Postmenopausal women are at a higher risk of developing dyslipidemia and osteoporosis due to estrogen deficiency, necessitating regular vitamin D supplementation and the use of cholesterol inhibitors, respectively, to prevent these conditions. Despite current treatments, alternatives are needed to address both conditions simultaneously. Ergosterol, a precursor of vitamin D2, is a fungal sterol converted to brassicasterol by 7-dehydrocholesterol reductase, a cholesterol biosynthesis enzyme that converts 7-dehydrocholesterol (a precursor of vitamin D3) into cholesterol. Our previous research demonstrated that ergosterol decreases cholesterol levels and increases 7-dehydrocholesterol levels in human HepG2 hepatoma cells. Furthermore, we reported that ergosterol increases vitamin D2 levels, inhibits the cholesterol biosynthetic pathway, and potentially promotes vitamin D3 biosynthesis in male rats fed a high-fat and high-sucrose diet. In this study, we investigated the effects of daily high ergosterol intake on cholesterol, vitamin D2, and D3 biosynthetic pathways in ovariectomized (OVX) rats using GC-MS and LC with tandem mass spectrometry. OVX rats treated with ergosterol for 14 weeks exhibited significantly decreased plasma cholesterol levels and markers of cholesterol absorption, such as the plant sterol sitosterol. Furthermore, 7-dehydrocholesterol levels increased in these rats compared to untreated OVX rats. We observed that 1α, 25-dihydroxyvitamin D3 levels slightly increased in OVX rats treated with ergosterol. Additionally, ergosterol improved bone strength and increased OVX-induced bone resorption. These results indicate that daily ergosterol intake may aid in the simultaneous prevention of dyslipidemia and osteoporosis in postmenopausal women.

Abstract Cardiorenal syndrome, characterized by reciprocal heart-kidney interactions that progressively promote dysfunction in both organs, is associated with a high mortality rate. However, the mechanisms linking the two organs are insufficiently understood. Here we report that semaphorin 3C (SEMA3C) is a novel cardioprotective mediator secreted from the kidney. SEMA3C was highly expressed in the renal proximal tubules in mice. Renal Sema3c expression and circulating SEM3C were reduced by the left ventricular pressure overload that induced renal remodeling. Proximal tubule-specific secretory Sema3c deletion exacerbated cardiac hypertrophy, fibrosis and dysfunction after the pressure overload, suggesting renal SEMA3C is important for the proper cardiac adaptive response. Mechanistically, SEMA3C inhibits pathological cardiac remodeling at least partly by inhibiting Akt, ERK and Wnt/β-catenin signaling in cardiomyocytes. In heart failure patients, the plasma SEMA3C level was decreased and the low plasma SEMA3C was associated with poor cardiac outcomes. Collectively, our results show that SEMA3C produced by the kidney pivotally contributes to the cardiac stress response and its reduction contributes to the progression of heart failure. SEMA3C signaling appears to be an attractive therapeutic and diagnostic target for cardiorenal syndrome.

Background: Functional foods play an important role in the prevention and ameliora-tion of metabolic syndromes leading to type 2 diabetes. Plant resources that have anti-metabolic syndromes activity, such as Morus alba L. and Cha [Camellia sinensis L.], have been used in functional foods against diabetes. Since Morus and Cha have different mechanisms of action against metabolic syndromes, such as prevention of sugar uptake and lipidosis, respectively, and the combination of both resources will be a reliable approach for developing more efficient functional food against type 2 diabetes because certain synergism is expected in their functions. Methods: Male Wister Rats were fed the high fat-high sucrose [HFHS] diet for 12 weeks, with and without supplementation of Morus and Cha alone and their combination, and the effect of their supplementation on the markers of the metabolic syndrome such as obesity, lipidosis, and fatty liver formation, were examined. Results: Several metabolic syndrome markers, including body weight gain, lipid deposit, and fatty liver formation, were more significantly prevented by the diet supplemented with Morus and Cha combination compared to Morus or Cha given separately . Conclusion: Appropriate formulation of food resources with different functional mechanisms is a promising strategy for developing effective dietary treatment of type 2 diabetes that is a typical Mibyou.

We came across two cases of gastric neoplasms. Both the cases showed erythematous lesions in the body of the stomach and were resected en bloc by endoscopic mucosal resection. The pathology was adenoma, MUC5AC-positive, and MUC6-negative, and the diagnosis of foveolar-type gastric neoplasm was made.

Background/Aim: The prognosis of patients with multiple myeloma (MM) has recently improved due to the emergence of new molecular targeting agents. However, MM remains incurable because MM stem cells are resistant to these agents. Therefore, it is essential to develop strategies to eradicate MM stem cells. We have previously demonstrated that MM cells cultured under prolonged hypoxic conditions (1% O2) (i.e., hypoxia-adapted MM cells; MM-HA cells) exhibited stem-cell-like characteristics. γδ T cells attack tumor cells by recognizing butyrophilin (BTN) 3A1 and BTN2A1, which are activated by the intracellular accumulation of isopentenyl pyrophosphate (IPP), an intermediate in the mevalonate pathway. In the present study, we investigated the cytotoxicity of γδ T cells against MM-HA stem-like cells. Materials and Methods: We used a combination of flow cytometry, liquid chromatography-tandem mass spectrometry, and western blotting methods to investigate the cytotoxicity of γδ T cells against MM-HA cells and measured the amounts of IPP in MM-HA cells and their supernatants. Results: The cytotoxicity of γδ T cells against MM-HA cells was significantly lower than that against MM cells cultured under normoxic conditions (20% O2; MM-Normo). Furthermore, the concentration of IPP in MM-HA cells was lower than that in MM-Normo cells. The expression of mevalonate decarboxylase and farnesyl diphosphate synthase proteins were decreased in MM-HA-cells. Conclusion: The cytotoxicity of γδ T cells against MM-HA cells was suppressed by the reduced IPP accumulation by modulating the mevalonate pathway in MM-HA cells.

Dyslipidemia is a lifestyle-related (physical inactivity or obesity) disease; therefore, dietary foods that can easily be consumed in daily life is important to prevent dyslipidemia. Ergosterol, a precursor of vitamin D2, is a fungal sterol present in the membranes of edible mushrooms and other fungi. Ergosterol is converted to brassicasterol by 7-dehydrocholesterol reductase (DHCR7), a cholesterol biosynthesis enzyme that converts 7-dehydrocholesterol (a precursor of vitamin D3) into cholesterol. Previously, we reported that ergosterol increases 7-dehydrocholesterol, decreases cholesterol levels by competitive effect of DHCR7, and reduces DHCR7 mRNA and protein levels in human HepG2 hepatoma cells. Here, we investigated the effects of long-term high ergosterol intake on the cholesterol, vitamin D2, and D3 biosynthetic pathways of rats fed a high-fat and high-sucrose (HFHS) diet using GC-MS and LC with tandem mass spectrometry. In HFHS rats, oral ergosterol administration for 14 weeks significantly decreased plasma low-density lipoprotein cholesterol, total bile acid, and cholesterol precursor (squalene and desmosterol) levels and increased 7-dehydrocholesterol levels compared to HFHS rats without ergosterol. Ergosterol, brassicasterol, and vitamin D2 were detected, cholesterol levels were slightly decreased, and levels of vitamin D3 and its metabolites were slightly increased in rats fed HFHS with ergosterol. These results showed that ergosterol increased vitamin D2 levels, inhibited the cholesterol biosynthetic pathway, and possibly promoted vitamin D3 biosynthesis in vivo. Therefore, daily ergosterol intake may aid in the prevention of dyslipidemia.

Simultaneous administration of enteral formula and phenytoin in the clinical setting is known to reduce the plasma concentration of phenytoin. In this study, we examined the binding of phenytoin with enteral formulas and its components by quantifying the free phenytoin concentration. Furthermore, we investigated the effect of enteral formulas on gastrointestinal absorption of phenytoin in rats. The free phenytoin rate was reduced in vitro when phenytoin and enteral formula or pectin, a dietary fiber in enteral formulas, were co-administered. In vivo, when phenytoin and the enteral formula Mei Balance R® were co-administered, the time to maximum plasma concentration (Tmax) after oral administration was significantly increased. Moreover, the area under the phenytoin concentration-time curve from time zero to 6 h (AUC0-6 h) was significantly increased by co-administration of phenytoin with the enteral formula PG Soft EJ®. These results showed the gastrointestinal absorption of phenytoin differs according to the type of enteral formula. In addition, we found the first time that plasma phenytoin levels increase when combined with enteral formula. Among the components of enteral formulas, in particular, milk protein delayed the absorption of phenytoin. Moreover, milk protein, casein and carrageenan tended to increase AUC0-6 h. These results suggest the change in phenytoin concentration is due not only to the binding of enteral formula but also to the disintegration of components such as protein. Therefore, when co-administrated of phenytoin and enteral formula, phenytoin must be monitored frequently according to the enteral formula interaction.

The purpose of this study was to clarify the effects of enteral formulas and their food protein and dietary fiber components on the pharmacokinetics of warfarin in rats. Blood samples were collected from 0 to 30 h after the oral administration of 0.5 (milk protein or casein), or dietary fiber (indigestible dextrin or carrageenan). Plasma warfarin concentration was determined by liquid chromatography-tandem mass spectrometry. Plasma warfarin concentration was lower at the initial phase after co-administration of F2 Light & REG;, milk protein, or casein compared with the control group, which might have been caused by the suppression of the gastrointestinal absorption of warfarin in accordance with the binding to food protein. Plasma warfarin concentration was significantly higher after co-administration of Mei Flow & REG;, indigestible dextrin, or carrageenan compared with the control group. This is the first study to find that the plasma concentration of warfarin increases when warfarin is co-administered with enteral formula Mei Flow & REG; or their dietary fiber components such as indigestible dextrin or carrageenan. Therefore, close attention should be paid to decreases or increases in the plasma warfarin concentration when warfarin is used with enteral formula.

This study aimed to investigate the direct influence of a decrease in the cellular thiamin level, before the onset of anorexia (one of the symptoms of thiamin deficiency) on glycogen metabolism and the AMP-activated protein kinase (AMPK) activation levels in skeletal muscle at rest and in response to exercise. Male Wistar rats were classified as the control diet (CON) group or the thiamin-deficient diet (TD) group and consumed the assigned diets for 1 week. Skeletal muscles were taken from the rats at rest, those that underwent low-intensity swimming (LIS), or high-intensity intermittent swimming (HIS) conducted immediately before dissection. There were no significant differences in food intake, locomotive activity, or body weight between groups, but thiamin pyrophosphate in the skeletal muscles of the TD group was significantly lower than that of the CON group. Muscle glycogen and lactate levels in the blood and muscle were equivalent between groups at rest and in response to exercise. The mitochondrial content was equal between groups, and AMPK in the skeletal muscles of TD rats was normally activated by LIS and HIS. In conclusion, with a lowered cellular thiamin level, the exercise-associated glycogen metabolism and AMPK activation level in skeletal muscle were normally regulated.

Current treatment approaches for hyperlipidemia rely mainly on reducing the cholesterol level by inhibiting 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), which is involved in the presqualene pathway of cholesterol biosynthesis. Finding a compound that instead targets the postsqualene pathway could aid in the treatment of hyperlipidemia and synergistically reduce the cholesterol level when used in conjunction with HMGCR inhibitors. Ergosterol is a fungal sterol that is converted to brassicasterol by 7-dehydrocholesterol reductase (DHCR7). DHCR7 is also a cholesterol biosynthesis enzyme, and thus ergosterol may cause the accumulation of 7-dehydrocholesterol, a precursor of cholesterol and vitamin D3 , by a competitive effect. In this study, we examined the effect of ergosterol on the postsqualene pathway by quantifying cholesterol precursors and related sterols using gas chromatography-mass spectrometry and by conducting quantitative RT-PCR and western blot analysis for human HepG2 hepatoma cells. We found that ergosterol is converted into brassicasterol by the action of DHCR7 from HepG2 cells and that it induced the accumulation of cholesterol precursors (lathosterol, 7-dehydrocholesterol, and desmosterol) and decreased the cholesterol level by altering the mRNA and protein levels of cholesterol biosynthesis enzymes (increase of sterol 8,7-isomerase [EBP] and decrease of DHCR7 and 24-dehydrocholesterol reductase [DHCR24]). These results demonstrate that ergosterol inhibits the postsqualene pathway and may be useful for the prevention of hyperlipidemia.

Depression can be activated by dysfunction of the hypothalamus–pituitary–adrenal (HPA) axis and is sometimes accompanied by increased cortisol production. In this study, the effects of Kampo extract products on cortisol production in bovine adrenal fasciculata cells via adrenocorticotropic hormone (ACTH) stimulation were investigated with the aim of identifying substances that can improve the function of the HPA axis. Daiokanzoto extract product, which is prepared from Rhei Rhizoma and Glycyrrhizae Radix as the constituent crude drugs, was found to potently inhibit cortisol production in bovine adrenal fasciculata cells. Because only Rhei Rhizoma decoction showed potent inhibitory effect, the cortisol production inhibitory substances in Rhei Rhizoma was analyzed. As a result, six anthraquinones: chrysophanol, emodin, aloe-emodin, rhein, chrysophanol-8-O-β-D-glucopyranoside, and physicion-8-O-β-D-glucopyranoside were isolated and identified from Rhei Rhizoma decoction. Among these compounds, emodin showed the strongest inhibition of the ACTH-induced cortisol production in cells (IC50 = 13.1 ± 1.9 µM). These results suggest that emodin may help of stress-induced illnesses such as depression.

Basidiomycetes-X, of which Japanese vernacular name is Echigoshirayukidake, is a local speciality mushroom found and cultivated in Japan that has been distributed as a precious cuisine material or as a functional food with medicinal properties. Antioxidant activity-guided isolation of major ingredients in Basidiomycetes-X revealed the presence of ergosterol, trans-10,cis-12-octadecadienoic acid (a conjugated linolenic acid, 10(E),12(Z)-CLA) and 2,3-dihydro-3,5-dihydroxy-6-methyl‑4H‑pyran-4-one (DDMP). Approximately 21% of the 2,2-diphenyl-1-(2,4,6-trinitrophenyl)hydrazino radical (DPPH) scavenging activities in the methanolic extract were related to 10(E),12(Z)-CLA, while approximately 6.2% of the activity was related to ergosterol. DDMP was present in both methanolic and water extracts, and the activity related to DDMP was conspicuously detected in water extracts. Moreover, uridine and adenosine were identified as major components of Basidiomycetes-X. The ingredients identified in Basidiomycetes-X are expected to be involved in biological functions observed in this mushroom, which is an attractive functional food resource.

We investigated the effect of medium high hydrostatic pressure (<100 MPa) on acrylamide generation and the Maillard reaction using an equimolar asparagine-glucose aqueous solution adjusted to pH 9.0. The amounts of acrylamide and melanoidins generated and pH were determined after treatment at 70℃ and 60 or 90 MPa pressure or atmospheric pressure for up to 72 hours. Comparison of acrylamide and melanoidins contents revealed that pressure inhibited acrylamide generation in this solution. When added to the same solution, cysteine markedly inhibited acrylamide generation independent of pressure under the condition of 70℃ at 90 MPa or atmospheric pressure for 24 hours. Based on these results, under the same condition as the cysteine addition experiment, we examined the inhibitory effect of pressure and cysteine on acrylamide generation using a non-centrifugal cane sugar (NCS) solution at pH 5.5, which contains a relatively large amount of acrylamide. Adding cysteine to the NCS solution reduced its original amount of acrylamide and inhibited acrylamide generation during heat treatment. Pressurization of a cysteine-free NCS solution promoted acrylamide generation, but that of an NCS solution with high cysteine concentration promoted acrylamide decrease. These results suggest that acrylamide generation and the Maillard reaction during food processing might be regulated by medium high hydrostatic pressure and cysteine addition.

Colored compounds formed by the Maillard reaction of carnosine with xylose or glucose were investigated in this study. Yellow pigments showing an absorption maximum at 450 nm were found in a heated solution of carnosine with xylose at pH 5.0. These pigments were then isolated and identified as dicarnosyl-dipyrrolones A and B. The generation of dipyrrolones in the absence of lysine suggests that dipyrrolone pigments can be formed by pentose as well as every amino compound such as amino acids, peptides and proteins possessing a free amino group. Analysis of α-dicarbonyls using LC-MS/MS showed that pentosone, 1-deoxypentosone, 3-deoxypentosone (3-DP), and methylglyoxal were predominantly generated via degradation of Amadori compounds. Also, a potential formation pathway of dypyrrolones was established, indicating that an Amadori compound that could form 3-DP is likely to play a role as a main precursor for dipyrrolones.

Many pharmaceuticals and dietary foods have been reported to inhibit cholesterol biosynthesis, mainly by inhibiting the presqualene enzyme 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase rather than a postsqualene enzyme. In this study, we examined the inhibitory effects of Latilactobacillus sakei UONUMA on cholesterol biosynthesis, especially postsqualene, in human HepG2 hepatoma cells. We quantified cholesterol and its precursors, and the mRNA and protein levels of enzymes involved in cholesterol biosynthesis. Three L. sakei UONUMA strains exhibited new inhibitory effects on cholesterol biosynthesis and inhibited the mRNA level of sterol-delta24-reductase (DHCR24), which is involved in the postsqualene cholesterol biosynthesis pathway. These strains will be useful for the prevention and treatment of hyperlipidemia.

A 62-year-old male was admitted to hospital the limb sensation and a weakness in the main complain. He had an emergency upper gastrointestinal endoscopy because a result of his blood test was severe anemia, Hb 4.9 ml/dL.

Echigoshirayukidake is an edible mushroom found in Uonuma, Japan in 1994. It was assigned to a new species of Basidiomycetes (BDM-X) but is uniquely defect of forming bashidium. The high antioxidant activity and β-glucan content of BDM-X suggest possible functions preventing type 2 diabetes. In the present study, anti-obesity and insulin resistance preventive functions of BDM-X were examined using genetically defined obese model rat, OLETF (Otsuka Long Evans Tokushima Fatty) by feeding regular diet with and without supplementation of 5% dried BDM-X powder (BDMP) for 15 weeks. BDMP supplementation to the diet significantly (p < 0.01) suppressed the body weight gain and also visceral fat accumulation during the feeding period compared to control diet. Simultaneously, the insulin resistance and the plasma levels of adiponectin and triglycerides were significantly (p = 0.003) ameliorated in the BDMP supplemented diet group. A statistical multivariate analysis showed the weight of three types of adipose tissue (epididymal, retroperirenal, and mesenteric fat) positively correlated with HOMA-IR (Homeostasis Model Assessment of Insulin Resistance), and negatively correlated with plasma adiponectin. These results indicate BDM-X is a new resource applicable to the functional foods or the complementary biomedicines to prevent metabolic syndromes leading to type 2 diabetes.

We investigated the effects on acrylamide generation under heating conditions by addition of lysine and cysteine using non-centrifugal cane sugar (NCS) aqueous solutions as food models. The four NCS samples tested contained relatively high concentrations of acrylamide. Treating an aqueous solution of NCS at 100 for 60 min significantly increased the amount of acrylamide. We determined the concentrations of reducing sugar and free amino acids in the NCS samples and in NCS-related products and confirmed that all contained large amounts of reducing sugar and asparagine, which are major acrylamide reactants. Adding cysteine to an NCS solution suppressed the amount of acrylamide formed by heating at 100 degrees C for 60 min, whereas adding lysine promoted it. These amino acids dose-dependently affected acrylamide generation. Moreover, adding cysteine to NCS solutions suppressed the generation of acrylamide over a wide range of pH values. These findings suggest a method for preventing the generation of acrylamide during food processing.

Three pyrrole alkaloid derivatives were isolated from the edible mushroom Basidiomycetes-X (Echigoshirayukidake) by water extraction followed by ethyl acetate fractionation. The chemical structures determined by MS and NMR were 4-[2-formyl-5-(hydroxymethyl)-1H-pyrrol-1-yl] butanoic acid (compound I), 4-[2-formyl-5-(hydroxymethyl)-1H-pyrrol-1-yl] butanamide (compound II), and 5-(hydroxymethyl)-1H-pyrrole-2-carboxaldehyde (compound III). Compound I was found to be the major component, followed by compound II, and compound III was the minor component. The dry powder of Basidiomycetes-X contained approximately 825 μg g−1 compound I and 484 μg g−1 compound II. Compound II was found to be a novel pyrrole aldehyde homologue not previously reported and thus is a specific component of this mushroom.