Review on the effect of glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors for the treatment of non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is a common liver disease and it represents the hepatic manifestation of metabolic syndrome, which includes type 2 diabetes mellitus (T2DM), dyslipidemia, central obesity and hypertension. Glucagon-like peptide-1 (GLP-1) analogues and dipeptidyl peptidase-4 (DPP-4) inhibitors were widely used to treat T2DM. These agents improve glycemic control, promote weight loss and improve lipid metabolism. Recent studies have demonstrated that the GLP-1 receptor (GLP-1R) is present and functional in human and rat hepatocytes. In this review, we present data from animal researches and human clinical studies that showed GLP-1 analogues and DPP-4 inhibitors can decrease hepatic triglyceride (TG) content and improve hepatic steatosis, although some effects could be a result of improvements in metabolic parameters. Multiple hepatocyte signal transduction pathways and mRNA from key enzymes in fatty acid metabolism appear to be activated by GLP-1 and its analogues. Thus, the data support the need for more rigorous prospective clinical trials to further investigate the potential of incretin therapies to treat patients with NAFLD.

FRAS1 knockdown reduces A549 cells migration and invasion through downregulation of FAK signaling.

Distal metastasis is the major cause of death for the vast majority of lung cancer patients. Many extracellular matrix (ECM)-related molecules are proposed to be associated with the migration and invasion of cancer cells. FRAS1 encodes an ECM protein, however, little is known about its function on tumorigenesis and metastasis of lung cancer. In this work, FRAS1 was silenced by shRNA in non-small cell lung cancer (NSCLC) A549 cell line. The capacities of A549 cells to migrate and invade were decreased markedly after FRAS1 knockdown. The shRNA knockdown of FRAS1 was found to be specific and had no effect on A549 cells proliferation. Western blot experiments demonstrated that FRAS1 knockdown inhibited FAK signaling but not Src signaling. Overall, we found that FRAS1 knockdown reduces A549 cells migration and invasion ability through downregulation of FAK signaling.

[Efficacy and safety of rh-endostatin combined with docetaxel in second-line or intolerant toxicity for first-line treatment in patients with advanced non-small cell lung cancer].

OBJECTIVE: To analyze the efficacy and safety of combination of rh-endostatin (Endostar) with docetaxel treatment on patients of non-small cell lung cancer (NSCLC) who presented PD or intolerable toxicity in/after first-line chemotherapy. METHODS: A randomized, double-blind, placebo-controlled and multi-center clinical trial was conducted. Patients with stage IIIB/IV of NSCLC experienced previous chemotherapy of one-regimen were screened for this trial. A total of 68 cases were included in this study. Single docetaxel and that combined with endostar were conducted in two arms. The response, time to progression (TTP) and adverse effects were observed in both arms. RESULTS: The objective response rate (ORR) and clinical benefit rate (CBR) were 0 and 62.5% in the combined arm, along with 0 and 53.3% in the single docetaxel arm, with a non-significant difference between the two groups (all P > 0.05), respectively. The median TTPs in the combined and single docetaxel arms were 2.63 and 2.07 months, respectively (P = 0.079). The median TTPs of the participants with progressive disease (PD) after first-line chemotherapy were 1.33 and 1.67 months in the combined and single docetaxel arms, respectively (P = 0.946). The median TTPs of the participants with intolerant adverse effects in first-line chemotherapy were 4.70 months and 3.17 months in the combined and single docetaxel arms, respectively (P = 0.070). The median TTPs of the patients with SD after 2 therapeutic cycles in the combined and single docetaxel arms were 6.23 months and 3.27 months, respectively (P = 0.040). The differences between two arms were non-significant in adverse, serious adverse and cardiovascular adverse effects (all P > 0.05). CONCLUSIONS: Endostar may prolong TTP in patients with advanced NSCLC benefited from docetaxel treatment without increased toxicities.

Starmerella jinningensis sp. nov., a yeast species isolated from flowers of Erianthus rufipilus.

Five yeast strains (Ym24403, Ym24404, Ym24408, Ym24409 and Ym24410(T)) were isolated from different flowers of Erianthus rufipilus (Gramineae), a wild plant growing in the phosphorus-rich region in Yunnan Province, south-western China, and were found to be phenotypically and genetically divergent from currently recognized yeast species. Sequence analysis of the D1/D2 domain of the large subunit rRNA gene revealed that the five strains represented a novel species described as Starmerella jinningensis sp. nov. The type strain is Ym24410(T) (= CBS 11864(T) =CCTCC AY 2011002(T)). Phylogenetic analysis based on the D1/D2 region of the large subunit rRNA gene suggested that S. jinningensis sp. nov. is placed within the Starmerella clade.

[Effects of deguelin on proliferation and apoptosis of MCF-7 breast cancer cells by phosphatidylinositol 3-kinase/Akt signaling pathway].

OBJECTIVE: To study the effects of deguelin on proliferation and apoptosis of human breast cancer cell line MCF-7 and on phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway. METHODS: After treatment with 0, 1, 5, 10, 15 and 20 µmol/L of deguelin for 6, 24, 48 and 72 hours, the proliferation inhibition rate of MCF-7 cells was measured by cell counting kit-8 assay. Apoptosis rate of MCF-7 cells was detected with Annexin V-fluorescein isothiocyanate/propidium iodide double staining by flow cytometry and the apoptotic morphology was observed under a transmission electron microscope. After treatment with 0, 1 and 5 µmol/L of deguelin for 6 hours, 5 proteins involved in the PI3K/Akt signaling pathway were examined by Western blot analysis. RESULTS: Deguelin at doses of 5, 10, 15 and 20 µmol/L inhibited the proliferation of MCF-7 cells at 6, 24, 48 and 72 hours. There was a significant difference in each group compared with the control group (P<0.01). The inhibitory effect was more marked with increasing concentration and duration of treatment. There were statistical differences (P<0.05) among 5, 10, 15 and 20 µmol/L groups. However, 1 µmol/L of deguelin had no obvious effects on the proliferation of MCF-7 cells at 6, 24, 48 and 72 hours, showing no significant difference compared with control group (P>0.05). Deguelin at doses of 5, 10, 15 and 20 µmol/L induced apoptosis of MCF-7 cells at 6 hours. There were significant differences (P<0.01) in the early and late apoptosis rate between the treated groups and the control group. The typical apoptotic MCF-7 cells were observed under the transmission electron microscopy. However, 1 µmol/L of deguelin had no apparent effect in inducing apoptosis of MCF-7 cells at 6 hours. After treatment with 5 µmol/L of deguelin for 6 hours the expression of phosphorylated phosphatase and tensin homologue deleted on chromosome 10 (PTEN) (Ser380), phosphorylated 3-phosphoinositide-dependent protein kinase 1 (PDK1) (Ser241), phosphorylated Akt (Thr308) and phosphorylated glycogen synthase kinase-3ß (GSK-3ß) (Ser9) proteins were significantly reduced in MCF-7 cells, while there was no significant change in the expression of total Akt protein. However, after treatment with 1 µmol/L of deguelin for 6 hours, there was no apparent change in the expression of these 5 proteins. CONCLUSION: Deguelin can inhibit the phosphorylation of GSK-3ß (Ser9) via inhibition of the phosphorylation of PTEN (Ser380) and PDK1 (Ser241) pathway, thus inducing apoptosis and inhibiting proliferation of MCF-7 cells.

Effects of glycerol pretreatment on recovery and antioxidant enzyme activities of lyophilized red blood cells.

Successful storage of red blood cells (RBCs) by freeze-drying technique has important implications in blood transfusion and clinical medicine. We presented a method of preservation RBCs by pretreating them with glycerol solution and then freeze-drying. The effects of glycerol pretreatment on recovery and antioxidant enzyme activities of lyophilized RBCs were investigated. Rehydration of pretreated in 40 percent glycerol and freeze-dried RBCs resulted in 55.3+/-4.3 percent numerical recovery and 53.5+/-3.9 percent hemoglobin recovery, which were significantly higher than freeze-dried RBCs without glycerol pretreatment (P less than 0.01). Superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-PX) activities of 40 percent glycerol pretreated and freeze-dried RBCs almost remained fully active after freeze-drying. After 180 days storage, the activities decreased by 25.6 percent , 21.5 percent and 18.4 percent, respectively, which are significantly less than those of freeze-dried RBCs without glycerol pretreatment (P < 0.1). These data demonstrated that glycerol pretreatment had beneficial effects on the recovery and antioxidant enzyme activities of lyophilized RBCs.

Freeze-drying of human platelets: influence of saccharide, freezing rate and cell concentration.

Freeze-drying of human platelets is one potentially ideal approach for long-term preservation of platelets. In this study, effects of concentration and type of saccharides, freezing rate and initial cell concentration on the recovery of freeze-dried platelets were investigated. Annexin V binding platelet activation assays, scanning electron microscopy and platelet aggregation upon thrombin (1 U/ml) addition were used to evaluate the effectiveness of platelet freeze-drying. The numerical recovery of freeze-dried platelets was reached as high as 93.0+/-5.2 percent and the recovery of nonactive platelets was reached up to 85.7 +/- 3.4 percent in the presence of 1% BSA and 20% trehalose. Frozen by shelf pre-cooling was the best way to freeze the sample in this study and the numerical recovery of freeze-dried platelets was reached 93.0 +/- 5.2 percent at about 10 degree C/min. When the platelet concentration was increased from 0.2 to 4x10(9) platelets/ml, recovery remained higher than 81.4 percent. The morphology of freeze-dried and rehydrated platelets was intact but a little rounder compared with fresh platelets. The maximum aggregation rate to thrombin (1 U/ml) of freeze-dried platelets was 83.9 percent of the fresh ones, but aggregation speed was 43.0 percent of the fresh ones. Further research on rehydration process and scale up are required.

Freeze-drying of human platelets: influence of intracellular trehalose and extracellular protectants.

Freeze-drying is an ideal alternative for long-term preservation of platelets in blood banks. Intracellular trehalose is believed to be an effective lyoprotectant for preserving cells during freeze-drying. In this study, 13 mM intracellular trehalose was loaded into human platelets through fluid-phase endocytosis pathway. Bovine serum albumin and trehalose were used as extracellular protectants. The effects of intracellular trehalose and extracellular protectants on freeze-dried platelets were studied respectively. The results showed 13 mM intracellular trehalose was beneficial to freeze-dried human platelets, but only slightly enhanced the protection afforded by extracellular protectants. Loaded with 13 mM intracellular trehalose, platelets were freeze-dried in a formulation of 1 percent bovine serum albumin and 1 percent trehalose, 40 days later, the survival rate of rehydrated platelets was about 85 percent, the morphology of rehydrated platelets was intact and the aggregation percentage with thrombin (1 U/ml) was 97.3 percent.

[A meta-analysis of the curative effects of carboplatin-based and cisplatin-based chemotherapeutic regimens on advance non-small cell lung cancer].

OBJECTIVE: To evaluate whether there is a difference in the curative effect of carboplatin-based and cisplatin-based chemotherapeutic regimens on advance non-small cell lung cancer (NSCLC). METHODS: The databases PudMed, CENTRAL, and Chinese biomedical database were retrieved by using the key words "non-small cell lung cancer" or "carcinoma, non-small cell lung" so as to search the materials about the randomized controlled clinical trials that had compared the curative effects of carboplatin-based and cisplatin-based chemotherapeutic regimens on advance NSCLC. A meta-analysis was conducted. RESULTS: Eighteen documents about randomized controlled clinical trials, including 6478 patients, from the retrieved 3531 documents accorded to the demand of enrollment. The overall response rates of the carboplatin-based and cisplatin-based chemotherapeutic groups were both 27% (RR = 0.93, 95% CI = 0.86 approximately 1.01, P = 0.10). Neither funnel plot nor rank correlation test regarding response rate indicated the existence of publication bias (chi(2) = 18.63, P = 0.63). The 0ne-year survival rate of the carboplatin-based regimen group was 36%, not significantly different from that of the cisplatin-based regimen group (35%, RR = 1.04, 95% CI = 0.93 - 1.17, P = 0.5). Sensitive analysis confirmed the non-existence of differences in the overall response rate and one-year survival rate between these 2 groups. CONCLUSION: The curative effects of the carboplatin-based and cisplatin-based chemotherapeutic regimens are similar. The choice of carboplatin or cisplatin depends on the toxicity of the drugs and the patients' tolerance.

[Combustion temperature measurement of pyrotechnic composition using remote sensing Fourier transform infrared spectrometry].

In this paper, combustion characterization of pyrotechnic composition is investigated using a remote sensing Fourier transform infrared spectrometry. The emission spectra have been recorded between 4,700 and 740 cm-1 with a spectral resolution of 4 cm-1. The combustion temperature can be determined remotely from spectral line intensity distribution of the fine structure of the emission fundamental band of gaseous products such as HF. The relationship between combustion temperature and combustion time has been given. Results show that there is a violent mutative temperature field with bigger temperature gradient near combustion surface. It reveals that the method of temperature measurement using remote sensing FTIR for flame temperature of unstable, violent and short time combustion on real time is a rapid, accurate and sensitive technique without interference the flame temperature field. Potential prospects of temperature measurement, gas product concentration measurement and combustion mechanism are also revealed.