[Electroacupuncture regulates glucose metabolism disorder through PI3K/Akt/GSK3ß signaling pathway in rats with depression].

OBJECTIVE: To explore the mechanism of electroacupuncture (EA) at "Zusanli" (ST36) on improving glucose metabolism disorder in chronic restraint induced depressed rats. METHODS: A total of 30 male SD rats were randomly divided into control, model and EA groups, with 10 rats in each group. The depression model was established by chronic restraint 2.5 h each day for 4 weeks. For rats in the EA group, EA stimulation (1 mA, 2 Hz, 30 min) was applied to bilateral ST36 during the modeling period, once a day for 4 weeks. The body weight of the rats was recorded before and after modeling. The behavior of rats was observed by sugar-water preference and forced swimming after modeling. The contents of glucose and glycosylated albumin in serum were determined by biochemical method. The histopathological morphology and liver glycogen content were observed by HE and PAS staining. The expression levels of phosphatidylinositol 3-kinase (PI3K), phosphorylated (p)-PI3K (p-PI3K), protein kinase B (Akt), p-Akt, glycogen synthase kinase-3ß (GSK3ß) and p-GSK3ß proteins in liver were determined by Western blot. RESULTS: Compared with the control group, the weight increment and sugar-water preference index decreased (P<0.01), the immobile swimming time was prolonged (P<0.01), the glucose and glycosylated albumin contents in serum increased (P<0.05), the expression of p-Akt protein and the ratio of p-Akt/Akt in liver tissues decreased (P<0.001), the expression of p-GSK3ß protein and the ratio of p-GSK3ß/GSK3ß in liver tissues increased (P<0.01,P<0.001) in the model group. Compared with the model group, the weight increment and sugar-water preference index increased (P<0.05), the immobile swimming time was shortened (P<0.05), the glucose and glycosylated albumin contents in serum decreased (P<0.05), the expressions of p-PI3K and p-Akt proteins and the ratio of p-PI3K/PI3K and p-Akt/Akt in liver tissues increased (P<0.05), the expression of p-GSK3ß protein and the ratio of p-GSK3ß/GSK3ß in liver tissues decreased (P<0.01) in the EA group. HE staining showed that the structure of the hepatic lobule was intact, no obvious inflammatory cell infiltration or fibrosis was observed in the lobule and interstitium, and no abnormalities were observed in the small bile duct, portal vein and artery in the portal area. PAS staining showed that the intensity of staining from the center of the hepatic lobule to the periphery of the hepatic lobule was gradually enhanced in the blank group, that is, the glycogen-rich granules in the hepatic cells were gradually increased; most of the hepatocytes were light colored and glycogen was lost significantly in the model group; while the intensity of hepatocyte staining increased, the staining intensity of the perilobular zone was weaker than that in the blank group, and the glycogen particles partially recovered in the EA group. CONCLUSION: EA intervention can regulate glucose metabolism disorder in chronic restraint induced depressed rats through PI3K/Akt/GSK3ß signaling pathway.

COMPASS functions as a module of the INO80 chromatin remodeling complex to mediate histone H3K4 methylation in Arabidopsis.

In the INO80 chromatin remodeling complex, all of the accessory subunits are assembled on the following three domains of INO80: N-terminal domain (NTD), HSA domain, and ATPase domain. Although the ATPase and HSA domains and their interacting accessory subunits are known to be responsible for chromatin remodeling, it is largely unknown how the accessory subunits that interact with the INO80 NTD regulate chromatin status. Here, we identify both conserved and nonconserved accessory subunits that interact with the three domains in the INO80 complex in Arabidopsis thaliana. While the accessory subunits that interact with all the three INO80 domains can mediate transcriptional repression, the INO80 NTD and the accessory subunits interact with it can contribute to transcriptional activation even when the ATPase domain is absent, suggesting that INO80 has an ATPase-independent role. A subclass of the COMPASS histone H3K4 methyltransferase complexes interact with the INO80 NTD in the INO80 complex and function together with the other accessory subunits that interact with the INO80 NTD, thereby facilitating H3K4 trimethylation and transcriptional activation. This study suggests that the opposite effects of the INO80 complex on transcription are required for the balance between vegetative growth and flowering under diverse environmental conditions.

The PEAT protein complexes are required for histone deacetylation and heterochromatin silencing.

In eukaryotes, heterochromatin regions are typically subjected to transcriptional silencing. DNA methylation has an important role in such silencing and has been studied extensively. However, little is known about how methylated heterochromatin regions are subjected to silencing. We conducted a genetic screen and identified an epcr (enhancer of polycomb-related) mutant that releases heterochromatin silencing in Arabidopsis thaliana We demonstrated that EPCR1 functions redundantly with its paralog EPCR2 and interacts with PWWP domain-containing proteins (PWWPs), AT-rich interaction domain-containing proteins (ARIDs), and telomere repeat binding proteins (TRBs), thus forming multiple functionally redundant protein complexes named PEAT (PWWPs-EPCRs-ARIDs-TRBs). The PEAT complexes mediate histone deacetylation and heterochromatin condensation and thereby facilitate heterochromatin silencing. In heterochromatin regions, the production of small interfering RNAs (siRNAs) and DNA methylation is repressed by the PEAT complexes. The study reveals how histone deacetylation, heterochromatin condensation, siRNA production, and DNA methylation interplay with each other and thereby maintain heterochromatin silencing.

Recombinant FIP-gat, a Fungal Immunomodulatory Protein from Ganoderma atrum, Induces Growth Inhibition and Cell Death in Breast Cancer Cells.

FIP-gat, an immunomodulatory protein isolated from Ganoderma atrum, is a new member of the FIP family. Little is known, however, about its expressional properties and antitumor activities. It was availably expressed in Escherichia coli with a total yield of 29.75 mg/L. The migration of recombinant FIP-gat (rFIP-gat) on SDS-PAGE corresponded to the predicted molecular mass, and the band was correctly detected by a specific antibody. To characterize the direct effects of rFIP-gat on MDA-MB-231 breast cancer cells, MDA-MB-231 cells were treated with different concentrations of rFIP-gat in vitro; the results showed that this protein could reduce cell viability dose-dependently with a median inhibitory concentration (IC50) of 9.96 µg/mL and agglutinate the MDA-MB-231 cells at a concentration as low as 5 µg/mL. Furthermore, FIP-gat at a concentration of 10 µg/mL can induce significant growth inhibition and cell death in MDA-MB-231 cells. Notably, FIP-gat treatment triggers significant cell cycle arrest at the G1/S transition and pronounced increase in apoptotic cell population. Molecular assays based on microarray and real-time PCR further revealed the potential mechanisms encompassing growth arrest, apoptosis, and autophagy underlying the phenotypic effects.

Recombinant murine fibroblast growth factor 21 ameliorates obesity-related inflammation in monosodium glutamate-induced obesity rats.

The aim of this study is to investigate the role of FGF21 in obesity-related inflammation in livers of monosodium glutamate (MSG)-induced obesity rats. The MSG rats were injected with recombinant murine fibroblast growth factor 21(FGF21) or equal volumes of vehicle. Metabolic parameters including body weight, Lee's index, food intake, visceral fat and liver weight, intraperitoneal glucose tolerance, glucose, and lipid levels were dynamically measured at specific time points. Liver function and routine blood test were also analyzed. Further, systemic inflammatory cytokines such as glucose transporter 1 (GLUT-1), leptin, TNF-α, and IL-6 mRNAs were determined by real-time PCR. FGF21 independently decreased body weight and whole-body fat mass without reducing food intake in the MSG rats. FGF21 reduced blood glucose level, Lee's index, visceral fat, and liver weight, and improved glucose tolerance, lipid metabolic spectrum, and hepatic steatosis in the MSG-obesity rats. Liver function parameters including AST, ALT, ALP, TP, T.Bili, and D.Bili levels significantly reduced in the FGF21-treated obesity rats compared to the controls. Further, FGF21 ameliorated the total and differential white blood cell (WBC) count, serum C-reactive protein (CRP), IL-6, and TNF-α levels in adipose tissues of the obesity rats, suggesting inflammation amelioration in the in the obesity rats by FGF21. FGF21 improves multiple metabolic disorders and ameliorates obesity-related inflammation in the MSG-induced obesity rats.