Network pharmacology of Huatan Tongluo decoction and clinical effects of its combination with acupuncture in the treatment of stroke.

OBJECTIVE: This study was carried out to probe the clinical effect and mechanism of Huatan Tongluo decoction combined with acupuncture in the treatment of patients with ischemic stroke. METHODS: The clinical data of 100 patients with ischemic stroke were retrospectively collected. On the basis of treatment method, they were split into two groups, each with 50 cases: the conventional treatment group (acupuncture) and the combined treatment group (Huatan Tongluo decoction + acupuncture). After treatment, the neurological function and clinical therapeutic effects of the two groups were evaluated. The treatment of ischemic stroke with Huatan Tongluo decoction was studied by the method of traditional Chinese medicine (TCM) network pharmacology. Resources from databases such as GeneCards, TCMSP, PubChem, Swiss Target Prediction, String, and WebGestalt were integrated, in order to screen for targets of stroke treatment, the active compound composition of Huatan Tongluo decoction, and the targets of compound composition by the use of Cytoscape and R language software. Finally, from the perspective of a protein-protein interaction (PPI) co-expression network, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, the significance of Huatan Tongluo decoction in the treatment of ischemic stroke was discussed. RESULTS: The total effectiveness rate in the combined treatment group was superior to the conventional treatment group. The combined group had higher scores of neurological function, limb movement function, and ability to perform daily living tasks than the conventional treatment group (all P < 0.05). 368 pharmacological targets for Huatan Tongluo decoction and a total of 5690 ischemic stroke targets were retrieved from the database, and 215 intersection targets were found. The results of the PPI network indicated that 43 targets, including EGFR (epidermal growth factor receptor), SRC (proto-oncogene, non-receptor tyrosine kinase), PTPN11 (protein tyrosine phosphatase non-receptor type 11), PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha), AKT1 (serine/threonine kinase 1), VEGFA (vascular endothelial growth factor A), STAT3 (signal transducer and activator of transcription 3), and FYN (FYN proto-oncogene, Src family tyrosine kinase), had the strongest interactions, so they could be used as targets for subsequent basic research verification. The results suggested that pathways such as vascular endothelial growth factor (VEGF) signaling pathway and other pathways were enriched. CONCLUSION: The combination of Huatan Tongluo decoction and acupuncture can help patients with sequelae of stroke promote the regaining of neurological function, thus improving their movement and enhancing their abilities to perform daily living. Huatan Tongluo decoction can mediate the VEGF signaling pathway and other pathways to treat ischemic stroke.

Effects of alcohol intake on cognitive function and ß-amyloid protein in APP/PS1 transgenic mice.

To investigate the effects of alcohol intake on cognitive function and ß-amyloid protein (Aß) in APP/PS1 double-transgenic mice with Alzheimer's disease (AD). Sixty APP/PS1 transgenic male mice were randomized into seven groups: control group, 0.5% alcohol group, 1% alcohol group, 2% alcohol group, 3% alcohol group, and 4% alcohol group, with 10 non-transgenic B6C3F1 mice of the same genetic background as the negative control group. All mice were pair-fed a liquid diet containing alcohol before assessment of learning and memory using the Y-maze test, and of Aß content and related enzyme activity on them. Immunohistochemistry was used to detect the expression of Aß1-42, Aß1-40, and ß-amyloid precursor protein (ß-APP) in the cerebral cortex. 3%, and 4% alcohol intake significantly impaired the learning and memory abilities. 2%, 3%, and 4% alcohol groups indicated a remarkable change in Aß1-42 content, α-secretase and γ-secretase activities in the hippocampus, and ß-APP in the cortex; 3% and 4% alcohol groups showed a significant increase in Aß1-42 content, ß-site amyloid cleavage enzyme 1 (BACE1) activity, and a significant decrease in α-secretase activity in the hippocampus or cortex; 2% and 3% alcohol groups showed a significant increase in Aß1-40 content in the hippocampus or cortex; and 2%, 3%, and 4% alcohol groups showed an increase in the expression of Aß1-42, Aß1-40, and ß-APP in the cortex; 1% alcohol groups showed a significant decline in the levels of Aß1-42, Aß1-40, ß-APP, and BACE1 activity in the hippocampus, and γ-secretase activity in the hippocampus and cortex, and 1% alcohol group showed a significant increase of α-secretase activity in the hippocampus. Besides, 0.5% alcohol showed statistically significant effects on the reduction of BACE1 and γ-secretase activities in the hippocampus. Long-term intake of high-dose alcohol can induce cognitive deficits and improve the activity of ß-APP decomposition-related enzymes, increase Aß content and deposition, and initiate AD progression, while long-term intake of low-dose alcohol can antagonize excessive production of Aß and slow down AD progression.

Optimized ultra-high-pressure-assisted extraction of procyanidins from lychee pericarp improves the antioxidant activity of extracts.

To establish optimal ultra-high-pressure (UHP)-assisted extraction conditions for procyanidins from lychee pericarp, a response surface analysis method with four factors and three levels was adopted. The optimum conditions were as follows: 295 MPa pressure, 13 min pressure holding time, 16.0 mL/g liquid-to-solid ratio, and 70% ethanol concentration. Compared with conventional ethanol extraction and ultrasonic-assisted extraction methods, the yields of the total procyanidins, flavonoids, and phenolics extracted using the UHP process were significantly increased; consequently, the oxygen radical absorbance capacity and cellular antioxidant activity of UHP-assisted lychee pericarp extracts were substantially enhanced. LC-MS/MS and high-performance liquid chromatography quantification results for individual phenolic compounds revealed that the yield of procyanidin compounds, including epicatechin, procyanidin A2, and procyanidin B2, from lychee pericarp could be significantly improved by the UHP-assisted extraction process. This UHP-assisted extraction process is thus a practical method for the extraction of procyanidins from lychee pericarp.

Comparative effects of EtOH consumption and thiamine deficiency on cognitive impairment, oxidative damage, and ß-amyloid peptide overproduction in the brain.

The effects of chronic EtOH consumption, associated or not with thiamine deficiency (TD), on cognitive impairment, oxidative damage, and ß-amyloid (Aß) peptide accumulation in the brain were investigated in male C57BL/6 mice. We established an alcoholic mouse model by feeding an EtOH liquid diet, a TD mouse model by feeding a thiamine-depleted liquid diet, and an EtOH treatment associated with TD mouse model by feeding a thiamine-depleted EtOH liquid diet for 7 weeks. The learning and memory functions of the mice were detected through the Y-maze test. Biochemical parameters were measured using corresponding commercial kits. The Aß expression in the hippocampus was observed by immunohistochemical staining. Several results were obtained. First, EtOH significantly reduced cognitive function by significantly decreasing the Glu content in the hippocampus; increasing the AChE activity in the cortex; and reducing the thiamine level, and superoxide dismutase (SOD), glutathione peroxidase (GPx), and choline acetyltransferase (ChAT) activities in both the hippocampus and cortex. The treatment also increased the levels of malondialdehyde (MDA), protein carbonyl, 8-hydroxydeoxyguanosine (8-OHdG), and nitric oxide (NO) and the activities of total nitric oxide synthase (tNOS), inducible nitric oxide synthase (iNOS), and monoamine oxidase B (MAO-B). Furthermore, EtOH enhanced the expression levels of Aß1-42 and Aß1-40 in the hippocampus. Second, TD induced the same dysfunctions caused by EtOH in the biochemical parameters, except for learning ability, 8-OHdG content, and GPx, tNOS, and AChE activities in the cortex. Third, the modification of MDA, protein carbonyl and NO levels, and GPx, iNOS, ChAT, and MAO-B activities in the brain induced by chronic EtOH treatment associated with TD was greater than that induced by EtOH or TD alone. The synergistic effects of EtOH and TD on Aß1-40 and Glu release, as well as on SOD activity, depended on their actions on the hippocampus or cortex. These findings suggest that chronic EtOH consumption can induce TD, cognitive impairment, Aß accumulation, oxidative stress injury, and neurotransmitter metabolic abnormalities. Furthermore, the association of chronic EtOH consumption with TD causes dramatic brain dysfunctions with a severe effect on the brain.

Lychee pulp phenolics ameliorate hepatic lipid accumulation by reducing miR-33 and miR-122 expression in mice fed a high-fat diet.

Dietary phenolics exhibit hypolipidemic activity by changing lipid metabolism-related microRNA (miRNA) expression. Quercetin 3-O-rutinoside-7-O-α-l-rhamnosidase (quercetin 3-rut-7-rha), rutin and (-)-epicatechin are the main phenolics in lychee (Litchi chinensis Sonn.) pulp. A previous study reported that quercetin 3-rut-7-rha and rutin had hypolipidemic effects. To elucidate these effects and the underlying molecular mechanisms of lychee pulp phenolics (LPPs), the hepatic mRNA and protein expression of lipid metabolism-related genes and their associated miRNAs were measured after ten weeks of treatment with a high-fat diet (HFD) alone or in combination with LPPs. The administration of LPPs significantly reduced the HFD-induced increase in serum total cholesterol and triglyceride levels but increased the HDL-c content. The mRNA and protein expression levels of hepatic adenosine triphosphate-binding cassette transporter A1 (ABCA1) and carnitine palmitoyltransferase 1a (CPT1a) were upregulated, while fatty acid synthase (FAS) mRNA and the corresponding protein expression levels were downregulated by LPPs. Furthermore, the expression levels of miR-33, which directly modulates ABCA1 and CPT1a, and miR-122, which indirectly regulates FAS, were downregulated in mouse hepatocytes. The repression of miR-33 and miR-122 is a possible molecular mechanism of the hypolipidemic effects of LPPs in the liver. Our results suggest a novel hypolipidemic mechanism of LPPs.

Improved treatment of early small hepatocellular carcinoma using sorafenib in combination with radiofrequency ablation.

Small hepatocellular carcinoma is an important leading cause of death amongst cancer patients, our study was designed in order to test the hypothesis that radiofrequency ablation (RFA) combined with a chemotherapeutic drug would improve the outcome for patients. Two groups of patients presenting early small hepatocellular carcinoma were treated with either conventional RFA alone (50 individuals in the control group), or with a combination of RFA and oral sorafenib (40 individuals in an observation group). Individual clinical and laboratory evaluations were done during an average follow-up time of 35 months, and all the data recorded was used to compare results of both treatment approaches. Tumor-free survival, relapse rate and survival rate, RFA interval and number of treatments, overall efficacy and the incidence of complications were analyzed. Serum levels of vascular endothelial growth factor (VEGF), connective tissue growth factor (CTGF), hypoxia inducible factor-1α (HIF-1α) and osteopontin (OPN) were measured and compared. Our results show that the patients in the treatment group had statistically significant prolonged tumor-free survival, decreased relapse and increased survival rates. Also, the patients in the treatment group had significantly more prolonged average intervals of RFA and a lower number of treatments. Furthermore, the overall efficacy in the treatment group was increased, yet the incidence of complications was similar between both groups. Moreover, the serum levels of known tumorigenic factors VEGF, CTGF, HIF-1α and OPN, which were similar between both groups before treatment, improved more markedly after the treatment in the observation group patients. Based on these findings, we propose that sorafenib in combination with percutaneous RFA is safe and efficacious, and a superior treatment for early small hepatocellular carcinoma. Larger studies are needed to corroborate our results.

[Relationship between chronic psychosocial stress and BMI among adolescents].

OBJECTIVE: To evaluate the influence of chronic psychosocial stress on BMI in adolescents. METHODS: Physical examination and questionnaire survey were conducted among the students of junior grade 1 and senior grade 1 in 10 middle schools in Xuzhou in September 2011. Their body height and weight were measured at baseline survey and the self-report information about socio-demographic data, emotional symptoms (depressive symptoms, anxiety symptoms), and life style/behavior were collected from them. Chronic psychosocial stress was assessed with Multidimensional Life Events Rating Questionnaire (MLERQ), which consists of five items, stress of family life, school life, peer relation, gender relation and health growth. RESULTS: A total of 5473 valid questionnaires were collected for analysis (2841 from boys and 2632 from girls). The follow-up measurement of body height and weight were conducted in September 2013. A total of 4316 students (2171 boys, 2145 girls) were surveyed, and 1157 students missed the follow up. The psychosocial stress score in the overweight and obese girls at baseline survey was positively associated with BMI-Z increase at follow up survey (P<0.01). No such effect was observed among the boys at follow-up survey. CONCLUSION: High level of chronic psychosocial stress could lead to BMI increase in overweight and obese girls, suggesting that female adolescents are susceptible population of psychosocial stress induced obesity.

Emotion regulation, emotional eating and the energy-rich dietary pattern. A population-based study in Chinese adolescents.

Research investigating the influence of emotion regulation (ER) strategies on emotional eating and diet among Chinese adolescents is scarce. The aim of this study was to test associations between two ER strategies (suppression/cognitive reappraisal), emotional eating, and an energy-rich dietary pattern. A total of 4316 adolescents from 10 high schools were surveyed. Dietary patterns were derived using factor analysis. Bivariate correlations were analyzed to examine associations between ER strategies, emotional eating behavior and an energy-rich dietary pattern, by gender. The mediating effect of emotional eating in the relationship between ER and energy-rich food consumption by gender was estimated using structural equation modeling. A higher level of suppression, but no lack of cognitive reappraisal, was associated with emotional eating in boys and girls. A higher level of suppression and lack of cognitive reappraisal were associated with a greater intake of energy-rich foods in girls only. Emotional eating mediated the relationship between a higher level of suppression and a greater intake of energy-rich food in girls. This study revealed significant associations between two ER strategies and an energy-rich dietary pattern in girls, and provided evidence that higher levels of suppression may put girls at risk for emotional eating, potentially affecting the energy-rich dietary pattern.

Ameliorative effect of lotus seedpod proanthocyanidins on cognitive impairment and brain aging induced by D-galactose.

This study mainly investigated the ameliorative effect of lotus seedpod proanthocyanidins (LSPC) and the mechanism underlying such effect on cognitive impairment and brain aging induced by d-galactose. Aging mice induced by d-galactose (150 mg/kg, sc injection daily for 6 weeks) were chosen for the experiment. LSPCs (30, 60, and 90 mg/kg, ig) were provided after d-galactose injection. Learning and memory functions were detected by Y-maze and step-down avoidance tests. Then, some biochemical indexes related to cognitive ability and aging were measured. Histopathological feature and P53 protein expression in the hippocampus were observed. Results showed that the three different doses of LSPC could significantly ameliorate the learning and memory abilities impaired by d-galactose. LSPC significantly reduced the levels of malondialdehyde and nitric oxide (i.e. 90 mg/kg LSPC group vs. model group, P=0.008), reduced the content of ß-amyloid peptide 1-42 (i.e. 90 mg/kg LSPC group vs. model group, P=0.009), decreased the activities of acetylcholinesterase, monoamine oxidase B, total nitric oxide synthase (i.e. 90 mg/kg LSPC group vs. model group, P=0.006), and neuronal nitric oxide synthase and synchronously increased the activities of superoxide dismutase and glutathione peroxidase in the brain. Furthermore, LSPC could prevent neuron damage and could lessen the expression of P53 protein in the hippocampus. These findings demonstrated that LSPC effectively attenuated cognitive damage and improved parameters related to brain aging in senescent mice induced by d-galactose, and may be used to treat Alzheimer's disease.

Silencing of angiotensin II type-1 receptor inhibits high glucose-induced epithelial-mesenchymal transition in human renal proximal tubular epithelial cells via inactivation of mTOR/p70S6K signaling pathway.

The epithelial-mesenchymal transition (EMT) plays a significant role in renal tubulointerstitial fibrosis (TIF), which is one of hallmark pathological feature of diabetic nephropathy (DN). Angiotensin II via its type-1 receptor AT1R is involved in the development of TIF. The purpose of our study was aimed to investigate the effect of silencing of AT1R on EMT and elucidate the possible mechanism underling these effects. EMT was induced by high glucose (HG) in human proximal tubular epithelial cell line HK-2 cells. The mRNA levels of AT1R were determined. The expression of AT1R was silenced by small interfering RNA (siRNA) technology and confirmed by quantitative real time PCR (qRT-PCR). After transfection with siAT1R, cell viability and expression levels of epithelial cell marker (epithelial (E)-cadherin), mesenchymal cell marker (alpha-smooth muscle actin (α-SMA)), four transcriptional factors (snail, slug, twist, and ZEB-1) were determined, as well as the roles of mechanistic target of rapamycin (mTOR)/p70S6K signaling pathway. The levels of AT1R were significantly higher after exposure to HG (P < 0.05). Transfection with siAT1R had no effect on cell viability, but reversed HG-induced EMT by up-regulation of E-cadherin expression and decrease of α-SMA, snail, and twist levels. MTOR/p70S6K signaling pathway was highly activated in HK-2 cells cultured under HG, but was inhibited by transfection with siAT1R. Our results suggest that silencing of AT1R inhibits EMT induced by HG in HK-2 cells via inactivation of mTOR/p70S6K signaling pathway. Silencing of AT1R might be a new strategy to treat DN.

[Relations between duration of sleep, dietary patterns and the prevalence of overweight/obesity among 11-13 year-olds in Xuzhou, Jiangsu province of China].

OBJECTIVE: To describe the relationships between sleep duration, dietary patterns and overweight/obesity among adolescents in Xuzhou, and to develop prevention and intervention strategies for adolescent-obesity. METHODS: Data of 3 103 boys and girls from 5 junior high schools were analyzed. Self-reported information on duration of sleep, dietary patterns, physical activities and time spent on watching video/audio program were assessed and physique data was also collected. Descriptive statistics, multiple liner regression and logistic regression models were used. RESULTS: The prevalence rates on overweight and obesity in boys were 23.5% and 22.5% , and in girls were 18.1% and 11.9%, respectively. Proportions of insufficient sleep (<8 h/d) in boys appeared 28.1% and in girls as 33.0% . From logistic regression analysis revealed that there appeared risk on the prevalence of overweight and obesity in boys who had sleep duration <7 h/d [OR(95% CI):1.72 (1.08-2.74)], but no significant association was found between duration of sleep and overweight/ obesity in girls. After adjusting on age, levels of parental education, family income, physical activities, time spent on watching video/audio programs, and weight status, boys who had sleep duration less than 7 h/d would have the odds ratio of 1.69 (1.10-2.73), for the likelihood of increasing the frequency of eating snacks compared to their counterparts who had sleep duration of ≥ 8 h/d. CONCLUSION: The Shortened duration of sleep seemed an independent risk factor on overweight/obesity among male adolescents, and it was associated with the increased frequency of eating snacks. Data from our study showed that the dietary patterns might play a role in the association between duration of sleep and overweight/ obesity, among male adolescents.

Comparison of the free and bound phenolic profiles and cellular antioxidant activities of litchi pulp extracts from different solvents.

BACKGROUND: The phenolic contents and antioxidant activities of fruits could be underestimated if the bound phenolic compounds are not considered. In the present study, the extraction efficiencies of various solvents were investigated in terms of the total content of the free and bound phenolic compounds, as well as the phenolic profiles and antioxidant activities of the extracts. METHODS: Five different solvent mixtures were used to extract the free phenolic compounds from litchi pulp. Alkaline and acidic hydrolysis methods were compared for the hydrolysis of bound phenolic compounds from litchi pulp residue. The phenolic compositions of the free and bound fractions from the litchi pulp were identified using HPLC-DAD. The antioxidant activities of the litchi pulp extracts were determined by oxygen radical absorbance capacity (ORAC) and cellular antioxidant activity (CAA) assays. RESULTS: Of the solvents tested, aqueous acetone extracted the largest amount of total free phenolic compounds (210.7 mg GAE/100 g FW) from litchi pulp, followed sequentially by aqueous mixtures of methanol, ethanol and ethyl acetate, and water itself. The acid hydrolysis method released twice as many bound phenolic compounds as the alkaline hydrolysis method. Nine phenolic compounds were detected in the aqueous acetone extract. In contrast, not all of these compounds were found in the other four extracts. The classification and content of the bound phenolic compounds released by the acid hydrolysis method were higher than those achieved by the alkaline hydrolysis. The aqueous acetone extract showing the highest ORAC value (3406.9 µmol TE/100 g FW) for the free phenolic extracts. For the CAA method, however, the aqueous acetone and methanol extracts (56.7 and 55.1 µmol QE/100 g FW) showed the highest levels of activity of the five extracts tested. The ORAC and CAA values of the bound phenolic compounds obtained by acid hydrolysis were 2.6- and 1.9-fold higher than those obtained using the alkaline hydrolysis method. CONCLUSIONS: The free and bound phenolic contents and profiles and antioxidant activities of the extracts were found to be dependent on the extraction solvent used. Litchi exhibited good cellular antioxidant activity and could be a potentially useful natural source of antioxidants.

Cortisol reactivity, delay discounting and percent body fat in Chinese urban young adolescents.

The purpose of this study is to test the relation of cortisol reactivity, delay discounting and percent body fat (PBF) in adolescents aged 12-13 years (N=87), and evaluate the delay discounting as potential components in models of adolescent obesity. Anthropometry and body composition measurements were assessed in adolescents. The cortisol reactivity to Trier Social Stress Test for Children (TSST-C) and delay discounting were measured. The result showed increased cortisol reactivity and greater delay discounting were associated with higher PBF in girls. Structural equation modeling supported greater delay discounting as a mediator of relations between increased cortisol reactivity and PBF in adolescent girls. The proposed mediation model indicated that cortisol reactivity is linked to PBF through delay discounting, thereby supporting a significant indirect relationship. The direct relationship between increased cortisol reactivity and higher PBF was significant in a model that did not include delay discounting, and was still significant in the mediation model that included delay discounting. This study provides the first evidence that greater delay discounting may partially account for the relationship of hyperactivity of the HPA-axis and higher PBF in girls.

Effects of emotional symptoms and life stress on eating behaviors among adolescents.

The aim of this study was to explore possible effects of emotional symptoms (depressive symptoms and anxiety symptoms) and life stress on eating behaviors (restrained, emotional and external eating behaviors) among junior and high school students in China. A total of 5473 students in Xuzhou, Jiangsu Province were sampled to participate in this survey based on a clustering sampling approach. The survey collected sociodemographic data, emotional symptoms, life stress and eating behaviors of adolescents. Spearman correlation coefficients were measured and tested to examine the relationship between eating behaviors and emotional symptoms as well as life stress. In addition, we analyzed the data using Chi-square tests and multivariate logistic regression models. The results showed positive correlation between emotional symptoms, life stress, and eating behaviors. Furthermore, depressive symptoms, anxiety symptoms and life stress were significantly associated with unhealthy eating behaviors, after adjusting for gender, age, BMI, parental education level and self-assessed family economic status. This study suggests that a comprehensive intervention focusing on emotion and stress management would be helpful for the prevention of unhealthy eating behaviors among Chinese adolescents.