Overexpression CPT1A reduces lipid accumulation via PPARα/CD36 axis to suppress the cell proliferation in ccRCC.

Clear cell renal carcinoma (ccRCC) is histologically defined by its cytoplasmic lipid deposits. Lipid metabolism disorder largely increases the risk of ccRCC. In this study, we aimed to investigate the biological functions and molecular mechanisms of carnitine palmitoyl transferase 1A (CPT1A) in ccRCC. Our results showed that CPT1A is decreased in ccRCC clinical samples and cell lines compared with that in normal samples. Lentivirus overexpressing CPT1A was used to investigate the neoplastic phenotypes of ccRCC, and the results showed that lipid accumulation and tumor growth are attenuated both and . In addition, CPT1A prevents cholesterol uptake and lipid accumulation by increasing the peroxisome proliferator-activated receptor α (PPARα) level through regulation of Class B scavenger receptor type 1 (SRB1) and cluster of differentiation 36 (CD36). Furthermore, PI3K/Akt signaling pathway promotes tumor cell proliferation in ccRCC, which is related to the enhanced expression of CD36. Functionally, weakened CPT1A expression is critical for lipid accumulation to promote ccRCC development. Collectively, our research unveiled a novel function of CPT1A in lipid metabolism via PPARα/CD36 axis, which provides a new theoretical explanation for the pathogenesis of ccRCC. Targeting CPT1A may be a potential therapeutic strategy to treat ccRCC.

Anti­glycolipid disorder effect of epigallocatechin­3­gallate on high­fat diet and STZ­induced T2DM in mice.

Epigallocatechin-3-gallate (EGCG) is beneficial for inhibiting dyslipidemia and reducing hyperlipidemic risk. The purpose of the present study was to investigate the glycolipid regulatory effects and potential mechanisms of EGCG in a high­fat diet and streptozotocin­induced type 2 diabetes mellitus (T2DM) mouse model. The results demonstrated that EGCG can decrease blood glucose levels and increase insulin resistance in T2DM mice. In addition, EGCG can regulate serum lipid levels, including those of total cholesterol, triglyceride and low­density lipoprotein receptor (LDL­r), and reduce lipid deposition in vascular endothelial cells in a dose­dependent manner. In addition, the gene and protein expression of related scavenger receptors, including cluster of differentiation 36, sterol regulatory element binding protein 2 (SREBP), SREBP cleavage­activating protein and LDL­r, were downregulated in a dose­dependent manner. The present study noted that EGCG possesses potential as a natural product for preventing and treating metabolic hyperlipidemia syndrome, probably by reducing the blood lipid levels, alleviating vascular endothelial cell damage, maintaining normal lipid metabolism in blood vessels and ameliorating glycolipid disorders.

Antichronic Gastric Ulcer Effect of Zinc-Baicalin Complex on the Acetic Acid-Induced Chronic Gastric Ulcer Rat Model.

BACKGROUND: Baicalin (BA) has been shown to have anti-inflammatory and antioxidant activity. Zinc is a nutrient element. OBJECTIVE: This study is aimed at investigating the antichronic gastric ulcer activity of Zn-Baicalin complex (BA-Zn) and its related mechanisms in an acetic acid-induced gastric ulcer rat model. RESULTS: The severely ulcerated gastric mucosa of model rats had lower GSH-Px (52.21 ± 7.13) and SOD (7.03 ± 0.10) activity, and higher MDA (2.39 ± 0.03) content compared to sham rats. BA-Zn reduced the gastric ulcer index in a dose-dependent manner, significantly increased SOD activity and GSH-Px level, and reduced the MDA content and IL-8 and TNF-α levels in the gastric mucosa. BA-Zn (6.5 and 13 mg/kg) exerted a greater antiulcerogenic effect than both BA and zinc-gluconate, leading to a reduced ulcer index (18.43 ± 1.11, 15.00 ± 1.44), decreased MDA content (1.33 ± 0.07, 0.63 ± 0.01), and increased SOD activity (17.62 ± 0.11, 20.12 ± 0.32) and GSH-Px levels (102.12 ± 9.11, 120.25 ± 9.07). In addition, our results from Western blot suggested that BA-Zn (6.5 and 13 mg/kg) has a greater antiulcerogenic effect than both BA and zinc-gluconate. CONCLUSION: The BA-Zn complex possesses greater antichronic gastric ulcer properties compared to BA and zinc-gluconate due to its ability of oxidation resistance and anti-inflammatory effects.

Ferulic acid exerts neuroprotective effects against cerebral ischemia/reperfusion-induced injury via antioxidant and anti-apoptotic mechanisms in vitro and in vivo.

Ferulic acid (FA) is a derivative of cinnamic acid. It is used in the treatment of heart head blood-vessel disease and exerts protective effects against hypoxia/ischemia-induced cell injury in the brain. This study investigated the potential neuroprotective effects of FA against ischemia/reperfusion (I/R)-induced brain injury in vivo and in vitro through hematoxylin and eosin (H&E) and Nissl staining assays, flow cytometry, Hoechst 33258 staining, quantitative PCR, western blot analysis and fluorescence microscopic analysis. In this study, models of cerebral I/R injury were established using rats and pheochromocytoma (PC-12) cells. The results revealed that treatment with FA significantly attenuated memory impairment, and reduced hippocampal neuronal apoptosis and oxidative stress in a dose-dependent manner. The results from in vitro experiments also indicated that FA protected the PC-12 cells against I/R-induced reactive oxygen species (ROS) generation and apoptosis by inhibiting apoptosis, Ca2+ influx, superoxide anion (O2-), malondialdehyde (MDA) and glutathione peroxidase (GSH-Px) production in a concentration-dependent manner. Moreover, FA inactivated the Toll-like receptor (TLR)/myeloid differentiation factor 88 (MyD88) pathway. MyD88 overexpression abolished the neuroprotective effects of FA. On the whole, we found that FA attenuated memory dysfunction and exerted protective effects against oxidative stress and apoptosis induced by I/R injury by inhibiting the TLR4/MyD88 signaling pathway. This study supports the view that FA may be a promising neuroprotective agent for use in the treatment of cerebral ischemia.