Association between green tea intake and digestive system cancer risk in European and East Asian populations: a Mendelian randomization study.

PURPOSE: Previous observational studies have shown that green tea consumption is associated with a reduced incidence of digestive system cancers (DSCs). However, the observed association could be due to confounding factors. Therefore, we used a two-sample Mendelian randomization (MR) approach to assess the causal effect of green tea intake on the risk of five common DSCs. METHODS: Independent genetic variants strongly associated with green tea consumption in European and East Asian populations were selected as instrumental variables in genome-wide association studies involving up to 64,949 European individuals and 152,653 East Asian individuals, respectively. The associations between genetic variants and DSCs were extracted from the FinnGen study and the Japan Biobank. The primary analysis was performed using random-effects inverse variance weighting (IVW). Other MR analyses, including weighted mode-based estimate, weighted-median, MR-Egger regression, Mendelian Randomization-Pleiotropy Residual Sum and Outlier (MR-PRESSO) analysis, were used for sensitivity analyses. In addition, a multivariate MR design was performed to adjust for smoking and alcohol consumption. RESULTS: The IVW results showed no causal relationship between tea intake and DSCs risk in European population (esophagus cancer: odds ratio (OR) = 1.044, 95% confidence interval (CI) 0.992-1.099, p = 0.096; stomach cancer: OR = 0.988, 95% CI 0.963-1.014, p = 0.368; colorectal cancer: OR = 1.003, 95% CI 0.992-1.015, p = 0.588; liver cancer: OR = 0.996, 95% CI 0.960-1.032, p = 0.808; pancreatic cancer: OR = 0.990, 95% CI 0.965-1.015, p = 0.432). The MR-Egger regression, MR-PRESSO analysis and other methods also confirmed the reliability of the conclusion. Similarly, no significant association was found between green tea consumption and the incidence of DSCs among East Asians. This relationship is not significant even after adjusting for smoking and alcohol consumption (P > 0.05). CONCLUSION: Our study provides evidence that genetically predicted green tea intake is not causally associated with the development of DSCs in the European and East Asian population.

Construction of Exosome SORL1 Detection Platform Based on 3D Porous Microfluidic Chip and its Application in Early Diagnosis of Colorectal Cancer.

Exosomes are promising new biomarkers for colorectal cancer (CRC) diagnosis, due to their rich biological fingerprints and high level of stability. However, the accurate detection of exosomes with specific surface receptors is limited to clinical application. Herein, an exosome enrichment platform on a 3D porous sponge microfluidic chip is constructed and the exosome capture efficiency of this chip is ≈90%. Also, deep mass spectrometry analysis followed by multi-level expression screenings revealed a CRC-specific exosome membrane protein (SORL1). A method of SORL1 detection by specific quantum dot labeling is further designed and the ensemble classification system is established by extracting features from 64-patched fluorescence images. Importantly, the area under the curve (AUC) using this system is 0.99, which is significantly higher (p < 0.001) than that using a conventional biomarker (carcinoembryonic antigen (CEA), AUC of 0.71). The above system showed similar diagnostic performance, dealing with early-stage CRC, young CRC, and CEA-negative CRC patients.

Influence of 60Co-γ Irradiation on the Components of Essential Oil of Curcuma.

The gas chromatography-ion mobility spectrometry (GC-IMS) method is a new technology for detecting volatile organic compounds. This study was carried out to evaluate the effects of volatile aroma compounds of Curcuma essential oils (EOs) after 60Co radiation by GC-IMS. Dosages of 0, 5, and 10 kGy of 60Co were used to analyze EOs of Curcuma after 60Co irradiation (named EZ-1, EZ-2, and EZ-3). The odor fingerprints of volatile organic compounds in different EOs of Curcuma samples were constructed by headspace solid-phase microextraction and GC-IMS after irradiation. The differences in odor fingerprints of EOs were compared by principal component analysis (PCA). A total of 92 compounds were detected and 65 compounds were identified, most of which were ketones, aldehydes, esters, and a small portion were furan compounds. It was found that the volatile matter content of 0 kGy and 5 kGy was closer, and the use of 10 kGy 60Co irradiation would have an unstable effect on the EOs. In summary, it is not advisable to use a higher dose when using 60Co irradiation for sterilization of Curcuma. Due to the small gradient of irradiation dose used in the experiment, the irradiation dose can be adjusted appropriately according to the required sterilization requirements during the production and storage process of Curcuma to obtain the best irradiation conditions. GC-IMS has the advantages of GC's high separation capability and IMS's fast response, high resolution, and high sensitivity, and the sample requires almost no pretreatment; it can be widely used in the analysis of traditional Chinese medicines containing volatile components. It is shown that irradiation technology has good application prospects in the sterilization of traditional Chinese medicines, but the changes in irradiation dose and chemical composition must be paid attention to.

Effects of Ganfule capsule on microbial and metabolic profiles in anti-hepatocellular carcinoma.

AIMS: Based on the gut microbiota and plasma metabolites, the underlying mechanism was analysed for the anti-hepatocellular carcinoma (HCC) effects of Ganfule capsule (GFL) in the study. METHODS AND RESULTS: The UPLC-Q-TOF/MS results showed that 13 key compounds were identified in GFL and the major active ingredients included amygdalin, saikosaponin A, astragaloside I, etc. The nude mice received HepG2 injection, and GFL showed lower volume and weight of the tumour. In addition, the apoptosis proteins (Bax and Bcl2) were altered in response to GFL treatment, and apoptosis cells were increased, indicating an anti-HCC effect. Interestingly, 16S rDNA results showed that GFL treatment improved gut microbiota diversity and compositions, especially for the beneficial bacteria, such as Bacilli, Lactobacillales, Lactobacillus, Lactobacillaceae, Firmicutes, Lactobacillus_reuteri and Lactobacillus_gasseri. Metabonomics further identified 426 metabolites and 343 metabolites variation in the positive and negative ion modes after GFL treatment, which might be associated with amino acid, lipid metabolism and carbohydrate metabolism pathways, indicating these metabolites might involve in the protective role of GFL in HCC. Correlation analysis showed a significant relationship between gut microbiota and plasma metabolites. CONCLUSION: In conclusion, GFL exerted an anti-HCC effect in the nude murine model, which might be associated with microbial and metabolic improvements. SIGNIFICANCE AND IMPACT OF THE STUDY: This study is the first to report the anti-HCC effect of GFL associated with gut microbiota and plasma metabolites. GFL may improve the gut microbiota structure, such as increasing probiotics - Lactobacillus. It also provides a new strategy for the scientific demonstration of the modernization of traditional Chinese medicine.

[A new sesquiterpene lactone from biological transformation of Hericium erinaceus and Artemisiae Annuae Herba].

This study aimed to investigate the chemical constituents from the biological transformation of Hericium erinaceus and Artemisiae Annuae Herba(HQ biological transformation). The chemical constituents of ethyl acetate fraction of 75% ethanol extract in HQ biological transformation were separated and purified by silica gel and Sephadex LH-20 gel column chromatographies together with semi-preparative high performance liquid chromatography(HPLC). Their structures were identified by physicochemical properties, spectroscopic analysis, as well as comparisons with the data reported in literature. Nine compounds were isolated and identified as 2α-hydroxydeoxyartemisinin(1), 6ß-hydroxy-stigmast-4,22-dien-3-one(2), 3ß,5α-dihydroxy-ergosta-7,22-dien-6-one(3), friedelin(4), dankasterone(5), ergosterol endoperoxide(6), 3ß-hydroxy-5,9-epoxy-(22E,24R)-ergosta-7,22-dien-6-one(7), 3α,5α,9α-trihydroxy-(22E,24R)-ergosta-7,22-dien-6-one(8), and stigmast-3-one(9). Compound 1 was a new sesquiterpene lactone named 2α-hydroxy-deoxyartemisinin. The activity against Helicobacter pylori(Hp) of compounds 1-9 in vitro was determined by Kirby-Bauer disk diffusion method. The screening results showed compounds 1, 2 and 5 had certain anti-Hp activity.

[Content determination of five flavonoids in Tibetan medicine Rhododendron anthopogonoides by quantitative analysis of multi-components by single marker (QAMS)].

To establish a quantitative analysis of multi-components by single marker(QAMS) method for five flavonoids in Rhododendron anthopogonoides and verify its feasibility and applicability in the medicinal materials of R. anthopogonoides. With hyperoside as the internal reference, relative correction factors(RCF) of rutin, quercetin, quercitrin and kaempferol were established by high-performance liquid chromatography(HPLC) analysis. RCFs were used to calculate the content of each component, system durability and relative retention time. Simultaneously, QAMS and external standard method(ESM) were used to determine the content of five flavonoids in 12 batches of R. anthopogonoides from different origins. The results were statistically analyzed to verify the accuracy and feasibility. The fingerprints and cluster analysis data of R. anthopogonoides analyzed and discussed differences among the batches. According to the results, the RCFs of rutin, quercetin, quercetin and kaempferol in R. anthopogonoides were 1.242 6, 0.990 5, 0.535 0, and 0.781 3, respectively. The RCFs represented a good reproducibility under different experimental conditions. Besides, there was no significant difference between QAMS and ESM. Besides, the fingerprint and cluster analysis data showed the consistency between the classification and with the origin distribution of the herbs. In conclusion, the QAMS method shows a good stability and accuracy in the quality control of R. anthopogonoides.

Identification of a novel bocaparvovirus in a wild squirrel in Kunming, Yunnan Province, China.

In December 2017, a squirrel (Callosciurus phayrei) died 2 days after capture in Kunming, and its intestinal tract, heart, liver, spleen, lung, and kidney were subjected to metagenomics analysis. Reassembly and verification by reverse transcription PCR of contigs generated by next-generation sequencing yielded a 5176-nt sequence, which was designated "squirrel bocaparvovirus" (SQBOV). Phylogenetic trees based on the aa sequences of NS1, NP1, and VP1 showed that SQBOV formed an independent branch in the bocaparvovirus phylogenetic tree. The amino acid sequence identity of the NS1 of SQBOV to those of other bocaparvoviruses was below the threshold of 85% that is used to demarcate species within the genus, indicating that it should be considered a member of a new bocaparvovirus species. To our knowledge, this is the first report of a bocaparvovirus in squirrels. Our findings will enable further studies of viral diversity in rodents and of the genetic diversity and host range of bocaparvoviruses.

A Novel Tropoloisoquinoline Alkaloid, Neotatarine, from Acorus calamus L.

A novel tropoloisoquinoline alkaloid, neotatarine (1), was isolated from the 95% ethanol extract of the rhizome parts of Acorus calamus L. The chemical structure was unambiguously elucidated by spectroscopic and single-crystal X-ray diffraction analysis. Neotatarine (1) exhibited significantly inhibitory activity against Aß25 - 35 induced PC12 cell death with 2, 4 and 8 µm comparing with the assay control (P < 0.01).

New Acorane-Type Sesquiterpene from Acorus calamus L.

A new sesquiterpene, named neo-acorane A (1), and two known ones, acoric acid (2) and calamusin D (3), were isolated from a 95% ethanol extract of the rhizome parts of Acorus calamus L. Their structures were elucidated by spectroscopic methods, and the absolute configurations were determined by single-crystal X-ray diffraction analysis. Compounds 1 and 2 are nonisoprenoid sesquiterpenoids, likely biosynthesized from an acorane-type sesquiterpene by oxidative fission of the six- or five-membered ring. Moreover, compounds 1 (10 µM), 2 (5 µM and 10 µM) and 3 (10 µM) showed cell proliferation activity on the SK-N-BE (2) cell line.

[A new sesquiterpene from Acorus calamus (â ¡)].

A new quaiane-tgpe sesquiterpene was isolated from the 95% ethanol extract of the rhizomes of Acorus calamus by silica gel and sephadex LH-20 column chromatographic methods. Structure and absolute configuration of the sesquiterpene were elucidated by spectroscopic data and X-ray crystallographic analysis, and named as 1R,5R,7S-guaiane-4R,10R-diol-6-one.

[Studies on identification of Phragmitis Rhizoma and its counterfeits].

The study aims to explore the main differential characteristics of Phragmites Rhizoma and its counterfeits (rhizomes of Arundo donax, Triarrhena lutarioriparia and Miscanthus sinensis) and provide experimental basis for the reasonable applications of gramineous plants through system research and comparison of plant morphogenesis, character, transverse organization characteristics and powder microscopic characteristics.

Inhibition of macrophage-derived foam cell formation by ezetimibe via the caveolin-1/MAPK pathway.

Ezetimibe, a selective inhibitor of intestinal cholesterol absorption, effectively reduces plasma cholesterol, but its effect on atherosclerosis is unclear. Foam cell formation has been implicated as a key mediator during the development of atherosclerosis. The purpose of this study was to investigate the effects of ezetimibe on foam cell formation and explore the underlying mechanism. The results presented here show that ezetimibe reduces atherosclerotic lesions in apolipoprotein E deficient (apoE-/-) mice by lowering cholesterol levels. Treatment of macrophages with Chol:MßCD resulted in foam cell formation, which was concentration-dependently inhibited by the presence of ezetimibe. Mechanically, ezetimibe treatment downregulated the expression of CD36 and scavenger receptor class B1 (SR-B1), but upregulated the expression of apoE and caveolin-1 in macrophage-derived foam cells, which kept consistent with our microarray results. Moreover, treatment with ezetimibe abrogated the increase of phospho-extracellular signal regulated kinase (ERK) 1/2 and their nuclear accumulation in foam cells. Inhibition of the MAPK pathway by the MEK inhibitor PD98059 attenuated the inhibitory effect of ezetimibe on the expression of p-ERK1/2 and caveolin-1. Taken together, these results showed that ezetimibe suppressed foam cell formation via the caveolin-1/MAPK signalling pathway, suggesting that inhibition of foam cell formation might be a novel mechanism underlying the anti-atherosclerotic effect of ezetimibe.

Assessment of Egg Yolk Oil Extraction Methods of for ShiZhenKang Oil by Pharmacodynamic Index Evaluation.

To assess the extraction methods of egg yolk oil in ShiZhenKang (SZK) oil, which is used to treat eczema, a mice model of eczema was established by using 2,4-dinitrochlorobenzene (DNCB). The therapeutic effects of egg yolk oil extracted by different methods from SZK oil on the model of acute eczema in mice were evaluated. The oil yield rate of ethanol extraction is 42.06%. Its egg yolk oil is orange and has a rich, sweet, egg smell. Moreover, the SZK oil prepared from it has a very good therapeutic effect on the model of acute eczema in mice. The alcohol extraction method is the preferable method according to a comprehensive evaluation of each index of seven kinds of methods to extract the egg yolk oil.

[Chemical Constituents from Fruit Dregs of Rhus chinensis( â ¡)].

Objective: To investigate the constituents from the fruit dregs of Rhus chinensis. Methods: The constituents were isolated and purified by chromatography on silica gel,Sephadex LH-20,RP-C18 and Pre-TLC and recrystalization. The structures were identified on the basis of the chemical evidence,spectroscopic data. Results: Ten compounds were obtained and elucidated as m-digalloyl acid( 1),ethyl-m-digallate( 2),apigenin( 3),kaempferol( 4),quercetin( 5),3,7-dimethoxy-5,3',4'-trihydroxy-flavone( 6),quercitrin( 7),kaempferol-3-O-α-L-rhamnoside( 8),myricetrin( 9) and quercetin-3-O-( 4″-methoxy)-α-L-rahmnopyranosyl( 10),respectively. Conclusion: Compounds 1 ~ 3,6 ~ 10 are separated from the Rhus genus for the first time.

[Sesquiterpenoids of Acori Calami Rhizoma].

To study the chemical constituents and antimicrobial activity of Acori Calami Rhizoma. Components were isolated through various chromatographic methods and identified by spectroscopic data. The agar dilution method was adopted to analyze antimicrobial activity of the compounds in vitro.Eleven sesquiterpenoids were isolated, and indentified as 4ß,6ß-dihydroxy-1α,5ß(H)-guai-9-ene(1),4ß,6ß-dihydroxy-1α,5ß(H)-guai-10(14)-ene(2), teuclatriol(3), isocalamendiol(4), calamendiol(5), calamusin H(6), oxyphyllenodiols A(7), oplodiol(8), ananosmin(9), epishyobunone(10), and bullatantriol(11). Compound 9 was isolated from genus Acorus for the first time. Compounds 3, 7-9, and 11 had significantly antimicrobial activity. There were good sterilizing effects that the MBC of compound 9 to the four tested strains were 20.00 mg•L⁻¹, and compound 11 to Pseudomonas aeruginosa was 12.50 mg•L⁻¹.

Effect of Processing on the Traditional Chinese Herbal Medicine Flos Lonicerae: An NMR-based Chemometric Approach.

The processing of medicinal materials, known as Pao Zhi in traditional Chinese medicine, is a unique part of traditional Chinese medicine and has been widely used for the preparation of Chinese materia medica. It is believed that processing can alter the properties and functions of remedies, increase medical potency, and reduce toxicity and side effects. Both processed and unprocessed Flos Lonicerae (flowers of Lonicera japonica) are important drug ingredients in traditional Chinese medicine. To gain insights on the effect of processing factors (heating temperature and duration) on the change of chemical composition, nuclear magnetic resonance combined with chemometric analysis was applied to investigate the processing of F. Lonicerae. Nuclear magnetic resonance spectral data were analyzed by means of a heat map and principal components analysis. The results indicated that the composition changed significantly, particularly when processing at the higher temperature (210 °C). Five chemical components, viz. 3,4-dicaffeoylquinic acid, 4,5-dicaffeoylquinic acid, 3,5-dicaffeoylquinic acid, chlorogenic acid, and myo-inositol, whose concentration changed significantly during the processing, were isolated and identified. The patterns for the concentration change observed from nuclear magnetic resonance analysis during the processing were confirmed and quantitatively determined by ultrahigh-performance liquid chromatography analysis. The study demonstrated that a nuclear magnetic resonance-based chemometric approach could be a promising tool for investigation of the processing of herbal medicines in traditional Chinese medicine.

[Crosstalk between Wnt5a and inflammatory signaling in inflammation].

Wnt5a belongs to the large WNT family of cysteine-rich secreted glycoproteins, which is involved in multiple signaling pathways that regulate a variety of cellular processes, including cell motility, proliferation differentiation and so on during development. The regulation and signaling transduction of Wnt5a have been reported to closely relate to inflammatory response, which indicates that Wnt5a plays a critical role in the occurrence and development of inflammatory diseases. In this review, we summarized data on Wnt5a and its signaling pathway, as well as their involvement in inflammatory response. Further comprehensive understanding of the function and relationship between Wnt5a and inflammatory response would help us to develop novel diagnostic and therapeutic strategies for prevention and treatment of inflammatory diseases.

[Chemical Constituents From Rhus chinensis Fruit Dregs].

OBJECTIVE: To isolate and elucidate the constituents from the fruit dregs of Rhus chinensis. METHODS: The constituents were isolated and purified by chromatography on silica gel,Sephadex LH-20, RP-C18 gel and recrystallization. The structures were elucidated on the basis of the chemical evidence and spectroscopic data. RESULTS: Ten compounds were obtained: ß-sitosterol (1), morolic acid (2), (2S) -1-O-heptatriacontanoyl glycerol (3), α-monpalmitin (4), palmitic acid (5), gallic acid (6), methyl gallate (7), ethyl gallate (8), propyl gallate (9), and protocatechuic acid (10). CONCLUSION: Compounds 3, 4 and 9 are isolated from the plants of Rhus genus for the first time.

Ezetimibe suppresses cholesterol accumulation in lipid-loaded vascular smooth muscle cells in vitro via MAPK signaling.

AIM: To investigate the mechanisms of anti-atherosclerotic action of ezetimibe in rat vascular smooth muscle cells (VSMCs) in vitro. METHODS: VSMCs of SD rats were cultured in the presence of Chol:MßCD (10 µg/mL) for 72 h, and intracellular lipid droplets and cholesterol levels were evaluated using Oil Red O staining, HPLC and Enzymatic Fluorescence Assay, respectively. The expression of caveolin-1, sterol response element-binding protein-1 (SREBP-1) and ERK1/2 were analyzed using Western blot assays. Translocation of SREBP-1 and ERK1/2 was detected with immunofluorescence. RESULTS: Treatment with Chol:MßCD dramatically increased the cellular levels of total cholesterol (TC), cholesterol ester (CE) and free cholesterol (FC) in VSMCs, which led to the formation of foam cells. Furthermore, Chol:MßCD treatment significantly decreased the expression of caveolin-1, and stimulated the expression and nuclear translocation of SREBP-1 in VSMCs. Co-treatment with ezetimibe (3 µmol/L) significantly decreased the cellular levels of TC, CE and FC, which was accompanied by elevation of caveolin-1 expression, and by a reduction of SREBP-1 expression and nuclear translocation. Co-treatment with ezetimibe dose-dependently decreased the expression of phosphor-ERK1/2 (p-ERK1/2) in VSMCs. The ERK1/2 inhibitor PD98059 (50 µmol/L) altered the cholesterol level and the expression of p-ERK1/2, SREBP-1 and caveolin-1 in the same manner as ezetimibe did. CONCLUSION: Ezetimibe suppresses cholesterol accumulation in rat VSMCs in vitro by regulating SREBP-1 and caveolin-1 expression, possibly via the MAPK signaling pathway.

The novel role and underlying mechanism of Wnt5a in regulating cellular cholesterol accumulation.

Cholesterol accumulation is a critical step during the development and progression of atherosclerosis. Recently, Wnt5a expression has been found to be markedly upregulated in both murine and human atherosclerotic lesions. However, the effect and mechanism of Wnt5a in atherosclerosis is poorly understood. In the present study, we investigated the effects and potential mechanisms of Wnt5a on cholesterol accumulation during atherosclerosis. We used RAW264.7 and vascular smooth muscle cells (VSMC) treated with oxidized low-density lipoprotein (oxLDL) as lipid-loaded cell models. We found that expression of Wnt5a protein was increased in a concentration (25, 50, 75 and 100 µg/mL)- and time (24, 48 and 72 h)-dependent manner by oxLDL treatment. To explore the underlying mechanism, we used Wnt5a short interference (si) RNA to knockdown Wnt5a expression in both RAW264.7 cells and VSMC, or applied recombinant Wnt5a (rWnt5a) to stimulate Wnt5a signalling. After Wnt5a knockdown, total cholesterol (TC) and free cholesterol (FC) content in both cell types increased significantly (P < 0.05) upon exposure to oxLDL. Conversely, the TC and FC content decreased markedly (P < 0.05) after treatment of cells with rWnt5a. More importantly, both protein and mRNA expression of Caveolin-1 and ATP-binding cassette transporter A1 (ABCA1) was significantly reduced after exposure of wnt5a siRNA-treated cells to oxLDL, whereas rWnt5a treatment of cells resulted in increased Caveolin-1 and ABCA1 protein expression after exposure of cells to oxLDL. Together, these findings demonstrate, for the first time, that Wnt5a reduces the accumulation of cholesterol in lipid-loaded cells by regulating the mRNA expression of Caveolin-1 and ABCA1, which are involved in reverse cholesterol transport. This may present a novel mechanism of Wnt5a-mediated cholesterol transportation in macrophages and VSMC. Therefore, targeting the Wnt5a signalling pathway may have clinical implications in atherosclerosis.