Obesity disrupts the pituitary-hepatic UPR communication leading to NAFLD progression.

Obesity alters levels of pituitary hormones that govern hepatic immune-metabolic homeostasis, dysregulation of which leads to nonalcoholic fatty liver disease (NAFLD). However, the impact of obesity on intra-pituitary homeostasis is largely unknown. Here, we uncovered a blunted unfolded protein response (UPR) but elevated inflammatory signatures in pituitary glands of obese mice and humans. Furthermore, we found that obesity inflames the pituitary gland, leading to impaired pituitary inositol-requiring enzyme 1α (IRE1α)-X-box-binding protein 1 (XBP1) UPR branch, which is essential for protecting against pituitary endocrine defects and NAFLD progression. Intriguingly, pituitary IRE1-deletion resulted in hypothyroidism and suppressed the thyroid hormone receptor B (THRB)-mediated activation of Xbp1 in the liver. Conversely, activation of the hepatic THRB-XBP1 axis improved NAFLD in mice with pituitary UPR defect. Our study provides the first evidence and mechanism of obesity-induced intra-pituitary cellular defects and the pathophysiological role of pituitary-liver UPR communication in NAFLD progression.

A Medium Chain Fatty Acid, 6-hydroxyhexanoic acid (6-HHA), Protects Against Obesity and Insulin Resistance.

Obesity, a worldwide health problem, increases the risk for developing metabolic diseases such as insulin resistance and diabetes. It is well recognized that obesity-associated chronic inflammation plays a key role in the pathogenesis of systemic metabolic dysfunction. Previously, we revealed an anti-inflammatory role for spent culture supernatants isolated from the oral commensal bacterial species Streptococcus gordonii (Sg-SCS). Here, we identified that 6-hydroxyhexanoic acid (6-HHA), a medium chain fatty acid (MCFA), is the one of the key components of Sg-SCS . We found that treatment of 6-HHA in mice fed a high-fat diet (HFD) significantly reduced HFD-mediated weight gain which was largely attributed to a decrease in fat mass. Systemically, 6-HHA improves obesity-associated glucose intolerance and insulin resistance. Furthermore, administration of 6-HHA suppressed obesity-associated systemic inflammation and dyslipidemia. At the cellular level, treatment of 6-HHA ameliorated aberrant inflammatory and metabolic transcriptomic signatures in white adipose tissue of mice with diet-induced obesity (HFD). Mechanistically, we found that 6-HHA suppressed adipocyte-proinflammatory cytokine production and lipolysis, the latter through Gαi-mediated signaling. This work provides direct evidence for the anti-obesity effects of a novel MCFA, which could be a new therapeutic treatment for combating obesity. KEY POINTS: Hydroxyhexanoic medium chain fatty acids (MCFAs) are dietary and bacterial-derived energy sources, however, the outcomes of using MCFAs in treating metabolic disorders are diverse and complex. The MCFA 6-hydroxyhexanoic acid (6-HHA) is a metabolite secreted by the oral bacterial commensal species Streptococcus gordonii; here we investigated its role in modulating high-fat diet (HFD)-induced metabolic dysfunction. In a murine model of obesity, we found 6-HHA-mediated improvement of diet-mediated adiposity, insulin resistance and inflammation were in part due to actions on white adipose tissue (WAT).6-HHA suppressed proinflammatory cytokine production and lipolysis through Gi-mediated signaling in differentiated white adipocytes.

ADH5-mediated NO bioactivity maintains metabolic homeostasis in brown adipose tissue.

Brown adipose tissue (BAT) thermogenic activity is tightly regulated by cellular redox status, but the underlying molecular mechanisms are incompletely understood. Protein S-nitrosylation, the nitric-oxide-mediated cysteine thiol protein modification, plays important roles in cellular redox regulation. Here we show that diet-induced obesity (DIO) and acute cold exposure elevate BAT protein S-nitrosylation, including UCP1. This thermogenic-induced nitric oxide bioactivity is regulated by S-nitrosoglutathione reductase (GSNOR; alcohol dehydrogenase 5 [ADH5]), a denitrosylase that balances the intracellular nitroso-redox status. Loss of ADH5 in BAT impairs cold-induced UCP1-dependent thermogenesis and worsens obesity-associated metabolic dysfunction. Mechanistically, we demonstrate that Adh5 expression is induced by the transcription factor heat shock factor 1 (HSF1), and administration of an HSF1 activator to BAT of DIO mice increases Adh5 expression and significantly improves UCP1-mediated respiration. Together, these data indicate that ADH5 controls BAT nitroso-redox homeostasis to regulate adipose thermogenesis, which may be therapeutically targeted to improve metabolic health.

BACE1 Inhibition Increases Susceptibility to Oxidative Stress by Promoting Mitochondrial Damage.

BACE1 is a key enzyme facilitating the generation of neurotoxic ß-amyloid (Aß) peptide. However, given that BACE1 has multiple substrates we explored the importance of BACE1 in the maintenance of retinal pigment epithelial (RPE) cell homeostasis under oxidative stress. Inhibition of BACE1 reduced mitochondrial membrane potential, increased mitochondrial fragmentation, and increased cleaved caspase-3 expression in cells under oxidative stress. BACE1 inhibition also resulted in significantly lower levels of mitochondrial fusion proteins OPA1 and MFN1 suggesting a higher rate of mitochondrial fission while increasing the levels of mitophagic proteins Parkin and PINK1 and autophagosome numbers. In contrast, BACE2 had minimal effect on cellular response to oxidative stress. In summary, our results emphasize the importance of BACE1 in augmenting cellular defense against oxidative stress by protecting mitochondrial dynamics.

A putative long noncoding RNA-encoded micropeptide maintains cellular homeostasis in pancreatic ß cells.

Micropeptides (microproteins) encoded by transcripts previously annotated as long noncoding RNAs (lncRNAs) are emerging as important mediators of fundamental biological processes in health and disease. Here, we applied two computational tools to identify putative micropeptides encoded by lncRNAs that are expressed in the human pancreas. We experimentally verified one such micropeptide encoded by a ß cell- and neural cell-enriched lncRNA TCL1 Upstream Neural Differentiation-Associated RNA (TUNAR, also known as TUNA, HI-LNC78, or LINC00617). We named this highly conserved 48-amino-acid micropeptide beta cell- and neural cell-regulin (BNLN). BNLN contains a single-pass transmembrane domain and localizes at the endoplasmic reticulum (ER) in pancreatic ß cells. Overexpression of BNLN lowered ER calcium levels, maintained ER homeostasis, and elevated glucose-stimulated insulin secretion in pancreatic ß cells. We further assessed the BNLN expression in islets from mice fed a high-fat diet and a regular diet and found that BNLN is suppressed by diet-induced obesity (DIO). Conversely, overexpression of BNLN enhanced insulin secretion in islets from lean and obese mice as well as from humans. Taken together, our study provides the first evidence that lncRNA-encoded micropeptides play a critical role in pancreatic ß cell functions and provides a foundation for future comprehensive analyses of micropeptide function and pathophysiological impact on diabetes.

Plasmid encoding microRNA-200c ameliorates periodontitis and systemic inflammation in obese mice.

The present study was conducted to characterize microRNA-200c (miR-200c) and its regulators in adipogenic differentiation, obesity, and periodontitis in obese subjects (PiOSs), and to determine the therapeutic efficacy of plasmid DNA encoding miR-200c as a treatment for PiOSs. We report that highly expressed miR-200c in gingival tissues was downregulated in diet-induced obese (DIO) mice and during adipogenic differentiation of human bone marrow mesenchymal stromal cells (hBMSCs). Local injection of Porphyromonas gingivalis lipopolysaccharide (Pg-LPS) in the maxilla interdental gingiva of DIO mice reduced miR-200c in gingival and adipose tissues and induced periodontal inflammation associated with systemic elevation of interleukin-6 (IL-6) and impaired glucose tolerance. The inhibitory functions of Pg-LPS and IL-6 on miR-200c and their effectiveness on Zeb1 were confirmed in vitro. Injection of naked plasmid DNA encoding miR-200c into the gingiva effectively rescued miR-200c downregulation, prevented periodontal and systemic inflammation, and alleviated the impaired glucose metabolism in obese mice with LPS-induced periodontitis. Increased circulating exosomal miR-200c and its function on suppressing proinflammatory cytokines and adipogenesis explained the mechanism(s) of gingival application of miR-200c in attenuating systemic inflammation in PiOSs. These results demonstrated that miR-200c reduced by Pg-LPS and IL-6 in periodontitis and obesity might lead to the pathogenesis of PiOSs, and upregulation of miR-200c in the gingiva presents a therapeutic approach for PiOSs.

The unfolded protein response regulates hepatic autophagy by sXBP1-mediated activation of TFEB.

Defective macroautophagy/autophagy and a failure to initiate the adaptive unfolded protein response (UPR) in response to the endoplasmic reticulum (ER) stress contributes to obesity-associated metabolic dysfunction. However, whether and how unresolved ER stress leads to defects in the autophagy pathway and to the progression of obesity-associated hepatic pathologies remains unclear. Obesity suppresses the expression of hepatic spliced XBP1 (X-box binding protein 1; sXBP1), the key transcription factor that promotes the adaptive UPR. Our RNA-seq analysis revealed that sXBP1 regulates genes involved in lysosomal function in the liver under fasting conditions. Chromatin immunoprecipitation (ChIP) analyzes of both primary hepatocytes and whole livers further showed that sXBP1 occupies the -743 to -523 site of the promoter of Tfeb (transcription factor EB), a master regulator of autophagy and lysosome biogenesis. Notably, this occupancy was significantly reduced in livers from patients with steatosis. In mice, hepatic deletion of Xbp1 (xbp1 LKO) suppressed the transcription of Tfeb as well as autophagy, whereas hepatic overexpression of sXbp1 enhanced Tfeb transcription and autophagy. Moreover, overexpression of Tfeb in the xbp1 LKO mouse liver ameliorated glucose intolerance and steatosis in mice with diet-induced obesity (DIO). Conversely, loss of TFEB function impaired the protective role of sXBP1 in hepatic steatosis in mice with DIO. These data indicate that sXBP1-Tfeb signaling has direct functional consequences in the context of obesity. Collectively, our data provide novel insight into how two organelle stress responses are integrated to protect against obesity-associated metabolic dysfunction.Abbreviations: AAV8: adeno-associated virus serotype 8; ACTB: actin, beta; ANOVA: analysis of variance; ATF6: activating transcription factor-6; ATG: autophagy related; BECN1: beclin 1; BMI: body mass index; ChIP: chromatin immunoprecipitation; CLEAR: coordinated lysosomal expression and regulation; Cre: cre recombinase; DIO: diet-induced obesity; EBSS: Earle's balanced salt solution; EIF2AK3/PERK: eukaryotic translation initiation factor 2 alpha kinase 3; ER: endoplasmic reticulum; ERN1/IRE1: endoplasmic reticulum (ER) to nucleus signaling 1; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GFP: green fluorescent protein; HFD: high-fat diet; h: hours; HSCs: hepatic stellate cells; INS: insulin; L/A: ammonium chloride and leupeptin; MAP1LC3B/LC3B: microtubule-associated protein 1 light chain 3 beta; mRNA: messenger RNA; NAFLD: nonalcoholic fatty liver disease; NASH: nonalcoholic steatohepatitis; RD: regular diet; RFP: red fluorescent protein; SERPINA7/TBG: serpin family A member 7; SQSTM1/p62: sequestome 1; sXbp1 LOE: liver-specific overexpression of spliced Xbp1; TFEB: transcription factor EB; TG: thapsigargin; TN: tunicamycin; UPR: unfolded protein response; wks: weeks; WT: wild type; XBP1: X-box binding protein 1; xbp1 LKO: liver-specific Xbp1 knockout.

A novel indicator, childhood lipid accumulation product, is associated with hypertension in Chinese children and adolescents.

Childhood hypertension has become an important public health issue. This study explored a novel indicator, namely, childhood lipid accumulation product (CLAP), which is associated with hypertension among children and adolescents. A total of 683 children and adolescents aged 8-15 years were measured for body weight, height, waist circumference (WC), abdominal skinfold thickness (AST), triacylglycerol (TG), blood pressure, dietary behaviors, and physical activity time. The novel childhood lipid accumulation product (CLAP) was the product of WC, AST, and TG (CLAP = WC (cm) × AST (mm) × TG (mmol/L)). The logarithmic CLAP (LnCLAP), height, weight, WC, WHtR, BMI, AST, and TG were standardized for sex and age using the z-score method (standardized variables: SLnCLAP, Sheight, Sweight, SWC, SWHtR, SBMI, SAST, and STG). The results showed that the overall prevalence of hypertension was 11.6% (13.1% in boys and 9.7% in girls). SLnCLAP ≥ 1, Sweight ≥ 1, SWC ≥ 1, SWHtR ≥ 1, SBMI ≥ 1, SAST ≥ 1, and STG ≥ 1 increased the statistical risk of childhood hypertension (odds ratio values (95% CI) were 3.70 (2.22-6.16), 2.58 (1.50-4.43), 3.08 (1.84-5.15), 2.33 (1.38-3.93), 2.96 (1.72-5.29), 2.38 (1.41-4.70), and 2.40 (1.38-4.19), respectively). The area under the ROC curve (AUC) for CLAP was higher than that for weight, WC, WHtR, BMI, AST, and TG in the prediction of hypertension. In conclusion, this study showed that CLAP is a novel indicator associated with hypertension in children and adolescents and can more effectively predict childhood hypertension than weight, WC, WHtR, BMI, AST, and TG can.

Tanshinone IIa protects retinal endothelial cells against mitochondrial fission induced by methylglyoxal through glyoxalase 1.

Advanced glycation end products (AGEs) play an important role in the onset of diabetic retinopathy. Therefore, in the current study, we investigate whether and how Tanshinone IIa (Tan IIa) from Salvia miltiorrhiza protects bovine retinal endothelial cells (BRECs) against methylglyoxal (MGO) mediated cell dysfunction. The results showed that MGO reduced cell viability in dose dependent manner. The treatment of Tan IIa (50 µM) significantly improved cell viability induced by MGO in BRECs. MGO increased cellular reactive oxygen species formation and cellular nitric oxide (NO) level; enhanced nox1 and iNOS mRNA levels; inhibited prdx1 mRNA level. The treatment of Tan IIa effectually ameliorated cellular oxidative stress. Exposure of MGO resulted in mitochondrial fission and decrease of opa1 and mfn1. No significant difference in mRNA levels of mfn2 and drp1 was detected between MGO and medium. Tan IIa reduced mitochondrial fragmentation, enhanced the mRNA levels of mfn1 and opa1 in MGO cultured BRECs. The short time exposure of cellular antioxidatants, dimethylthiourea (10 mM) and tiron (10 mM) had no effect on mitochondrial fission although they ameliorated cellular reactive oxygen species level. Moreover, overexpression of glyoxalase 1 (GLO1) increased key proteins of mitochondrial fusion, including opa1 and mfn1 in BRECs cultured with MGO. However, inhibition of GLO1 by siRNA abolished the effect of Tan IIa on induction of mitochondrial fusion in MGO cultured BRECs. In conclusion, MGO caused the injury of retinal endothelial cells through induction of mitochondrial dysfunction and mitochondrial fission, the treatment of Tan IIa ameliorated mitochondrial dysfunction and fission induced by AGEs through enhancing GLO1.

Hepatic Lysosomal iNOS Activity Impairs Autophagy in Obesity.

BACKGROUND & AIMS: The lysosome is an acidic organelle that is important for maintaining cellular and metabolic homeostasis in hepatocytes. Lysosomal dysfunction and chronic inflammation coexist, and both contribute to obesity-associated hepatic insulin resistance. However, in the context of obesity, the interplay between inflammatory signals and hepatic lysosomal function remains largely unknown. Inducible nitric oxide synthase (iNOS) is a hallmark for inflammation, and is activated in obesity. The aim of this study is to understand the molecular link between iNOS-mediated lysosomal nitric oxide (NO) production, hepatic lysosomal function, and autophagy in the context of obesity-associated insulin resistance. METHODS: The role of iNOS in hepatic autophagy, as related to insulin and glucose homeostasis were studied in mice with diet-induced obesity (DIO). The effects and mechanisms of iNOS-mediated lysosomal NO production on lysosomal function and hepatic autophagy were studied in primary hepatocytes as well as in a mouse model of DIO. RESULTS: We demonstrate that obesity promotes iNOS localization to the lysosome and decreases levels of lysosomal arginine, resulting in an accumulation of NO in hepatic lysosomes. This lysosomal NO production is attenuated by treatment with a NO scavenger, while co-overexpression of mTOR and a lysosomal arginine transporter (SLC38A9) enhances lysosomal NO production and suppresses autophagy. In addition, we show that deletion of iNOS ameliorates lysosomal nitrosative stress in the livers of DIO mice, promotes lysosomal biogenesis by activating transcription factor EB (TFEB), and enhances lysosomal function and autophagy. Lastly, deletion of iNOS in mice with DIO improves hepatic insulin sensitivity, which is diminished by suppression of TFEB or autophagy related 7 (Atg7). CONCLUSIONS: Our studies suggest that lysosomal iNOS-mediated NO signaling disrupts hepatic lysosomal function, contributing to obesity-associated defective hepatic autophagy and insulin resistance.

IRE1α prevents hepatic steatosis by processing and promoting the degradation of select microRNAs.

Obesity or a high-fat diet represses the endoribonuclease activity of inositol-requiring enzyme 1α (IRE1α), a transducer of the unfolded protein response (UPR) in cells under endoplasmic reticulum (ER) stress. An impaired UPR is associated with hepatic steatosis and nonalcoholic fatty liver disease (NAFLD), which is caused by lipid accumulation in the liver. We found that IRE1α was critical to maintaining lipid homeostasis in the liver by repressing the biogenesis of microRNAs (miRNAs) that regulate lipid mobilization. In mice fed normal chow, the endoribonuclease function of IRE1α processed a subset of precursor miRNAs in the liver, including those of the miR-200 and miR-34 families, such that IRE1α promoted their degradation through the process of regulated IRE1-dependent decay (RIDD). A high-fat diet in mice or hepatic steatosis in patients was associated with the S-nitrosylation of IRE1α and inactivation of its endoribonuclease activity. This resulted in an increased abundance of these miRNA families in the liver and, consequently, a decreased abundance of their targets, which included peroxisome proliferator-activated receptor α (PPARα) and the deacetylase sirtuin 1 (SIRT1), regulators of fatty acid oxidation and triglyceride lipolysis. IRE1α deficiency exacerbated hepatic steatosis in mice. The abundance of the miR-200 and miR-34 families was also increased in cultured, lipid-overloaded hepatocytes and in the livers of patients with hepatic steatosis. Our findings reveal a mechanism by which IRE1α maintains lipid homeostasis through its regulation of miRNAs, a regulatory pathway distinct from the canonical IRE1α-UPR pathway under acute ER stress.

S-Nitrosoglutathione Reductase Dysfunction Contributes to Obesity-Associated Hepatic Insulin Resistance via Regulating Autophagy.

Obesity is associated with elevated intracellular nitric oxide (NO) production, which promotes nitrosative stress in metabolic tissues such as liver and skeletal muscle, contributing to insulin resistance. The onset of obesity-associated insulin resistance is due, in part, to the compromise of hepatic autophagy, a process that leads to lysosomal degradation of cellular components. However, it is not known how NO bioactivity might impact autophagy in obesity. Here, we establish that S-nitrosoglutathione reductase (GSNOR), a major protein denitrosylase, provides a key regulatory link between inflammation and autophagy, which is disrupted in obesity and diabetes. We demonstrate that obesity promotes S-nitrosylation of lysosomal proteins in the liver, thereby impairing lysosomal enzyme activities. Moreover, in mice and humans, obesity and diabetes are accompanied by decreases in GSNOR activity, engendering nitrosative stress. In mice with a GSNOR deletion, diet-induced obesity increases lysosomal nitrosative stress and impairs autophagy in the liver, leading to hepatic insulin resistance. Conversely, liver-specific overexpression of GSNOR in obese mice markedly enhances lysosomal function and autophagy and, remarkably, improves insulin action and glucose homeostasis. Furthermore, overexpression of S-nitrosylation-resistant variants of lysosomal enzymes enhances autophagy, and pharmacologically and genetically enhancing autophagy improves hepatic insulin sensitivity in GSNOR-deficient hepatocytes. Taken together, our data indicate that obesity-induced protein S-nitrosylation is a key mechanism compromising the hepatic autophagy, contributing to hepatic insulin resistance.

A Non-Canonical Role for ß-Secretase in the Retina.

It has long been established that ß-Secretase (BACE) plays a critical role in the formation of amyloid plaques in Alzheimer's Disease patients, but it is only recently that the importance of ß-secretases in retinal pathophysiology has been recognized. BACE expression is elevated in response to stress, and downregulation results in lysosomal abnormalities and mitochondrial changes. Inhibition of BACE can lead to reduced retinal function, retinal thinning, lipofuscin accumulation and vascular dysfunction in mice. Furthermore, BACE inhibition accelerates choroidal neovascularization (CNV) in mice. We propose that BACE plays an important role in retinal homeostasis and that BACE upregulation in response to stress is a protective measure.

EPA, not DHA, prevents fibrosis in pressure overload-induced heart failure: potential role of free fatty acid receptor 4.

Heart failure with preserved ejection fraction (HFpEF) is half of all HF, but standard HF therapies are ineffective. Diastolic dysfunction, often secondary to interstitial fibrosis, is common in HFpEF. Previously, we found that supra-physiologic levels of ω3-PUFAs produced by 12 weeks of ω3-dietary supplementation prevented fibrosis and contractile dysfunction following pressure overload [transverse aortic constriction (TAC)], a model that resembles aspects of remodeling in HFpEF. This raised several questions regarding ω3-concentration-dependent cardioprotection, the specific role of EPA and DHA, and the relationship between prevention of fibrosis and contractile dysfunction. To achieve more clinically relevant ω3-levels and test individual ω3-PUFAs, we shortened the ω3-diet regimen and used EPA- and DHA-specific diets to examine remodeling following TAC. The shorter diet regimen produced ω3-PUFA levels closer to Western clinics. Further, EPA, but not DHA, prevented fibrosis following TAC. However, neither ω3-PUFA prevented contractile dysfunction, perhaps due to reduced uptake of ω3-PUFA. Interestingly, EPA did not accumulate in cardiac fibroblasts. However, FFA receptor 4, a G protein-coupled receptor for ω3-PUFAs, was sufficient and required to block transforming growth factor ß1-fibrotic signaling in cultured cardiac fibroblasts, suggesting a novel mechanism for EPA. In summary, EPA-mediated prevention of fibrosis could represent a novel therapy for HFpEF.

[Relationship on the prevalence of physical activity to depressive symptoms and satisfaction of school life among middle school students in Bengbu, Anhui province].

OBJECTIVE: To describe the prevalence and relationship between physical activity (PA), depressive symptoms and school life satisfaction among middle school students in Bengbu, Anhui province. METHODS: A total number of 5268 boys and girls were analyzed from 4 middle schools. Depressive symptoms were assessed, using the Depression Self-rating Scale for Children, school life satisfaction via the School Life Satisfaction Rating Questionnaire. Self-reported PA and sedentary behaviors were also assessed. Descriptive statistics and logistic regression models were used. RESULTS: Adolescents self-reported rates of participating in sufficient moderate, vigorous and insufficient PA were 14.7%, 36.0% and 59.1%, respectively. The prevalence rates on depressive symptoms and school life dissatisfaction were 24.4% and 25.9%. After adjusting on sedentary behaviors and other potential confounders, participants who had engaged in sufficient moderate and vigorous PA had odds ratios of 0.73 (0.60 - 0.89), 0.68 (0.59 - 0.79) and 0.76 (0.63 - 0.92), 0.70 (0.61 - 0.81) for likelihood of being depressive and school life dissatisfaction, compared to their counterparts who participating in insufficient moderate and vigorous PA. Insufficient PA was positively associated with depression and dissatisfaction of their school lives [OR (95%CI): 1.42 (1.24 - 1.63) and 1.45 (1.27 - 1.66)]. CONCLUSION: High prevalence of insufficient PA was seen among adolescents and PA was closely related to the presence of depressive symptoms and school life dissatisfaction among middle school students.

Effect of Salvia miltiorrhiza hydrophilic extract on the endothelial biomarkers in diabetic patients with chronic artery disease.

The aim of this pilot study was to investigate whether the administration of Salvia miltiorrhiza hydrophilic extract (SMHE) reduced the level of soluble vascular cell adhesion molecule-1 (sVCAM-1) and von Willebrand factor (vWF) in diabetic patients with coronary heart disease (CHD). Sixty-two diabetic patients with CHD were recruited and randomly assigned into placebo and treatment groups. Patients were given SMHE for 60 days. Levels of sVCAM-1, vWF and oxidative low density lipoprotein (oxLDL) were determined by using enzyme linked immunosorbent assay (ELISA). The results showed that the levels of VCAM-1 and vWF positively correlated with the level of oxLDL in diabetic patients with CHD. Levels of sVCAM-1 and vWF in serum were reduced significantly in patients receiving SMHE treatment at day 60 in comparison with the baseline. Administration of SMHE also led to a clear decrease in the levels of oxLDL in diabetic patients with CHD. In summary, this study suggests that SMHE has a potential protective effect on the development of diabetic cardiovascular disease.

Effect of Salvia miltiorrhiza hydrophilic extract on antioxidant enzymes in diabetic patients with chronic heart disease: a randomized controlled trial.

To investigate whether Salvia miltiorrhiza hydrophilic extract (SMHE) has the ability to ameliorate oxidative stress in diabetic patients with chronic heart disease (CHD), 62 patients with CHD were recruited. These patients were assigned randomly into two groups: (1) placebo group receiving hypoglycemic therapy; (2) treatment group receiving hypoglycemic therapy plus SMHE. The biological markers related to oxidative stress were measured to determine the effect of treatment. Thirty patients in the placebo group and 24 patients in the treatment group were followed to completion in this study. Overall, the malondialdehyde (MDA) level at day 30 in the treatment group was significantly lower than in the placebo group. However, no significant difference in the serum antioxidant enzymes activities was observed between the groups. At day 60, the serum glutathione (GSH) level, superoxide dismutase (SOD), Paraoxonase (PONase) and glutathione reductase (GSSG-R) activities increased markedly in the treatment group compared with the placebo group. There was no significant difference in the level of lipid profile between the two groups. This study indicated that SMHE clearly reduced oxidative stress in diabetic patients with CHD.

Is there any relationship between dietary patterns and depression and anxiety in Chinese adolescents?

OBJECTIVE: To determine the association between major dietary patterns characterized by factor analysis and risk of depression and anxiety symptoms among adolescents. DESIGN: Diet and symptoms of depression and anxiety were assessed in a cross-sectional survey among students attending junior high school. Dietary patterns were derived from a self-reported FFQ, which consisted of thirty-eight items. Anthropometric measurements were also performed. SETTING: Four junior high schools in Bengbu city, China. SUBJECTS: A random sample of 5003 adolescents, 11-16 years of age (mean 13·21 years). RESULTS: Three major dietary patterns were identified in the study based on factor analysis: 'snack', 'animal food' and 'traditional'. The prevalence of depression symptoms, anxiety disorders and the coexistence of both were 11·2% (560/5003), 14·6% (732/5003) and 12·6% (629/5003), respectively. After adjustment for potential confounders, adolescents in the highest tertile of snack dietary pattern scores had a higher odds for 'pure' psychological symptoms ('depression without anxiety', OR = 1·64; 95% CI 1·30, 2·06; and 'anxiety without depression', OR = 1·87; 95% CI 1·51, 2·31) compared with coexisting depression and anxiety (OR = 1·93; 95% CI 1·54, 2·43). Similar to snacks, high consumption of animal foods was associated with a higher risk of psychological symptoms. Compared with low consumption, adolescents in the highest tertile of traditional dietary pattern scores had lower odds for 'pure' depression (OR = 0·38; 95% CI 0·30, 0·49), 'pure' anxiety (OR = 0·85; 95% CI 0·69, 1·04) and coexisting anxiety and depression (OR = 0·50; 95% CI 0·39, 0·63). CONCLUSIONS: Data from Chinese secondary-school adolescents validated findings from adult populations. Dietary patterns should be considered as important predictors of depression and anxiety among adolescents in further studies.

Screen time, physical activity and mental health among urban adolescents in China.

OBJECTIVE: To test the association between screen time (ST), physical activity (PA) and self-reported psychological problems among urban adolescents aged 11 to 16 years. METHODS: In 2010, total 5003 boys and girls were analyzed from 4 junior high schools in Bengbu city of China. The Depression Self-rating Scale for Children, Screen for Child Anxiety Related Emotional Disorders and School Life Satisfaction Rating Questionnaire were administered to obtain information on current mental health. Self-reported ST, PA and dietary intake were also assessed. Logistic regression analyses were used to explore the effects of ST and PA on psychological problems. RESULTS: Approximately 26.1% of adolescents were exposed to ST for more than 2h/day. High ST was a risk factor for depressive symptoms (odds ratio (OR)=1.52, 95% confidence interval (CI): 1.31-1.76), anxiety symptoms (OR=1.36, 95%CI: 1.18-1.57) and school life dissatisfaction (OR=2.07, 95%CI: 1.79-2.38). Sufficient vigorous PA (VPA) was a protective factor for depressive symptoms (OR=0.78, 95%CI: 0.67-0.91) and school life dissatisfaction (OR=0.73, 95%CI: 0.62-0.85). The combination of high ST and insufficient VPA was associated with the highest prevalence of various psychological problems. CONCLUSIONS: High ST and insufficient VPA interact to increase depressive, anxiety symptoms and school life dissatisfaction among Chinese adolescents.