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Objective(s): This study aimed to investigate the glucose and lipid metabolism improving effect of the total flavonoids from Selaginella tamariscina (Beauv.) Spring (TFST) on db/db mice, and to study its mechanism of action. Materials and Methods: The db/db mice were divided into 5 groups: the normal group (NC), the diabetic group (DM), the gliclazide group (GZ), the DM+TFST (110 mg/kg), and the DM+TFST (220 mg/kg). The body weight, blood glucose, INS, GC, TC, TG, LDL, and HDL were detected. HE staining was used to observe the liver and pancreas. Urine was tested by UPLC-QTOF-MS to study the metabolic differences of each group, coupled with SIMCA-P13.0 for PCA and OPLS-DA analysis, to identify potential biomarkers, find the metabolic pathway. Western blot was used to examine liver tissue of mice for studying effect of TFST on the PPAR-γ/PI3K/GLU4 pathway. Results: TFST can reduce the weight and levels of TC, TG, and LDL-C, increase the level of GC in blood, and reduce the fat accumulation and inflammation in the liver, and repair the islet cell. 13 biomarkers were identified, they are mainly involved in amino acid metabolism, and purine and pyrimidine metabolism. The results of Western blot show TFST can improve the utilization rate of GLU4 by regulating PPAR-γ and PI3K expression in the liver of db/db mice. Conclusion: TFST can improve glucose and lipid metabolism of DM, which relates to regulation of the PPAR-γ/PI3K/GLU4 signaling pathway, and affect the amino acid metabolism, purine, and pyrimidine metabolism. [ABSTRACT FROM AUTHOR]

Lepidium apetalum Willd has been used to reduce edema and promote urination. Cis-desulfoglucotropaeolin (cis-DG) and trans-desulfoglucotropaeolin (trans-DG) were isolated from Lepidium apetalum Willd, and caused a significant increase in cell viability in a hypertonic model in NRK52e cells. In the hypertonic model, cis-DG and trans-DG significantly promoted the cell viability of NRK52e cells and inhibited the elevation of Na+ in the supernatant, inhibited the renin-angiotensin-aldosterone (RAAS) system, significantly reduced the levels of angiotensin II (Ang II) and aldosterone (ALD), and lowered aquaporin-2 (AQP2) and Na+-K+ ATP content in renal medulla. After treatment with cis-DG and trans-DG, expression of calcineurin (CAN) and Ca/calmodulin-dependent protein kinase II (CaMK II) was decreased in renal tissue and Ca2+ influx was inhibited, thereby reducing the secretion of transforming growth factor-β (TGFβ), reversing the increase in adhesion and inflammatory factor E-selectin and monocyte chemotactic protein 1 (MCP-1) induced by high NaCl, while reducing oxidative stress status and decreasing the expression of cyclooxygenase-2 (COX2). Furthermore, inhibition of protein kinase C (PKC) expression also contributed to these improvements. The cis-DG and trans-DG reduced the expression of p-p44/42 MAPK, p-JNK and p-p38, inhibited the phosphorylation of the MAPK signaling pathway in NRN52e cells induced by high salt, decreased the overexpression of p-p38 and p-HSP27, and inhibited the overactivation of the p38-MAPK signaling pathway, suggesting that the p38-MAPK pathway may play a vital role in the hypertonic-induced adhesion and inflammatory response. From the results of this study, it can be concluded that the mechanism of cis-DG and trans-DG may mainly be through inhibiting the p38-MAPK signaling pathway, inhibiting the excessive activation of the RAAS system, and thereby reducing adhesion and inflammatory factors. [ABSTRACT FROM AUTHOR]

Background: Prototype foamy virus (PFV) is a member of the Spumaretrovirinae subfamily of retroviruses, which maintains lifelong latent infection while being nonpathogenic to their natural hosts. Autophagy is a cell-programmed mechanism that plays a pivotal role in controlling homeostasis and defense against exotic pathogens. However, whether autophagy is the mechanism for host defense in PFV infection has not been investigated. Findings: Our results revealed that PFV infection induced the accumulation of autophagosomes and triggered complete autophagic flux in BHK-21 cells. PFV infection also altered endoplasmic reticulum (ER) homeostasis. The PERK, IRE1 and ATF6 pathways, all of which are components of the ER stress-related unfolded protein response (UPR), were activated in PFV-infected cells. In addition, accelerating autophagy suppressed PFV replication, and inhibition of autophagy promoted viral replication. Conclusions: Our data indicate that PFV infection can induce complete autophagy through activating the ER stressrelated UPR pathway in BHK-21 cells. In turn, autophagy negatively regulates PFV replication. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to explore the mechanism by which amentoflavone (AME) improves insulin resistance in a human hepatocellular liver carcinoma cell line (HepG2). Methods: A model of insulin resistant cells was established in HepG2 by treatment with high glucose and insulin. The glucose oxidase method was used to detect the glucose consumption in each group. To determine the mechanism by which AME improves insulin resistance in HepG2 cells, enzyme-linked immunosorbent assay (ELISA) and western blotting were used to detect the expression of phosphatidyl inositol 3-kinase (PI3K), Akt, and pAkt; the activity of the enzymes involved in glucose metabolism; and the levels of inflammatory cytokines. Results: Insulin resistance was successfully induced in HepG2 cells. After treatment with AME, the glucose consumption increased significantly in HepG2 cells compared with the model group (MG). The expression of PI3K, Akt, and pAkt and the activity of 6-phosphofructokinas (PFK-1), glucokinase (GCK), and pyruvate kinase (PK) increased, while the activity of glycogen synthase kinase-3 (GSK-3), phosphoenolpyruvate carboxylase kinase (PEPCK), and glucose-6-phosphatase (G-6-Pase) as well as the levels of interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor- (TNF- ), and C reactive protein (CRP) decreased. Conclusions: The mechanism by which treatment with AME improves insulin resistance in HepG2 cells may involve the PI3K-Akt signaling pathway, the processes of glucose oxygenolysis, glycogen synthesis, gluconeogenesis and inflammatory cytokine expression. [ABSTRACT FROM AUTHOR]

Prototype foamy virus (PFV) is a member of the unconventional and nonpathogenic retroviruses. PFV causes lifelong chronic infections, which are partially attributable to a number of host cell factors that restrict viral replication. Herein, we identified human p53-induced RING-H2 protein (Pirh2) as a novel inhibitor of prototype foamy virus. Overexpression of Pirh2 decreased the replication of PFV, whereas knockdown of Pirh2 with specific siRNA increased PFV replication. Dual-luciferase assays and coimmunoprecipitation demonstrated that Pirh2 negatively influences the Tas-dependent transcriptional activation of the PFV long terminal repeat (LTR) and internal promoter (IP) by interacting with the transactivator Tas and down-regulating its expression. In addition, the viral inhibitory function of Pirh2 is N-terminal and RING domain dependent. Together, these results indicated that Pirh2 suppresses PFV replication by negatively impacting its transactivator Tas and the transcription of two viral promoters, which may contribute to the latency of PFV infection. [ABSTRACT FROM AUTHOR]