Neuroprotective effects of hesperetin on H2O2-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 (H2O2)-treated SH-SY5Y cells. MATERIALS/METHODS: SH-SY5Y cells were treated with H2O2 (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 H2O2-treated SH-SY5Y cells (P < 0.05). Furthermore, hesperetin inhibited H2O2-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 NF-κB translocation into H2O2-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 H2O2-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.

Neuroprotective Effects of Zerumbone on H2O2-Induced Oxidative Injury in Human Neuroblastoma SH-SY5Y Cells.

Oxidative stress is recognized as one of the main reasons for cellular damage and neurodegenerative diseases. Zerumbone is one of the sesquiterpenoid compounds in the essential oil of Zingiber zerumbet Smith. Zerumbone exhibits various physiological activities, such as anticancer, antioxidant, and antibacterial effects. However, studies on the neuroprotective efficacy of zerumbone and the mechanism behind it are lacking. In this study, we explored the neuroprotective efficacy of zerumbone and its mechanism in hydrogen peroxide-treated human neuroblastoma SH-SY5Y cells. H2O2 treatment (400 µM) for 24 h enhanced the generation of intracellular reactive oxygen species (ROS) compared to untreated cells. By contrast, zerumbone treatment significantly suppressed the production of intracellular ROS. Zerumbone significantly inhibited H2O2-induced nitric oxide production and expression of inflammation-related genes. Moreover, zerumbone decreased H2O2-induced mitogen-activated protein kinase (MAPK) protein expression. Various hallmarks of apoptosis in H2O2-treated cells were suppressed in a dose-dependent manner through downregulation of the Bax/Bcl-2 expression ratio by zerumbone. Since activation of AMP-activated kinase (AMPK) is a promising therapeutic target for neurodegenerative diseases, we also investigated the mammalian target of rapamycin (mTOR) as part of the autophagy mechanism in H2O2-treated SH-SY5Y cells. In this study, zerumbone upregulated the expression of Sirtuin 1 (SIRT1) and p-AMPK (which were downregulated by the H2O2 treatment) and downregulated p-mTOR. Altogether, our results propose that inhibition of apoptosis and inflammation by autophagy activation plays an important neuroprotective role in H2O2-treated SH-SY5Y cells. Zerumbone may thus be a potent dietary agent that reduces the onset and progression, as well as prevents neurodegenerative diseases.

Prevalence and clinical characteristics of low skeletal muscle index among adults visiting a health promotion center: Cross-sectional study.

Sarcopenia causes a variety of functional impairments and is associated with all-cause mortality, but once it occurs, it is difficult to treat and reverse. However, the prevalence of sarcopenia in healthy people has never been investigated due to the low awareness of sarcopenia in healthy people. This cross-sectional study was conducted in a single health promotion center from the January 1st 2020 to the December 31st 2021. Adults aged 18 years and older with an Inbody as part of their health checkup were included, and all data was collected from the EMR. Obesity was defined as a body mass index (BMI) of 23 (kg/m2) or more by Korean standards, and low skeletal muscle mass was defined as a skeletal muscle index (SMI) of <0.789 for men and <0.512 for women. 60.5% of the total participants (n = 5993) had low skeletal muscle mass. The low SMI group had lower BMI, waist circumference, and abdominal skinfold than the normal SMI group (low SMI group vs normal SMI: BMI; 25.47 ±â€…2.96 vs 22.98 ±â€…3.05, P < .001, waist circumference; 90.31 ±â€…8.80 cm vs 82.69 ±â€…9.71 cm, P < .001, abdominal skinfold; 18.78 ±â€…2.44 mm vs 15.99 ±â€…2.12 mm, P < .001). The body fat percentage was higher in the low SMI group than in the normal SMI group 25.30 ±â€…6.23% versus 29.82 ±â€…7.07%, P < .001. Triglyceride and uric acid levels were low in the low SMI group (TG; 147.69 ±â€…97.27 vs 115.86 ±â€…68.31, P < .001, uric acid level; 6.30 ±â€…1.38 vs 5.23 ±â€…1.30, P < .001) and high-density lipid (HDL) was high (HDL; 53.17 ±â€…11.41 vs 59.89 ±â€…14.72, P < .001). The odds ratio of low SMI prevalence for age, sex, BMI, fat body percent, and triglycerides relative to normal SMI was 1.05 (P = .031), 0.14 (P < .001), 0.12 (P < .001), 2.05 (P < .001), and 0.99 (P = .003), respectively. Of those who visited the Health Promotion Center, more than 60% had low SMI identified through Inbody. Low BMI and high body fat percentage increase the risk of low SMI. Compared to normal and low SMI based on obesity, Sex, height, BW, abdominal skinfold, and waist circumflex showed significant P values in both groups. The factors related to low SMI were TG, HDL, and uric acid levels.

Effectiveness of SBAR-based simulation programs for nursing students: a systematic review.

BACKGROUND: Situation, background, assessment, and recommendation (SBAR) has been extensively used in clinical and nursing education. A structured communication program increases effective communication, positivity, and education satisfaction during inter-professional collaboration among nursing students. This systematic review aimed to identify and synthesize evidence on the effectiveness of SBAR-based simulation training for nursing students. METHODS: A research protocol was developed according to the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guidelines. The protocol for this study was registered in PROSPERO (CRD42021234068). Eight bibliographical databases were searched for studies published between 2001 and 2021, using relevant search terms. Searches were conducted in PubMed, Embase, Cumulative Index to Nursing and Allied Health, and Cochrane Central Register of Controlled Trials for literature in English, and DBpia, Research Information Sharing Service, Korean Studies Information Service System, and Korea Institute of Science and Technology Information for literature in Korean. After screening titles, abstracts, and full-text papers, pertinent data were extracted, and critical appraisals of the retrieved studies were performed. Data were analyzed using the framework approach, and the findings were presented in a narrative summary. The Effective Public Health Practice Project "Quality Assessment Tool for Quantitative Studies" was used to assess the quality of the included studies. RESULTS: Twelve studies were included: 3 randomized controlled trials and 9 quasi-experimental studies. Two overarching themes were noted, namely communication clarity and critical thinking. The results of six out of 12 studies produced significant results in favor of SBAR-based simulation in terms of communication clarity. Divergent results were obtained regarding communication ability, critical thinking, confidence, learning self-efficacy, and attitude toward patient safety. The results of these studies highlight that communication clarity ultimately leads to positive results in terms of nursing students' behaviors related to patient safety. CONCLUSIONS: This review provides a comprehensive update of the literature on the effectiveness of SBAR-based nursing simulation programs for nursing students. These programs were found to have positive learning outcomes because of clear and concise communication. Further studies on the effectiveness of various learning outcomes derived from SBAR-based programs are required.

Comparison of Sleep Disturbance, Physical Activity, and Health-Related Quality of Life According to Depressive Symptoms in Patients with Metabolic Syndrome: A Secondary Analysis from the Korea National Health and Nutrition Examination Survey Using a Propensity Score Matching Analysis.

Metabolic syndrome has become a global epidemic, and the age of its onset is decreasing. However, its prevalence can be reduced by lifestyle modifications. This study examined the differences in sleep disturbance, physical activity, and health-related quality of life associated with depressive symptoms in patients with metabolic syndrome aged ≥ 40 years. This cross-sectional secondary analysis of data from the 2016 and 2018 Korean National Health and Nutrition Examination Surveys. Of 1404 patients with metabolic syndrome aged ≥ 40 years, depressed and non-depressed patients (103 vs. 103) were matched 1:1 on demographic characteristics using propensity score matching. The outcome variables were then compared between the two groups. We investigated health status, including metabolic syndrome indices, health behaviors, such as sleep disturbances and physical activity, and health-related quality of life. After propensity score matching, health-related quality of life was the only variable that differed significantly between the groups; it was significantly lower in patients with depression (0.77) than in those without depression (0.88) (p = 0.001). Our results suggest that depression with metabolic syndrome is likely to cause a decrease in patients' quality of life; therefore, development of management systems and programs for early intervention to tackle at-risk groups is necessary.

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

BACKGROUND/OBJECTIVES: Hyperglycemia is a major cause of diabetes and diabetes-related 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.

Dysregulated Sulfide Metabolism in Multiple Sclerosis: Serum and Vascular Endothelial Inflammatory Responses.

Multiple sclerosis (MS) is a leading cause of neurodegenerative disability in younger individuals. When diagnosed early, MS can be managed more effectively, stabilizing clinical symptoms and delaying disease progression. The identification of specific serum biomarkers for early-stage MS could facilitate more successful treatment of this condition. Because MS is an inflammatory disease, we assessed changes in enzymes of the endothelial hydrogen sulfide (H2S) pathway in response to inflammatory cytokines. Blotting analysis was conducted to detect Cystathionine γ-lyase (CSE), Cystathionine beta synthase (CBS), and 3-mercaptopyruvate sulfurtransferase (MST) in human brain microvascular endothelial apical and basolateral microparticles (MPs) and cells following exposure to tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ). CSE was increased in MPs and cells by exposure to TNF-α/IFN-γ; CBS was elevated in apical MPs but not in cells or basolateral MPs; MST was not significantly affected by cytokine exposure. To test how our findings relate to MS patients, we evaluated levels of CSE, CBS, and MST in serum samples from healthy control and MS patients. We found significantly decreased levels of CBS and MST (p = 0.0004, 0.009) in MS serum samples, whereas serum levels of CSE were marginally increased (p = 0.06). These observations support increased CSE and lower CBS and MST expression being associated with the vascular inflammation in MS. These changes in endothelial-derived sulfide enzymes at sites of inflammation in the brain may help to explain sulfide-dependent changes in vascular dysfunction/neuroinflammation underlying MS. These findings further support the use of serum samples to assess enzymatic biomarkers derived from circulating MPs. For example, "liquid biopsy" can be an important tool for allowing early diagnosis of MS, prior to the advanced progression of neurodegeneration associated with this disease.

A comparison of health-related quality of life and personal, social, and environmental factors of older adults according to a residential area: a propensity score matching analysis.

PURPOSE: This study identified individual, social, and environmental factors affecting the health-related quality of life (HRQoL) of older individuals living in urban and non-urban areas of the Republic of Korea and investigated their effects on HRQoL. METHODS: A secondary data analysis study was conducted using raw data from Korea's 2017 Community Health Survey. Propensity score matching (PSM) was performed to compare the individual, social, and environmental characteristics of older individuals living in urban and non-urban areas (16,695 and 29,106 individuals, respectively). Statistical analyses were performed using R program 4.0.5. The differences between variables were analyzed using chi-squared and t-tests, whereas factors influencing HRQoL were analyzed using multiple regression analysis. RESULTS: Among the individual factors, the living arrangement (p = 0.001, confidence interval [CI] = 0.00-0.02) was an influencing factor in urban areas, whereas it showed no statistical significance in non-urban areas. Moreover, Helping their neighbors (p = 0.001, CI = 0.00-0.01) among the social factors and satisfaction with the living environment (p = 0.011, CI = 0.00-0.02) and with healthcare services (p = 0.047, CI = 0.00-0.01) among the environmental factors were influencing factors in urban areas, whereas they showed no statistical significance in non-urban areas. CONCLUSION: Satisfaction with the living environment and with healthcare services was positively associated with HRQoL among older individuals living in urban areas. Therefore, factors associated with regional health inequality should be identified, and health equality sought through the development of local government policies that consider diversity in population composition and health indicators by region.

Zerumbone suppresses high glucose and LPS-induced inflammation in THP-1-derived macrophages by inhibiting the NF-κB/TLR signaling pathway.

Diabetes mellitus is characterized by hyperglycemia. Low-grade bacterial infection with hyperglycemia in patients with diabetes is associated with atherosclerosis development. Therefore, this study hypothesized that macrophages lead to more severe diabetic complications under combined conditions of high glucose and lipopolysaccharide (LPS)-induced inflammation than under normoglycemic conditions. Zerumbone is the main component of Zingiber zerumbet Smith essential oil, a type of wild ginger. It possesses various biomedical activities, including antibacterial, antioxidant, anti-inflammatory, and anticancer activities; however, the precise mechanism of its anti-inflammatory and epigenetic effects is not fully understood. In this study, the effects of zerumbone on the secretion of proinflammatory cytokines and its underlying regulatory mechanism were investigated in THP-1-derived macrophages exposed to high glucose and LPS. THP-1-derived macrophages were cultured under normoglycemic (5.5 mmol/L glucose) or hyperglycemic (25 mmol/L glucose) conditions in the absence or presence of zerumbone (5-50 µM) for 48 hours and then treated with 100 ng/mL LPS for 6 hours. Zerumbone (25 and 50 µM) suppressed the production of tumor necrosis factor-α and interleukin-6 and the activation of cyclooxygenase-2, nuclear factor-κB, histone deacetylases 3 proteins, and Toll-like receptor messenger RNA (mRNA) and increased the transcription of the sirtuin 1 (SIRT1), SIRT3, and SIRT6 mRNAs. Taken together, our results suggest that zerumbone may exert beneficial effects on diabetes and its 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 anti-inflammatory 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 pro-inflammatory 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.

Neck Circumference as a Predictor of Metabolic Syndrome in Koreans: A Cross-Sectional Study.

Metabolic syndrome (MetS) is a complex metabolic disorder and a high-risk condition for type 2 diabetes and cardiovascular disease. Rapid screening of at-risk individuals using accurate and time-saving tools is effective in disease management. Using the Korea National Health and Nutrition Examination Survey (KNHANES) data, we collected data from 2234 participants suitable for the study design, of which 974 (43.6%) were men and 1260 (56.4%) were women. We used receiver operating characteristic (ROC) curve analysis to estimate the optimal sex-specific neck circumference (NC) cut-off point to predict the MetS risk. To analyze the risk of MetS according to the estimated NC, logistic regression analysis was performed to identify the confounding factors. The result of the ROC analysis showed that the optimal neck cut-off points for predicting the risk of MetS were 38.25 cm (AUC: 0.759, 95% CI: 0.729-0.790) in men and 33.65 cm (AUC: 0.811, 95% CI: 0.782-0.840) in women. In the upper NC cut-off point compared to the lower NC cut-off point, NC was associated with an increased MetS risk by 2.014-fold (p = 0.010) in men and 3.650-fold (p < 0.001) in women, after adjustments. The current study supports NC as an effective anthropometric indicator for predicting the risk of MetS. It is suggested that more studies should be conducted to analyze the disease prediction effect of the combined application of anthropometric indicators currently in use and NC.

Stress- and Work-Related Burnout in Frontline Health-Care Professionals During the COVID-19 Pandemic.

OBJECTIVE: The coronavirus disease 2019 (COVID-19) pandemic is affecting humankind in unprecedented and monumental ways. Health-care professionals (HCPs) have had to deal with traumatic and complex situations at work. However, the current understanding of the emotional effects on HCPs and their vulnerability during the pandemic is limited. We investigated the effects of HCPs' viral epidemic-related stress, professional quality of life (ProQOL), depression, and anxiety on their health-related quality of life (HRQOL). METHODS: We recruited a convenience sample of 60 HCPs at 2 tertiary hospitals in provinces P and Y, Republic of Korea. We analyzed their demographics, viral epidemic-related distress, ProQOL (compassion satisfaction, burnout, and secondary traumatic stress), depression, anxiety, and HRQOL through self-reported questionnaires. RESULTS: Burnout had a significant direct effect on depression, anxiety, physical health, and psychological HRQOL and indirectly affected all subcategories of HRQOL. Viral epidemic-related stress had no significant direct effect on any variable, but indirectly affected all subcategories of HRQOL. Depression and anxiety were endogenous variables (mediators). Depression was a pathway that directly and significantly affected all subcategories of HRQOL. Burnout had the most significant effect on physical health and psychological HRQOL, whereas depression had the greatest effect on social relationships and environmental HRQOL. CONCLUSIONS: Low compassion satisfaction caused burnout in HCPs, and burnout was significantly associated with depression, anxiety, and HRQOL. Furthermore, HRQOL showed a greater response when affected by indirect burnout through depression and anxiety than when directly affected by burnout.

Dietary Patterns and Mild Cognitive Impairment Risk in Korean Adults over 50 Years Old.

The prevalence of age-related diseases such as dementia and cognitive disorders is rapidly increasing. This study aimed to identify the dietary patterns associated with mild cognitive impairment (MCI) in adults aged over 50 years. This cross-sectional study investigated dietary patterns associated with cognitive function among older adults hospitalized in Gwangju province. Global cognitive function was assessed using the Mini-Mental State Examination. Diet information was obtained using a food frequency questionnaire with 112 food items and 24-h dietary recall. Using a principal component analysis, we identified three dietary patterns, "legumes and vegetables", "beverage and nuts", and "white rice". The "beverage and nuts" pattern was inversely associated with the prevalence of high MCI after adjusting for covariates (third vs. first tertile, adjusted odds ratio: 0.333; 95% confidence interval: 0.133∼0.831; P<0.05). The white rice pattern was associated with the prevalence of MCI in the crude analysis. However, after adjusting for all confounding factors, no association was found. The "beverage and nuts" pattern was inversely associated with the prevalence of MCI. In the future, longitudinal population-based studies and randomized clinical trials are required to confirm the effect of potential dietary patterns on cognitive impairment and reveal the underlying mechanism of their association.

Phenethyl Isothiocyanate Improves Lipid Metabolism and Inflammation via mTOR/PPARγ/AMPK Signaling in the Adipose Tissue of Obese Mice.

Obesity is defined as excess adipose mass that causes serious health problems. Phenethyl isothiocyanate (PEITC) is a major and relatively nontoxic compound of the isothiocyanates. Although many studies have demonstrated that PEITC is a potent substance with physiological activities, such as anticancer activity, the precise mechanism for the effects of PEITC on inflammation and lipid metabolism in adipose tissue is not clear. Our study aimed to clarify the effects of PEITC supplements on the adipose tissue in obesity induced with a high-fat/cholesterol diet, and the underlying mechanisms. We induced obesity by feeding the mice with high fat with 1% cholesterol diet (HFCD) for 13 weeks. Mice were divided into five groups: normal diet (CON), HFCD, HFCD with 3 mg/(kg·d) gallic acid (HFCD+G), and HFCD with 30 and 75 mg/(kg·d) PEITC (HFCD+P30 and HFCD+P75, respectively). Using western blotting and quantitative polymerase chain reaction (qPCR) analysis of the adipose tissue, we determined the expression of lipid metabolism-related genes and inflammation-related genes. In the HFCD, the expression level of nuclear factor-κB (NF-κB), lectin-like oxidized low-density lipoprotein receptor 1 (LOX-1), and cyclooxygenase-2 (COX-2), was higher compared with that in the CON. Moreover, in the HFCD, the expression of p-mechanical targets of the rapamycin (mTOR) was increased, whereas that of p-AMP-activated protein kinase (AMPK) was decreased compared with that in the CON. Nevertheless, these decreased expression levels of p-AMPK and increased levels of LOX-1, p-mTOR, peroxisome proliferator-activated receptor gamma (PPARγ), NF-κB, and COX-2, were alleviated by PEITC supplementation. Therefore, we suggest that PEITC might be a potential preventive agent for ameliorating obesity-induced inflammation and adipogenesis by modulating the mTOR/AMPK/PPARγ pathway.

Human placenta mesenchymal stem cell protection in ischemic stroke is angiotensin converting enzyme-2 and masR receptor-dependent.

Thromboembolic stroke remains a major cause of neurological disability and death. Current stroke treatments (aspirin, tissue plasminogen activator) are significantly limited by timing and risks for hemorrhage which have driven researchers to explore other approaches. Stem cell-based therapy appears to be an effective option for ischemic stroke. Besides trans-differentiation into neural cells, stem cells also provide acute protection via paracrine signaling pathways through which releasing neuroprotective factors. We previously reported that intraperitoneal administration of human placenta mesenchymal stem cell (hPMSC) therapy upon reperfusion significantly protected the brain against middle cerebral artery occlusion (MCAO)-induced injury. In the present study, we specifically investigated the role of hPMSC-derived angiotensin converting enzyme-2 (ACE-2) in protection of MCAO-induced brain injury by measurement of brain tissue viability, cerebral blood flow, and neurological score. Here, we report for the first time that hPMSC expressing substantial amount of ACE-2, which mediates hPMSC protection in the MCAO model. Strikingly, we found that the protective effects of hPMSC in MCAO-induced brain injury could be attenuated by pretreatment of hPMSCs with MLN-4760, a specific inhibitor of ACE-2 activity, or by transfection of hPMSCs with ACE-2-shRNA-lentivirus. The hPMSC-derived ACE-2 specific protective mechanism was further demonstrated by administration of PD123319, an Angiotensin type-2 receptor antagonist, or A779, a MasR antagonist. Importantly, our study demonstrated that the protective effects of hPMSC in experimental stroke are ACE-2/MasR dependent and this signaling pathway represents an innovative and highly promising approach for targeted stroke therapy.

Protective effects of phenethyl isothiocyanate on foam cell formation by combined treatment of oxidized low-density lipoprotein and lipopolysaccharide in THP-1 macrophage.

Accumulation of cholesterol-laden macrophage foam cells characteristic of early stage atherosclerotic lesions. Phenethyl isothiocyanate (PEITC) is a naturally occurring isothiocyanate found in cruciferous vegetables that has reported a variety of activities including antioxidant and anti-inflammatory properties. However, the protective effect of PEITC on foam cell formation and its precise mechanism is not yet clear. Therefore, we investigated whether PEITC suppresses foam cell formation and regulates the expression of genes related to lipid accumulation, cholesterol efflux, and inflammation in THP-1 derived-macrophages. We exposed THP-1 derived-macrophages to oxidized low-density lipoprotein (ox-LDL) (20 µg/mL) and lipopolysaccharide (LPS) (500 ng/ml) to mimic foam cell formation. Here, PEITC downregulated the expression of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), cluster of differentiation 36 (CD36), scavenger receptor A1 (SR-A1), and nuclear factor-κB (NF-κB), while upregulated ATP binding cassette subfamily A member 1 (ABCA1)/liver-X-receptor α (LXR-α)/peroxisome proliferator-activated receptor gamma (PPARγ) and sirtuin 1 (SIRT1) expression compared to co-treated with ox-LDL and LPS. Taken together, PEITC, at least in part, inhibits foam cell formation and reduces lipid accumulation in foam cells. Therefore, we suggest that PEITC may be a potential candidate for the treatment and prevention of vascular inflammation and atherosclerosis.

Phenethyl Isothiocyanate Protects against High Fat/Cholesterol Diet-Induced Obesity and Atherosclerosis in C57BL/6 Mice.

This study concerns obesity-related atherosclerosis, hyperlipidemia, and chronic inflammation. We studied the anti-obesity and anti-atherosclerosis effects of phenethyl isothiocyanate (PEITC) and explored their underlying mechanisms. We established an animal model of high fat/cholesterol-induced obesity in C57BL/6 mice fed for 13 weeks. We divided the mice into five groups: control (CON), high fat/cholesterol (HFCD), HFCD with 3 mg/kg/day gallic acid (HFCD + G), and HFCD with PEITC (30 and 75 mg/kg/day; HFCD + P30 and P75). The body weight, total cholesterol, and triglyceride were significantly lower in the HFCD + P75 group than in the HFCD group. Hepatic lipid accumulation and atherosclerotic plaque formation in the aorta were significantly lower in both HFCD + PEITC groups than in the HFCD group, as revealed by hematoxylin and eosin (H&E) staining. To elucidate the mechanism, we identified the expression of genes related to inflammation, reverse cholesterol transport, and lipid accumulation pathway in the liver. The expression levels of peroxisome proliferator activated receptor gamma (PPARγ), liver-X-receptor α (LXR-α), and ATP binding cassette subfamily A member 1 (ABCA1) were increased, while those of scavenger receptor A (SR-A1), cluster of differentiation 36 (CD36), and nuclear factor-kappa B (NF-κB) were decreased in the HFCD + P75 group compared with those in the HFCD group. Moreover, PEITC modulated H3K9 and H3K27 acetylation, H3K4 dimethylation, and H3K27 di-/trimethylation in the HFCD + P75 group. We, therefore, suggest that supplementation with PEITC may be a potential candidate for the treatment and prevention of atherosclerosis and obesity.

Effects of healthcare interventions on psychosocial factors of patients with multimorbidity: A systematic review and meta-analysis.

PURPOSE: A systematic review and meta-analysis was conducted to assess the types of healthcare intervention programs offered to patients with multimorbidity and their effects on key psychosocial factors. METHODS: For this systematic review and meta-analysis, we searched databases like Cochrane Library, PubMed, Embase, CINAHL RISS, KISS, etc. for studies published between January 1, 2009, and April 30, 2019. In total, 8,248 studies in English or Korean were reviewed. We included only randomized controlled trials or quasi-experimental studies that applied healthcare interventions and had major effects on the psychosocial factors in adult patients with multimorbidity. Methodological quality was assessed using Cochrane collaboration risk of bias tool. Meta-analysis was performed using the Review Manager 5.3 version to estimate the effect size. RESULTS: We identified six randomized controlled trials and 1446 subjects were enrolled. The results reveal that healthcare interventions have an effect on self-rated health (SMD = 0.53 95 % CI: 0.26, 0.79, p < .001), reducing anxiety (SMD = -0.19 95 % CI: -0.36, -0.01, p = .030) and depression (SMD = -0.27 95 % CI: -0.44, -0.10, p = .002), and improving self-efficacy (SMD = 0.21 95 % CI: 0.06, 0.35, p = .005) for patients with multimorbidity. However, there was no significant effect on quality of life. CONCLUSION: Healthcare interventions had significant positive effects on self-rated health, anxiety, depression, and self-efficacy of patients with multimorbidity. These results are expected to serve as basic data for the development of a community-based integrated healthcare intervention program and health policy, especially for the vulnerable older population with multimorbidity.

MeCP2 regulates gene expression through recognition of H3K27me3.

MeCP2 plays a multifaceted role in gene expression regulation and chromatin organization. Interaction between MeCP2 and methylated DNA in the regulation of gene expression is well established. However, the widespread distribution of MeCP2 suggests it has additional interactions with chromatin. Here we demonstrate, by both biochemical and genomic analyses, that MeCP2 directly interacts with nucleosomes and its genomic distribution correlates with that of H3K27me3. In particular, the methyl-CpG-binding domain of MeCP2 shows preferential interactions with H3K27me3. We further observe that the impact of MeCP2 on transcriptional changes correlates with histone post-translational modification patterns. Our findings indicate that MeCP2 interacts with genomic loci via binding to DNA as well as histones, and that interaction between MeCP2 and histone proteins plays a key role in gene expression regulation.