Protective Role of Ethanol Extract of Cibotium barometz (Cibotium Rhizome) against Dexamethasone-Induced Muscle Atrophy in C2C12 Myotubes.

Sarcopenia is a progressive muscle disease characterized by the loss of skeletal muscle mass, strength, function, and physical performance. Since the disease code was assigned, attention has been focused on natural products that can protect against muscle atrophy. Cibotium barometz (Cibotium Rhizome) has been used as an herbal medicine for the treatment of bone or joint diseases in Asian countries. However, no studies have identified the mechanism of action of Cibotium Rhizome on muscle atrophy related to sarcopenia at the site of myotubes. The aim of this study was to investigate the improvement effect of the ethanol extract of Cibotium Rhizome (ECR) on dexamethasone-induced muscle atrophy in an in vitro cell model, i.e., the C2C12 myotubes. High-performance liquid chromatography was performed to examine the phytochemicals in ECR. Seven peaks in the ECR were identified, corresponding to the following compounds: protocatechuic acid, (+)-catechin hydrate, p-coumaric acid, ellagic acid, chlorogenic acid, caffeic acid, and ferulic acid. In atrophy-like conditions induced by 100 µM dexamethasone for 24 h in C2C12, ECR increased the expression of the myosin heavy chain, p-Akt, the p-mammalian target of rapamycin (mTOR), p-p70S6K, and repressed the expression of regulated in development and DNA damage responses 1 (REDD1), kruppel-like factor 15 (KLF 15), muscle atrophy F-box, and muscle-specific RING finger protein-1 in C2C12. In addition, ECR alleviated dexamethasone-induced muscle atrophy by repressing REDD1 and KLF15 transcription in C2C12 myotubes, indicating the need for further studies to provide a scientific basis for the development of useful therapeutic agents using ECR to alleviate the effects of skeletal muscle atrophy or sarcopenia.

Recent Trends in Controlling the Enzymatic Browning of Fruit and Vegetable Products.

Enzymatic browning because of polyphenol oxidases (PPOs) contributes to the color quality of fruit and vegetable (FV) products. Physical and chemical methods have been developed to inhibit the activity of PPOs, and several synthetic chemical compounds are commonly being used as PPO inhibitors in FV products. Recently, there has been an emphasis on consumer-oriented innovations in the food industry. Consumers tend to urge the use of natural and environment-friendly PPO inhibitors. The purpose of this review is to summarize the mechanisms underlying the anti-browning action of chemical PPO inhibitors and current trends in the research on these inhibitors. Based on their mechanisms of action, chemical inhibitors can be categorized as antioxidants, reducing agents, chelating agents, acidulants, and/or mixed-type PPO inhibitors. Here, we focused on the food ingredients, dietary components, food by-products, and waste associated with anti-browning activity.

Natural Products and Obesity: A Focus on the Regulation of Mitotic Clonal Expansion during Adipogenesis.

Obesity is recognized as a worldwide health crisis. Obesity and its associated health complications such as diabetes, dyslipidemia, hypertension, and cardiovascular diseases impose a big social and economic burden. In an effort to identify safe, efficient, and long-term effective methods to treat obesity, various natural products with potential for inhibiting adipogenesis were revealed. This review aimed to discuss the molecular mechanisms underlying adipogenesis and the inhibitory effects of various phytochemicals, including those from natural sources, on the early stage of adipogenesis. We discuss key steps (proliferation and cell cycle) and their regulators (cell-cycle regulator, transcription factors, and intracellular signaling pathways) at the early stage of adipocyte differentiation as the mechanisms responsible for obesity.

Selenate Prevents Adipogenesis through Induction of Selenoprotein S and Attenuation of Endoplasmic Reticulum Stress.

The conversion of preadipocytes to adipocytes (adipogenesis) is a potential target to treat or prevent obesity. Selenate, an inorganic form of selenium, elicits diverse health benefits, mainly through its incorporation into selenoproteins. The individual roles of selenium and certain selenoproteins have been reported. However, the effects of selenate treatment on selenoproteins in adipocytes are unclear. In this study, the effects of selenate pretreatment on selenoprotein and endoplasmic reticulum (ER) stress during adipogenesis were examined in vitro. The selenate pretreatment dose-dependently suppressed the adipogenesis of 3T3-L1 preadipocytes. The selenate pretreatment at 50 µM for 24 h almost completely suppressed adipogenesis without cytotoxic effects. The expression of the adipogenic genes peroxisome proliferator-activated receptor gamma, CCAAT-enhancer binding protein alpha, and leptin was suppressed by selenate. This pretreatment also upregulated selenoprotein S (SEPS1), an ER resident selenoprotein that reduces ER stress, and prevented dexamethasone-induced SEPS1 degradation during the early stage of adipogenesis. The selenate-inhibited adipogenesis was associated with an attenuation of ER stress. The expression of the ER stress marker genes was upregulated during the early stage of differentiation, whereas the selenate pretreatment suppressed the mRNA expression of the XBP1 and C/EBP homologous protein. The collective data suggest a preventive role of selenate and SEPS1 in adipogenesis, and support a novel dietary approach to prevent obesity.

Quantitative metabolic parameters measured on F-18 FDG PET/CT predict survival after relapse in patients with relapsed epithelial ovarian cancer.

OBJECTIVE: This study aimed to evaluate the prognostic value of quantitative metabolic parameters measured on F-18 FDG PET/CT (FDG PET/CT) at the time of the first relapse in patients with relapsed epithelial ovarian cancer (EOC). METHODS: Fifty-six relapsed EOC patients were retrospectively included. Quantitative metabolic parameters including maximum standardized uptake value (SUVmax), whole-body metabolic tumor volume (WBMTV), and whole-body total lesion glycolysis (WBTLG) were measured on FDG PET/CT at the time of the first relapse. Post-relapse survival (PRS) was calculated from the date of diagnosis of relapsed disease to the date of death or last follow-up. Univariate and multivariate analyses for PRS were performed using clinical and quantitative metabolic parameters. RESULTS: Thirty-two patients died from the disease during the follow-up period (median: 46.2 months). On univariate and multivariate analyses, the platinum-free interval, type of second-line treatment, WBMTV, and WBTLG were all significant prognostic factors for PRS. The subgroup of patients who were platinum-sensitive with low WBMTV and low WBTLG showed better prognosis, when compared with other subgroups (log-rank test, p<0.001). Patients treated with secondary cytoreductive surgery (SCS) followed by second-line chemotherapy showed significantly longer duration of PRS than patients treated with second-line chemotherapy only (mean PRS=61 vs. 36 months, χ(2)=8.68, p=0.032). CONCLUSION: Our results suggest that quantitative metabolic parameters measured on FDG PET/CT at the time of the first relapse have significant predictive values for PRS. Incorporating quantitative metabolic parameters and conventional clinical parameters has a superior prognostic discrimination compared with conventional clinical parameters alone.

Prediction for recurrence using F-18 FDG PET/CT in pathologic N0 lung adenocarcinoma after curative surgery.

BACKGROUND: The aim of this study was to investigate risk factors for recurrence in patients with lung adenocarcinoma (LAD) who were pathologically N0 (pN0) after curative surgical resection. METHODS: A total of 102 LAD patients (M/F = 55/47, mean age, 62.6 ± 9.4 years) diagnosed as pN0 after curative surgery were included in this study. Clinical, biochemical, radiologic, and pathologic findings were reviewed and analyzed for recurrence. Metabolic parameters [SUVmax, metabolic tumor volume (MTV), total lesion glycolysis (TLG)] on pretreatment F-18 FDG PET/CT were also obtained and analyzed for recurrence. RESULTS: Of 102 patients, 38 (37.3%) were found to experience recurrence for 33.6 ± 16.3 months. SUVmax, MTV, and TLG were significantly higher in patients with recurrence. The optimal cutoff values determined using a receiver-operating characteristic curve were 6.90 for SUVmax, 10.78 cm(3) for MTV, and 39.68 for TLG. Univariate analysis showed that tumor size, tumor marker, SUVmax, MTV, and TLG were prognostic factors for recurrence. In multivariate analyses, after adjusting for age, sex, tumor size, pathologic T stage, and tumor marker, high SUVmax, MTV, and TLG showed an association with an increased risk of recurrence. CONCLUSIONS: Metabolic parameters on pretreatment F-18 FDG PET/CT can predict recurrence in pN0 LAD patients who underwent curative surgery. Therefore, patients with high metabolic parameters on PET can be considered as candidates for adjuvant therapy to reduce recurrence and should be monitored carefully for early detection of possible recurrence.

Prognostic implication of intratumoral metabolic heterogeneity in invasive ductal carcinoma of the breast.

BACKGROUND: The purpose of this study was to evaluate the prognostic implication of findings of intratumoral metabolic heterogeneity on pretreatment (18)F-FDG PET/CT scans in patients with invasive ductal carcinoma (IDC) of the breast. METHODS: One hundred and twenty-three female IDC patients who underwent pretreatment 18F-fluorodeoxyglucose positron-emission tomography/computed tomography ((18)F-FDG PET/CT) scans were retrospectively evaluated in this study. The heterogeneity factor (HF) defined as the derivative (dV/dT) of a volume threshold function from 40% to 80%, was computed for each primary tumor. Other metabolic PET parameters (maximum standardized uptake value [SUVmax], metabolic tumor volume [MTV], and total lesion glycolysis [TLG]) were measured. The HF was compared with clinicopathologic factors and other PET parameters. Univariate and multivariate analyses for the overall survival (OS) were performed. RESULTS: The HF ranged from 0.02 to 6.72 (mean, 0.35 ± 0.82) and significantly correlated with MTV (r = 0.955; p < 0.0001) and TLG (r = 0.354; p = 0.0001). The HF was significantly higher (implying more heterogeneity) in tumors with higher T and N stages. The optimal cut-off values for the OS determined using a receiver operating characteristic (ROC) curve were 0.34 for the HF, 5.6 for SUVmax, 8.55 cm(3) for MTV, and 14.43 for TLG. The OS rate among the 123 patients was 86.2%. T stage (1, 2 vs. 3, 4), N stage (0, 1 vs. 2, 3), M stage (0 vs. 1), ER status (+ vs. -), SUVmax (≤ 5.6 vs. > 5.6), MTV (≤ 8.55 cm(3) vs. > 8.55 cm(3)), TLG (≤ 14.43 vs. > 14.43), and HF (< 0.34 vs. ≥ 0.34) affected the OS on univariate analysis. After adjustment for the effects of TNM stage and ER status, the HF and MTV were significant predictors of OS. Among the PET parameters, the best prognostic factor for OS was the HF. CONCLUSIONS: Intratumoral metabolic heterogeneity correlated closely with the MTV and significantly affected the OS in IDC patients. The HF may act as a robust surrogate marker for the prediction of OS in IDC patients.

Incidental detection of increased (18)F-FDG uptake and its follow-up in patients with granulomatous prostatitis after BCG treatment for urinary bladder cancer.

Incidental prostate uptake of fluorine-18-fluorodeoxyglucose in positron emission tomography/computed tomography ((18)F-FDG PET/CT) may represent malignancies like prostate malignancy, inflammation or benign prostatic lesions. We report two cases of bacillus Calmette-Guérin (BCG)-induced granulomatous prostatitis that showed (18)F-FDG uptake of the prostate gland on (18)F-FDG PET/CT in patients who had previously received intravesical BCG treatment for bladder cancer. The degree of (18)F-FDG uptake was decreased on the follow-up PET/CT scan after one year, without any specific treatment.

Role of Corn Peptide Powder in Lipopolysaccharide-Induced Inflammatory Responses in 3T3-L1 Adipocytes.

Corn peptide (CP) is a short, naturally occurring, and physiologically active peptide generated from corn-protease-catalyzed hydrolysis. CP plays a role in preventing obesity-related disorders, but its impact on reducing inflammation is unknown. Hence, this study examined the possible protective effects of corn peptide powder (CPP) against the harmful effects of lipopolysaccharide (LPS), with a particular emphasis on reducing oxidative damage and inflammation in adipocytes. Hence, mature 3T3-L1 adipocytes underwent exposure to 10 ng/mL LPS, with or without CPP (10 and 20 µg/mL). LPS stimulation increased reactive oxygen species and superoxide anion generation. However, this effect was reduced in a dose-dependent manner by pretreatment with CPP. CPP treatment elevated the mRNA expressions of the antioxidant enzymes manganese superoxide dismutase (mnSOD) and glutathione peroxidase 1 (Gpx1) while reducing the mRNA expressions of the cytosolic reactive oxygen species indicators p40 and p67 (NADPH oxidase 2). In addition, CPP inhibited the monocyte chemoattractant protein-1, tumor necrosis factor-alpha, Toll-like receptor 4, and nuclear factor kappa B mRNA expressions induced by LPS. These findings demonstrate that CPP may ameliorate adipocyte dysfunction by suppressing oxidative damage and inflammatory responses through a new mechanism known as Toll-like receptor 4/nuclear factor kappa B-mediated signaling.

Dexamethasone-induced selenoprotein S degradation is required for adipogenesis.

Although adipogenesis is associated with induction of endoplasmic reticulum (ER) stress, the role of selenoprotein S (SEPS1), an ER resident selenoprotein known to regulate ER stress and ER-associated protein degradation, is unknown. We found an inverse relationship between SEPS1 level in adipose tissue and adiposity in mice. While SEPS1 expression was increased during adipogenesis, a markedly reduced SEPS1 protein level was found in the early phase of adipogenesis due to dexamethasone (DEX)-induced proteosomal degradation of SEPS1. Overexpression of SEPS1 in the early phase of cell differentiation resulted in impairment of adipogenesis with reduced levels of CCAAT/enhancer binding protein α and other adipocyte marker genes during the course of adipogenesis. Conversely, knockdown of SEPS1 resulted in the promotion of adipogenesis. Additionally, altered SEPS1 expression was associated with changes in expression of ER stress marker genes in the early phase of adipogenesis, and ubiquitin-proteasome system (UPS)-related ubiquitination and proteasome function. Our study reveals that SEPS1 is a novel anti-adipogenic selenoprotein that modulates ER stress- and UPS-dependent adipogenesis. Our results also identifies a novel function of DEX in the regulation of adipogenesis through induction of SEPS1 degradation. Taken together, DEX-dependent degradation of SEPS1 in the early phase of adipogenesis is necessary for initiating ER stress- and UPS-dependent maturation of adipocytes.

Prognostic value of whole-body metabolic tumour volume and total lesion glycolysis measured on ¹8F-FDG PET/CT in patients with extranodal NK/T-cell lymphoma.

PURPOSE: The aim of this study was to determine whether maximum standardized uptake value (SUVmax), whole-body metabolic tumour volume (WBMTV), and whole-body total lesion glycolysis (WBTLG) measured on pretreatment ¹8F-FDG PET/CT can predict prognosis in patients with extranodal natural killer/T-cell lymphoma (ENKTL). METHODS: We conducted a retrospective analysis of 20 patients with newly-diagnosed ENKTL who underwent pretreatment ¹8F-FDG PET/CT. WBMTV and WBTLG were measured automatically using the boundaries of voxels presenting SUV>3.0. Uni- and multivariate analyses for survival and disease progression were performed using clinical variables and PET parameters (SUVmax, WBMTV, and WBTLG). RESULTS: During the follow-up period (median 26.3 months), 12 patients showed disease progression and 10 patients died from the disease. Receiver operating characteristic curve analysis showed cut-off values for SUVmax, WBMTV and WBTLG of 8.1, 14.4 cm³ and 52.7, respectively. Univariate analysis showed that the International Prognostic Index (IPI) score and PET parameters were significant predictors of overall survival (OS) and progression-free survival (PFS). Multivariate analysis, even after adjustment for the IPI score, showed that high WBMTV was the best predictor of OS and PFS, and high SUVmax and WBTLG were significant predictors of PFS. CONCLUSION: Our results suggested that the use of PET parameters together with the IPI score may be useful for detailed prediction of prognosis in ENKTL patients. Therefore, despite a lower IPI score, patients with high PET parameter values might be considered candidates for aggressive therapy to improve clinical outcomes.

Allium macrostemon whole extract ameliorates obesity-induced inflammation and endoplasmic reticulum stress in adipose tissue of high-fat diet-fed C57BL/6N mice.

Background: Obesity is a major risk factor for metabolic syndrome and a serious health concern worldwide. Various strategies exist to treat and prevent obesity, including dietary approaches using bioactive ingredients from natural sources. Objective: This study aimed to investigate the anti-obesity effect of whole-plant Allium macrostemon (also called as long-stamen chive) extract (AME) as a potential new functional food. Design: C57BL/6N mice were divided into three groups and fed either a control diet (CD), high-fat diet (HFD), or HFD with AME treatment (200 mg/kg BW daily) for 9 weeks. The mice in the CD and HFD groups were treated with vehicle control. Results: AME supplementation reduced HFD-induced body weight gain, fat mass, and adipocyte size. AME suppressed peroxisome proliferator-activated receptor γ and fatty acid synthase mRNA expression, indicating reduced adipogenesis and lipogenesis in adipose tissue. In addition, AME lowered inflammation in adipose tissue, as demonstrated by the lower number of crown-like structures, mRNA, and/or protein expression of macrophage filtration markers, as well as pro-inflammatory cytokines, including F4/80 and IL-6. Endoplasmic reticulum stress was also alleviated by AME administration in adipose tissue. Several phenolic acids known to have anti-obesity effects, including ellagic acid, protocatechuic acid, and catechin, have been identified in AME. Conclusion: By suppressing adipose tissue expansion and inflammation, AME is a potential functional food for the prevention and/or treatment of obesity and its complications.

A Comprehensive Review of Pathological Mechanisms and Natural Dietary Ingredients for the Management and Prevention of Sarcopenia.

Sarcopenia is characterized by an age-related loss of skeletal muscle mass and function and has been recognized as a clinical disease by the World Health Organization since 2016. Substantial evidence has suggested that dietary modification can be a feasible tool to combat sarcopenia. Among various natural dietary ingredients, the present study focused on botanical and marine extracts, phytochemicals, and probiotics. Aims of this review were (1) to provide basic concepts including the definition, diagnosis, prevalence, and adverse effects of sarcopenia, (2) to describe possible pathological mechanisms including protein homeostasis imbalance, inflammation, mitochondrial dysfunction, and satellite cells dysfunction, and (3) to analyze recent experimental studies reporting potential biological functions against sarcopenia. A recent literature review for dietary ingredients demonstrated that protein homeostasis is maintained via an increase in the PI3K/Akt pathway and/or a decrease in the ubiquitin-proteasome system. Regulation of inflammation has primarily targeted inhibition of NF-κB signaling. Elevated Pgc-1α or Pax7 expression reverses mitochondrial or satellite cell dysfunction. This review provides the current knowledge on dietary components with the potential to assist sarcopenia prevention and/or treatment. Further in-depth studies are required to elucidate the role of and develop various dietary materials for healthier aging, particularly concerning muscle health.

JUUL preference among Korean adult tobacco users and its effect on attempts to quit tobacco: A follow-up survey four months post JUUL launch.

INTRODUCTION: This study examined the various factors in the selection of JUUL (and/or), a pod-mod type electronic cigarette (EC), and the changes in EC patterns before and after the JUUL debut on 24 May 2019, using follow-up survey data of adult tobacco users in South Korea. METHODS: This study examined transition outcomes among tobacco users and factors associated with future JUUL use. Convenience sample data were collected from adult tobacco users in South Korea, from March-April 2019 (baseline, n=2173) to September 2019 (follow-up, n=779). Results were obtained from the 779 respondents in the follow-up survey, and user data of one or more tobacco products were analyzed. The changes in the proportion of EC and JUUL use during this period were calculated, and multivariate logistic regression analysis was conducted to investigate the selection factors of JUUL. RESULTS: Four months after the JUUL launch, the proportion of current EC and JUUL users among the whole sample increased by 10.3% (42.6-52.9%, p<0.001) and 17.7 % (4.0-21.7%, p<0.001), respectively, while the proportion of triple users doubled (18.7% vs 37.5%, p<0.001). Among current EC users, the percentage of quitting EC within one month decreased from 18.7% to 8.7%; this change was more pronounced among concurrent JUUL users than non-JUUL users (p<0.001). In the multivariate logistic analysis with adjustment for possible confounders, JUUL use was significantly associated with male sex, young and middle age, and metropolitan residency status at the baseline survey. CONCLUSIONS: After the launch of JUUL in South Korea, EC users, including JUUL and triple users, increased significantly, but the intention to stop EC decreased significantly. Given the serious interests of the tobacco industry in these products, additional regulation is warranted.

Application of Milk Exosomes for Musculoskeletal Health: Talking Points in Recent Outcomes.

Milk is a nutrient-rich food source, and among the various milks, breast milk is a nutrient source provided by mothers to newborns in many mammals. Exosomes are nano-sized membranous extracellular vesicles that play important roles in cell-to-cell communication. Exosomes originate from endogenous synthesis and dietary sources such as milk. Discovered through electron microscopy as floating vesicles, the existence of exosomes in human milk was confirmed owing to a density between 1.10 and 1.18 g/mL in a sucrose gradient corresponding to the known density of exosomes and detection of MHC classes I and II, CD63, CD81, and CD86 on the vesicles. To date, milk exosomes have been used for treating many diseases, including cancers, and are widely proposed as promising carriers for the delivery of chemotherapeutic agents. However, few studies on milk exosomes focus on geriatric health, especially sarcopenia and osteoporosis related to bone and muscle. Therefore, the present study focused on milk exosomes and their cargoes, which are potential candidates for dietary supplements, and when combined with drugs, they can be effective in treating musculoskeletal diseases. In this review, we introduce the basic concepts, including the definition, various sources, and cargoes of milk exosomes, and exosome isolation and characterization methods. Additionally, we review recent literature on the musculoskeletal system and milk exosomes. Since inflammation and oxidative stress underly musculoskeletal disorders, studies reporting the antioxidant and anti-inflammatory properties of milk exosomes are also summarized. Finally, the therapeutic potential of milk exosomes in targeting muscle and bone health is proposed.

Effects of Allium macrostemon Bunge Extract on Adipose Tissue Inflammation and Hepatic Endoplasmic Reticulum Stress in High-Fat Diet-Fed and Bisphenol A-Treated C57BL/6N Mice.

The simultaneous exposure to a high-fat (HF) diet and to bisphenol A (BPA) from delivered foods and food-delivery containers is on the rise in humans, according to the increased frequency of food delivery during the COVID-19 pandemic. This co-exposure could cause harmful tissue toxicity in the human body. Here, the preventive effect of Allium macrostemon Bunge (AM) extract against dysfunction in adipose tissue and the liver under co-exposure to BPA and an HF diet was examined using mice. C57BL/6N mice were divided into four groups (n = 6 or 7/group) according to diet and treatment: control diet with vehicle (CON), HF diet with vehicle (HF), HF diet with an oral injection of BPA (HF + BP), and HF diet with an oral injection of BPA and AM extract (HF + BP + AM). HF feeding increased body weight gain compared to CON feeding, while BP + HF and BP + HF + AM feeding suppressed body weight gain compared with HF feeding. The BP + HF group had lower body weight than the HF group, but the two groups had similar epididymal fat mass. The HF + BP + AM group showed lower pro-inflammatory gene expression levels in adipose tissue and epididymal fat mass compared to the HF + BP group. Altered endoplasmic reticulum (ER) stress response in the liver was partly observed in the HF + BP group, as shown by increased total phosphorylated Jun N-terminal kinase protein levels compared to those in the HF group. In addition, ecdysterone 25-O-ß-D-glucopyranoside and 6-gingerol were identified in AM extract by mass spectrometry and molecular networking analysis. In summary, the AM extract diminished adipose tissue inflammation and hepatic ER stress in an HF diet and BPA co-exposure condition. To utilize AM as a potential food component to alleviate the harmful effect of an HF diet and BPA exposure, further research investigating the specific impact of AM extract supplementation using additional experimental groups or various treatment doses is warranted.

The Association of Smoking Status and Clustering of Obesity and Depression on the Risk of Early-Onset Cardiovascular Disease in Young Adults: A Nationwide Cohort Study.

BACKGROUND AND OBJECTIVES: To evaluate the impact of smoking in young adults on the risk of cardiovascular disease (CVD) and the clustering effect of behavioral risk factors such as smoking, obesity, and depression. METHODS: A Korean nationwide population-based cohort of a total of 3,280,826 participants aged 20-39 years old who underwent 2 consecutive health examinations were included. They were followed up until the date of CVD (myocardial infarction [MI] or stroke), or December 2018 (median, 6 years). RESULTS: Current smoking, early age of smoking initiation, and smoking intensity were associated with an increased risk of CVD incidence. Even after quitting smoking, the risk of MI was still high in quitters compared with non-smokers. Cigarette smoking, obesity, and depression were independently associated with a 1.3-1.7 times increased risk of CVD, and clustering of 2 or more of these behavioral risk factors was associated with a 2-3 times increased risk of CVD in young adults. CONCLUSIONS: In young adults, cigarette smoking was associated with the risk of CVD, and the clustering of 2 or more behavioral risk factors showed an additive risk of CVD.

The Antioxidant and Anti-Inflammatory Properties of Merremia umbellata Extract.

Merremia umbellata Hallier f. (MU) has been used as an anti-inflammatory agent to treat burns and scales. However, the potential anti-inflammatory mechanisms of action of this plant have not been elucidated. This study aimed to assess the antioxidant and anti-inflammatory effects of the leaf and shoot of MU grown in Bangladesh. The MU extract exhibited antioxidant activities as demonstrated by DPPH and ABTS free-radical-scavenging activities and the total polyphenol and total flavonoid contents. MU extract significantly reduced the lipopolysaccharide (LPS)-stimulated nitric oxide (NO) production in RAW264.7 macrophage. Accordingly, the gene levels of inducible NO synthase and cyclooxygenase-2 were suppressed. The MU extract alleviated the LPS-induced expression of TLR4, NF-κB, and inflammatory cytokines (TNF-α, IL-6, and IL-1ß). The constituents of a MU extract were tentatively identified using UHPLC-PDA-QTOF/MS techniques. The main compounds were identified as 3,4-dicaffeoylquinic acid, 3,5-dicaffeoylquinic acid, quercitrin, and 4,5-dicaffeoylquinic acid. Molecular docking analysis revealed that these compounds interact with TLR4 protein, with quercitrin showing the highest binding affinity among them. Overall, our findings demonstrate the antioxidant and in vitro anti-inflammatory activities of MU and its potential compounds to target the TLR4-NF-κB signaling pathway. These findings are potentially used to further explore promising natural food ingredients that are effective in regulating inflammation.

Gamma-tocotrienol induces apoptosis and autophagy in prostate cancer cells by increasing intracellular dihydrosphingosine and dihydroceramide.

Although cell-based studies have shown that γ-tocotrienol (γTE) exhibits stronger anticancer activities than other forms of vitamin E including γ-tocopherol (γT), the molecular bases underlying γTE-exerted effects remains to be elucidated. Here we showed that γTE treatment promoted apoptosis, necrosis and autophagy in human prostate PC-3 and LNCaP cancer cells. In search of potential mechanisms of γTE-provoked effects, we found that γTE treatment led to marked increase of intracellular dihydroceramide and dihydrosphingosine, the sphingolipid intermediates in de novo sphingolipid synthesis pathway but had no effects on ceramide or sphingosine. The elevation of these sphingolipids by γTE preceded or coincided with biochemical and morphological signs of cell death and was much more pronounced than that induced by γT, which accompanied with much higher cellular uptake of γTE than γT. The importance of sphingolipid accumulation in γTE-caused fatality was underscored by the observation that dihydrosphingosine and dihydroceramide potently reduced the viability of both prostate cell lines and LNCaP cells, respectively. In addition, myriosin, a specific inhibitor of de novo sphingolipid synthesis, counteracted γTE-induced cell death. In agreement with these cell-based studies, γTE inhibited LNCaP xenograft growth by 53% (p < 0.05), compared to 33% (p = 0.07) by γT, in nude mice. These findings provide a molecular basis of γTE-stimulated cancer cell death and support the notion that elevation of intracellular dihydroceramide and dihydrosphingosine is likely a novel anticancer mechanism.

Selenate inhibits adipogenesis through induction of transforming growth factor-ß1 (TGF-ß1) signaling.

Selenium is essential for many aspects of human health. While selenium is known to protect against cancer and cardiovascular diseases, the role of selenium in adipose development is unknown. Here we show that selenate at non-toxic concentration exhibits an anti-adipogenic function in vitro and ex vivo. In addition, selenate induced a morphological change of these cells from fibroblast-like to spindle cell shape. However, other forms of selenium, including selenite and methylseleninic acid, showed either toxic or no effect on adipogenesis and morphology change of preadipocytes. The effects of selenate on adipogenesis and cell morphology change were blunted by the treatment with SB431542, a specific inhibitor of transforming growth factor-ß1 (TGF-ß1) receptor, neutralization TGF-ß1 by its antibody, and knockdown of TGF-ß1 in preadipocytes, suggesting a requirement of TGF-ß signaling for the anti-adipogenic function of selenate. Among tested forms of selenium, selenate appears to be an effective activator of TGF-ß1 expression in preadipocytes. These results indicate that selenate is a novel dietary micromineral that activates TGF-ß1 signaling in preadipocytes and modulates adipogenesis.