Metabolomics Analysis Reveals the Effects of Compound Fuzhuan Brick Tea (CFBT) on Regulating Dyslipidemia and Metabolic Disorders in Mice Induced by High-Fat Diet.

BACKGROUND: It is well known that obesity induced by high-fat diet (HFD) poses a serious threat to people's health. Fuzhuan brick tea, one of the most popular beverages, is reported to possess a significant effect on regulating lipid metabolism, attributed to its many bioactive ingredients. However, the efficacy and mechanism of compound Fuzhuan brick tea (CFBT) made from Fuzhuan brick tea and other six Chinese herbal medicines are still not well defined. METHODS: Sixty mice were divided into six groups: normal control group (CK), high-fat model group (NK), positive control group with anti-hyperlipidemic drug (YK), CFBT at low-(FL), medium-(FM) and high-(FH) dosage. Intervening for 30 days, conventional indexes analysis combined with metabolomics were performed to evaluate the changes in biochemical indexes and liver metabolic profiles in mice submitted to HFD. RESULTS: CFBT treatment was able to ameliorate obesity, serum biochemical parameters, antioxidant activity and hepatic steatosis. In addition, significant alterations in the liver tissue metabolic profiles were observed, with most of these associated with inflammation, glucose and lipid metabolism. CONCLUSIONS: This study provides evidence that consumption of CFBT is capable of preventing dyslipidemia, reducing weight gain, restoring liver injury, as well as improving metabolic disorders.

The interaction of YBX1 with G3BP1 promotes renal cell carcinoma cell metastasis via YBX1/G3BP1-SPP1- NF-κB signaling axis.

BACKGROUND: Renal cell carcinoma (RCC) is a deadly urological tumor that remains largely incurable. Our limited understanding of key molecular mechanisms underlying RCC invasion and metastasis has hampered efforts to identify molecular drivers with therapeutic potential. With evidence from our previous study revealing that nuclear overexpression of YBX1 is associated with RCC T stage and metastasis, we investigated the effects of YBX1 in RCC migration, invasion, and adhesion, and then characterized its interaction with RCC-associated proteins G3BP1 and SPP1. METHODS: Renal cancer cell lines, human embryonic kidney cells, and clinical samples were analyzed to investigate the functional role of YBX1 in RCC metastasis. YBX1 knockdown cells were established via lentiviral infection and subjected to adhesion, transwell migration, and invasion assay. Microarray, immunoprecipitation, dual-luciferase reporter assay, and classical biochemical assays were applied to characterize the mechanism of YBX1 interaction with RCC-associated proteins G3BP1 and SPP1. RESULTS: Knockdown of YBX1 in RCC cells dramatically inhibited cell adhesion, migration, and invasion. Mechanistic investigations revealed that YBX1 interaction with G3BP1 upregulated their downstream target SPP1 in vitro and in vivo, which led to an activated NF-κB signaling pathway. Meanwhile, knockdown of SPP1 rescued the YBX1/G3BP1-mediated activation of NF-κB signaling pathway, and RCC cell migration and invasion. We further showed that YBX1 expression was positively correlated with G3BP1 and SPP1 expression levels in clinical RCC samples. CONCLUSIONS: YBX1 interacts with G3BP1 to promote metastasis of RCC by activating the YBX1/G3BP1-SPP1-NF-κB signaling axis.

Lexicon development and quantitative descriptive analysis of Hunan fuzhuan brick tea infusion.

Twenty-seven representative Hunan fuzhuan brick teas were collected to develop a terminology lexicon and a quantitative descriptive analysis (QDA) method suitable for the sensory evaluation of Hunan fuzhuan brick tea infusion. Ten trained panelists developed a terminology lexicon comprised of eleven aroma and six taste attributes and evaluated the intensities of sensory attributes of each sample by conducting the QDA method. The QDA results showed that seventeen attributes listed in the final lexicon can be used to evaluate the quality of Hunan fuzhuan brick tea infusion properly, among which five aroma attributes, overall aroma, smoky, floral, fermented, and sweet (fruit), and one taste attribute, bitter, were the characteristic attributes to distinguish the differences in the sample qualities. Another panel made up of four professional cuppers evaluated samples by the cupping method to analyze the applicability and accuracy of the lexicon and the QDA method. The results showed that both the cupping method and QDA can be effectively used to evaluate Hunan fuzhuan brick tea quality, and their evaluation results showed high consistency and mutual complementation. This information will be beneficial for developing a sensory evaluation method and quality control for Hunan fuzhuan brick tea.

The Role of YB1 in Renal Cell Carcinoma Cell Adhesion.

Background: Y-box binding protein 1 (YB1) is a multifunctional protein involved in many processes related to cancer progression and metastasis. Methods: In this study, we constructed YB1 knockdown stable renal cell carcinoma (RCC) cell line 786-0. The gene expression profile of 786-0 was performed by DNA microarray analysis to identify genes that were regulated by YB1. Real-time PCR and western blotting were used to test the genes and proteins expression. Transforming growth factor-ß (TGF-ß) activity was detected by dual-luciferase reporter assay. Cell adhesion assay was used to determine RCC cell adhesion ability. Results: Pathway analysis revealed that YB1 knockdown influenced cell adhesion molecules (CAMs). We further verified four genes (CLDN4, NRXN3, ITGB8, and VCAN) related to CAMs by real-time PCR, and confirmed that YB1 regulated the expression of ITGB8 in RCC. Functional assays demonstrated that knockdown of YB1 significantly inhibited the cell adhesion of 786-0 cells in vitro. In addition, YB1 affected TGF-ß activation. Conclusion: Our study demonstrated that YB1 modulated the adhesion ability of renal cell carcinoma cells by regulating ITGB8 and TGF-ß.

G3BP1 promotes tumor progression and metastasis through IL-6/G3BP1/STAT3 signaling axis in renal cell carcinomas.

The chronic inflammatory microenvironment within or surrounding the primary renal cell carcinoma (RCC) site promotes oncogenic transformation as well as contributes to the development of metastasis. G3BP stress granule assembly factor 1 (G3BP1) was found to be involved in the regulation of multiple cellular functions. However, its functions in RCC have not been previously explored. Here, we first showed that the expression of G3BP1 is elevated in human RCC and correlates with RCC progression. In cultured RCC cells, knockdown of G3BP1 results in inhibition of tumor cell proliferation, migration, and invasion, consistently with the alteration of epithelial-mesenchymal transition (EMT) and cell proliferative markers, including Cadherins, Vimentin, Snail, Slug, c-Myc, and cyclin D1. Remarkably, knockdown of G3BP1 dramatically impaired the signaling connection of pro-inflammatory cytokine IL-6 stimulation and downstream STAT3 activation in RCC, thus eventually contributing to the disruption of IL-6-elicited RCC migration and metastasis. In addition, in vivo orthotopic tumor xenografts results confirmed that knockdown of G3BP1 suppressed RCC tumor growth and metastasis in mice. Collectively, our findings support the notion that G3BP1 promotes tumor progression and metastasis through IL-6/G3BP1/STAT3 signaling axis in RCC.

CD4 + T cells promote renal cell carcinoma proliferation via modulating YBX1.

Renal cell carcinoma (RCC) is a common urologic tumor and the third leading cause of death among urological tumors. Recent studies demonstrate that RCC tumors are more heavily infiltrated by lymphocytes than other cancers. However, the exact roles played by CD4 + T cells in RCC proliferation remain unknown. In this study, we cocultured RCC cells with CD4 + T cells. Stable knockdown of YBX1 in RCC cells was constructed. The effects of CD4 + T cells, TGFß1 and YBX1 on RCC cells were investigated using cell viability assays. In situ RCC nude mouse model was used to observe the tumor growth. The potential mechanisms of CD4 + T cells and YBX1 in RCC cells proliferation were explored by qRT-PCR and western blot. Expression of CD4, Foxp3 and TGFß1 in RCC were quantified by immunohistochemical staining. The results indicated that CD4, Foxp3 and TGFß1 were significantly up-regulated in RCC tissues. Human clinical sample and in vitro cell lines studies showed that RCC cells had better capacity than its surrounding normal kidney epithelial cells to recruit the CD4 + T cells. In vivo mouse model studies were consistent with the results by in vitro cell lines studies showing infiltrating T cells enhanced RCC cell proliferation. qRT-PCR and western blot exhibited that CD4 + T cells could enhance RCC cell proliferation via activating YBX1/HIF2α signaling pathway. Furthermore, CD4 + T cells functioned through inducing TGFß1 expression. In a word, infiltrating CD4 + T cells promoted TGFß1 expression in both RCC and T cells and regulated RCC cells proliferation via modulating TGFß1/YBX1/ HIF2α signals.

The role of C1QBP in CSF-1-dependent PKCζ activation and macrophage migration.

Macrophages view as double agents in tumor progression. Trafficking of macrophages to the proximity of tumors is mediated by colony-stimulating factor-1 (CSF-1), a growth factor. In this study, we investigated the role of complement1q-binding protein (C1QBP)/ atypical protein kinase C ζ (PKCζ) in CSF-1-induced macrophage migration. Disruption of C1QBP expression impaired chemotaxis and adhesion of macrophage. Phosphorylation of PKCζ is an essential component in macrophage chemotaxis signaling pathway. C1QBP could interact with PKCζ in macrophage. C1QBP knockdown inhibited CSF-1 induced phosphorylation of PKCζ and integrin-ß1. However, C1QBP knockdown didn't affect the phosphorylation of PKCζ induced by MCP-1. Furthermore, CSF-1 from RCC cell condition medium promoted macrophage chemotaxis and adhesion. Taken together, our results demonstrated that C1QBP plays an essential role in CSF-1 induced migration of macrophages.

C1QBP suppresses cell adhesion and metastasis of renal carcinoma cells.

Complement component 1q subcomponent binding protein (C1QBP) is a ubiquitously expressed cellular protein and can be upregulated or activated in a variety of malignant tumors, including those from thyroid, colon and breast, but its role remains unclear in renal cell carcinoma (RCC). In this study, C1QBP knockdown in RCC cell influenced expression of multiple genes associated with cell adhesion, among which L1 cell adhesion molecule (L1CAM) was significantly higher upon a reduction of C1QBP. In turn, cell adhesion and invasion abilities were significantly increased with increased metastasis to lung and liver in vivo. C1QBP may regulate RCC cell adhesion and invasion through influencing the p-GSK3/ß-Catenin/L1CAM expression. Over all, our study demonstrated that C1QBP could regulate RCC metastasis by regulating the GSK3/ß-Catenin/L1CAM signaling pathway.