BDNF gene hydroxymethylation in hippocampus related to neuroinflammation-induced depression-like behaviors in mice.

BACKGROUND: Neuroinflammation is a multifactorial condition related to glial cells and neurons activation, and it is implicated in CNS disorders including depression. BDNF is a crucial molecule that related to the pathology of depression, and it is the target of DNA methylation. DNA hydroxymethylation, an active demethylation process can convert 5-mC to 5-hmC by Tets catalyzation to regulate gene transcription. The regulatory function for BDNF gene in response to neuroinflammation remains poorly understood. METHODS: Neuroinflammation and depressive-like behaviors were induced by lipopolysaccharide (LPS) administration in mice. The microglial activation and cellular 5-hmC localization in the hippocampus were confirmed by immunostaining. The transcripts of Tets and BDNF were examined by qPCR method. The global 5-hmC levels and enrichment of 5-hmC in BDNF gene in the hippocampus were analyzed using dot bolt and hMeDIP-sequencing analysis. RESULTS: LPS administration induced a spectrum of depression-like behaviors (including behavioral despair and anhedonia) and increased expression of Iba-1, a marker for microglia activation, in hippocampus, demonstrating that LPS treatment cloud provide stable model of neuroinflammation with depressive-like behaviors as expected. Our results showed that Tet1, Tet2 and Tet3 mRNA expressions and consequent global 5-hmC levels were significantly decreased in the hippocampus of LPS group compared to saline group. We also demonstrated that 5-hmC fluorescence in the hippocampus located in excitatory neurons identified by CaMK II immunostaining. Furthermore, we demonstrated that the enrichment of 5-hmC in BDNF gene was decreased and corresponding BDNF mRNA was down-regulated in the hippocampus in LPS group compared to saline group. CONCLUSION: Neuroinflammation-triggered aberrant BDNF gene hydroxymethylation in the hippocampus is an important epigenetic element that relates with depression-like behaviors.

Role of DNA hypomethylation in lateral habenular nucleus in the development of depressive-like behavior in rats.

BACKGROUND: Lateral habenula nucleus (LHb) has recently been noted for its role in stress-induced depressive disorder. Yet little is known about the mechanisms by which external stimuli or depression induces pathological alteration in the LHb. METHODS: Chronic unpredictable mild stress (CUMS) was employed to model depressive-like behaviors in adult rats. We examined expressions of DNA methyltransferases (Dnmts) mRNA and protein and global DNA methylation levels in LHb of CUMS-induced depressive rats. Then 5-aza-2'-deoxycytidine (5-aza), a Dnmts inhibitor, was infused into the LHb of native rats to test the effects of hypomethylation in the LHb. The gene expressions in the LHb and the levels of 5-HT and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) in dorsal raphe nucleus (DRN) were examined in 5-aza infusion rats by quantitative real-time PCR and high performance liquid chromatography, respectively. RESULTS: Rats were exposed to CUMS for 21 days and depressive-like behaviors were induced as expected. We observed significant decrease in mRNA and protein expressions of Dnmt1 and DNA hypomethylation in LHb of depressive rats. These phenomenon suggests that CUMS-induced depressive-like behaviors are related with DNA hypomethylation in the LHb. Local 5-aza infusion into LHb of native rat resulted in global DNA hypomethylation in the LHb and induced depressive-like behaviors which are featured with lack of interest and investment in the environment, behavioral despair and anhedonia. Moreover, DNA hypomethylation in the LHb increased transcription of ß calcium/calmodulin dependent protein kinase II and glutamate receptor 1 in the LHb and attenuated the levels of 5-HT and 5-HIAA in the DRN. Our data suggested that alteration of DNA methylation in the LHb may control 5-HT neuronal activity in the DRN to regulate emotional state. CONCLUSIONS: DNA hypomethylation in the LHb is involved in the development of depressive-like behavior and suitable methylation state contributes to the emotional stabilization.

Far-Infrared Optimization of the Fragrance-Improving Process with Temperature and Humidity Control for Green Tea.

In this study, a Box-Behnken design was used to explore the effect of a new technology on green tea fragrance improvement and to optimize fragrance-improving with a bilayer far-infrared fragrance-improving machine with temperature and humidity control. Based on the results of previous single-factor experiments, the main biochemical composition and sensory evaluation scores of the fragrance-improved samples were used as investigation indices. The new fragrance-improving technology was compared with the traditional far-infrared fragrance-improving process, roller pot fragrance improvement, and hot air rotary fragrance improvement. The results show that the optimal parameter combination of the new technology consists of a temperature of 128.00 °C, relative humidity of 70.00 g/h, and transmission speed of 435.00 r/min. With these process parameters, the amino acids, tea polyphenols, flavonoids, soluble sugar, catechins, and caffeine in the fragrance-improved samples reached 3.86%, 32.29%, 5.59%, 4.45%, 8.97%, and 2.75%, respectively. The quality material weight value was 11.72%. The shape, color, taste, and aroma of the fragrance-improved samples made using these parameters were found to be best, with a sensory quality score of 87.40, which is significantly higher than that of other fragrance-improving methods. The energy consumption was 0.19 RMB/kg, which was reduced by more than 50% compared with the other methods, and the production efficiency was more than 30% higher than the traditional methods. This new far-infrared fragrance-improving technology overcomes the yellowish and grayish color of fragrance-improved tea samples that is caused by the traditional fragrance-improving approach, and will provide technical guidance for actual green tea production. PRACTICAL APPLICATION: Our proposed approach innovatively integrates humidity and rotational speed as factors for fragrance improvement in Chinese tea process. The findings of this work provide new technical for fragrance improvement processes.

Characterization of the volatile components in green tea by IRAE-HS-SPME/GC-MS combined with multivariate analysis.

In the present work, a novel infrared-assisted extraction coupled to headspace solid-phase microextraction (IRAE-HS-SPME) followed by gas chromatography-mass spectrometry (GC-MS) was developed for rapid determination of the volatile components in green tea. The extraction parameters such as fiber type, sample amount, infrared power, extraction time, and infrared lamp distance were optimized by orthogonal experimental design. Under optimum conditions, a total of 82 volatile compounds in 21 green tea samples from different geographical origins were identified. Compared with classical water-bath heating, the proposed technique has remarkable advantages of considerably reducing the analytical time and high efficiency. In addition, an effective classification of green teas based on their volatile profiles was achieved by partial least square-discriminant analysis (PLS-DA) and hierarchical clustering analysis (HCA). Furthermore, the application of a dual criterion based on the variable importance in the projection (VIP) values of the PLS-DA models and on the category from one-way univariate analysis (ANOVA) allowed the identification of 12 potential volatile markers, which were considered to make the most important contribution to the discrimination of the samples. The results suggest that IRAE-HS-SPME/GC-MS technique combined with multivariate analysis offers a valuable tool to assess geographical traceability of different tea varieties.

Potent Inhibition of miR-34b on Migration and Invasion in Metastatic Prostate Cancer Cells by Regulating the TGF-ß Pathway.

The importance of miRNAs in the progression of prostate cancer (PCa) has further been supported by the finding that miRNAs have been identified as potential oncogenes or tumor suppressors in PCa. Indeed, in eukaryotes, miRNAs have been found to regulate and control gene expression by degrading mRNA at the post-transcriptional level. In this study, we investigated the expression of miR-34 family members, miR-34b and miR-34c, in different PCa cell lines, and discussed the molecular mechanism of miR-34b in the invasion and migration of PCa cells in vitro. The difference analyses of the transcriptome between the DU145 and PC3 cell lines demonstrated that both miR-34b and -34c target critical pathways that are involved in metabolism, such as proliferation, and migration, and invasion. The molecular expression of miR-34b/c were lower in PC3 cells. Moreover, over-expression of miR-34b/c in PC3 cells caused profound phenotypic changes, including decreased cell proliferation, migration and invasion. Moreover, the players that regulate expression levels of transforming growth factor-ß (TGF-ß), TGF-ß receptor 1 (TGF-ßR1), and p53 or phosphorylation levels of mothers against decapentaplegic 3 (SMAD3) in the TGF-ß/Smad3 signaling pathway have yet to be elucidated, and will provide novel tools for diagnosis and treatment of metastatic PCa.

Sensory quality evaluation for appearance of needle-shaped green tea based on computer vision and nonlinear tools.

Tea is one of the three greatest beverages in the world. In China, green tea has the largest consumption, and needle-shaped green tea, such as Maofeng tea and Sparrow Tongue tea, accounts for more than 40% of green tea (Zhu et al., 2017). The appearance of green tea is one of the important indexes during the evaluation of green tea quality. Especially in market transactions, the price of tea is usually determined by its appearance (Zhou et al., 2012). Human sensory evaluation is usually conducted by experts, and is also easily affected by various factors such as light, experience, psychological and visual factors. In the meantime, people may distinguish the slight differences between similar colors or textures, but the specific levels of the tea are hard to determine (Chen et al., 2008). As human description of color and texture is qualitative, it is hard to evaluate the sensory quality accurately, in a standard manner, and objectively. Color is an important visual property of a computer image (Xie et al., 2014; Khulal et al., 2016); texture is a visual performance of image grayscale and color changing with spatial positions, which can be used to describe the roughness and directivity of the surface of an object (Sanaeifar et al., 2016). There are already researchers who have used computer visual image technologies to identify the varieties, levels, and origins of tea (Chen et al., 2008; Xie et al., 2014; Zhu et al., 2017). Most of their research targets are crush, tear, and curl (CTC) red (green) broken tea, curly green tea (Bilochun tea), and flat-typed green tea (West Lake Dragon-well green tea) as the information sources. However, the target of the above research is to establish a qualitative evaluation method on tea quality (Fu et al., 2013). There is little literature on the sensory evaluation of the appearance quality of needle-shaped green tea, especially research on a quantitative evaluation model (Zhou et al., 2012; Zhu et al., 2017).

Preventive Effects of Catechins on Cardiovascular Disease.

Catechins are polyphenolic phytochemicals with many important physiological activities that play a multifaceted health care function in the human body, especially in the prevention of cardiovascular disease. In this paper, various experimental and clinical studies have revealed the role of catechins in the prevention and treatment of cardiovascular disorders, and we review the preventive effects of catechins on cardiovascular disease from the following aspects: Regulating lipid metabolism, regulating blood lipid metabolism, vascular endothelial protection, and reducing blood pressure.

The major factors influencing the formation of sediments in reconstituted green tea infusion.

The effects of Ca(2+), caffeine and polyphenols on the formation of reversible tea sediments (RTS) and irreversible tea sediments (IRS) in green tea infusion were studied. Adding Ca(2+) (2 mmol/l) was found to increase the formation of RTS by 8% and IRS by 92%, while adding chelating ions of Na2EDTA significantly decreased the amount of RTS by 14.6%, but not the amount of IRS. Under acid conditions, Ca(2+) combined with oxalic ions to form indissoluble oxalate that is the principal constituent of IRS, despite the existence of the chelating ions. Decaffeination largely inhibited the formation of RTS (73%) and IRS (60%), even in the presence of Ca(2+). The amount of sediment could be reduced by removing polyphenols using polyvinyl-polypyrrolidone. The results suggest that sediment formation in green tea infusions can be inhibited by lowering the concentration of Ca(2+), caffeine or polyphenols.

Sediments in concentrated green tea during low-temperature storage.

The formation and the main chemical components of sediments, including reversible tea sediments (RTS) and irreversible tea sediments (IRS), in concentrated green tea during low-temperature storage were studied. RTS was mainly formed in the first 10 days, and IRS was mainly formed between 20 and 40 days of storage. The RTS were the primary sediment, contributing more than 90% of the total sediment. The RTS comprised of polyphenols, total sugar, caffeine, flavones and proteins, while the IRS mainly comprised of oxalates of Ca, Mg, Ga and Mn. The total mineral content in the IRS (17.1%) was much higher than that in the RTS (2.6%) after 80 days of storage. The Ca, Mg, Mn and Ga contents in IRS were over 1.0% (w/w) each. About 75% of the IRS was soluble in 0.1 M aqueous HCl, with the oxalate accounting for 68%. Minerals and oxalic acid were the crucial factors in the IRS formation.

The impact of Ca2+ combination with organic acids on green tea infusions.

The effect of Ca(2+) in brewing water on the organic acid content, turbidity, and formation of tea cream and sediment in green tea infusions was studied. When the Ca(2+) concentration of the brewing water was >40 mg L(-1), the green tea infusion became more turbid. The turbidity of the tea infusion was highly negatively correlated with the contents of oxalic acid (R=-0.89, p<0.01), quinic acid (R=-0.90, p<0.01) and tartaric acid (R=-0.82, p<0.01). Oxalic acid on its own interacted with Ca(2+) at low concentrations, whereas polyphenols and protein did not. In conclusion, Ca(2+) in brewing water influences the quality of a tea infusion by inducing tea cream and sediment formation from combination of Ca(2+) and organic acids, such as oxalic acid, quinic acid and tartaric acid. Ca(2+) and oxalate are the main metal ion and anion, respectively, involved in tea cream and sediment formation on tea infusion cooling or concentrating.

Intracoronary versus intravenous administration of abciximab in patients with acute coronary syndrome: a meta-analysis.

BACKGROUND: Abciximab is a widely used adjunctive therapy for acute coronary syndrome (ACS). However, the effect of intracoronary (i.c.) administration of abciximab on cardiovascular events remains unclear when compared with intravenous (i.v.) therapy. METHODOLOGY AND PRINCIPAL FINDINGS: We systematically searched the Medline, Embase, and Cochrane Central Register of Controlled Trials databases and reference lists of articles and proceedings of major meetings for obtaining relevant literature. All eligible trials included ACS patients who received either i.c. administration of abciximab or i.v. therapy. The primary outcome was major cardiovascular events, and secondary outcomes included total mortality, reinfarction, and any possible adverse events. Of 660 identified studies, we included 9 trials reporting data on 3916 ACS patients. Overall, i.c. administration of abciximab resulted in 45% reduction in relative risk for major cardiovascular events (RR; 95% confidence interval [CI], 24-60%), 41% reduction in RR for reinfarction (95% CI, 7-63%), and 44% reduction in RR for congestive heart failure relative to i.v. therapy (95% CI, 8-66%); however, compared to i.v. therapy, i.c. administration of abciximab had no effect on total mortality (RR, 0.69; 95% CI, 0.45-1.07). No other significant differences were identified between the effect of i.c. abciximab administration and i.v. therapy. CONCLUSIONS/SIGNIFICANCE: I.c. administration of abciximab can reduce the risk of major cardiovascular events, reinfarction, and congestive heart failure when compared with i.v. therapy.

Irreversible sediment formation in green tea infusions.

The formation of irreversible tea sediment (IRS) and its chemical components in green tea infusions were investigated. The results showed that the amounts of IRS in the green tea infusions from various tea cultivars ranged from 0.10 to 1.47 mg/mL. The amount of IRS was influenced remarkably by the chemical components in the green tea infusion. Principal component analysis and regression analysis indicated that gallated catechins, Mn, Ca, caffeine, Na, and (-)-gallocatechin gallate (GCG) were the principal components. IRS (mg/mL) = -4.226 + 0.275 gallated catechins + 79.551 Na + 7.321 Mn + 21.055 Ca + 0.513 caffeine - 0.129 GCG (R2 = 0.697). The contents of the main chemical components in the reversible tea sediment (RTS) and IRS were markedly different, especially the minerals. Large amount of minerals participated in the formation of irreversible green tea sediment. The amount of IRS increased with the extraction temperature.

Analysis of cream formation in green tea concentrates with different solid concentrations.

The formation of tea cream in the green tea concentrates of different solid concentrations (5, 10, 20, 30, 40, 50 and 60°Brix) was investigated. The results showed a good positive correlation (γ = 0.98, p ≤ 0.05) between the amount of tea cream and the solid concentrations from 5 to 40°Brix, while the amount of tea cream in the tea concentrates of 50 and 60°Brix decreased acutely. Total sugar, caffeine and catechins were found to be the main chemical components of tea cream in the green tea concentrate. The large decrease of the amount of tea cream in the tea concentrates of 50 and 60°Brix may be induced by a sharp increase of the viscosity of the tea concentrates, which helped to improve the stability of tea concentrate. It may be indicated that the stability of green tea concentrate enhanced when the concentration higher than 50°Brix, which helped to restrain the formation of tea cream.