MiR-424 Inhibits neuronal apoptosis in rats with cerebral infarction through regulating TGF-ß1/Smad3 signaling pathway.

It has been reported that micro ribonucleic acid (miR)-424 is an important molecule in cerebral ischemia. However, the precise mechanism of action and biological effects of miR-424 remain to be further explored. miR-424 mimic and miR-424 inhibitor were injected via the caudal vein in rats, and the effect of miR-424 expression on brain tissue damage induced by middle cerebral artery occlusion (MCAO) was detected. The miR-424 mimic-induced changes in genomic levels were detected via the gene chip assay, and the signaling pathways regulated by miR-424 and its potential targets were explored combined with target prediction. Then the effect of miR-424 mimic on apoptosis of PC12 cells induced by oxygen-glucose deprivation (OGD) was determined using Annexin V/PI assay. Finally, drosophila mothers against decapentaplegic protein 7 (Smad7) was overexpressed to further verify the mechanism of action of miR-424 mimic. Compared with that in the sham group, the expression of miR-424 in brain tissues significantly declined in the model group. The results of 2,3,5-triphenyltetrazolium chloride (TTC) staining and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay revealed that the miR-424 mimic obviously reduced the cerebral infarction area and apoptosis level of brain tissues, while the miR-424 inhibitor obviously increased the cerebral infarction area and apoptosis level of brain tissues. It was found, using bioinformatics and KEGG enrichment analysis, that differentially expressed genes induced by miR-424 were significantly enriched in the transforming growth factor-ß (TGF-ß) signaling pathway. According to the results of reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blotting, the miR-424 mimic could evidently lower the expression of Smad7, thus activating the TGF-ß1/Smad3 signaling pathway. Overexpression of Smad7 could weaken the protective effect of miR-424 mimic on ischemic-hypoxic cells. Increasing the expression of miR-424 can inhibit Smad7 to activate the TGF-ß1/Smad3 signaling pathway, thereby exerting a protective effect against the brain tissue damage induced by MCAO.

Peripheral telomere length and hippocampal volume in adolescents with major depressive disorder.

Several studies have reported that adults with major depressive disorder have shorter telomere length and reduced hippocampal volumes. Moreover, studies of adult populations without major depressive disorder suggest a relationship between peripheral telomere length and hippocampal volume. However, the relationship of these findings in adolescents with major depressive disorder has yet to be explored. We examined whether adolescent major depressive disorder is associated with altered peripheral telomere length and hippocampal volume, and whether these measures relate to one another. In 54 unmedicated adolescents (13-18 years) with major depressive disorder and 63 well-matched healthy controls, telomere length was assessed from saliva using quantitative polymerase chain reaction methods, and bilateral hippocampal volumes were measured with magnetic resonance imaging. After adjusting for age and sex (and total brain volume in the hippocampal analysis), adolescents with major depressive disorder exhibited significantly shorter telomere length and significantly smaller right, but not left hippocampal volume. When corrected for age, sex, diagnostic group and total brain volume, telomere length was not significantly associated with left or right hippocampal volume, suggesting that these cellular and neural processes may be mechanistically distinct during adolescence. Our findings suggest that shortening of telomere length and reduction of hippocampal volume are already present in early-onset major depressive disorder and thus unlikely to be only a result of accumulated years of exposure to major depressive disorder.

Antibody depletion prolongs xenograft survival.

BACKGROUND: The lack of human organ donors has prompted a renewed interest in xenotransplantation. Xenoantibody is believed to be an initiator of a complex cascade of events ultimately ending in rapid xenograft destruction. METHODS: Cell-free plasma was obtained via plasmapheresis of the recipient canine. This plasma was then perfused in an ex vivo fashion through either the donor (pig) spleen or liver, allowing for specific antidonor antibody deposition in the "screening" organ, and is then returned to the animal. A porcine kidney is then transplanted to the dog, and the outcome is observed. RESULTS: We have used specific antibody depletion to prolong xenotransplant survival. In the untreated pig-to-dog combination, the transplanted pig kidney is destroyed by the dog in 13 minutes (mean). Adsorption using either the donor spleen or liver resulted in an increase of 3.4 hours and 7.8 hours of graft survival, respectively. The histologic picture of rejected kidneys after adsorption shows a modified form of rejection. CONCLUSIONS: In this pig-to-dog xenograft combination, xenoantibody adsorption allows for prolonged graft survival as compared with control animals. Subsequent xenograft destruction occurs but in a modified manner.

Stress echocardiography, contrast echocardiography, and tissue characterization: applications for the future.

During the last three decades the application of ultrasonography has expanded rapidly. The information available to the clinician from ultrasound imaging today is vastly more significant than it was in the early years of the development of this technology. In addition to automatic information, there is an increasing potential to provide functional, dynamic perfusion and even cellular information about the heart. This article attempts to summarize briefly the advances in these areas.

[Studies on chemical constituents of leaves of Salix matsudana Koidz and their influence on lipolysis].

OBJECTIVE: To study the chemical constituents of the leaves Salix matsudana and their influence on norepinephrine-induced lipolysis. METHOD: The chemical constituents were studied by means of chemical methods and spectral analysis. Rat's epididymal lipocytes were used to observe the effect of these constituents on the lipolysis promoted by norepinephrine (NE). RESULT: Three constituents were isolated from the leaves of S. matsudana, and identified as apigenin-7-O-beta-D-glucopyranoside, luteolin-7-O-beta-D-glucopyranoside, luteolin-3'-methyl ether-7-O-beta-D-glucopyranoside, of which two can increase the release of free fatty acids(FFA) in the process lipolysis promoted by NE. CONCLUSION: All the three constituents were isolated from the leaves of Salix spp. for the first time.

Does pulmonary rehabilitation give additional benefit over tiotropium therapy in primary care management of chronic obstructive pulmonary disease? Randomized controlled clinical trial in Hong Kong Chinese.

OBJECTIVE: To evaluate whether multidisciplinary pulmonary rehabilitation programme (PRP) provides additional benefit over tiotropium therapy in managing chronic obstructive pulmonary disease (COPD) in primary care. DESIGN: A randomized controlled trial to analyse the difference in outcomes of COPD patients receiving tiotropium plus PRP vs. tiotropium treatment alone. SETTING: Two primary care teaching clinics affiliated with a university which serves a population of 600,000. PARTICIPANTS: Fifty primary care COPD patients. METHODS: Fifty subjects underwent spirometry and their status of COPD was confirmed by using the Vitalograph Gold Standard. They were then assessed by the 6-min walking distance (6MWD), Peak Visual Analogue Scale (Peak VAS) and Chronic Respiratory Disease Questionnaire (CRQ). All subjects were given tiotropium to optimize their treatment. After a 6-week period, half were randomized to the intervention group (i.e. receiving PRP), whereas the rest were randomized to control group which received only medication. Spirometry, 6MWD, Peak VAS and CRQ were performed in both groups at 6 weeks, 12 weeks and 3 months. OUTCOMES: Spirometry, 6MWD, Peak VAS and CRQ. RESULTS: Significant improvement (P < 0.05) was seen in 6MWD, symptoms of dyspnoea measured by Peak VAS and CRQ. The improvement was sustained at 3-month follow-up. However, no additional significant improvement was seen in the intervention group when compared with control. CONCLUSION: Tiotropium therapy has improved health outcomes in COPD patients in primary care settings. A 6 weekly PRP did not give any additional benefits in patients already given tiotropium.

[Medicinal plant and its related metabolic modulators].

We suggested a strategy for identifying anti-obesity drugs. The strategy aimed to prevent obesity through inhibiting intestinal absorption of dietary fat. Intestinal absorption of dietary fat was found to be reduced by tea saponin and chitosan through inhibiting pancreatic lipase activity, by chondroitin sulfate through inhibiting both pancreatic lipase activity and fatty acid absorption, and by lactosucrose through inhibiting beta-monoglyceride absorption. All these functional substances reduced plasma triglyceride levels previously elevated by oral administration of a lipid emulsion containing corn oil. Furthermore, these substances were found to cause reduction in perimetrial adipose tissue weight, which had been elevated by oral administration of a high fat diet (containing 40% of beef tallow) to female mice. Based on these results, a strategy for identifying anti-obesity drugs was discussed.

Reduction in fat storage during chitin-chitosan treatment in mice fed a high-fat diet.

OBJECTIVE: Chitin and chitosan are polymers containing more than 5000 acetylglucosamine and glucosamine units, respectively, and their molecular weights are over one million Daltons. The present study assessed the effects of chitin-chitosan on the activity of pancreatic lipase in vitro and on the degree of fat storage induced in mice by the oral administration of a high-fat diet for nine weeks. DESIGN: Mice were fed a high-fat diet and treated with chitin-chitosan for nine weeks. Experiments were also carried out to clarify whether or not chitin-chitosan inhibited pancreatic lipase activity in assay systems using triolein emulsified with lecithin, gum arabic or Triton X-100. RESULTS: Chitin-chitosan prevented the increase of body weight, hyperlipidaemia and fatty liver induced by a high-fat diet. Chitin-chitosan inhibited hydrolysis of triolein, emulsified with phosphatidylcholine, but not that of triolein emulsified with gum arabic and Triton X-100. These results suggest that the site of inhibitory action of chitin-chitosan may not be the enzyme but its substrate. CONCLUSION: The anti-obesity effects of chitin-chitosan in high-fat diet-treated mice might be partly due to the inhibition of intestinal absorption of dietary fat. Consequently, chitin-chitosan might cause improvement of the fatty liver and hyperlipidaemia in mice fed a high fat diet through inhibiting intestinal absorption of dietary fat.

Platycodi radix affects lipid metabolism in mice with high fat diet-induced obesity.

An aqueous extract of Platycodi radix inhibited the hydrolysis of triolein emulsified with phosphatidylcholine by pancreatic lipase in vitro and it reduced the elevation of rat plasma triacylglycerol level 2-4 h after oral administration of a lipid emulsion containing corn oil. These preliminary results suggested that the aqueous extract of Platycodi radix may inhibit the intestinal absorption of dietary fat by inhibiting its hydrolysis. Therefore, we examined the antiobesity activity of the aqueous extract of Platycodi radix by testing whether the extract prevented the obesity induced by feeding a high fat diet to mice for 8 wk. Body weights at 3-8 wk and the final parametrial adipose tissue weights were significantly lower in mice fed the high fat diet containing 5% aqueous extract of Platycodi radix than in the controls fed the high fat diet. The aqueous extract of Platycodi radix also significantly reduced hepatic triacylglycerol concentrations that were elevated in mice fed the high fat diet alone. Inulin, which is a major component of Platycodi radix, had no effect on the hydrolysis of triolein emulsified with phosphatidylcholine by pancreatic lipase in vitro, and did not prevent obesity or the fatty liver induced by the high fat diet. On the other hand, the total saponin fraction of the aqueous extract inhibited pancreatic lipase activity in vitro. Therefore, the antiobesity effect of the aqueous extract of Platycodi radix in mice fed a high fat diet may be due in part to the inhibition of intestinal absorption of dietary fat by the saponins of Platycodi radix.

Norepinephrine-augmenting lipolytic effectors from Astilbe thunbergii rhizomes.

An EtOAc-soluble fraction from a 80% Me2CO extract of the rhizomes of Astilbe thunbergii enhanced norepinephrine-induced lipolysis in rat fat cells, while an EtOAc-insoluble fraction had no effect. The active substances isolated from the EtOAc-soluble fraction of the rhizomes were identified as eucryphin (1), bergenin (2), and astilbin (3), which enhanced norepinephrine-induced lipolysis at concentrations of 10-1000 microgram/mL, while they themselves did not cause lipolysis. Furthermore, these compounds slightly stimulated adrenocorticotrophic hormone-induced lipolysis and inhibited insulin-induced lipogenesis from glucose.

Isolation of lipolytic substances caffeine and 1,7-dimethylxanthine from the stem and rhizome of Sinomenium actum.

We attempted to isolate lipolytic substances from the stem and rhizome of Sinomenium actum Rehder et Wilson by using high-performance liquid chromatography (HPLC). S-I and S-II were isolated from the fractions showing lipolytic activity. S-I and S-II were identified as caffeine and 1,7-dimethylxanthine, respectively, by direct comparison with authentic samples. Caffeine (S-I) dose-dependently stimulated lipolytic activity in isolated fat cells of rats, at concentrations of 500 to 1000 microM. 1,7-Dimethylxanthine (S-II) also stimulated lipolytic activity at concentrations of 500 to 1000 microM. Furthermore, we found that caffeine and 1,7-dimethylxanthine enhanced catecholamine-induced lipolysis at lower concentrations of 0.1 to 1 microM.

Anti-obesity action of oolong tea.

OBJECTIVE: Oolong tea is traditionally reported to have anti-obesity and hypolipidaemic effects. The present study was performed to clarify whether oolong tea prevented obesity induced in mice by the oral administration of a high-fat diet for 10 weeks. DESIGN: High-fat diet-induced obese mice were treated with oolong tea for 10 weeks. The effects of various active fractions isolated from oolong tea on noradrenaline-induced lipolysis were examined with isolated fat cells and a cell-free system consisting of lipid droplets and hormone-sensitive lipase (HSL). RESULTS: The mean food consumption was not significantly different between high-fat diet-treated mice and high-fat plus oolong tea diet-treated mice. Oolong tea prevented the obesity and fatty liver induced by a high-fat diet. A water extract of oolong tea enhanced noradrenaline-induced lipolysis, and the active substance was identified as caffeine. Caffeine enhanced noradrenaline-induced lipolysis in fat cells without a concomitant increase in HSL activity and also accelerated the hormone-induced lipolysis in a cell-free system consisting of lipid droplets and HSL, but not in the cell-free system with sonicated lipid droplets and HSL. Oolong tea extract inhibited pancreatic lipase activity. CONCLUSION: It was demonstrated that the anti-obesity effects of oolong tea in high-fat diet-treated mice might be due partly to the enhancing effect of caffeine isolated from oolong tea on noradrenaline-induced lipolysis in adipose tissue, and to the inhibitory action of some other substance in oolong tea on pancreatic lipase activity. Caffeine was found to enhance lipolysis through acting on lipid droplets but not on HSL. The results suggest that oolong tea may be an effective crude drug for the treatment of obesity and fatty liver caused by a high-fat diet.

Inhibitory effects of chondroitin sulfate prepared from salmon nasal cartilage on fat storage in mice fed a high-fat diet.

OBJECTIVE: Chondroitin sulfate is an acidic polymer consisting of repeating D-glucuronic acid and D-N-acetylgalactosamine units, and the N-acetylgalactosamine is substituted with the sulfate at either the 4' or 6' position, with approximately one sulfate being present per disaccharide unit. The present study assessed the effects of chondroitin sulfate on the activity of pancreatic lipase and lipid uptake into brush border membrane vesicles of the rat small intestine in vitro, and on the degree of fat storage induced in mice by the oral administration of a high-fat diet for 8 weeks. DESIGN AND MEASUREMENTS: Experiments were carried out to clarify whether or not chondroitin sulfate inhibited pancreatic lipase activity in assay systems using triolein emulsified with phosphatidylcholine or gum arabic. In addition, the effects of chondroitin sulfate on lipid absorption by brush border membrane vesicles were examined. Moreover, mice were fed a high-fat diet and treated with chondroitin sulfate for 8 weeks. RESULTS: Chondroitin sulfate dose-dependently inhibited the pancreatic lipase activity in an assay system using triolein emulsified with phosphatidylcholine. In addition, chondroitin sulfate inhibited the palmitic acid uptake into the brush border membrane vesicles of the rat jejunum. Chondroitin sulfate caused the reduction of body weight and parametrial adipose tissue weight, and prevention of fatty liver and hyperlipidemia in mice fed a high-fat diet. CONCLUSION: The reduction of fat storage and the antihyperlipidemic action of chondroitin sulfate might be due to the inhibition of small intestinal absorption of dietary fat through the inhibition of pancreatic lipase activity and fatty acid uptake through brush border membrane.

Anti-obesity effects in rodents of dietary teasaponin, a lipase inhibitor.

OBJECTIVE: Based on the inhibitory effects of teasaponin on pancreatic lipase activity in vitro, this study was performed to clarify whether teasaponin prevented obesity induced in mice by a high-fat diet for 11 weeks. DESIGN: For in vitro experiments, assay for the inhibitory effects of teasaponin on pancreatic lipase activity was performed by measuring the rate of release of oleic acid from triolein in an assay system using triolein emulsified with lecithin, gum arabic, Triton X-100 or 4-methylumbelliferyloleate. For in vivo experiments, female ICR mice were fed a high-fat diet with or without 0.5% teasaponin for 11 weeks. RESULTS: Teasaponin competitively inhibited the hydrolysis of triolein emulsified with lecithin, gum arabic, Triton X-100 or 4-methylumbelliferyloleate. Teasaponin inhibited the elevations of plasma triacylglycerol levels 3, 4 and 5 h after oral administration of lipid emulsion containing corn oil. Teasaponin suppressed the increases in body, parametrial adipose tissue weights and diameter in adipose cell size induced by a high-fat diet. Furthermore, feeding a high-fat diet plus teasaponin had no effect on stool frequency and content, but significantly increased triacylglycerol contents in feces as compared to feeding a high-fat diet. CONCLUSIONS: The anti-obesity effects of teasaponin in high-fat diet-treated mice may be partly mediated through delaying the intestinal absorption of dietary fat by inhibiting pancreatic lipase activity.