Chemoprevention of hepatocellular carcinoma (HCC) is one of the most challenging aspects of medical research. Vitamin K2 (VK2) has been suggested for its chemopreventive role in treatment of HCC, while inconsistent results in clinical trials have been reported. The present study was initiated to add to our insight into the anti-HCC cell proliferative effect of VK2 and its derivatives from a viewpoint of chemical structure. No significant effect was observed with original VK2, while VK2 derivatives bearing both isoprene units and a carboxyl-terminated side chain dose-dependently inhibited the growth of HCC cells without affecting normal liver cells. Loss-of-function analyses revealed that the anti-HCC cell activity by the VK2 derivatives was not mediated by a VK2 binding protein Bcl-2 homologous antagonist/killer (Bak) but rather associated with caspase/transglutaminase-related signaling pathways. Further studies on the carboxylic derivatives of VK2 bearing isoprene structural units introduced in this study might shed new light on the systemic treatment and prevention of HCC.
We wished to examine potential associations among blood concentrations of fatty acid-binding protein (FABP) 4 and parameters in health check-ups such as abdominal fat area (AFA) and blood pressure (BP) in middle-aged Japanese males. We conducted a cross-sectional study of males who participated in health check-ups in Japan. We excluded participants diagnosed with metabolic diseases by the time of their check-up. A total of 305 subjects (30–64 [mean±standard deviation, 47.3±8.5] y) were recruited. Areas of total-abdominal, visceral and subcutaneous fat were measured using computed tomography. We compared the association of serum concentrations of FABP4 with various clinical parameters by Pearson product–moment correlation coefficient (PPMCC) analyses, and by step-wise multivariate linear regression analyses (MLRA). PPMCC analyses showed that blood concentrations of FABP4 were positively associated with: body mass index; areas of fat (total abdominal, visceral, subcutaneous); systolic BP; diastolic BP; total cholesterol; low-density lipoprotein-cholesterol; triacylglycerol; activities of γ-glutamyl transpeptidase, aspartate aminotransferase and alanine aminotransferase; white blood cell count; and levels of creatinine. Step-wise MLRA showed that AFAs (visceral and subcutaneous) and diastolic BP were positively and independently associated with serum concentrations of FABP4 among the parameters tested. These data suggest that serum concentrations of FABP4 are independently and positively associated with BP and AFA among parameters measured in health check-ups in middle-aged Japanese males.
We examined the acute effects of postprandial aerobic exercise on glucose and lipid metabolism following cookie ingestion. Fifteen healthy young women with a sedentary lifestyle, normal weight and apolipoprotein E3/3 participated. After a 12-h overnight fast, each subject ingested a cookie (1.53 g/kg, Meal Test C) and then performed two trials, one with postprandial exercise (E trial) and one without exercise (C trial), in a randomized crossover design. A single 30-min bout of walking exercise was performed 20 min after the cookie intake. Venous blood samples were drawn before (0 h) and 20 min and 1, 2, 4, and 6 h after cookie ingestion. The Δglucose concentration was not significantly different between the two trials, but the Δinsulin concentration at 1 h and the incremental area under the curve (IAUC) (0–2 h)-insulin in the E trial were significantly lower than in the C trial. The ratio of glucose/insulin at 1 h was significantly higher in the E trial than in the C trial. The ΔTG, ΔRLP-TG, ΔapoB48 and ΔRemL-C concentrations at 1 h in the E trial were significantly higher than in the C trial. The IAUC (0–2 h)-apoB48 in the E trial was significantly larger than in the C trial. Postprandial exercise showed an insulin-sparing effect following the cookie ingestion by increasing insulin sensitivity. However, postprandial exercise transiently stimulated the secretion of exogenous apoB48-containing lipoprotein during the early period, and no further effects were observed. These results suggest that postprandial aerobic exercise is effective for the promotion of postprandial carbohydrate metabolism, but not lipidemia.
Boysenberry, a hybrid Rubus berry, is mainly cultivated in New Zealand. We previously reported that consumption of boysenberry juice (BBJ) exhibited anti-obesity effects in high-fat feeding rats. In this study, we focused on the suppressive effect of BBJ and its fraction on triglyceride absorption from the gastrointestinal tract. BBJ effectively inhibited pancreatic lipase activity in vitro, and was separated into four fractions (Fr1, Fr2, Fr3 and Fr4) by HP-20 column chromatography. Among all the fractions, Fr3, the ellagic acid-rich fraction, showed the most potent inhibition against pancreatic lipase in vitro with Fr2, the anthocyanin-rich fraction, second. Authentic ellagic acid equivalent in Fr3 showed poor activity against pancreatic lipase. Then, each fraction was orally administered with corn oil to rats fitted with a jugular catheter to examine the effects of each fraction on plasma triglyceride levels. Both Fr2 and Fr3 effectively suppressed the plasma triglyceride level elevation at a dose of 1,000 mg/kg body weight. These findings demonstrated that BBJ contains chemical components which inhibit triglyceride absorption from the gastrointestinal tract.
It has been reported that postprandial hyperglycemia from the pre-diabetic stage, especially from the impaired glucose tolerance (IGT) stage, is positively associated with subsequent incidences of cardiovascular diseases (CVD) and type 2 diabetes. In this study, we aimed to investigate whether treatment with a dipeptidyl peptidase-4 inhibitor (DPP-4I) or an α-glucosidase inhibitor (α-GI), either of which suppresses postprandial hyperglycemia, reduces the expression of CVD risk factors in an IGT animal model. A DPP-4I, anagliptin (1,200 ppm), or an α-GI, miglitol (600 ppm), in the diet was administered for 47 wk to Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a model for spontaneously-developed type 2 diabetes, at the IGT stage. We examined whether each treatment reduced the expression of CVD risk factors such as inflammatory cytokines/cytokine-like factors in peripheral leukocytes and adhesion molecules in the aortic tissues and circulation. Treatment with either drug reduced IGT development and repressed expression of the interleukin-1β, tumor necrosis factor-α, S100a9, and S100a11 genes in peripheral leukocytes in the fasting state at weeks 25 and 39. The mRNA levels of E-selectin in aortic tissues and protein levels of the soluble forms of E-selectin and ICAM-1 in arterial blood were significantly lower in the anagliptin and miglitol groups than in the control group. Our results suggest that long-term treatment with anagliptin or miglitol in OLETF rats at the IGT stage suppresses the expression of inflammatory cytokines in peripheral leukocytes and adhesion molecules in aortic tissues.
The Indonesian Ministry of Health has predicted that the national prevalence of hypertension in Indonesia may reach 26.5% in 2013. Increasing age, stress, lack of physical activity, obesity and passive smoking are known to be risk factors of hypertension. In women over 50 y, hormonal changes that occur post-menopause may also increase the risk of hypertension and other vascular diseases. Antioxidant precursors, such as selenium, however, are known to provide protection against the development of several oxidative stress-related diseases, including hypertension. To prove the hypothesis, we compared the levels of consumption of selenium in hypertensive and normotensive post-menopausal women. An observational comparative study with cross-sectional design was conducted in groups of post-menopausal women with hypertension and those who are normotensive. Structured interviews and food recall of 2×24 h were used to determine the level of consumption, and the Depression, Anxiety and Stress Scale (DASS) questionnaire was used to measure the level of stress. The result suggests a significant difference in the levels of selenium intake between the normotensive and hypertensive groups (p=0.008). Furthermore, the passive smoking and stress levels of the hypertensive group were significantly higher than those of the normotensive group. These result support the hypothesis that selenium may play a protective role in vascular disease.
We investigated the efficacy and safety of a new type of dietary fiber (high specific volume polysaccharide) for use in treating constipation of different etiologies. Functional constipation patients and irritable bowel syndrome-constipation (IBS-C) patients were administrated high specific volume polysaccharide (HSVP) three times daily for a period of 2 wk to relieve their symptoms. Scores on a stool form scale, and patient reports of straining during a bowel movement, having sensations of an incomplete bowel movement or a blocked anorectum, and abnormal defecation intervals were recorded, graded, and scored by a functional constipation sample group. Similarly, a cohort of IBS-C patients reported their occurrence of abdominal discomfort or pain, abnormal stool formation, defecation frequency, and straining during a bowel movement. Additionally, both groups reported any adverse reactions associated with taking HSVP. All patients in both groups returned for follow-up visits, and no adverse reactions to treatment with HSVP were reported. In the functional constipation group, HSVP was effective for treating symptoms of constipation in 81.46% and 93.17% of patients after 7 and 14 d of dosing, respectively (both p<0.05). In the IBS-C group, symptoms of constipation were relieved in 71.67% and 88.34% of patients after 7 and 14 d of dosing, respectively (both p<0.05). High specific volume polysaccharide was shown be effective for treatment of functional constipation and IBS-C, without causing significant adverse events.
Kiwifruit is a good source of dietary components and has beneficial effects for health. In this study, we investigated the effects of two types of kiwifruit, green kiwifruit (GRK) and gold kiwifruit (GOK), on bone metabolism in ovariectomized (OVX) mice. Seven-week-old female Balb/c-strain mice were divided into four groups: sham-operated (sham) group, OVX group, and OVX mice that were fed a GRK-supplemented diet or GOK-supplemented diet. Freeze-dried GRK and GOK were prepared and added in the diet at a concentration of 3 g/100 g. After 9 wk, the mice were sacrificed, and the serum, uterus, and femurs were obtained. Final body weight did not differ significantly among the four groups. Compared to the sham group, uterine weight was significantly lower and serum C-terminal telopeptide of type I collagen (CTx) levels and receptor activator of NF-κB ligand (RANKL) mRNA expression of the whole femur were significantly higher in the OVX group. Compared to the OVX group, GRK, but not GOK, reduced serum CTx concentrations and RANKL mRNA expression of the whole femur without changes in uterine weight. These results suggest that the GRK inhibited bone resorption, which might be due to a decrease in RANKL mRNA expression in OVX mice.
An association between the dietary intake of polyphenols and human health has been shown in many epidemiological studies. Since beverages are rich sources of polyphenols, we aimed to evaluate the polyphenol intake from beverages in Japanese individuals with a focus on differences according to year, age, gender and season. More than 10,000 Japanese male and female subjects aged 1–99 y old participated in this survey every year from 1996 to 2013, and their beverage consumption and amount of polyphenol intake were calculated. Polyphenol intake from beverages in Japan showed no tendency to increase or decrease over the 18-y period, and the major sources of polyphenols in Japanese daily life were coffee and green tea. Polyphenol intake was larger in participants with higher age up to 59 y old in both male and female subjects. There was a slight difference in polyphenol intake by gender, with adult males consuming more polyphenols than adult females. Polyphenols were consumed slightly more in the winter than the summer, although the seasonal difference in polyphenol intake was not large. Our results suggest that polyphenol intake from beverages is influenced by age rather than gender or season in Japan, and may not have changed over time, at least over the 18-y period beginning in 1996 in Japan.
The objective of the present study was to evaluate bowel habits induced by ingestion of 10 g polydextrose (PDX) fed to Japanese hemodialysis (HD) patients. This was a randomized, placebo-controlled, triple-blind, parallel-group controlled, 8-wk study. A total of 50 HD outpatients capable of self-management (51–79 y of age) were recruited at H Clinic, Japan. Inclusion criteria for participation in the study were ingestion of one or more laxative tablets for more than 3 mo and having received HD for more than 6 mo. The participants were randomly assigned to 2 groups: A (0 g polydextrose/d; control), B (10 g polydextrose/d; PDX). The primary outcome measure was stool frequency. Secondary outcomes were stool consistency, abdominal pain, intestinal bloating and clinical biochemistry indexes. PDX had no significant effect on blood biochemistry indexes. The PDX group showed significant improvements in bowel function (stool frequency increased from 3.0 times per week to 7.5 times per week) and reported no laxation problems (abdominal distention, cramps, and diarrhea) (p<0.01). Regular consumption of the PDX products increased dietary fiber intake to recommended levels and improved bowel habits.