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The angiotensin-converting enzyme 2 (ACE2)/angiotensin 1-7/MAS axis and the gamma-aminobutyric acid (GABA)ergic signaling system have both been shown to have the dual potential to improve insulin resistance (IR) and hepatic steatosis associated with obesity in the liver. Recent studies have demonstrated that ACE2 can regulate the GABA signal in various tissues. Notwithstanding this evidence, the functional relationship between ACE2 and GABA signal in the liver under IR remains elusive. Here, we used high-fat diet-induced models of IR in C57BL/6 mice as well as ACE2KO and adeno-associated virus-mediated ACE2 overexpression mouse models to address this knowledge gap. Our analysis showed that glutamate decarboxylase (GAD)67/GABA signaling was weakened in the liver during IR, whereas the expression of GAD67 and GABA decreased significantly in ACE2KO mice. Furthermore, exogenous administration of angiotensin 1-7 and adeno-associated virus- or lentivirus-mediated overexpression of ACE2 significantly increased hepatic GABA signaling in models of IR both in vivo and in vitro. We found that this treatment prevented lipid accumulation and promoted fatty acid β oxidation in hepatocytes as well as inhibited the expression of gluconeogenesis- and inflammation-related genes, which could be reversed by allylglycine, a specific GAD67 inhibitor. Collectively, our findings show that signaling via the ACE2/A1-7/MAS axis can improve hepatic IR by regulating hepatic GABA signaling. We propose that this research might indicate a potential strategy for the management of diabetes.

Eleven new highly oxygenated germacrane-type sesquiterpenoids (1–11) and 16 known analogues (12–27) were isolated from the aerial parts of Sigesbeckia orientalis. Their structures, including absolute configurations, were determined by comprehensive spectroscopic methods especially NMR and ECD analyses. Compounds 13, 21 and 23 possessing an 8-methacryloxy group showed stronger in vitro cytotoxicity against human A549 and MDA-MB-231 cancer cell lines than other co-metabolites, with IC50 values ranging from 6.02 to 10.77 μM comparable to the positive control adriamycin.

Parkinson's disease (PD) is a common disease which occurs in aged people with chronic, progressive degenerative character of the central nervous system. Until now there is no effective treatment method in PD patients before they show obvious symptoms for prevention and early diagnosis. In order to find out early disease specific biomarkers, two-dimensional liquid chromatography-tandem mass spectrometry coupled with isobaric tags for relative and absolute quantification (iTRAQ) labeling was employed to quantitatively identify the differentially expressed proteins among the different disease progress types of PD. 26 proteins were differentially expressed in a total of 258 identified proteins by proteomic techniques. The expression level of eight proteins which included sero-transferrin and clusterin increased. The expression level of eighteen proteins which include complement component 4B, apolipoprotein A-I, α-2-antiplasmin and coagulation factor V decreased. Those proteins may be associated with oxidative stress, mitochondrial dysfunction, abnormal protein aggregation and inflammation. In this study, the expression level of apolipoprotein A-I decreased, particularly in the early stage of PD patients. This protein regulated not only the lipid metabolism in the central nervous system, but also influenced the deposition process of proteins which are involved in neural degenerative diseases, such as the pathogenesis of PD.

Given the importance of secreted proteins as a source for early detection and diagnosis of disease, secreted proteins have been arousing considerable attention. However, the analysis of secreted proteins represents a challenge for current proteomic techniques. One of the difficulties in secretomic study is to concentrate proteins from large volume of growth media, particularly, the low abundant and low molecular weight proteins (molecular weight

Preeclampsia (PE) is a complex and serious condition of pregnancy. Trophoblasts in human placenta can be separated and collected by laser capture micro-dissection (LCM). Protein in trophoblasts have been extracted and separated by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), finally 962 unique proteins are identified by liquid chromatography coupled to mass spectrometry (LC-MS/MS). Comparison of differential expressed proteins in normal and those in PE are investigated. Two-dimensional electrophoresis (2DE) and MS were used to identify differential expressed proteins. 13 differential expressed proteins include signal transduction protein, molecular chaperone, cell skeleton proteins are identified, in which 3 proteins are down-regulated and 10 proteins are up-regulated. They might be correlated with the cause of PE.

The human hepatoma 3B cell line was chosen as an experimental model for in vitro test of drug screening. The drugs included chlorophyllin and its derivatives such as fluo-chlorophyllin, sodium copper chlorophyllin, and sodium iron chlorophyllin. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) method was used in this study to obtain the primary screening results. The results showed that sodium iron chlorophyllin had the best LC(50) value. Proteomic analysis was then performed for further investigation of the effect of sodium iron chlorophyllin addition to the Hep 3B cell line. The proteins identified from a total protein extract of Hep 3B before and after the drug addition were compared by two-dimensional-gel-electrophoresis. Then 32 three-fold differentially expressed proteins were successfully identified by MALDI-TOF-TOF-MS. There are 29 unique proteins among those identified proteins. These proteins include proliferating cell nuclear antigen (PCNA), T-complex protein, heterogeneous nuclear protein, nucleophosmin, heat shock protein A5 (HspA5) and peroxiredoxin. HspA5 is one of the proteins which are involved in protecting cancer cells against stress-induced apoptosis in cultured cells, protecting them against apoptosis through various mechanisms. Peroxiredoxin has anti-oxidant function and is related to cell proliferation, and signal transduction. It can protect the oxidation of other proteins. Peroxiredoxin has a close relationship with cancer and can eventually become a disease biomarker. This might help to develop a novel treatment method for carcinoma cancer.

Cytotrophoblast cell differentiation into syncytiotrophoblast cells is a complex and delicate process, and the mechanism needs a large number of further studies. Knockout of 14-3-3τ expression and some further investigations were performed in the syncytiotrophoblast cell formation with RNA interference (RNAi) technology. The study found that the 14-3-3τ expression level with the formation of syncytiotrophoblast cells increased. Hypoxia inhibited the formation of syncytiotrophoblast cells where 14-3-3τ expression level decreased. RNAi reduced 14-3-3τ expression, and reduced the formation of syncytiotrophoblast cells. So that 14-3-3τ is not only involved in the cell regulation, but also in the formation of syncytiotrophoblast cells. 14-3-3τ is an important regulatory factor which inhibits the formation of hypoxia.