Prediabetes is an abnormal condition between normal glucose metabolism and diabetes mellitus. Impaired glucose tolerance (IGT) is an indicator of high-risk state of prediabetes. Positive interventions of IGT, including life style changes and pharmacological intervention, can effectively postpone and reduce the development of prediabetes into type 2 diabetes mellitus, suggesting that IGT is a key point of diabetes prevention. Currently, pharmacological intervention for prediabetes is still at early stage. In this review, we summarizes recent clinical and preclinical studies on pharmacological intervention for prediabetes, and studies in the development of animal models with IGT and the application of new techniques. We also discuss the prospects of drugs for diabetes prevention, especially with the traditional Chinese medicine.
Animals ; Diabetes Mellitus, Type 2 ; prevention & control ; Disease Models, Animal ; Drugs, Chinese Herbal ; therapeutic use ; Glucose Intolerance ; Humans ; Prediabetic State ; drug therapy

Objective To elucidate whether down-regulation of homo sapiens eukaryotic translation elongation factor 1 alpha 2 (EEF1A2) expression induces apoptosis in pancreatic cancer cells and its possible mechanisms. Methods Two siRNAs targeting human EEF1A2 were synthesized and the siRNA/liposome complexes were transfected into the pancreatic cancer cell line BxPC-3. RTPCR and Western blot were used to analyze the change of EEF1A2 expression and the apoptosis rate of BxPC-3 cells was studied using Annexin-V/PI assay. To identify the mechanisms involved, the apoptosis associated proteins such as caspase-3, caspase-8, caspase-9, PARP, cytochrome C and Bid were detected by Western blotting. Results Both EEF1A2-targeting siRNAs reduced the EEF1A2expression, and the No. 2 siRNA inhibited EEF1A2 expression to less than 25 % in mRNA and protein levels. Down-regulation of EEF1A2 expression in BxPC-3 cells enhanced cell apoptosis (15.28% ±3.65%) at a greater level than negative siRNA-expressing cells (10. 11% ± 3. 05%) or mock cells (9.41 % ±4.14 %). Furthermore, reduction of EEF1A2 activated the pro-caspase-8, pro-caspase-3,pro-caspase-9,PARP and Bid to their active forms, and increased the expression of cytochrome C.Conclusions These data suggest that EEF1A2 down-regulation could significantly induce apoptosis of pancreatic cancer cell line BxPC-3, which is likely mediated by the death receptor and mitochondrial apoptotic pathways.

Objective To explore the effect and the possible mechanisms of silent homo sapiens eukaryotic translation elongation factor 1 alpha 2(EEF1A2)gene on the growth of pancreatic cancer cell in vivo.Methods The pancreatic cancer xenograft models in mice were established.The mice were equally divided into control group,negative control group and EEF1A2 group,which were injected with PBS,negative control siRNA and EEF1A2 siRNA into xenograft tumors respectively.The size and weight of tumors in each group were measured.The expression of EEF1A2 and PCNA in tumor tissue of each group was detected by immunohistochemistry.The cell apoptosis rate in tumor tissue of each group was determined by TUNEL.Results In xenograft nude mice models,since the 17th day of injection,the growth of tumor size in EEF1A2 group was obviously slower than that of negative control group and control group(all P＜0.05).By the end of the treatment,the tumors were cut off and weighted.The weight of tumors in EEF1A2 group(0.27g± 0.06g)were significantly lower than those of control group and negative control group(0.39g± 0.08g and 0.43g± 0.07g,P＜0.05).EEF1A2 mostly expressed in cytoplasm of pancreatic cancer cell.In negative control group and control group,the positive cells distributed densely and the positive rate was(72.58 ± 25.47)％ and (76.75±23.19)％ respectively.The distribution of positive cells in EEF1A2 group was scattered and the positive rate was(34.78±21.36)％,the difference was statisically significant(P＜0.01).The expression of PCNA at protein level in EEF1A2 group was significantly lower those that of control group and negative control group(P＜ 0.01).The result of TUNEL test indicated that the cell apoptosis rate in EEF1A2 group was higher than those of control group and negative control group (P＜0.01).Conclusions The EEF1A2 gene can be effectively silented in vivo,which significantly inhibits the growth of pancreatic cancer cell.It may be related with inhibition of cell proliferation and promotion cell apoptosis.

The pancreatic enzyme-II type collagenase digestion method was adopted for primary culture of osteoblasts, inoculation and passage. They were identified by alkaline phosphatase dye-liquor. N-butanol extract fractions from different processed products of Cibotium barometz were prepared. The above osteoblasts were jointly cultured with protocatechuic acid, protocatechuic aldehyde, kojic acid and the mixed control liquid of the above three substances, and their proliferation was detected by CCK-8. Various n-butanol extract fractions from different processed products of C. barometz showed a significant proliferative effect on osteoblasts in the order of the wined > the heated > the salted > the sand-heated and wined system > the alcohol-processed > the steamed > the crude. The q test showed no significant difference among sand-heated, alcohol-processed and steamed C. barometz, no significant difference between heated and salted C. barometz. Various control substances also showed a certain proliferative effect on osteoblasts in the order of the mixed control > protocatechuic aldehyde > protocatechuic acid > kojic acid. The q test showed no significant difference between protocatechuic aldehyde and protocatechuic acid. All of n-butanol extract fractions from different processed products of C. barometz showed a significant effect on osteoblast proliferation, of which wined C. barometz showed the best effect. All of phenolic compounds such as protocatechuic aldehyde, protocatechuic acid and kojic acid showed a significant proliferative effect on osteoblasts.
Animals ; Cell Proliferation ; drug effects ; Drug Compounding ; methods ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; Osteoblasts ; cytology ; drug effects ; Pteridophyta ; chemistry ; Rats ; Rats, Sprague-Dawley

To study the chemical constituents of Lysimachia patungensis Hand.-Mazz., silica gel column chromatography, reverse phase ODS column chromatography, MCI and Sephadex LH-20, were used to separate the 95% EtOH extract of the whole plant of Lysimachia patungensis Hand.-Mazz.. The structures of the isolated compounds have been established on the basis of chemical and NMR spectroscopic evidence as well as ESI-MS in some cases. Twelve phenolic compounds were obtained and identified as quercetin-3, 3'-di- O-alpha-L-rhamnoside (1), myricetrin (2), quercitrin (3), rutin (4), 2-hydroxynaringenin-4'-O-glucopyranoside (5), naringenin 7-O-glucopyranoside (6), liquiritin apioside (7), licochalcone B (8), tetrahydroxymethoxy chalcone (9), methyl-p-coumarate (10), 2, 4, 6-trihydroxy acetophenone-2-O-glucopyranoside (11) and vaccihein A (12). Among them, compound 1 is a new compound, and compounds 5, 11 and 12 are isolated from the genus Lysimachia L. for the first time, and the others are isolated from the plant for the first time.

Objective To study the regulatory effect of interferons(IFNs) on retinoic acid-inducible gene-Ⅰ(RIG-Ⅰ) and the roles of RIG-Ⅰ in IFNs signaling pathway. Methods RIG-Ⅰ expression before and after IFNs treatment in mouse embryonic fibroblasts(MEFs) were analyzed with Northern blotting and semi-quantitative RT-PCR assay.MEFs isolated from wild-type and RIG-Ⅰ-/-mice were used to test growth inhibition and antiviral activity of IFNs with MTT assay and cytopathic effect inhibition assay. Results Both IFN-? and IFN-? could induce RIG-Ⅰ expression in MEFs.Treated with 100 U/mL IFN-?,growth inhibition and antiviral activity of MEFs from wild-type mice were more significant than those from RIG-Ⅰ-/-mice.With the absence of RIG-Ⅰ,the antiviral protective role IFN-? plays was significantly weaker than the wild type. Conclusion RIG-Ⅰ gene is a novel mediator of interferon effects on cells.It may participate in the inflammation responses mediated by IFNs through modulating cytokines production.

Exosomes are a kind of endosomal vesicles that are secreted by most if not all living cells. Due to their capability of delivering a variety of cargos, such as tissue- or cell-specific proteins, lipids, and genetic materials, and their broad biological activities, exosomes have gained substantial attention as emerging therapeutics. Exosomes derived from mesenchymal stem cells (MSCs) and dendritic cells (DCs) are two types of exosomes that are widely studied. Many preclinical and clinical studies have shown that they have a satisfactory treatment effect in lung diseases, liver diseases, nervous system diseases, tumors, and other diseases. In addition, exosomes from macrophages, tumor cells, plant cells, and many other cells are getting more attention due to their therapeutic potential. Besides natural exosomes, research on engineered exosomes has also made plenty of progress. There have been several engineering methods of exosomes, such as targeting modification and loading of active ingredients. In this review, we summarize the research progress of therapeutic exosomes from different sources, and further discusses the application prospects of exosomes and possible challenges in the future.

Altitude ; Altitude Sickness ; Animals ; Hypoxia ; Iron ; Mice ; Spleen

Objective To investigate whether expression of XAF1 mediated by edenovirus vector AdS/F35 could induce apoptosis in pancreatic cancer cell line BxPC-3 and its possible mechanisms.Methods Preconstructed recombinant Ad5/F35-XAF1 virus and negative control Ad5/F35-Null was tranfected into BxPC3:the expression of XAF1 mRNA and protein before and after tranfection was,analyzed by semi-quantitative RT-PCR and Western blot.The expressions of proteins including Caspase-3,PARP,Caspase-8 and bcl-2 were detected by Western blots.Cell apoptosis was assessed by Annexin-v/PI and TUNEL staining.Results After Ad5/F35-XAF1 tranfection,XAF1 mRNA and protein expression significantly increased,and the difference was statistically significant when compared with control group and Ad5/F35-Null group(P＜0.05).The apoptosis rate was(19.90±3.09)%and(9.29±2.13)%,which was significantly different(P＜0.01)from those in the Ad5/F35-Null group[(6.72±0.7)6%,(2.73±0.51)%]or in the control group[(7.22±1.53)%,(1.56±0.47)%].The expression of Caspase-3,PARP and Caspase-8 significantly increased,but the expression of bcl-2 decreased.Conclusions XAF1 plays a major role in the apoptosis of pancreatic cancer that acts thriugh the activation of death receptor pathway and mitochondrial pathway of apoptosis.

Objective To investigate the expression of the ternary complex factor Net in human pancreatic carcinoma cell line BxPC3 and its effect on cell proliferation and the expression of c-fos.Methods pEGFP-Net prokaryotic expression plasmid and empty vector pEGFP were transfed into BxPC3 cens by using lipofectamine 2000,then monoclonal cell which stably expressing Net was established.Human pancreatic carcinoma cells proliferation was detected by MTT and flow cytometry.The tuRNA and protein expression of Net and c-fos in BxPC3 cells were detected by real.time PCR and Western blot.Results Net was low expressed in BxPC3 cells.After pEGFP-Net transfection,Net wag stably expressed and the expression of c-fos was inhibited,cell proliferation was also inhibited after pEGFP-Net transfection,the inhibitory rates at the 3rd, 5th,7th day was 38.81%,55.34%and 56.92%respectively,which were significantly higher than those in the empty vector group(5.09%,12.42%,8.6%,P<0.05).G_0/G_1 phase cell was(61.79±5.67)%,which were significantly higher than(45.14±3.37)%in the empty vector group(P<0.05).Conclusions The ternary complex factor Net could inhibit pancreatic carcinoma cell line BxPC3 proliferation.Its mechanism was possibly repressing expression of oncogene c-fos.