5.38, 95% CI (3.52, 8.24), P < 0.001]. Among them, 9 studies compared the healing time of wounds. The healing time of the treatment group was significantly longer than that of the control group [SMD = -2.13, 95% CI (-2.85, -1.41), P < 0.001]. Five studies compared the length of stay, and the length of stay in the treatment group was shorter than that in the control group [SMD = -3.68, 95% CI (-5.38, -1.97), P < 0.001]. Compared with basic treatment, Kangfuxin Liquid combined with basic treatment has an ideal effect in the treatment of diabetic skin ulcers, which can improve the overall treatment efficiency and shorten the wound rehabilitation time and the length of stay., Competing Interests: The authors claim that there area no conflicts of interest between them., (Copyright © 2021 Xiaoping Wan et al.)

Background: C9orf72 repeat expansion (C9exp) is the most common genetic cause underlying frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). However, detection of the C9exp requires elaborative methods., Objective: Identification of C9exp carriers from genotyped cohorts could be facilitated by using single nucleotide polymorphisms (SNPs) as markers for the C9exp., Methods: We elucidated the potential of the previously described Finnish risk haplotype, defined by the SNP rs3849942, to identify potential C9exp carriers among 218,792 Finns using the FinnGen database. The haplotype approach was first tested in an idiopathic normal pressure hydrocephalus (iNPH) patient cohort (European Alzheimer's Disease DNA BioBank) containing C9exp carriers by comparing intermediate (15-30) and full-length (> 60 repeats) C9exp carriers (n = 41) to C9exp negative patients (< 15 repeats, n = 801)., Results: In this analysis, rs3849942 was associated with carriership of C9exp (OR 8.44, p < 2×10-15), while the strongest association was found with rs139185008 (OR 39.4, p < 5×10-18). Unbiased analysis of rs139185008 in FinnGen showed the strongest association with FTLD (OR 4.38, 3×10-15) and motor neuron disease ALS (OR 5.19, 3×10-21). rs139185008 was the top SNP in all diseases (iNPH, FTLD, ALS), and further showed a strong association with ALS in the UK Biobank (p = 9.0×10-8)., Conclusion: Our findings suggest that rs139185008 is a useful marker to identify potential C9exp carriers in the genotyped cohorts and biobanks originating from Finland.

An exploration of physiological correlates of subjective hedonic responses while eating food has practical and theoretical significance. Previous psychophysiological studies have suggested that some physiological measures, including facial electromyography (EMG), may correspond to hedonic responses while viewing food images or drinking liquids. However, whether consuming solid food could produce such subjective-physiological concordance remains untested. To investigate this issue, we assessed participants' subjective ratings of liking, wanting, valence, and arousal while they consumed gel-type food stimuli of various flavors and textures. We additionally measured their physiological signals, including facial EMG from the corrugator supercilii. The results showed that liking, wanting, and valence ratings were negatively correlated with corrugator supercilii EMG activity. Only the liking rating maintained a negative association with corrugator supercilii activity when the other ratings were partialed out. These data suggest that the subjective hedonic experience, specifically the liking state, during food consumption can be objectively assessed using facial EMG signals and may be influenced by such somatic signals.

Objective: The aim of this study was to evaluate tongue movement and its biomechanical effects during squeezing, one of the oral strategies for processing soft foods, by tongue pressure sensors, videofluorography, and surface electromyography., Design: Fifteen healthy men (mean age, 31.0 ± 4.1 years) without dysphagia were recruited. A 0.1-mm-thick pressure sensor sheet with five measuring points, videofluorography, and surface electromyography were used for synchronous measurements of tongue pressure, hyoid movement, and suprahyoid muscles activity, respectively, while squeezing 5 mL of gels. Amplitude, duration, area, and their sequential order during initial squeezing were analyzed. Differences in hyoid position at the onset, peak, and offset of hyoid movement were also analyzed., Results: At the beginning of initial squeezing, tongue pressure at the middle area of the hard palate, hyoid movement, and suprahyoid muscle activity appeared simultaneously, followed by tongue pressure at the anterior area and then at the posterior area. When the hyoid was in an elevated position, the amplitude of suprahyoid muscle activity and tongue pressure peaked. At the end of initial squeezing, the hyoid position at the offset of hyoid excursion was superior to that at the onset. All evaluation items of tongue pressure, hyoid movement, and suprahyoid muscle activity were modulated according to the texture of gels., Conclusions: During initial squeezing, tongue pressure, hyoid movement, and suprahyoid muscle activity were coordinated while being modulated by the food texture. At the end of initial squeezing, the hyoid was maintained in an elevated position, which might be beneficial for subsequent squeezing., Competing Interests: Declaration of Competing Interest There are no conflict of interests in connection with this article., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Care food is increasingly required in the advanced-aged society. Mechanical properties of such foods must be modified such that the foods are easily broken by the tongue without chewing. When foods are compressed between the tongue and the hard palate, the tongue deforms considerably, and only soft foods are broken. To simulate tongue compression of soft foods, artificial tongues with stiffness similar to that of the human tongue were created using clear soft materials. Model soft gels were prepared using gellan gums. A piece of gel on an artificial tongue was compressed using a texture analyzer. The deformation profile during the compression test was obtained using a video capture system. The soft machine equipped a soft artificial tongue sometimes fractured food gels unlike hard machine, which always fracture gels. The fracture properties measured using the soft machine were better than those obtained from a conventional test between hard plates to mimic natural oral processing in humans. The fracture force on foods measured using this soft machine may prove useful for the evaluation of food texture that can be mashed using the tongue., Competing Interests: The authors declare no conflict of interest.

Studies of past forest use traditions are crucial in both understanding the present state of the oldest European forests, and in guiding decisions on future forest conservation and management. Current management of Poland's Białowieża Forest (BF), one of the best-preserved forests of the European lowlands, is heavily influenced by anecdotal knowledge on forest history. Therefore, it is important to gain knowledge of the forest's past in order to answer questions about its historical administration, utilisation, and associated anthropogenic changes. Such understanding can then inform future management. This study, based on surveys in Belarussian and Russian archives and a preliminary field survey in ten forest compartments of Białowieża National Park, focuses on culturally-modified trees (CMTs), which in this case are by-products of different forms of traditional forest use. Information about the formation of the CMTs can then be used to provide insight into former forest usage. Two types of CMTs were discovered to be still present in the contemporary BF. One type found in two forms was of 1) pine trees scorched and chopped in the bottom part of the trunk and 2) pine trees with carved beehives. A second type based on written accounts, and therefore known to be present in the past (what we call a 'ghost CMT'), was of 3) lime-trees with strips of bark peeled from the trunk. Written accounts cover the period of transition between the traditional forest management (BF as a Polish royal hunting ground, until the end of the eighteenth century) and modern, "scientific" forestry (in most European countries introduced in the second half of the nineteenth century). These accounts document that both types of CMTs and the traditional forest uses responsible for their creation were considered harmful to "rational forestry" by the nineteenth-century forest administration. Thus the practices which created CMTs were banned and the trees gradually removed from the forest. Indeed, these activities drew the attention of forest administrators for several decades, and in our view delayed the introduction of new, timber-oriented, forest management in the BF., Competing Interests: The authors have declared that no competing interests exist.

When a comet assay, an increasingly popular in vivo genotoxicity test, shows a positive test result, interpretation of that response requires ruling out any confounding tissue site toxicity. Since the comet assay typically uses only two or three daily doses of test agent, precursor tissue changes indicative of toxicity may be easily overlooked. Using case examples for two flavoring agents, perillaldehyde and 4,5-epoxydec-2( trans )-enal, we highlight the role of pathology peer review in verifying precursor tissue changes indicative of tissue site toxicity, thereby increasing confidence in final interpretation of comet assay results. Given global deliberation regarding safety assessment of compounds entering the marketplace, we recommend consideration of pathology peer review for equivocal and positive comet assays so that interpretations are universally consistent.

Administration of the diuretic, spironolactone (SR), can inhibit chronic liver diseases. We determined the effects of SR alone or in combination with the antioxidant α-glycosyl isoquercitrin (AGIQ) on hyperlipidemia- and steatosis-related precancerous lesions in high-fat diet (HFD)-fed rats subjected to a two-stage hepatocarcinogenesis model. Rats were fed with control basal diet or HFD, which was administered with SR alone or in combination with an antioxidant AGIQ in drinking water. An HFD increased body weight, intra-abdominal fat (adipose) tissue weight, and plasma lipids, which were reduced by coadministration of SR and AGIQ. SR and AGIQ coadministration also reduced hepatic steatosis and preneoplastic glutathione S-transferase placental form-positive foci, in association with decrease in NADPH oxidase (NOX) subunit p22phox-positive cells and an increase in active-caspase-3-positive cells in the foci. Hepatic gene expression analysis revealed that the coadministration of SR and AGIQ altered mRNA levels of lipogenic enzymes ( Scd1 and Fasn), antioxidant-related enzymes ( Catalase), NOX component ( P67phox), and anti-inflammatory transcriptional factor ( Pparg). Our results indicated that SR in combination with AGIQ had the potential of suppressing hyperlipidemia- and steatosis-related early hepatocarcinogenesis through the reduced expression of NOX subunits.

Mineralocorticoid receptor (MR)/NADPH oxidase (NOX) signaling is involved in the development of obesity, insulin resistance, and renal diseases; however, the role of this signaling on steatotic preneoplastic liver lesions is not fully elucidated. We determined the effects of the MR antagonist potassium canrenoate (PC) on MR/NOX signaling in hepatic steatosis and preneoplastic glutathione S-transferase placental form (GST-P)-positive liver foci. Rats were subjected to a two-stage hepatocarcinogenesis model and fed with basal diet or high fat diet (HFD) that was co-administered with PC alone or in combination with the antioxidant alpha-glycosyl isoquercitrin (AGIQ). PC reduced obesity and renal changes (basophilic tubules that expressed MR and p22phox) but did not affect blood glucose tolerance and non-alcoholic fatty liver disease activity score (NAS) in HFD-fed rats. However, the drug increased the area of GST-P-positive liver foci that expressed MR and p22phox as well as increased expression of NOX genes (p22phox, Poldip2, and NOX4). PC in combination with AGIQ had the potential of inhibiting the effects of PC on the area of GST-P-positive liver foci and the effects were associated with increasing expression of an anti-oxidative enzyme (Catalase). The results suggested that MR/NOX signaling might be involved in development of preneoplastic liver foci and renal basophilic changes in HFD-fed rats; however, the impacts of PC were different in each organ.

In the gastrointestinal tract, the immediate healing response to mucosal damage is critical to sustain mucosal homeostasis. The migration of surrounding epithelial cells to cover the denuded area without proliferation is termed restitution, followed by early reparation of the damage. In this study, we determined the role of A-kinase anchor protein 13 (AKAP13) in mice with dextran sulphate sodium (DSS)-induced colitis upon mucosal injury and restitution, and investigated whether inhibition of Rho-associated coiled-coil containing protein kinase (ROCK), downstream effector of AKAP13, affects these mucosal responses. BALB/c mice were challenged with 4% or 2% DSS in their drinking water for up to 8 or 16days, respectively. During this period, mice received subcutaneous injections of fasudil hydrochloride hydrate (FH, 10mg/kg, twice per day), an inhibitor of phosphorylation of ROCK. In immunohistochemistry, AKAP13 was highly expressed in the mucosal epithelium prior to DSS-induced mucosal injury, and also expressed in ulcer-covering non-proliferative epithelium, which corresponded to restituted epithelial cells. Coadministration of FH increased serum amyloid A levels and histopathological scores for mucosal injury, as compared with the DSS group. The effects were associated with a decrease in gene expression of Akap13 in the mucosal tissue and the inhibition of restitution rata (the length of restituted epithelial cells per ulcer). These results suggested that AKAP13 and ROCK are involved in mucosal response at early injury and restitution during healing in DSS-induced colitis in mice., (Copyright © 2017 Elsevier GmbH. All rights reserved.)

We demonstrate the expression patterns of A-kinase anchor protein 13 (AKAP13), a scaffold protein that acts upstream of Rho signaling, and Rho-associated coiled-coil containing protein kinase (ROCK) 1/2 in mouse colorectal cancer and during the healing stage of mouse colitis. BALB/c mice received an intraperitoneal injection of azoxymethane at 10mg/kg, followed by two 7-day cycles of 3% dextran sulfate sodium (DSS) administered through their drinking water to induce colon cancer, or a 7-day administration of 4% DSS to induce colitis. The colorectal tissue was then analyzed for gene expression, histopathology, and immunohistochemistry. In the colorectal cancer, AKAP13 and ROCK1/2 were highly expressed in adenocarcinoma compared to the control tissue and low-grade dysplasia. In colitis, AKAP13 and ROCK1 were highly expressed in the restituted and regenerated mucosa but were only moderately expressed in the injured mucosal epithelium, compared to the normal epithelium that exhibited weak expression levels. ROCK2 was weakly expressed in these cells, consistent with the expression of AKAP13 and ROCK1. Furthermore, we found several clumps of epithelial cells expressing AKAP13 and ROCK1/2 in the lamina propria during the mucosal healing process, and these cells also expressed interleukin-6, which is a multipotential cytokine for both inflammation and healing. These data suggest that AKAP13 was expressed in relation with ROCK1/2, which probably play an overall role in both mucosal healing and tumorigenesis., (Copyright © 2017 Elsevier GmbH. All rights reserved.)

Developing effective treatments and preventing inflammatory bowel disease (IBD) are urgent challenges in improving patients' health. It has been suggested that platelet activation and reactive oxidative species generation are involved in the pathogenesis of IBD. We examined the inhibitory effects of a selective phosphodiesterase-3 inhibitor, cilostazol (CZ), and two antioxidants, enzymatically modified isoquercitrin (EMIQ) and α-lipoic acid (ALA), against dextran sulphate sodium (DSS)-induced colitis. BALB/c mice were treated with 0.3% CZ, 1.5% EMIQ, and 0.2% ALA in their feed. Colitis was induced by administering 5% DSS in drinking water for 8days. The inhibitory effects of these substances were evaluated by measuring relevant clinical symptoms (faecal blood, diarrhoea, and body weight loss), colon length, plasma cytokine and chemokine levels, whole genome gene expression, and histopathology. Diarrhoea was suppressed by each treatment, while CZ prevented shortening of the colon length. All treatment groups exhibited decreased plasma levels of interleukin (IL)-6 and tumour necrosis factor (TNF)-α compared with the DSS group. Microarray analysis showed that cell adhesion, cytoskeleton regulation, cell proliferation, and apoptosis, which might be related to inflammatory cell infiltration and mucosal healing, were affected in all the groups. DSS-induced mucosal injuries such as mucosal loss, submucosal oedema, and inflammatory cell infiltration in the distal colon were prevented by CZ or antioxidant treatment. These results suggest that anti-inflammatory effects of these agents reduced DSS-induced mucosal injuries in mice and, therefore, may provide therapeutic benefits in IBD., (Copyright © 2016 Elsevier GmbH. All rights reserved.)

We previously reported the anti-inflammatory effects of cilostazol, a selective inhibitor of phosphodiesterase 3, and two antioxidants, enzymatically modified isoquercitrin and α-lipoic acid in a dextran sodium sulphate-induced colitis mouse model. We further examined the chemopreventive effects of these substances in a murine azoxymethane/dextran sodium sulphate -induced colorectal carcinoma model and compared the effects with those of the well-known anticancer natural plant pigment, anthocyanin. In addition, the effects on cell proliferation activity were evaluated in colon cancer cell lines and mucosal epithelial cells in a model of acute dextran sodium sulphate-induced colitis. Cilostazol and enzymatically modified isoquercitrin improved the outcome of azoxymethane/dextran sodium sulphate-induced colorectal cancer along with anthocyanin though inhibiting inflammation and cell proliferation, but the effect of α-lipoic acid was minimal. Inhibition of cell proliferation by cilostazol was confirmed in vitro. In the acute dextran sodium sulphate-induced colitis model, cilostazol and enzymatically modified isoquercitrin prevented the decrease in epithelial proliferative cells. These results indicate that cilostazol and enzymatically modified isoquercitrin first exhibited an anti-dextran sodium sulphate effect at the initial stage of colitis and then showed antitumour effects throughout subsequent inflammation-related cancer developmental stages., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

The objectives of this study were to examine the effects of mouthful quantities and mechanical properties of gels on natural mastication behaviors using electromyography (EMG). Two types of hydrocolloid gels (A and K) with similar fracture loads but different moduli and fracture strains were served to eleven normal women in 3-, 6-, 12-, and 24-g masses in a randomized order. EMG activities from both masseter muscles were recorded during natural mastication. Because of the similar fracture loads, the numbers of chews, total muscle activities, and entire oral processing times were similar for similar masses of both gel types. Prior to the first swallow, the more elastic K gel with a higher fracture strain required higher muscle activities than the brittle A gel, which had higher modulus. Majority of subjects had preferred sides of chewing, but all subjects with or without preferred sides used both masseters during the consumption of gels. Similar effects of masses and types of gels were observed in EMG activities of both sides of masseters. Contributions of the dominant side of chewing were diminished with increasing masses of gels, and the mass dependency on ratio of the dominant side was more pronounced with K gel. More repetitions of smaller masses required greater muscle activities and longer periods for the consumption of 24-g gel portions. Reduction in the masses with an increased number of repetitions necessitated slower eating and more mastication to consume the gel portions. These observations suggest that chewing using both sides is more effective and unconsciously reduces mastication times during the consumption of gels., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Unlabelled: We generated a recombinant Akabane virus (AKAV) expressing enhanced green fluorescence protein (eGFP-AKAV) by using reverse genetics. We artificially constructed an ambisense AKAV S genome encoding N/NSs on the negative-sense strand, and eGFP on the positive-sense strand with an intergenic region (IGR) derived from the Rift Valley fever virus (RVFV) S genome. The recombinant virus exhibited eGFP fluorescence and had a cytopathic effect in cell cultures, even after several passages. These results indicate that the gene encoding eGFP in the ambisense RNA could be stably maintained. Transcription of N/NSs and eGFP mRNAs of eGFP-AKAV was terminated within the IGR. The mechanism responsible for this appears to be different from that in RVFV, where the termination sites for N and NSs are determined by a defined signal sequence. We inoculated suckling mice intraperitoneally with eGFP-AKAV, which resulted in neurological signs and lethality equivalent to those seen for the parent AKAV. Fluorescence from eGFP in frozen brain slices from the eGFP-AKAV-infected mice was localized to the cerebellum, pons, and medulla oblongata. Our approach to producing a fluorescent virus, using an ambisense genome, helped obtain eGFP-AKAV, a fluorescent bunyavirus whose viral genes are intact and which can be easily visualized., Importance: AKAV is the etiological agent of arthrogryposis-hydranencephaly syndrome in ruminants, which causes considerable economic loss to the livestock industry. We successfully generated a recombinant enhanced green fluorescent protein-tagged AKAV containing an artificial ambisense S genome. This virus could become a useful tool for analyzing AKAV pathogenesis in host animals. In addition, our approach of using an ambisense genome to generate an orthobunyavirus stably expressing a foreign gene could contribute to establishing alternative vaccine strategies, such as bivalent vaccine virus constructs, for veterinary use against infectious diseases., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)

Bovine herpesvirus 1 (BoHV1) is one of the most important pathogens of cattle; however, its effect on somatic cell count and milk components is not completely understood. The aim of the current study was to examine the effect of BoHV1 infection on quality of bovine bulk tank milk (BTM). A total of 1,790 individual blood samples collected at 28 dairy farms were used to determine the BoHV1 infection status of the herds with ELISA tests. The quality parameters of milk were evaluated by instrumental methods with BTM samples collected at monthly intervals from May 2011 to May 2012. The statistical analysis was performed to study the associations between BoHV1 herd status, quality of BTM, and herd-specific parameters. The risk factors influencing bulk milk somatic cell count (BMSCC) were estimated using the multivariable mixed-effects maximum likelihood regression model. The true prevalences of BoHV1 infection at the animal and herd levels were 49.3 and 64.6%, respectively. The average BMSCC differed significantly between the herds grouped accordingly to their BoHV1 infection status. Interestingly, the highest BMSCC was observed in the vaccinated herds (240.3×10(3) cells/mL). Additionally, the BoHV1 herd status had a significant effect on the fat content of BTM. The largest herds that were investigated had a BoHV1 seroprevalence over 30%. The herd status was considerably influenced by the numbers of cows in the herds. Besides, no significant differences in total bacterial count or protein content in milk from BoHV1-infected und uninfected herds were observed. An increase in BMSCC was observed during summer compared with the winter months regardless of the BoHV1 status of the herds. In the final multivariable regression model, the main risk factors associated with BMSCC were BoHV1 herd status, the percentage of BoHV1 infected animals in a herd, the number of cows in a herd, and the season. Our study suggests that BoHV1 infection may influence BMSCC levels, which are key parameters of BTM quality and a reference for subclinical mastitis in a herd. In conclusion, BoHV1 infection may cause economic losses by decrease both of quantity and quality of milk., (Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

The aim of the study was to examine the effect of bovine viral diarrhoea virus (BVDV) infection on bulk tank milk somatic cell counts (BMSCC). Twenty nine dairy farms supplying milk to a dairy in Eastern Poland were recruited for the study. Bulk milk ELISA and RT-PCR were used to determine the BVDV infection status and the presence of PI animals in the farms. The BMSCC mean values for the BVDV seronegative (218.7 × 10(3)cells/ml; SD: 89.8) and seropositive (214.9 × 10(3)cells/ml; SD: 74.0) herds did not differ significantly. To assess the relationship between BVDV infection and BMSCC a multilevel mixed-effects linear model was used. No statistically significant effect of BVDV infection on BMSCC was found. The mean values of BMSCC for the herds with PI individuals measured before (230.1 × 10(3)cells/ml, SD: 64.9) and after (223.3 × 10(3)cells/ml, SD: 62.4) the PI removal were not statistically different. An increase in herd size was associated with a significant decrease in BMSCC. An increase in BMSCC was observed during summer (from May to September) compared to during winter (from October to April)., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Influenza A viruses possess two surface glycoproteins, hemagglutinin (HA), which binds to sialic-acid-containing receptors, and neuraminidase (NA), which removes sialic acid from host cells. It is well established that the HA-NA functional balance regulates the efficiency of virus replication. Here, we selected a plaque variant of the WSN (H1N1) strain that grew better than the wild-type virus in NA-expressing MDCK cell culture. A reverse genetics study revealed that the single mutation HA E190K, which occurs infrequently in naturally isolated H1N1 viruses, was responsible for the phenotype of this variant. Receptor assays indicated that this mutation did not affect the receptor specificity of HA but enhanced its receptor-binding affinity, resulting in altered HA-NA functional balance relative to that of the wild-type virus. We also found that this variant replicated in nasal turbinates at an equivalent level but in lungs at a lower level compared with wild-type virus, demonstrating its attenuation in mice. Together, our data demonstrated the importance of the HA-NA functional balance for influenza virus replication in an in vivo biological setting.

Recently, many accidents relating to food happened in Japan. The consumer's distrust for food, food companies, and the administration is increasing. The consumer especially has an extreme refusal feeling for chemicals such as food additives and agricultural chemicals, and begins to request agricultural chemical-free vegetables and food additive-free food. Food companies also state no agricultural chemicals and no food additives to correspond with consumers' request and aim at differentiating. The food additive is that the Ministry of Health, Labour and Welfare specifies the one that person's health might not be ruined by providing for Food Sanitation Law Article 10 in our country. The standard for food additives and standard for use of food additives are provided according to regulations of Food Sanitation Law Article 11. Therefore, it is thought that the food additive used is safe now. Then, it reports on the procedure and the safety examination, etc. in our country for designation for food additive this time.

The generation of 2-(2',4'-dihydroxybenzoyl) benzoic acid (DHBBA) and 2-(2',4'-dihydroxy-3',5'-diiodobenzoyl) benzoic acid (DHDIBBA) during the manufacture of erythrosine (Food Red No. 3) was examined. DHBBA is formed as an intermediate during the synthesis of fluorescein, and as fluorescein is produced, it is gradually consumed. However, under inappropriate reaction conditions, it remains in the resulting fluorescein at the termination of synthesis. DHDIBBA is easily obtained by the iodination of DHBBA. These compounds are also found when erythrosine is heated in excessive alkali. The results of the Ames test using DHBBA and DHDIBBA showed they did not possess mutagenic activity. The results clearly demonstrated that establishment of an upper limit for DHBBA and DHDIBBA is important in the quality control of fluorescein and erythrosine.

The aim of the study is to construct cDNA libraries from the normal liver and regeneration liver of rat by SMART (switching mechanism at 5' end of RNA transcript) technique and analyze their quality. The total RNA was separated from the normal liver and regeneration liver of rat and the frist-strand cDNA was synthesized through reverse transcription by a modified oligo (dT) primer (contained sfi IB site) while the SMART oligonucleotide (contained sfi IA site) was utilized as a template so that the first-strand cDNA could be extended over the 5' end of mRNA. The double-strand cDNA was amplified by LD-PCR (long-distance PCR) with the above two primers and then digested by sfi I (IA & IB) restriction, enzyme. After cDNA size fractionation through Chroma Spin 400 column, the double-strand cDNA was ligated into the sfi I-digested lambda TripIEx2 vector and then the recombinant DNA was packagedin vitro. The unamplified rat normal liver cDNA library consists of 1.3×10(7) pfu/ml, and regeneration liver cDNA library consists of 1.6×10(7) pfu/ml in which the percentage of recombinant clones both are about 100%. Through testing, the high quality cDNA libraries containing full-length cDNA of rat normal liver and regeneration liver have been constructed. The titer of the amplified cDNA library is 4.5×10(10) pfu/ml and 3.6×10(10) pfu/ml. the average exogenous inserts of the recombinants both are about 1.5 kb. These results show that the normal liver and regeneration liver of rat cDNA libraries both have an excellent quality and lay solid foundation to study liver functions and the mechanism of liver regeneration.

To evaluate the mutagenicity of 1-carboxyl-5,7-dibromo-6-hydroxy-2,3,4-trichloroxanthone (HXCA), which is an impurity present in Food Red No. 104 (FR104, Phloxine B, the Japanese counterpart of D&C Red No. 28), HXCA was isolatedfrom FR104 using pH-zone-refining counter-current chromatography and preparative HPLC. A large amount of HXCA was synthesized to perform the Ames test, and its identity was confirmed by comparison of its HPLC retention time, UV-Vis, MS and NMR spectra with those of HXCA isolated from FR104. The results of the Ames test using synthetic HXCA showed that it did not possess mutagenic activity. The results of the mutagenicity test for HXCA will provide useful information for the establishment of an upper limit for HXCA in FR104 (or D&C Red No. 28) for use in regulatory considerations.

Degraded carrageenan (known as poligeenan molecular weight: 20 kDa to 30 kDa) causes ulcerative colitis in experimental animals. In this paper, the molecular weight distributions of 29 samples of food-grade refined carrageenans were studied by high performance liquid gel permeation chromatography (GPC) directly connected to vacuum-ultraviolet inductively coupled plasma-atomic emission spectrometry (ICP) (GPC/ICP) as well as GPC/refractive index (RI) detection. All samples of food-grade carrageenan had a major broad peak of high molecular weight which eluted at around 6.5 min in both RI and ICP mode (sulphur and carbon), and each sample of them had no obvious peak of poligeenan (the detection limit was about 5%). The number average molecular weights of these carrageenans ranged from 193 kDa to 324 kDa, and the weight average molecular weights ranged from 453 kDa to 652 kDa based on RI data. Some samples had a few minor peaks which eluted around 10-12 min. These peaks came from ionic sulphate, sucrose or glucose. It was considered that if the data-sampling programme was improved, the GPC/ICP system would become a more powerful technique for evaluation of carrageenan samples containing ionic substances and sugar.

Buddleja yellow colorant derived from Buddleja officinalis Maxim. has recently been approved for use as a new kind of natural colorant for food additives in China. In order to distinguish Buddleja yellow colorant from other yellow colorants, two known phenylpropanoid glycosides, acteoside (= verbascoside) and poliumoside, were isolated from the colorant as marker substances for Buddleja yellow colorant. Poliumoside has not been detected in B. officinalis Maxim. previously. These phenylpropanoid glycosides were not detected in the fruits of Gardenia jasminoides Ellis or in the stamens of the flowers of Crocus sativus L., which also contain crocetin derivatives as coloring components, using a photodiode array and mass chromatograms. Thus, an analytical HPLC method was developed to distinguish foods that have been colored with yellow colorants containing crocetin derivatives, using phenylpropanoid glycosides as markers.