Neuroprotective effects of hesperetin on H 2 O 2 -induced damage in neuroblastoma SH-SY5Y cells

BACKGROUND/OBJECTIVES@#Oxidative stress is a fundamental neurodegenerative disease trigger that damages and decimates nerve cells. Neurodegenerative diseases are chronic central nervous system disorders that progress and result from neuronal degradation and loss. Recent studies have extensively focused on neurodegenerative disease treatment and prevention using dietary compounds. Heseperetin is an aglycone hesperidin form with various physiological activities, such as anti-inflammation, antioxidant, and antitumor. However, few studies have considered hesperetin’s neuroprotective effects and mechanisms; thus, our study investigated this in hydrogen peroxide ( H 2 O 2 )-treated SH-SY5Y cells.MATERIALS/METHODS: SH-SY5Y cells were treated with H 2 O 2 (400 µM) in hesperetin absence or presence (10–40 µM) for 24 h. Three-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assays detected cell viability, and 4′,6-diamidino-2-phenylindole staining allowed us to observe nuclear morphology changes such as chromatin condensation and apoptotic nuclei. Reactive oxygen species (ROS) detection assays measured intracellular ROS production; Griess reaction assays assessed nitric oxide (NO) production. Western blotting and quantitative polymerase chain reactions quantified corresponding mRNA and proteins. @*RESULTS@#Subsequent experiments utilized various non-toxic hesperetin concentrations, establishing that hesperetin notably decreased intracellular ROS and NO production in H 2 O 2 -treated SH-SY5Y cells (P < 0.05). Furthermore, hesperetin inhibited H 2 O 2 -induced inflammation-related gene expression, including interluekin-6, tumor necrosis factor-α, and nuclear factor kappa B (NF-κB) p65 activation. In addition, hesperetin inhibited NFκB translocation into H 2 O 2 -treated SH-SY5Y cell nuclei and suppressed mitogen-activated protein kinase protein expression, an essential apoptotic cell death regulator. Various apoptosis hallmarks, including shrinkage and nuclear condensation in H 2 O 2 -treated cells, were suppressed dose-dependently. Additionally, hesperetin treatment down-regulated Bax/ Bcl-2 expression ratios and activated AMP-activated protein kinase-mammalian target of rapamycin autophagy pathways. @*CONCLUSION@#These results substantiate that hesperetin activates autophagy and inhibits apoptosis and inflammation. Hesperetin is a potentially potent dietary agent that reduces neurodegenerative disease onset, progression, and prevention

Sodium butyrate inhibits high glucose-induced inflammation bycontrolling the acetylation of NF-κB p65 in human monocytes

BACKGROUND/OBJECTIVES@#Hyperglycemia is a major cause of diabetes and diabetesrelated diseases. Sodium butyrate (NaB) is a short-chain fatty acid derivative that produces dietary fiber by anaerobic bacterial fermentation in the large intestine and occurs in foods, such as Parmesan cheese and butter. Butyrate has been shown to prevent obesity, improve insulin sensitivity, and ameliorate dyslipidemia in diet-induced obese mice. Therefore, this study examined the effects and mechanism of NaB on the secretion of inflammatory cytokines induced by high glucose (HG) in THP-1 cells.MATERIALS/METHODS: THP-1 cells were used as an in vitro model for HG-induced inflammation. The cells were cultured under normal glycemic or hyperglycemic conditions with or without NaB (0–25 μM). Western blotting and quantitative polymerase chain reaction were used to evaluate the protein and mRNA levels of nuclear factor-κB (NF-κB), interleukin-6, tumor necrosis factor-α, acetylated p65, acetyl CREB-binding protein/p300 (CBP/p300), and p300 using THP-1 cells. Histone acetyltransferase (HAT), histone deacetylase (HDAC), and pro-inflammatory cytokine secretion activity were analyzed using an enzyme-linked immunosorbent assay. @*RESULTS@#HG significantly upregulated histone acetylation, acetylation levels of p300, NF-κB activation, and inflammatory cytokine release in THP-1 cells. Conversely, the NaB treatment reduced cytokine release and NF-κB activation in HG-treated cells. It also significantly reduced p65 acetylation, CBP/p300 HAT activity, and CBP/p300 gene expression. In addition, NaB decreased the interaction of p300 in acetylated NF-κB and TNF-α. @*CONCLUSIONS@#These results suggest that NaB suppresses HG-induced inflammatory cytokine production through HAT/HDAC regulation in monocytes. NaB has the potential for preventing and treating diabetes and its related complications.

Dietary glucosinolates inhibit splenic inflammation in high fat/cholesterol diet-fed C57BL/6 mice

BACKGROUND/OBJECTIVES@#Obesity is associated with chronic inflammation. The spleen is the largest organ of the lymphatic system and has an important role in immunity.Obesity-induced inflammatory responses are triggered by Toll-like receptor (TLR)-myeloid differentiation primary response 88 (MyD88) pathway signaling. Phenethyl isothiocyanate (PEITC) and 3,3′-diindolylmethane (DIM), major dietary glucosinolates present in cruciferous vegetables, have been reported to produce anti-inflammatory effects on various diseases. However, the effects of PEITC and DIM on the obesity-induced inflammatory response in the spleen are unclear. The purpose of this study was to examine the antiinflammatory effects of PEITC and DIM on the spleen and their mechanism in high fat/ cholesterol diet (HFCD)-fed C57BL/6 mice.MATERIALS/METHODS: We established an animal model of HFCD-induced obesity using C57BL/6 mice. The mice were divided into six groups: normal diet with AIN-93G diet (CON), high fat diet (60% calories from fat) with 1% cholesterol (HFCD), HFCD with PEITC 30 mg/kg/ day or 75 mg/kg/day (HFCD+P30, HFCD+P75), and HFCD with DIM 1.5 mg/kg/day or 7.5 mg/kg/ day (HFCD+D1.5, HFCD+D7.5). Enzyme-linked immunosorbent assay was used to evaluate proinflammatory cytokine secretion. Western blot and quantitative polymerase chain reaction were used to analyze protein and mRNA levels of nuclear factor kappa B (NF-κB) p65, interleukin 6 (IL-6), cyclooxygenase 2 (COX-2), TLR2, TLR4, and MyD88 in spleen tissue. @*RESULTS@#Serum IL-6 levels were significantly higher in the HFCD group than in groups fed a HFCD with PEITC or DIM. Levels of NF-κB p65 protein and TLR2/4, MyD88, NF-κB p65, IL-6, and COX-2 mRNA were significantly higher in the HFCD group than in the CON group and were reduced by the PEITC and DIM supplements. @*CONCLUSIONS@#PEITC- and DIM-supplemented diets improved splenic inflammation by modulating the TLR2/4-MyD88 pathway in HFCD-fed mice. We suggest that dietary glucosinolates may at least partially improve obesity-induced inflammation of the spleen.

Hesperetin suppresses LPS/high glucose-induced inflammatory responses via TLR/MyD88/NF-κB signaling pathways in THP-1 cells

BACKGROUND/OBJECTIVES@#Unregulated inflammatory responses caused by hyperglycemia may induce diabetes complications. Hesperetin, a bioflavonoid, is a glycoside in citrus fruits and is known to have antioxidant and anticarcinogenic properties. However, the effect of inflammation on the diabetic environment has not been reported to date. In this study, we investigated the effect of hesperetin on proinflammatory cytokine secretion and its underlying mechanistic regulation in THP-1 macrophages with co-treatment LPS and hyperglycemic conditions.MATERIALS/METHODS: THP-1 cells differentiated by PMA (1 μM) were cultured for 48 h in the presence or absence of hesperetin under normoglycemic (5.5 mM/L glucose) or hyperglycemic (25 mM/L glucose) conditions and then treated with LPS (100 ng/mL) for 6 h before harvesting. Inflammation-related proteins and mRNA levels were evaluated by enzyme-linked immunosorbent assay, western blot, and quantitative polymerase chain reaction analyses. @*RESULTS@#Hesperetin (0–100 μM, 48 h) treatment did not affect cell viability. The tumor necrosis factor-α and interleukin-6 levels increased in cells co-treated with LPS under hyperglycemic conditions compared to normoglycemic conditions, and these increases were decreased by hesperetin treatment. The TLR2/4 and MyD88 activity levels increased in cells co-treated with LPS under hyperglycemic conditions compared to normoglycemic conditions; however, hesperetin treatment inhibited the TLR2/4 and MyD88 activity increases. In addition, nuclear factor-κB (NF-κB) and Acetyl-NF-κB levels increased in response to treatment with LPS under hyperglycemic conditions compared to normoglycemic conditions, but those levels were decreased when treated with hesperetin. SIRT3 and SIRT6 expressions were increased by hesperetin treatment. @*CONCLUSIONS@#Our results suggest that hesperetin may be a potential agent for suppressing inflammation in diabetes.

Hesperetin suppresses LPS/high glucose-induced inflammatory responses via TLR/MyD88/NF-κB signaling pathways in THP-1 cells

BACKGROUND/OBJECTIVES@#Unregulated inflammatory responses caused by hyperglycemia may induce diabetes complications. Hesperetin, a bioflavonoid, is a glycoside in citrus fruits and is known to have antioxidant and anticarcinogenic properties. However, the effect of inflammation on the diabetic environment has not been reported to date. In this study, we investigated the effect of hesperetin on proinflammatory cytokine secretion and its underlying mechanistic regulation in THP-1 macrophages with co-treatment LPS and hyperglycemic conditions.MATERIALS/METHODS: THP-1 cells differentiated by PMA (1 μM) were cultured for 48 h in the presence or absence of hesperetin under normoglycemic (5.5 mM/L glucose) or hyperglycemic (25 mM/L glucose) conditions and then treated with LPS (100 ng/mL) for 6 h before harvesting. Inflammation-related proteins and mRNA levels were evaluated by enzyme-linked immunosorbent assay, western blot, and quantitative polymerase chain reaction analyses. @*RESULTS@#Hesperetin (0–100 μM, 48 h) treatment did not affect cell viability. The tumor necrosis factor-α and interleukin-6 levels increased in cells co-treated with LPS under hyperglycemic conditions compared to normoglycemic conditions, and these increases were decreased by hesperetin treatment. The TLR2/4 and MyD88 activity levels increased in cells co-treated with LPS under hyperglycemic conditions compared to normoglycemic conditions; however, hesperetin treatment inhibited the TLR2/4 and MyD88 activity increases. In addition, nuclear factor-κB (NF-κB) and Acetyl-NF-κB levels increased in response to treatment with LPS under hyperglycemic conditions compared to normoglycemic conditions, but those levels were decreased when treated with hesperetin. SIRT3 and SIRT6 expressions were increased by hesperetin treatment. @*CONCLUSIONS@#Our results suggest that hesperetin may be a potential agent for suppressing inflammation in diabetes.

Involvement of Up-regulation of Death Receptors and Bim in Hispolon-mediated TNF-related Apoptosis-inducing Ligand Sensitization in Human Renal Carcinoma

BACKGROUND: Hispolon has been shown to possess antitumor effects in various cancer cells. However, the underlying mechanisms are not fully understood. In this study, we evaluated the sensitizing effect of hispolon on TNF-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis in human renal carcinoma cells. METHODS: Apoptosis was analyzed by using cell-based cytometer. The mRNA levels were assessed by reverse transcription-PCR. Bax activation was determined by oligomerization and fluorescence-activated cell sorting with Bax-NT monoclonal antibody. The protein expression was measured by Western blotting. RESULTS: Hispolon induced up-regulation of Bim and death receptors expression at the post-translational level. CONCLUSIONS: Hispolon enhanced TRAIL-mediated apoptosis in renal carcinoma cells, but not in normal cells.

Analysis of the association between health-related and work-related factors among workers and metabolic syndrome using data from the Korean National Health and Nutrition Examination Survey (2016)

BACKGROUND/OBJECTIVE: This study analyzed health-related factors for metabolic syndrome (Mets) among workers in South Korea. SUBJECTS/METHODS: This analysis included 4,666 adults aged 19–64 years to analyzed health-related risk factors for Mets from the Korean National Health and Nutrition Examination Survey (2016). The sociodemographic, working, health-related, and biochemical characteristics were presented as percentages (%) by chi-square tests. Multiple logistic regression analysis was performed to analyze the 95% confidence intervals (CIs) and associations between health-related factors characteristic of workers and the odds ratios of Mets. RESULTS: An increased prevalence of Mets was associated with male day workers compared to male shift workers (1.726-fold increase, 95% CI: 1.077–2.765), and with ≥ 8 hrs/day sleep duration compared to < 6 hrs/day sleep duration in female workers (2.133-fold, 95% CI: 1.041–4.368). In addition, reduced odds of high Mets were associated with male workers consumed of breakfast 5–7 times/wk compared to those consumed < 1 time/wk (0.593-fold decrease, 95% CI: 0.372–0.944). CONCLUSIONS: Health-related factors (sleep duration, frequency of breakfast) and working type in Korean workers may affect the prevalence of Mets.

Association between diets and mild cognitive impairment in adults aged 50 years or older

BACKGROUND/OBJECTIVE: As aging progresses, the number of patients with cognitive impairment also increases. Cognitive function is not generally correlated with diet, and there is debate over that association. Thus, the present study aimed to investigate the association between dietary intake and cognitive function among adults aged 50 years or older. SUBJECTS/METHODS: Between July 2017 and March 2018, 324 adults aged over 50 years from Gwangju Sun-Han hospital participated in a dietary survey. The frequency of food intake and related information were collected using a semi-quantitative food frequency questionnaire (SQ-FFQ) and determining the mini-mental state examination (MMSE) level for 276 participants. The association between dietary intake and cognitive function was assessed by performing logistic regression analysis. RESULTS: Depending on the MMSE score, the participants' age, education level, inhabitation status, medications, alcohol consumption, sleep duration, physical activity, and short geriatric depression scale score were significantly different (P < 0.05). Moreover, those participant characteristics were associated with either decreased or increased odds ratios (OR) for the risk of mild cognitive impairment (MCI). Based on analysis of the participants' intake of 112 detailed food items, which were categorized into 20 food types, intakes of cooked white rice (< 2 times/day compared with ≥3 times/day) (P < 0.05), properly cooked rice with other grains and legumes (P < 0.001), fruits (P < 0.05), milk (low fat and normal) (P = 0.044), liquid-type yogurt (P = 0.019), and curd-type yogurt (P = 0.015) were found to significantly decrease the OR for the risk of MCI. CONCLUSIONS: Associations were significant between the risk of MCI and the intake of certain food types. Specifically, a moderate intake of cooked white rice and an adequate intake of whole grains, fruits, milk, and dairy products were associated with reduced risks of MCI among adults aged over 50 years.

Luteolin and fisetin suppress oxidative stress by modulating sirtuins and forkhead box O3a expression under in vitro diabetic conditions

BACKGROUND/OBJECTIVE: Chronic hyperglycemia induces oxidative stress via accumulation of reactive oxygen species (ROS) and contributes to diabetic complications. Hyperglycemia induces mitochondrial superoxide anion production through the increased activity of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. This study aimed to determine whether fisetin and luteolin treatments suppress the oxidative stress by modulating the expression of sirtuins (SIRTs) and forkhead box O3a (FOXO3a) under hyperglycemic conditions in human monocytes. MATERIALS/METHODS: Human monocytic cells (THP-1) were cultured under osmotic control (14.5 mmol/L mannitol), normoglycemic (NG, 5.5 mmol/L glucose), or hyperglycemic (HG, 20 mmol/L glucose) conditions, in the absence or presence of fisetin and luteolin for 48 h. To determine the effect of fisetin and luteolin treatments on high glucose-induced oxidative stress, western blotting and intracellular staining were performed. RESULTS: Hyperglycemic conditions increased the ROS production, as compared to normoglycemic condition. However, fisetin and luteolin treatments inhibited ROS production under hyperglycemia. To obtain further insight into ROS production in hyperglycemic conditions, evaluation of p47phox expression revealed that fisetin and luteolin treatments inhibited p47phox expression under hyperglycemic conditions. Conversely, the expression levels of SIRT1, SIRT3, SIRT6, and FOXO3a were decreased under high glucose conditions compared to normal glucose conditions, but exposure to fisetin and luteolin induced the expression of SIRT1, SIRT3, SIRT6, and FOXO3a. The above findings suggest that fisetin and luteolin inhibited high glucose-induced ROS production in monocytes through the activation of SIRTs and FOXO3a. CONCLUSIONS: The results of our study supports current researches that state fisetin and luteolin as potential agents for the development of novel strategies for diabetes.

Association of Diabetes with Serum Vitamin D in Korean Adults : Analysis of the Korea National Health and Nutrition Examination Survey (2013~2014)

Insufficient vitamin D intake is a major health problem around the world. Recently, many studies have suggested that vitamin D intake may influence insulin resistance. However, little is known about the association between vitamin D and diabetes mellitus. The aim of this study was to investigate the association between serum 25-hydroxy vitamin D (25(OH)D) levels and diabetes mellitus in Korean adults. This study was a cross-sectional analysis of 3,686 participants of the Korean National Health and Nutrition Examination Survey (KNHANES) 2013~2014 aged 19 years and higher. The results showed that the mean serum 25-hydroxy vitamin D (25(OH)D) level in Korean adults was 16.77 ng/mL, and 74.2% of them had an insufficient serum 25-hydroxy vitamin D (25(OH)D) level (below 20 ng/mL). In normal and pre-diabetic groups, the serum 25-hydroxy vitamin D (25(OH)D) level significantly increased with age (P30 ng/mL), after adjusting for variables that may affect fasting blood glucose, but this result was not significant. In conclusion, although no significant association was observed between diabetes prevalence and vitamin D levels in this study, further studies are needed because the effect of vitamin D on diabetes remains controversial. This nutrient plays a crucial role in the body, and levels are insufficient in the Korean population.

Relationship between Diabetes Mellitus and Anemia in Korean Adults-Based on the Korean National Health and Nutritional Examination Survey VI

Anemia, defined as a reduction in the hemoglobin concentration of blood, is common in diabetes mellitus (DM) patients, can be potentially caused by diabetes complications such as nephropathy. Recent research suggests that diabetes mellitus (DM) itself may be a major risk factor of anemia. However, there are few Korean studies on the relationship between diabetes mellitus (DM) and anemia. This study was performed to investigate the association between anemia and diabetes mellitus (DM) in Korean adults. A total of 10,151 Korean adults over aged 19 years (4,422 male, 5,729 female) were selected from the participants of the Korean National Health and Nutrition Examination Survey VI (KNHANES VI). Korean adults with anemia had a higher prevalence of diabetes mellitus (DM) than the normal adults (11.4% vs. 30.4% in male, 8.8% vs. 9.4% in female). The unadjusted odds ratio (OR) for anemia was greater in adults with DM than in normal male (OR=3.28; 95% CI: 2.27~4.73). After adjusting for other risk factors including age, education, family income, smoking, drinking, and menstrual status, anemia and diabetes were not associated (OR=1.33; 95% CI: 0.84~2.09). Similarly, there was no association between anemia and diabetes in female. In conclusion, this study shows that the prevalence of anemia is similar in diabetic and non-diabetic Korean adults after adjusting for multiple risk factors. Further research is required to elucidate the mechanism of anemia caused as a consequence of diabetes mellitus (DM).

Critical Thinking, Self-Concept and Stress Adaptation of Transfer Nursing Students / 기본간호학회지

PURPOSE: The purpose of this study was to evaluate the effect of critical thinking and self-concept on stress adaptation in transfer nursing students. METHODS: For this study, data were collected from 196 transfer nursing students from Busan and South Gyeongsang Province Data collection was done during the period from September to December, 2015. Data were analyzed using descriptive statistics, t-test, one-way ANOVA, Pearson correlation coefficients and multiple regression. RESULTS: The results showed that for critical thinking gender (t=2.48, p=.014), age (F=2.90, p=.044) and club activities (t=2.05, p=.041) were significant. Stress adaptation was significant according to academic year (F=3.81, p=.025). Critical thinking, self-concept and stress adaptation had positive correlations. CONCLUSION: Findings indicate that college adjustment for transfer nursing students could be enhanced through the development of programs to promote critical thinking and self-concept in the nursing curriculum.

Retrospective Cohort Study on the Administration of Sedative for Delirium in Terminally Ill Cancer Patients and Survival Time / 한국호스피스완화의료학회지

PURPOSE: This study analyzed the difference in survival time of patients with delirium according to sedative medication. METHODS: From January 2012 through December 2013, a retrospective cohort study was performed using the electronic medical records (EMR) of Pusan National University Hospital. Among 900 patients who died from cancer, we selected 240 who suffered delirium based on the EMR. The Nu-DESC delirium screening test was used to diagnose delirium. RESULTS: The median length of delirium period was five days. Delirium characteristics were dominated by inappropriate behaviors (35.0%). Sedatives were administered in 72.1% of the cases. The most frequently used sedative was haloperidol which was used in 59.6% of cases. The delirium period significantly differed by patients' age (F=3.96, P=0.021), cancer type (F=3.31, P=0.010), chemotherapy (t=−3.44 P=0.001). The average survival time was 16.85 days for the sedative medication group and 9.37 days for the non-medication group, which, however, was not significant (t=1.766, P=0.079). CONCLUSION: In this study, the use of sedatives did not affect patients' survival time. Thus, appropriate sedative medication can be positively recommended to comfort terminal cancer patients and their families.

Suppression of β-catenin Signaling Pathway in Human Prostate Cancer PC3 Cells by Delphinidin

Delphinidin possesses strong anti-oxidant, anti-inflammatory, and anti-cancer properties. Suppression of the Wnt/β-catenin signaling pathway is a potential strategy for chemoprevention and therapy. As aberrant activation of the β-catenin signaling pathway contributes to prostate cancer progression, we evaluated the effect of delphinidin on this pathway in human PC3 prostate cancer cells. An MTT assay showed that treatment with delphinidin (15-180 μM, 72 hours) resulted in a dose-dependent growth inhibition of cells. Treatment with delphinidin increased the phosphorylation of serine or threonine residues on β-catenin and decreased the levels of cytoplasmic β-catenin. Moreover, treatment with delphinidin inhibited the nuclear translocation of β-catenin and the expression of β-catenin target genes such as cyclin D1, c-myc, Axin-2, and T cell factor-1. Delphinidin also induced the phosphorylation of glycogen synthase kinase 3β and the expression of adenomatous polyposis coli and Axin proteins. Our results indicate that inhibition of cell growth by delphinidin is mediated, at least in part, through modulation of the β-catenin signaling pathway. We suggest that delphinidin is a potent inhibitor of Wnt/β-catenin signaling in prostate cancer cells.

Perception of the Patient Safety Risk Factors and Safety Management by Nurses in Emergency Service, Hospitals / 기본간호학회지

PURPOSE: This was a descriptive research study to examine the patient safety risk factors and the level of safety management of nurses in emergency service, hospitals and to analyze the relationship between the two factors. METHOD: Data for analysis were collected from 232 nurses in emergency service, hospitals in Busan and Gyeongnam from July 30 to September 7, 2013. Data were analyzed using descriptive statistics, t-test, one-way ANOVA, and Pearson correlation coefficients. RESULTS: Therapeutic agents showed the highest risk level. The prevention of transfusion errors showed the highest performance. As the nurses were working in regional emergency medical centers and received education more than 7 sessions on patient safety, they readily recognized the riskiness of the safety risk factors. In addition, as the nurses were older than 40, married, having more education about safety and understood the incident report registration system well, they performed safety management better. There were significant correlations between perception of the patient safety risk factors and performance for safety management. CONCLUSION: Nurses in emergency service, hospitals should try to improve safety management to reduce the risk factors shown to be higher based on the results and ensure the patient safety.