BACKGROUND/OBJECTIVES: p-Coumaric acid (CA), a 4-hydroxycinnamic acid derivative, is widely distributed in nature and exerts various beneficial biological effects. However, the effects of CA on metabolic abnormalities triggered by excessive fructose intake, such as dyslipidemia, hyperglycemia, non-alcoholic fatty liver disease (NAFLD), and insulin resistance, have not been sufficiently investigated. Our objective was to investigate whether CA ameliorates high-fructose diet (HFrD)-induced metabolic dysregulation.MATERIALS/METHODS: Golden Syrian hamsters were randomly assigned to 3 groups and were fed diets containing 60% cornstarch (CON group), 60% fructose (HFrD group), or 60% fructose with CA (0.02%) (HFrD+CA group) for 5 weeks. RESULTS: HFrD feeding significantly increased the levels of plasma triglyceride, apolipoprotein (apo)-CIII, fasting blood glucose, and homeostatic model assessment insulin resistance, and tended to increase plasma total cholesterol (TC) and low-density lipoprotein/very low-density lipoprotein cholesterol (LDL/VLDL-C) compared with the CON group. In HFrD-fed hamsters, CA supplementation significantly decreased plasma TC, LDL/VLDL-C, apo-CIII, and fasting blood glucose levels. Moreover, CA significantly decreased the hepatic lipid levels and fibrosis induced by HFrD. The plasma and hepatic lipid-lowering effects of CA were associated with decreased enzyme activity and mRNA expression of genes involved in fatty acid, triglyceride, and cholesterol synthesis as well as increased activity of carnitine palmitoyltransferase, a rate-limiting enzyme in fatty acid oxidation, in the liver. CA-treated hamsters also exhibited decreased hepatic gluconeogenic enzyme activity and increased hepatic glycolytic enzyme activity, with mRNA expression changes similar to these activity patterns. CONCLUSION Our findings indicate that CA potentially improves metabolic abnormalities associated with excessive fructose intake, such as hyperglycemia, dyslipidemia, and NAFLD.

BACKGROUND/OBJECTIVES: p-Coumaric acid (CA), a 4-hydroxycinnamic acid derivative, is widely distributed in nature and exerts various beneficial biological effects. However, the effects of CA on metabolic abnormalities triggered by excessive fructose intake, such as dyslipidemia, hyperglycemia, non-alcoholic fatty liver disease (NAFLD), and insulin resistance, have not been sufficiently investigated. Our objective was to investigate whether CA ameliorates high-fructose diet (HFrD)-induced metabolic dysregulation.MATERIALS/METHODS: Golden Syrian hamsters were randomly assigned to 3 groups and were fed diets containing 60% cornstarch (CON group), 60% fructose (HFrD group), or 60% fructose with CA (0.02%) (HFrD+CA group) for 5 weeks. RESULTS: HFrD feeding significantly increased the levels of plasma triglyceride, apolipoprotein (apo)-CIII, fasting blood glucose, and homeostatic model assessment insulin resistance, and tended to increase plasma total cholesterol (TC) and low-density lipoprotein/very low-density lipoprotein cholesterol (LDL/VLDL-C) compared with the CON group. In HFrD-fed hamsters, CA supplementation significantly decreased plasma TC, LDL/VLDL-C, apo-CIII, and fasting blood glucose levels. Moreover, CA significantly decreased the hepatic lipid levels and fibrosis induced by HFrD. The plasma and hepatic lipid-lowering effects of CA were associated with decreased enzyme activity and mRNA expression of genes involved in fatty acid, triglyceride, and cholesterol synthesis as well as increased activity of carnitine palmitoyltransferase, a rate-limiting enzyme in fatty acid oxidation, in the liver. CA-treated hamsters also exhibited decreased hepatic gluconeogenic enzyme activity and increased hepatic glycolytic enzyme activity, with mRNA expression changes similar to these activity patterns. CONCLUSION Our findings indicate that CA potentially improves metabolic abnormalities associated with excessive fructose intake, such as hyperglycemia, dyslipidemia, and NAFLD.

BACKGROUND/OBJECTIVES: p-Coumaric acid (CA), a 4-hydroxycinnamic acid derivative, is widely distributed in nature and exerts various beneficial biological effects. However, the effects of CA on metabolic abnormalities triggered by excessive fructose intake, such as dyslipidemia, hyperglycemia, non-alcoholic fatty liver disease (NAFLD), and insulin resistance, have not been sufficiently investigated. Our objective was to investigate whether CA ameliorates high-fructose diet (HFrD)-induced metabolic dysregulation.MATERIALS/METHODS: Golden Syrian hamsters were randomly assigned to 3 groups and were fed diets containing 60% cornstarch (CON group), 60% fructose (HFrD group), or 60% fructose with CA (0.02%) (HFrD+CA group) for 5 weeks. RESULTS: HFrD feeding significantly increased the levels of plasma triglyceride, apolipoprotein (apo)-CIII, fasting blood glucose, and homeostatic model assessment insulin resistance, and tended to increase plasma total cholesterol (TC) and low-density lipoprotein/very low-density lipoprotein cholesterol (LDL/VLDL-C) compared with the CON group. In HFrD-fed hamsters, CA supplementation significantly decreased plasma TC, LDL/VLDL-C, apo-CIII, and fasting blood glucose levels. Moreover, CA significantly decreased the hepatic lipid levels and fibrosis induced by HFrD. The plasma and hepatic lipid-lowering effects of CA were associated with decreased enzyme activity and mRNA expression of genes involved in fatty acid, triglyceride, and cholesterol synthesis as well as increased activity of carnitine palmitoyltransferase, a rate-limiting enzyme in fatty acid oxidation, in the liver. CA-treated hamsters also exhibited decreased hepatic gluconeogenic enzyme activity and increased hepatic glycolytic enzyme activity, with mRNA expression changes similar to these activity patterns. CONCLUSION Our findings indicate that CA potentially improves metabolic abnormalities associated with excessive fructose intake, such as hyperglycemia, dyslipidemia, and NAFLD.

BACKGROUND/OBJECTIVES: p-Coumaric acid (CA), a 4-hydroxycinnamic acid derivative, is widely distributed in nature and exerts various beneficial biological effects. However, the effects of CA on metabolic abnormalities triggered by excessive fructose intake, such as dyslipidemia, hyperglycemia, non-alcoholic fatty liver disease (NAFLD), and insulin resistance, have not been sufficiently investigated. Our objective was to investigate whether CA ameliorates high-fructose diet (HFrD)-induced metabolic dysregulation.MATERIALS/METHODS: Golden Syrian hamsters were randomly assigned to 3 groups and were fed diets containing 60% cornstarch (CON group), 60% fructose (HFrD group), or 60% fructose with CA (0.02%) (HFrD+CA group) for 5 weeks. RESULTS: HFrD feeding significantly increased the levels of plasma triglyceride, apolipoprotein (apo)-CIII, fasting blood glucose, and homeostatic model assessment insulin resistance, and tended to increase plasma total cholesterol (TC) and low-density lipoprotein/very low-density lipoprotein cholesterol (LDL/VLDL-C) compared with the CON group. In HFrD-fed hamsters, CA supplementation significantly decreased plasma TC, LDL/VLDL-C, apo-CIII, and fasting blood glucose levels. Moreover, CA significantly decreased the hepatic lipid levels and fibrosis induced by HFrD. The plasma and hepatic lipid-lowering effects of CA were associated with decreased enzyme activity and mRNA expression of genes involved in fatty acid, triglyceride, and cholesterol synthesis as well as increased activity of carnitine palmitoyltransferase, a rate-limiting enzyme in fatty acid oxidation, in the liver. CA-treated hamsters also exhibited decreased hepatic gluconeogenic enzyme activity and increased hepatic glycolytic enzyme activity, with mRNA expression changes similar to these activity patterns. CONCLUSION Our findings indicate that CA potentially improves metabolic abnormalities associated with excessive fructose intake, such as hyperglycemia, dyslipidemia, and NAFLD.

BACKGROUND/OBJECTIVES: p-Coumaric acid (CA), a 4-hydroxycinnamic acid derivative, is widely distributed in nature and exerts various beneficial biological effects. However, the effects of CA on metabolic abnormalities triggered by excessive fructose intake, such as dyslipidemia, hyperglycemia, non-alcoholic fatty liver disease (NAFLD), and insulin resistance, have not been sufficiently investigated. Our objective was to investigate whether CA ameliorates high-fructose diet (HFrD)-induced metabolic dysregulation.MATERIALS/METHODS: Golden Syrian hamsters were randomly assigned to 3 groups and were fed diets containing 60% cornstarch (CON group), 60% fructose (HFrD group), or 60% fructose with CA (0.02%) (HFrD+CA group) for 5 weeks. RESULTS: HFrD feeding significantly increased the levels of plasma triglyceride, apolipoprotein (apo)-CIII, fasting blood glucose, and homeostatic model assessment insulin resistance, and tended to increase plasma total cholesterol (TC) and low-density lipoprotein/very low-density lipoprotein cholesterol (LDL/VLDL-C) compared with the CON group. In HFrD-fed hamsters, CA supplementation significantly decreased plasma TC, LDL/VLDL-C, apo-CIII, and fasting blood glucose levels. Moreover, CA significantly decreased the hepatic lipid levels and fibrosis induced by HFrD. The plasma and hepatic lipid-lowering effects of CA were associated with decreased enzyme activity and mRNA expression of genes involved in fatty acid, triglyceride, and cholesterol synthesis as well as increased activity of carnitine palmitoyltransferase, a rate-limiting enzyme in fatty acid oxidation, in the liver. CA-treated hamsters also exhibited decreased hepatic gluconeogenic enzyme activity and increased hepatic glycolytic enzyme activity, with mRNA expression changes similar to these activity patterns. CONCLUSION Our findings indicate that CA potentially improves metabolic abnormalities associated with excessive fructose intake, such as hyperglycemia, dyslipidemia, and NAFLD.

Objective: This study was performed to evaluate the efficacy and safety of lurasidone (160 mg/day) compared to quetiapine XR (QXR; 600 mg/day) in the treatment of acutely psychotic patients with schizophrenia. Methods: Patients were randomly assigned to 6 weeks of double-blind treatment with lurasidone 160 mg/day (n=105) or QXR 600 mg/day (n=105). Primary efficacy measure was the change from baseline to week 6 in Positive and Negative Syndrome Scale (PANSS) total score and Clinical Global Impressions severity (CGI-S) score. Adverse events, body measurements, and laboratory parameters were assessed. Results: Lurasidone demonstrated non-inferiority to QXR on the PANSS total score. Adjusted mean±standard error change at week 6 on the PANSS total score was -26.42±2.02 and -27.33±2.01 in the lurasidone and QXR group, respectively. The mean difference score was -0.91 (95% confidence interval -6.35–4.53). The lurasidone group showed a greater reduction in PANSS total and negative subscale on week 1 and a greater reduction in end-point CGI-S score compared to the QXR group. Body weight, body mass index, and waist circumference in the lurasidone group were reduced, with significantly lower mean change compared to QXR. Endpoint changes in glucose, cholesterol, triglycerides, and low-density lipoprotein levels were also significantly lower. The most common adverse drug reactions with lurasidone were akathisia and nausea. Conclusion Lurasidone 160 mg/day was found to be non-inferior to QXR 600 mg/day in the treatment of schizophrenia with comparable efficacy and tolerability. Adverse effects of lurasidone were generally tolerable, and beneficial effects on metabolic parameters can be expected.

Objectives: Rasmussen’s aneurysm may cause life-threatening hemoptysis. We investigated the clinical characteristics and outcomes of patients with hemoptysis and Rasmussen’s aneurysm. Methods: We retrospectively investigated patients who clinically presented with hemoptysis and were diagnosed with a Rasmussen’s aneurysm on spiral chest computed tomography (CT). Results: Our study included 16 patients (men:women, 12:4; mean age, 65.25 ± 13.0 years). Massive hemoptysis was observed in nine patients (56%) and blood-tinged sputum in four patients (25%). Ten patients (62.5%) had a history of pulmonary tuberculosis, and three patients (18.7%) had underlying lung cancer. Chest CT revealed coexisting fungal balls in seven patients (43.7%). Bronchial artery embolization (BAE) was performed in 12 patients (75%). One patient died of uncontrolled massive hemoptysis. Conclusions Patients with Rasmussen’s aneurysm showed hemoptysis during the course of the disease; however, bleeding can be controlled with conservative therapy and radiological interventions, such as BAE.

BACKGROUND/OBJECTIVES: Nobiletin (NOB), a citrus flavonoid, is reported to have beneficial effects on cardiovascular and metabolic health. However, there is limited research investigating the effect of long-term supplementation with low-dose NOB on highcholesterol diet (HCD)-induced hypercholesterolemia and non-obese nonalcoholic fatty liver disease (NAFLD). Therefore, we investigated the influence of NOB on hypercholesterolemia and NAFLD in HCD-fed mice. SUBJECTS/METHODS: C57BL/6J mice were fed a normal diet (ND) or HCD (35 kcal% fat, 1.25% cholesterol, 0.5% cholic acid) with or without NOB (0.02%) for 20 weeks. RESULTS: HCD feeding markedly reduced the final body weight compared to ND feeding, with no apparent energy intake differences. NOB supplementation suppressed HCD-induced weight loss without altering energy intake. Moreover, NOB significantly decreased the total cholesterol (TC) levels and the low-density lipoprotein (LDL)/very-LDL-cholesterol to TC ratio, and increased the high-density lipoprotein-cholesterol/TC ratio in plasma, compared to those for HCD feeding alone. The plasma levels of inflammatory and atherosclerosis markers (C-reactive protein, oxidized LDL, interleukin [IL]-1β, IL-6, and plasminogen activator inhibitor-1) were significantly lower, whereas those of anti-atherogenic adiponectin and paraoxonase were higher in the NOB-supplemented group than in the HCD control group. Furthermore, NOB significantly decreased liver weight, hepatic cholesterol and triglyceride contents, and lipid droplet accumulation by inhibiting messenger RNA expression of hepatic genes and activity levels of cholesterol synthesis-, esterification-, and fatty acid synthesis-associated enzymes, concomitantly enhancing fatty acid oxidationrelated gene expression and enzyme activities. Dietary NOB supplementation may protect against hypercholesterolemia and NAFLD via regulation of hepatic lipid metabolism in HCDfed mice; these effects are associated with the amelioration of inflammation and reductions in the levels of atherosclerosis-associated cardiovascular markers. CONCLUSIONS The present study suggests that NOB may serve as a potential therapeutic agent for the treatment of HCD-induced hypercholesterolemia and NAFLD.

BACKGROUND/OBJECTIVES: Nobiletin (NOB), a citrus flavonoid, is reported to have beneficial effects on cardiovascular and metabolic health. However, there is limited research investigating the effect of long-term supplementation with low-dose NOB on highcholesterol diet (HCD)-induced hypercholesterolemia and non-obese nonalcoholic fatty liver disease (NAFLD). Therefore, we investigated the influence of NOB on hypercholesterolemia and NAFLD in HCD-fed mice. SUBJECTS/METHODS: C57BL/6J mice were fed a normal diet (ND) or HCD (35 kcal% fat, 1.25% cholesterol, 0.5% cholic acid) with or without NOB (0.02%) for 20 weeks. RESULTS: HCD feeding markedly reduced the final body weight compared to ND feeding, with no apparent energy intake differences. NOB supplementation suppressed HCD-induced weight loss without altering energy intake. Moreover, NOB significantly decreased the total cholesterol (TC) levels and the low-density lipoprotein (LDL)/very-LDL-cholesterol to TC ratio, and increased the high-density lipoprotein-cholesterol/TC ratio in plasma, compared to those for HCD feeding alone. The plasma levels of inflammatory and atherosclerosis markers (C-reactive protein, oxidized LDL, interleukin [IL]-1β, IL-6, and plasminogen activator inhibitor-1) were significantly lower, whereas those of anti-atherogenic adiponectin and paraoxonase were higher in the NOB-supplemented group than in the HCD control group. Furthermore, NOB significantly decreased liver weight, hepatic cholesterol and triglyceride contents, and lipid droplet accumulation by inhibiting messenger RNA expression of hepatic genes and activity levels of cholesterol synthesis-, esterification-, and fatty acid synthesis-associated enzymes, concomitantly enhancing fatty acid oxidationrelated gene expression and enzyme activities. Dietary NOB supplementation may protect against hypercholesterolemia and NAFLD via regulation of hepatic lipid metabolism in HCDfed mice; these effects are associated with the amelioration of inflammation and reductions in the levels of atherosclerosis-associated cardiovascular markers. CONCLUSIONS The present study suggests that NOB may serve as a potential therapeutic agent for the treatment of HCD-induced hypercholesterolemia and NAFLD.

An abnormal reorganization of the dentate gyrus and neurotoxic events are important phenotypes in the hippocampus of patients with temporal lobe epilepsy (TLE). The effects of morin, a bioflavonoid constituent of many herbs and fruits, on epileptic seizures have not yet been elucidated, though its beneficial effects, such as its anti-inflammatory and neuroprotective properties, are well-described in various neurodegenerative diseases. In the present study, we investigated whether treatment with morin hydrate (MH) can reduce the susceptibility to seizures, granule cell dispersion (GCD), mammalian target of rapamycin complex 1 (mTORC1) activity, and the increases in the levels of apoptotic molecules and inflammatory cytokines in the kainic acid (KA)-induced seizure mouse model. Our results showed that oral administration of MH could reduce susceptibility to seizures and lead to the inhibition of GCD and mTORC1 activity in the KA-treated hippocampus. Moreover, treatment with MH significantly reduced the increased levels of apoptotic signaling molecules and pro-inflammatory mediators in the KA-treated hippocampus compared with control mice, suggesting a neuroprotective role. Therefore, these results suggest that morin has a therapeutic potential against epilepsy through its abilities to inhibit GCD and neurotoxic events in the in vivo hippocampus.
Administration, Oral ; Animals ; Cytokines ; Dentate Gyrus ; Epilepsy ; Epilepsy, Temporal Lobe ; Fruit ; Hippocampus ; Humans ; Kainic Acid ; Mice ; Neurodegenerative Diseases ; Neuroprotection ; Phenotype ; Seizures* ; Sirolimus