Dynamic change of the carotenoid metabolic pathway profile during oolong tea processing with supplementary LED light.

Carotenoid-derived volatiles are important contributors to tea aroma quality. However, the profile of the carotenoid pathway and carotenoid-derived volatiles (CDVs) artificial regulation in oolong tea processing has yet to be investigated. In the present work, the content and varieties of carotenoid-derived volatiles, the genome-wide identification of carotenoid cleavage dioxygenase (CsCCD) gene family, the expression level of CsCCD and other key genes in the carotenoid pathway, and the profile of carotenoid substances were analyzed by multi-omics and bioinformatics methods with innovative postharvest supplementary LED light during oolong tea processing. The results showed that during oolong tea processing, a total of 17 CDVs were identified. The content of ß-ionone increased up to 26.07 times that of fresh leaves and its formation was significantly promoted with supplementary LED light from 0.54 µg/g to 0.83 µg/g in the third turning over treatment. A total of 11 CsCCD gene family members were identified and 119 light response cis-acting regulatory elements of CsCCD were found. However, the expression level of most genes in the carotenoid pathway including CsCCD were reduced due to mechanical stress. 'Huangdan' fresh tea leaves had a total of 1 430.46 µg/g 22 varieties of carotenoids, which mainly composed of lutein(78.10%), ß-carotene(8.24%) and zeaxanthin(8.18%). With supplementary LED light, the content of antherxanthin and zeaxanthin in xanthophyll cycle was regulated and CDVs such as α-ionone, ß-ionone, pseudoionone, damascenone, 6,10-dimethyl-5,9-undecadien-2-one, citral, geranyl acetate and α-farnesene were promoted significantly in different phases during oolong tea processing. Our results revealed the profile of the carotenoid metabolism pathway in oolong tea processing from the perspective of precursors, gene expression and products, and put forward an innovative way to improve CDVs by postharvest supplementary LED light.

Integrated RNA-sequencing and network pharmacology approach reveals the protection of Yiqi Huoxue formula against idiopathic pulmonary fibrosis by interfering with core transcription factors.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a refractory disease. Therefore, developing effective therapies for IPF is the need of the hour. PURPOSE: Yiqi Huoxue Formula (YQHX) is an herbal formula comprising three herbal medicines: Ligusticum chuanxiong Hort. (Chuanxiong Rhizoma, CR), Panax notoginseng (Burk.) F. H. Chen (Notoginseng Radix Et Rhizoma, NR) and Panax ginseng C. A. Mey. (Ginseng Radix Et Rhizoma, GR). This study aims to determine the anti-pulmonary fibrosis effect of YQHX and explore its mechanism of action. STUDY: Design and Methods: The chemical components in the GR, CR and NR extracts were identified by High Performance Liquid Chromatography. A TGF-ß1-induced myofibroblast cell model was used to test the anti-fibrosis effect of GR, CR, NR and YQHX. RNA-sequencing was used to identify the differentially expressed genes (DEGs) after YQHX treatment. Subsequently, gene enrichment analysis and key transcription factors (TFs) prediction for YQHX-regulated DEGs was performed. The active constituents of GR, CR and NR were obtained from the Traditional Chinese Medicine Database and Analysis Platform. Targets of the active constituents were predicted using the similarity ensemble approach search server and Swiss Target Prediction tool. YQHX-targeted key TFs that transcribed the DEGs were screened out. Then, the effect of YQHX on the bleomycin-induced pulmonary fibrosis mouse model was studied. Finally, one of the predicted TFs, STAT3, was selected to validate the prediction accuracy. RESULTS: Seven, two, and five compounds were identified in the GR, CR, and NR extracts, respectively. YQHX and its constituents-GR, CR and NR-inhibited the expression of fibrotic markers, including α -SMA and fibronectin, indicating that YQHX inhibited TGF-ß1-induced myofibroblast activation. RNA-sequencing identified 291 genes that were up-regulated in the TGF-ß1 group but down-regulated after YQHX treatment. In total, 55 key TFs that transcribed YQHX-regulated targets were predicted. A regulatory network of 24 active ingredients and 232 corresponding targets for YQHX was established. Among YQHX's predicted targets, 20 were TFs. On overlapping YQHX-targeted TFs and DEGs' key TFs, six key TFs, including HIF1A, STAT6, STAT3, PPARA, DDIT3 and AR, were identified as the targets of YQHX. Additionally, YQHX alleviated bleomycin-induced pulmonary fibrosis in a mouse model by inhibiting the phosphorylation of STAT3 in the lungs of pulmonary fibrosis mice. CONCLUSIONS: This study provides pharmacological support for the use of YQHX in the treatment of IPF. The potential mechanism of action of YQHX is speculated to involve the modulation of core TFs and inhibition of pathogenetic gene expressions in IPF.

Matcha Green Tea Alleviates Non-Alcoholic Fatty Liver Disease in High-Fat Diet-Induced Obese Mice by Regulating Lipid Metabolism and Inflammatory Responses.

Lately, matcha green tea has gained popularity as a beverage and food additive. It has proved to be effective in preventing obesity and related metabolic syndromes. However, the underlying mechanisms of its control effects against non-alcoholic fatty liver disease (NAFLD) are complicated and remain elusive. In the present study, we performed an in vivo experiment using male C57BL/6 mice fed with a high-fat diet and simultaneously treated with matcha for six weeks. Serum biochemical parameters, histological changes, lipid accumulation, inflammatory cytokines, and relevant indicators were examined. Dietary supplementation of matcha effectively prevented excessive accumulation of visceral and hepatic lipid, elevated blood glucose, dyslipidemia, abnormal liver function, and steatosis hepatitis. RNA sequencing analyses of differentially expressed genes in liver samples indicated that matcha treatment decreased the activity of lipid droplet-associated proteins and increased the activity of cytochrome P450 enzymes, suggesting improved metabolic capacity and liver function. The current study provided evidence for new dietary strategies based on matcha supplementation to ameliorate lipotoxicity-induced obesity and NALFD.

Thermo-responsive polymer encapsulated gold nanorods for single continuous wave laser-induced photodynamic/photothermal tumour therapy.

Owing to strong and tunable surface plasmon resonance (SPR) effect and good biocompatibility, gold nanoparticles have been suggested to be a versatile platform for a broad range of biomedical applications. In this study, a new nanoplatform of thermo-responsive polymer encapsulated gold nanorods incorporating indocyanine green (ICG) was designed to couple the photothermal properties of gold nanorods (AuNRs) and the photodynamic properties of ICG to enhance the photodynamic/photothermal combination therapy (PDT/PTT). In addition to the significantly increased payload and enhancing photostability of ICG, the polymer shell in the nanoplatform also has thermo-responsive characteristics that can control the release of drugs at tumour sites upon the laser irradiation. On the basis of these improvements, the nanoplatform strongly increased drug aggregation at the tumour site and improved the photothermal/photodynamic therapeutic efficacy. These results suggest that this nanoplatform would be a great potential system for tumour imaging and antitumour therapy.

Matcha green tea prevents obesity-induced hypothalamic inflammation via suppressing the JAK2/STAT3 signaling pathway.

Obesity is an increasingly severe global health problem, leading to chronic inflammation and metabolic disorders in both peripheral tissues and the central nervous system. Matcha is a powdered green tea, and it is very popular in recent years as a beverage and food additive. Matcha green tea has been reported to have outstanding potential in regulating obesity-related metabolic syndrome. However, there are few studies on the regulation mechanism of matcha green tea on the central nervous system. In this study, we established a high-fat diet-induced obese mouse model. The results showed that dietary supplementation with matcha could effectively inhibit the weight gain, fat accumulation, glycemia and lipidemia increase, and excessive activation of microglia in the arcuate nucleus of the hypothalamus. Furthermore, we used different concentrations (100%, 80%, 60%, 40%, and 20%, v/v) of ethanol solution to prepare matcha ethanol extracts, and investigated their effects on palmitic acid-induced inflammation of microglial BV-2 cells. The results showed that matcha ethanol extracts could significantly reduce the release of inflammatory cytokines and the expression and phosphorylation of JAK2 and STAT3.

Green Tea Polyphenol (-)-Epigallocatechin Gallate (EGCG) Attenuates Neuroinflammation in Palmitic Acid-Stimulated BV-2 Microglia and High-Fat Diet-Induced Obese Mice.

Obesity is closely associated with neuroinflammation in the hypothalamus, which is characterized by over-activated microglia and excessive production of pro-inflammatory cytokines. The present study was aimed at elucidating the effects of (-)-epigallocatechin gallate (EGCG) on palmitic acid-stimulated BV-2 microglia and high-fat-diet-induced obese mice. The results indicated the suppressive effect of EGCG on lipid accumulation, pro-inflammatory cytokines (TNF-α, IL-6, and IL-1ß) release, and microglial activation in both cellular and high-fat-diet rodent models. These results were associated with lower phosphorylated levels of the janus kinase 2/signal transducers and activators of transcription 3 (JAK2/STAT3) signaling pathway. In conclusion, EGCG can attenuate high-fat-induced hypothalamic inflammation via inhibiting the JAK2/STAT3 signaling pathways in microglia.

Effects of (-)-Epigallocatechin Gallate (EGCG) on Energy Expenditure and Microglia-Mediated Hypothalamic Inflammation in Mice Fed a High-Fat Diet.

Obesity is an escalating global epidemic caused by an imbalance between energy intake and expenditure. (-)-Epigallocatechin-3-gallate (EGCG), the major polyphenol in green tea, has been reported to be conducive to preventing obesity and alleviating obesity-related chronic diseases. However, the role of EGCG in energy metabolism disorders and central nervous system dysfunction induced by a high-fat diet (HFD) remains to be elucidated. The aim of this study was to evaluate the effects of EGCG on brown adipose tissue (BAT) thermogenesis and neuroinflammation in HFD-induced obese C57BL/6J mice. Mice were randomly divided into four groups with different diets: normal chow diet (NCD), normal chow diet supplemented with 1% EGCG (NCD + EGCG), high-fat diet (HFD), and high-fat diet supplemented with 1% EGCG (HFD + EGCG). Investigations based on a four-week experiment were carried out including the BAT activity, energy consumption, mRNA expression of major inflammatory cytokines in the hypothalamus, nuclear factor-kappa B (NF-κB) and signal transducer and activator of transcription 3 (STAT3) phosphorylation, and immunofluorescence staining of microglial marker Iba1 in hypothalamic arcuate nucleus (ARC). Experimental results demonstrated that dietary supplementation of EGCG significantly inhibited HFD-induced obesity by enhancing BAT thermogenesis, and attenuated the hypothalamic inflammation and microglia overactivation by regulating the NF-κB and STAT3 signaling pathways.

Competing endogenous RNA screening based on long noncoding RNA-messenger RNA co-expression profile in Hepatitis B virus-associated hepatocarcinogenesis.

OBJECTIVE: To profile the liver cancer specific long noncoding RNAs (lncRNAs) and competing endogenous RNA (ceRNA) networks of Hepatitis B virus (HBV)-associated hepatocarcinogensis (HCG) and to examine the effect of compound K on the expression of identified ceRNA networks. METHODS: Based on lncRNA and messenger RNA (mRNA) microarray data of HBV-associated liver cancer, the current study profiles the cancer specific lncRNAs and ceRNA networks of HBV-associated HCG through comprehensive application of RegRNA 2, miRTarBase and Pearson correlation coefficient analysis. Compound K-treated liver cancer cells were harvested for analysis of transcriptional levels of both enoyl-CoA hydratase and 3-hydroxyacyl CoA dehydrogenase (EHHADH)-AS1 and ENTPD5. RESULTS: The results revealed that 11 Encyclopedia of DNA Elements annotated lncRNAs were differentially expressed in the process of HBV-associated HCG. Among these lncRNAs, 95 potential ceRNA networks with highly positively correlated expression profiles between the interacting lncRNAs and mRNAs (Pearson correlation coefficient > 0.7) were constructed. Of note, two HBV-associated ceRNA networks, EHHADH-AS1-hsa-miR-4459-ectonucleoside triphosphate diphosphohydrolase 5 and LINC01018-hsa-miRNA-574-5p-glucose-6-phosphatase catalytic subunit, with Pearson correlation coefficient > 0.9, may play a critical role in hepatocellular carcinoma development, which was supported by experimental evidence. Interestingly, compound K, an intestinal bacterial metabolite of ginseng protopanaxadiol saponin, which has been proven to promote apoptosis of human hepatocellular carcinoma cells, was found to impede the down-regulation of EHHADH-AS1 in several liver cancer cell lines including HepG3B, Huh-7 and plc/prf/5 cells. CONCLUSION: Comprehensive application of co-expression network analysis and prediction of RNA interaction may be a feasible strategy to unravel the potential ceRNA networks involved in the process of human diseases.

Optimization of diesel oil biodegradation in seawater using statistical experimental methodology.

Petroleum hydrocarbons released into the environment can be harmful to higher organisms, but they can be utilized by microorganisms as the sole source of energy for metabolism. To investigate the optimal conditions of diesel oil biodegradation, the Plackett-Burman (PB) design was used for the optimization in the first step, and N source (NaNO3), P source (KH2PO4) and pH were found to be significant factors affecting oil degradation. Then the response surface methodology (RSM) using a central composite design (CCD) was adopted for the augmentation of diesel oil biodegradation and a fitted quadratic model was obtained. The model F-value of 27.25 and the low probability value (<0.0001) indicate that the model is significant and that the concentration of NaNO3N, KH2PO4 and pH had significant effects on oil removal during the study. Three-dimensional response surface plots were constructed by plotting the response (oil degradation efficiency) on the z-axis against any two independent variables, and the optimal biodegradation conditions of diesel oil (original total petroleum hydrocarbons 125 mg/L) were determined as follows: NaNO3 0.143 g, KH2PO4 0.022 g and pH 7.4. These results fit quite well with the C, N and P ratio in biological cells. Results from the present study might provide a new method to estimate the optimal nitrogen and phosphorus concentration in advance for oil biodegradation according to the composition of petroleum.

High-dose glucocorticoids induce decreases calcium in hypothalamus neurons via plasma membrane Ca(2+) pumps.

In our previous studies, we occasionally found that high-dose glucocorticoids (GC) induced decrease in [Ca(2+)](i) in hypothalamus neurons. In previous articles, modulation of Ca(2+) channels by GC has been shown to contribute to the elementary regulation of several neuronal functions. However, little is known about the regulation of the Ca efflux pathways that counterbalance the Ca(2+) influx in neurons caused by high-dose GC. In this study, we demonstrate that a high-dose of GC (10 M dexamethasone) caused a 20% decrease in [Ca(2+)](i) within 2 s in cultured hypothalamic neurons; furthermore, we show that an antagonist of the GC receptor blocks this action. To ascertain the temporal sequence of relevant calcium transport mechanisms we selectively blocked the main calcium transporters, including sodium/calcium exchanger (NCX), plasma membrane calcium pumps (PMCA), and P-type Ca(2+)-ATPases of the sarcoplasmic reticulum (SERCA). The GC-induced [Ca(2+)](i) decrease disappeared completely when PMCA was blocked, but not when NCX and SERCA were blocked. These results suggest that high-dose GC (10(-6) M) rapidly decreases [Ca(2+)](i) by activating PMCA but not NCX or SERCA.