scholarly journals Zishen Qingre Tongluo Formula Improves Renal Fatty Acid Oxidation and Alleviated Fibrosis via the Regulation of the TGF-β1/Smad3 Signaling Pathway in Hyperuricemic Nephrology Rats

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Peng Liu ◽  
Chen Wang ◽  
Yun Wang ◽  
Honghong Zhang ◽  
Baoli Liu ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Real Time ◽  
Signaling Pathway ◽  
Fatty Acid Oxidation ◽  
Western Blotting ◽  
Real Time Pcr ◽  
Acid Oxidation ◽  
Immunohistochemistry Staining ◽  
The Relationship ◽  
Tgf Β1

Hyperuricemia, an independent risk factor for ensuing chronic kidney disease (CKD), contributed to tubulointerstitial fibrosis and insufficiency of renal fatty acid oxidation. Many studies have shown that renal fatty acid oxidation dysfunction is related to the TGF-β1/Smad3 signaling pathway. We experimented the effects of Zishen Qingre Tongluo Formula (ZQTF) on the adenine/yeast-induced HN rats and uric acid-induced renal mouse tubular epithelial cells (mTECs), determined whether this effect was related to the TGF-β1/Smad3 signaling pathway, and further investigated the relationship between this effect and renal fatty acid oxidation. Rats were given intraperitoneally with adenine (100 mg/kg) and feed chow with 10% yeast for 18 days and then received ZQTF (12.04 g/kg/day) via intragastric gavage for eight weeks. The TGF-β1/Smad3 signaling pathway and renal fatty acid oxidation protein were detected by using western blotting, real-time PCR, and immunohistochemistry staining. mTECs induced by UA were used to investigate the relationship between the TGF-β1/Smad3 signaling pathway and renal fatty acid oxidation. After treatment with ZQTF, levels of UA, 24 h UTP, BUN, and Scr were significantly decreased and histologic injuries were visibly ameliorated in HN rats. Western blotting, real-time PCR, and immunohistochemistry staining revealed that PGC-1α, PPARγ, and PPARα significantly increased, and fibronectin, collagen 1, and P-Smad3 significantly decreased in HN rats and UA-induced mTECs after ZQTF treatment. SIS3 (a specific inhibitor of Smad3) treatment significantly increased the expressions of PGC-1α, PPARγ, and PPARα and decreased the expressions of fibronectin, collagen 1, and P-Smad3 in UA-induced mTECs. Our study demonstrated that ZQTF exhibited renoprotective effects by promoting renal fatty acid oxidation via the regulation of the TGF-β1/Smad3 signaling pathway. Thus, the present results indicated that ZQTF was a novel antifibrotic strategy for hyperuricemic nephropathy.

Theobromine ameliorates nonalcoholic fatty liver disease by regulating hepatic lipid metabolism via mTOR signaling pathway in vivo and in vitro

2020 ◽  
Author(s):  
Dan Wei ◽  
Shaofei Wu ◽  
Jie Liu ◽  
Xiaoqian Zhang ◽  
Xiaoling Guan ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Signaling Pathway ◽  
Fatty Acid Oxidation ◽  
Fatty Acid Uptake ◽  
Mtor Signaling ◽  
Acid Oxidation ◽  
Acid Uptake ◽  
Mtor Signaling Pathway

Theobromine, a methylxanthine present in cocoa, has been shown to possess many beneficial pharmacological properties such as anti-oxidative stress, anti-inflammatory property, and anti-microbial activity. In this study, we investigated the effects of theobromine on NAFLD and the possible underlying mechanisms in vivo and in vitro. The results showed that theobromine reduced body weight, fat mass and improved dyslipidemia. Theobromine decreased liver weight, mitigated liver injury, and significantly reduced hepatic TG level in mice with obesity. Histological examinations also showed hepatic steatosis was alleviated after theobromine treatment. Furthermore, theobromine reversed the elevated mRNA and protein expression of SREBP-1c, FASN, CD36, FABP4 and the suppressed expression of PPARα, CPT1a in the liver of mice with obesity, which were responsible for lipogenesis, fatty acid uptake and fatty acid oxidation respectively. In vitro, theobromine also downregulated SREBP-1c, FASN, CD36, FABP4 and upregulated PPARα, CPT1a mRNA and protein levels in hepatocytes in a dose-dependent manner, while these changes were reversed by L-Leucine, an mTOR agonist. The present study demonstrated that theobromine improved NAFLD by inhibiting lipogenesis, fatty acid uptake and promoting fatty acid oxidation in the liver and hepatocytes, which might be associated with its suppression of mTOR signaling pathway.

scholarly journals SETDB1 Promotes the Growth of Glioma via CSF-1-dependent Macrophage Recruitment by Activating the AKT/mTOR Signaling Pathway

2020 ◽  
Author(s):  
Shuai Han ◽  
Wei Zhen ◽  
Tongqi Guo ◽  
Jianjun Zou ◽  
fuyong li
Keyword(s):  
Real Time ◽  
Signaling Pathway ◽  
Western Blotting ◽  
Real Time Pcr ◽  
Mtor Signaling ◽  
Migration And Invasion ◽  
High Morbidity ◽  
Mtor Signaling Pathway ◽  
Macrophage Recruitment ◽  
Syngeneic Mouse Model

Abstract Background: Glioma is a common disease of the central nervous system (CNS), with high morbidity and mortality. Among the infiltrates in the tumor microenvironment, tumor-associated macrophages (TAMs) are abundant and they are significant factors in glioma progression. However, the exact details of disease progression have yet to be determined. Methods: The clinical relevance of SETDB1 was analyzed by immunohistochemistry, real-time PCR and Western blotting and of glioma cancer tissues. Tumor cell proliferation, migration and invasion were investigated by MTS assay, colony formation assay, xenograft, wound healing and Transwell assay. The relationship between SETDB1 and CSF-1, as well as TAMS was examined by Western blotting, real-time PCR and syngeneic mouse model.Results: This work shows the presence and upregulation of SETDB1 in gliomaand its relationship with disease prognosis. Gain and loss of function approaches showed the inhibition of apoptosis and the promotion of growth, migration and invasion of the disease with SETDB1 overexpression and converse effects with SETDB1 silencing in vitro. Mechanistically, SETDB1 promotes CSF-1 expression by activating the AKT/mTOR signaling pathway. This leads to macrophage recruitment in the tumor, leading to tumor growth. Conclusion: This studyclarifies the modulation of tumor functions by SETDB1 and hence presents a future avenue for treating glioma.

scholarly journals Glucose-induced lipid deposition in goose primary hepatocytes is dependent on the PI3K-Akt-mTOR signaling pathway

2016 ◽  
Vol 68 (4) ◽  
pp. 853-861
Author(s):  
Chunchun Han ◽  
Shouhai We ◽  
Fang He ◽  
Song Qi ◽  
Xiangping Xiong ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Lipid Metabolism ◽  
Signaling Pathway ◽  
Fatty Acid Oxidation ◽  
Mtor Pathway ◽  
Mtor Signaling ◽  
Acid Oxidation ◽  
Lipid Deposition ◽  
Mtor Signaling Pathway ◽  
Primary Hepatocytes

Previously we showed that fatty liver formation in overfed geese was accompanied by PI3K-Akt-mTOR pathway activation and changes in plasma glucose concentrations. Here, we show that glucose acts in goose hepatocellular lipid metabolism through the PI3K-Akt-mTOR signaling pathway. We observed that glucose increased lipogenesis, decreased fatty acid oxidation and increased very low density lipoprotein triglyceride (VLDL-TG) assembly and secretion. Co-treatment with glucose and inhibitors of the PI3K-Akt-mTOR pathway (LY294002, rapamycin, NVP-BEZ235) decreased the levels of factors involved in lipogenesis and increased the levels of factors involved in fatty acid oxidation and VLDL-TG assembly and secretion. These findings show that inhibition of the PI3K-Akt-mTOR pathway decreased glucose-induced lipogenesis, inhibited the downregulation of fatty acid oxidation by glucose and increased the upregulation of VLDL-TG assembly and secretion by glucose. The results presented herein provide further support for the role of the PI3K-Akt-mTOR pathway in lipid metabolism as we showed that in goose primary hepatocytes, glucose acts through the PI3K-Akt-mTOR-dependent pathway to stimulate lipid deposition by increasing lipogenesis and decreasing fatty acid oxidation and VLDL-TG assembly and secretion.

scholarly journals Isoimperatorin exerts anti-inflammatory activity by targeting the LPS-TLR4/MD-2-NF-κB pathway

2021 ◽  
Vol 19 ◽  
pp. 205873922110005
Author(s):  
Guirong Chen ◽  
Yunong Liu ◽  
Yubin Xu ◽  
Mingbo Zhang ◽  
Song Guo ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Real Time ◽  
Signaling Pathway ◽  
Western Blotting ◽  
Inflammatory Cytokines ◽  
Real Time Pcr ◽  
Inflammatory Responses ◽  
Inflammatory Activity ◽  
Tnf Α ◽  
Anti Inflammatory

Isoimperatorin (QHS) is a phytoconstituent found in the methanolic extracts obtained from the roots of Angelica dahurica, which contains anti-inflammatory, anti-bacterial, analgesic, anti-tumor, and vasodilatory activities. QHS possesses potent antagonistic activity against lipopolysaccharide (LPS)-induced inflammation; however, the mechanism of action remains unclear. In this study, we investigated the anti-inflammatory effect of QHS and explored the underlying mechanisms. The QHS was purchased from Jiangsu Yongjian Pharmaceutical Co., Ltd. (Jiangsu, China). We performed MTT assay, real-time PCR, ELISA, and western blotting experiments to assess the anti-inflammatory activity and the possible mechanism of QHS in vitro. Molecular docking was performed to study the binding of QHS and myeloid differentiation protein-2 (MD-2) and elucidate the possible anti-inflammatory mechanism. QHS had no significant effect on cell viability. Moreover, pre-treatment with QHS significantly decreased the release of inflammatory cytokines and mediators including NO, TNF-α, IL-6, and IL-1β. In addition, real-time PCR showed that QHS decreased the mRNA expressions of iNOS, COX-2 TNF-α, IL-6, and IL-1β. Western blotting indicated that QHS could inhibit the expression of the proteins associated with the LPS-TLR4/MD-2-NF-κB signaling pathway. Lastly, molecular docking revealed a possible binding mechanism between QHS and MD-2. QHS exhibited anti-inflammatory activity when combined with MD-2, regulating the LPS-TLR4/MD-2-NF-κB signaling pathway, and inhibiting the release and expression of inflammatory cytokines and mediators. Furthermore, QHS can be used as a potential TLR4 antagonist, which blocks MD-2 binding, for treating inflammatory responses induced by LPS.

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