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Ling He

Publications and source records attributed to Ling He.

At least 19 recordsLinked to original sources
PubMed2006

Chemical genetics suggests a critical role for lysyl oxidase in zebrafish notochord morphogenesis.

As a result of a chemical genetic screen for modulators of metalloprotease activity, we report that 2-mercaptopyridine-N-oxide induces a conspicuous undulating notochord defect in zebrafish embryos, a phenocopy of the leviathan mutant. The location of the chemically-induced wavy notochord correlated with the timing of application, thus defining a narrow chemical sensitivity window during segmentation stages. Microscopic observations revealed that notochord undulations appeared during the phase of notochord cell vacuolation and notochord elongation. Notochord cells become swollen as well as disorganized, while electron microscopy revealed disrupted organization of collagen fibrils in the surrounding sheath. We demonstrate by assay in zebrafish extracts that 2-mercaptopyridine-N-oxide inhibits lysyl oxidase. Thus, we provide insight into notochord morphogenesis and reveal novel compounds for lysyl oxidase inhibition. Taken together, these data underline the utility of small molecules for elucidating the dynamic mechanisms of early morphogenesis and provide a potential explanation for the recently established role of copper in zebrafish notochord formation.

Animals↗
PubMed2006

[Decrease of FOXP3 mRNA in CD4+ T cells in latent autoimmune diabetes in adult].

OBJECTIVE: To study the percentage of peripheral blood CD4(+)CD25(+) T cells and the expression of FOXP3 mRNA in the patients with latent autoimmune diabetes in adult (LADA). METHODS: Fresh peripheral blood samples were obtained from 60 patients with LADA, 30 patients with type 2 diabetes and 30 age- and sex-matched matched healthy nondiabetic control subjects without diabetic family history. Two-color staining (anti-CD4, anti-CD25, anti-CD3, and anti-CD8) flow cytometric analysis was employed to measure the CD4(+)CD25(+) T cells. The CD4 positive human cells were isolated with immunomagnetic beads, and then real time-PCR was used to test the expression of FOXP3 mRNA in the CD4(+) T cells. RESULTS: In the LADA group, the percentage of CD4(+)CD25(+) T cells was 4.1 +/- 1.9, significantly higher than that of the normal control group (2.8 +/- 1.5, P < 0.01), the ratio of CD4(+)CD25(+) to the CD4(+) T cells was 11.9 +/- 5.0, significantly higher than that of the normal control group (8.2 +/- 3.7, P < 0.01), the percentage CD8(+) T cells was 24.6 +/- 6.8, significantly higher than that of the normal control group (19.4 +/- 7.1, P < 0.01) and the CD4(+)/CD8(+) ratio was 1.5 +/- 0.5, significantly lower (1.9 +/- 0.6, P < 0.01). The expression of FOXP3 mRNA in CD4(+) T cells of the LADA group was 0.52 time that of the control group (P < 0.01). The CD4(+)/CD8(+) ratio of LADA group was significantly lower that of the type 2 diabetes group (1.8 +/- 0.8, P < 0.05), however, the other results were not significantly different between these 2 groups. The percentage of was positively correlated with the titer of glutamic acid decarboxylase antibody (GADA) (r = 0.292, P < 0.05). CONCLUSION: Though the percentage of CD4(+)CD25(+) T cells and the level of CD25 expression in CD4(+) T cells are elevated, the expression of FOXP3 mRNA in CD4(+) T cells is lower. in the patients with LADA. The regulatory T cells may have defective suppressor function in patients with LADA.

Adult↗
PubMed2006

Recombinant canarypox virus vaccine co-expressing genes encoding the VP2 and VP5 outer capsid proteins of bluetongue virus induces high level protection in sheep.

We describe the development and preliminary characterization of a recombinant canarypox virus vectored vaccine for protective immunization of ruminants against bluetongue virus (BTV) infection. Sheep (n=6) immunized with recombinant canarypox virus vector (BTV-CP) co-expressing synthetic genes encoding the two outer capsid proteins (VP2 and VP5) of BTV serotype 17 (BTV-17) developed high titers (40-160) of virus-specific neutralizing antibodies and were resistant to challenge with a field strain of BTV-17. In contrast, sheep (n=5) immunized with a commercial recombinant canarypox virus vector expressing the E and preM genes of West Nile virus were seronegative to BTV and developed pyrexia, lymphopenia, and extended, high-titered viremias following challenge exposure to the field strain of BTV-17. These data confirm that the BTV-CP vaccine may be useful for the protective immunization of ruminants against bluetongue, and it may avoid the problems inherent to live-attenuated (LA) BTV vaccines.

Animals↗
PubMed2006

Chronic ethanol intake impairs insulin signaling in rats by disrupting Akt association with the cell membrane. Role of TRB3 in inhibition of Akt/protein kinase B activation.

Chronic and excessive alcohol consumption is an important and modifiable risk factor for type 2 diabetes. We previously reported elevations in hepatic Class 1 alcohol dehydrogenase (ADH) expression in ethanol-fed rats correspondent with reduced levels of mature, nuclear sterol-regulatory element-binding protein-1 (SREBP-1), an insulin-induced transcriptional repressor of the ADH gene. In this report, we have studied the effects of insulin and ethanol on ADH gene expression in a highly differentiated rat hepatoma cell line (FGC-4), as well as the in vivo effects of chronic intake of an ethanol-containing diet on hepatic insulin signaling. Insulin inhibited ADH gene expression, and this was abolished by LY294002 (a phosphatidylinositol 3-kinase inhibitor) and small interfering RNA knockdown of SREBP-1. Chronic ethanol intake led to decreased phosphorylation of Akt (protein kinase B) at Thr308, increased phosphorylation of Akt at Ser473, and decreased phosphorylation of glycogen synthase kinase-3beta (a downstream effector of Akt). Hepatic membrane-associated Akt content was decreased and cytosolic Akt content was increased in rats fed an ethanol-containing diet. Thus, disruptive effects of ethanol on insulin signaling occurred via impaired phosphorylation of Akt at Thr308. TRB3, a negative regulator of Akt, was induced in liver of ethanol-fed rats. In ethanol-treated FGC-4 cells, small interfering RNA knockdown of TRB3 increased membrane-associated Akt and the phosphorylation of Akt at Thr308. Our results suggest that ethanol induces TRB3, which, through binding to the pleckstrin homology domain of Akt, prevents its plasma membrane association, Akt-Thr308 phosphorylation, and subsequent Akt-mediated signaling. Ethanol inhibition of insulin signaling reduces nuclear SREBP accumulation and results in disinhibition of Class 1 ADH transcription.

Alcohol Dehydrogenase↗
PubMed2006

Inhibition of growth and induction of apoptosis in human cancer cell lines by an ethyl acetate fraction from shiitake mushrooms.

OBJECTIVE: Shiitake (Lentinus edodes) mushrooms have been reported to have cancer-preventing properties. However, little research has been conducted verifying the antitumor activities of "mycochemicals" in shiitake mushrooms. In this study, potential roles of an ethyl acetate fraction from shiitake mushrooms were investigated by in vitro bioassays. DESIGN: The activities of an ethyl acetate fraction were evaluated by [3-(4,5-dimethylthiazol-yl)-2,5-diphenyltetrazolium bromide] (MTT), apoptosis bioassay, cell cycle analysis, and Western blot analysis using two human breast carcinoma cell lines (MDA-MB-453 and MCF-7), one human nonmalignant breast epithelial cell line (MCF-10F), and two myeloma cell lines (RPMI-8226 and IM-9). RESULTS: Concentration-dependent antiproliferative effects of the fraction were observed in all cell lines using the MTT assay. Approximately 50 mg/L concentration of the fraction induced apoptosis in 50% of the population of four human tumor cell lines and the fraction-induced apoptosis may have been mediated through the pro-apoptotic bax protein which was up-regulated. Cell cycle analysis revealed that the fraction induced cell cycle arrest by significant decrease of S phase, which was associated with the induction of cdk inhibitors p21 and the suppression of cdk4 and cyclin D1 activity. Compared to malignant tumor cells, nonmalignant cells were less sensitive to the fraction for the suppression of cell growth and regulation of bax, p21, cyclin D1, and cdk4 expression. A 51% antiproliferative effect occurred at the highest concentration of the fraction (800 mg/L). CONCLUSIONS: These data suggest that inhibition of growth in tumor cells by "mycochemicals" in shiitake mushrooms may result from induction of apoptosis.

Acetates↗
PubMed2006

CJZ3, a lomerizine derivative, modulates P-glycoprotein function in rat brain microvessel endothelial cells.

AIM: To investigate the modulatory effect of CJZ3, a lomerizine derivative, on P-glycoprotein (P-gp) function in rat brain microvessel endothelial cells (RBMEC). METHODS: RBMEC were isolated and cultured in Dulbecco modified Eagle medium/F12 (1:1) medium, and the amount of intracellular rhodamine 123 (Rh123) was determined using a fluorescence spectrophotometer to evaluate the modulatory effect of CJZ3 on P-gp function. RESULTS: The accumulation of Rh123 was potentiated in a concentration-dependent manner after incubation with CJZ3 for RBMEC, but not for human umbilical vein endothelial cells (HUVEC). CJZ3 caused the accumulation of intracellular Rh123 in a time-dependent manner and significantly decreased the efflux of Rh123 from the cells. The inhibitory effect of CJZ3 on P-gp function was reversible and remained for 120 min after CJZ3 (2.5 micromol/L) was removed from the medium. CONCLUSION: CJZ3 has a potent in vitro effect on the inhibition of P-gp function.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2005

Synthesis and evaluation of a technetium-99m-labeled diethylenetriaminepentaacetate-deoxyglucose complex ([99mTc]-DTPA-DG) as a potential imaging modality for tumors.

This study describes the radiolabeling and preliminary biologic testing of diethylenetriaminepentaacetic acid (DTPA)-deoxyglucose (DG) labeled with (99m)Tc. A one-step [(99m)Tc]-DTPA-DG kit was prepared using the stannous chloride reduction method. When (99m)TcO(4)(-) was added to the DTPA-DG kit at room temperature the radiochemical purity 30 min later was 99.2%, and it remained >98.6% for 6 h. Rapid blood clearance of [(99m)Tc]-DTPA-DG was observed in in vivo biodistribution, the main route of clearance was via the kidneys. No significant accumulation in any other organs was seen. The tumor-to-brain and tumor-to-muscle concentration ratios for [(99m)Tc]-DTPA-DG uptake were higher than those for fluorine-18-flurodeoxyglucose ((18)F-FDG). Scintigraphic results demonstrated the feasibility of [(99m)Tc]-DTPA-DG imaging tumors. The [(99m)Tc]-DTPA-DG complex is a potential imaging agent due to the ideal physical characteristics of the radionuclide, ease of preparation, low cost, early accumulation and the preference for the renal route of excretion.

Animals↗
PubMed2005

Reversal of p-glycoprotein-mediated multidrug resistance by CJX1, an amlodipine derivative, in doxorubicin-resistant human myelogenous leukemia (K562/DOX) cells.

P-glycoprotein-mediated drug efflux can yield a multidrug resistance (MDR) phenotype that is associated with a poor response to cancer chemotherapy. Development of safe and effective MDR reversing agents is an important approach in the clinic. The aim of this study was to observe the effects of CJX1, an amlodipine derivative, on the inhibition of P-gp function and P-gp-mediated MDR in K562/DOX cells and parental K562 cells. Based on the flow cytometric technology, the uptake, accumulation and efflux of rhodamine123 (Rh123) were detected in these cells by measuring Rh123-associated mean fluorescence intensity (MFI). The effects of CJX1 on the doxorubicin cytotoxicity were evaluated by assaying for MTT (3-(4,5-dimethylthiazol)-2,5-diphenyltetrazolium bromide) reduction and the reversal fold (RF) values. The DNA content, percentage of apoptosis and cell cycle analysis were monitored with flow cytometry. Intracellular accumulation of doxorubicin was also assessed by the determination of doxorubicin-associated MFI. Verapamil was employed as a comparative agent. Incubation of K562/DOX cells with CJX1 caused a marked increase in uptake and a notable decrease in efflux of Rh123, No such results were found in parental K562 cells. The inhibitory effect of the agent of P-gp function was reversible, but it persisted at least for 90 min after removal of 2.5 microM CJX1 from incubation medium. The doxorubicin-induced cytotoxicity, apoptosis and cell cycle perturbations were significantly potentiated by CJX1. The intracellular accumulation of doxorubicin was enhanced in the presence of various concentrations of CJX1. The CJX1 exhibited potent effects in vitro in the reversal of P-gp-mediated MDR, suggesting that the compound may become a candidate of effective MDR reversing agent in cancer chemotherapy.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2005

[Diagnostic role of SOX13 antibody in latent autoimmune diabetes of adults].

OBJECTIVE: To explore the diagnostic role of SOX13 antibody in latent autoimmune diabetes of adults (LADA). METHODS: Sera of 328 patients with slow-onset diabetes and 120 sex and age-matched healthy controls underwent radiochemical test to detect the positive rates of SOX13-Ab, glutamic acid decarboxylace antibody (GAD-Ab) and carboxypeptidase H antibody (CPH-Ab). According to the GAD-Ab and CPH-Ab status the patients were divided into autoimmune (GAD-Ab and/or CPH-Ab positive, n = 130) and non-autoimmune (GAD-Ab and CPH-Ab negative, n = 198) diabetic subgroups. Then according to SOX13-Ab, GAD-Ab and CPH-Ab status, the diabetic patients were divided into 4 groups: SOX13-Ab positive, GAD-Ab positive, CPH-Ab positive, and antibody-negative group to compare their clinical characteristics. The effect of SOX13-Ab on islet beta-cell function was evaluated by comparison of C-peptide among the four subgroups. RESULTS: The positive rates of SOX13-Ab in the slow-onset diabetic patients (10.4%), autoimmune subgroup patients (13.1%), and non-autoimmune subgroup patients (8.6%) were all higher than that in the healthy controls (2.5%, all P < 0.05). Thirteen patients were positive for both SOX13-Ab and CPH-Ab (13/328, 4.0%), but only 2 were positive for both SOX13-Ab and GAD-Ab (2/328, 0.6%). The highest prevalence of SOX13-Ab was observed in the patients with the duration of disease ranging from 16 to 20 years. There were no differences in the clinical parameters between the SOX13-Ab positive and antibody-negative diabetic patients. CONCLUSION: SOX13-Ab testing helps improve the sensitivity of screening for LADA. SOX13-Ab positive patients tend to have a longer course of disease and varied clinical manifestations.

Adolescent↗
PubMed2005

Modulation of P-glycoprotein function by amlodipine derivatives in brain microvessel endothelial cells of rats.

AIM: To investigate whether the amlodipine derivatives, CJX1 and CJX2, have a modulative effect on P-glycoprotein (P-gp) function in rat brain microvessel endothelial cells (RBMEC). METHODS: Isolated RBMEC were cultured in DMEM/F12 (1:1) medium. The amount of intracellular rhodamine (Rh123) was determined, using a fluorescence spectrophotometer, to evaluate the function of P-gp. RESULTS: The accumulation of Rh123 in RBMEC was potentiated in a concentration-dependent manner after incubation with CJX1 and CJX2 at 1, 2.5, 5, and 10 micromol/L (P<0.01), but no accumulation of Rh123 was observed in human umbilical vein endothelial cells after incubation with CJX1 and CJX2 10 micromol/L (P>0.05). Accumulation of intracellular Rh123 was increased and efflux of intracellular Rh123 was decreased in a time-dependent manner from 0-100 min after CJX1 and CXJ2 at 10 micromol/L treatment. The inhibitory effect of CJX1 and CJX2 on P-gp function was reversible and remained even at 120 min after removal of CJX1 and CJX2 at 2.5 micromol/L from the medium. CONCLUSION: CJX1 and CJX2 exhibited a potent effect in the inhibition of P-gp function in vitro.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2004

[Mechanisms of human glutamic acid decarboxylase 65 DNA vaccine preventing diabetes in non-obese diabetic mice].

OBJECTIVE: To investigate the mechanisms of human GAD65 DNA vaccine preventing insulitis and diabetes in NOD mice. METHODS: Female NOD mice at 4 weeks of age were randomly divided into PBS (n = 21), pcDNA (n = 20), and hGAD65 (n = 21) groups. Mice in each group received two intramuscular injections of 0.05 ml PBS alone, 50 microg pcDNA3.1 and 50 microg DNA vaccine emulsified in 0.05 ml PBS 7 days apart respectively. The accumulative diabetes incidence was followed-up to 30 weeks of age in each group of NOD mice. Pancreas was removed from NOD mice at 12 weeks of age in each group (n = 10) to score insulitis severity by routine H-E staining. The apoptotic beta cells in islets were observed with double-labeling technique of TUNEL in situ combined standard sensitive avdin-biotin complex (sABC) immunohistochemical method. Their spleens were for cell culture and total RNA extraction. Spleen IL-4, IFN-gamma, NF-ATc and NF-ATp mRNA levels were tested by RT-PCR. IL-4 and IFN-gamma levels in sera and supernatants of spleen cells were measured by ELISA. RESULTS: (1) At 30 weeks of age, the diabetes incidence was 95.2%, 80.0% and 61.9% in PBS, pcDNA and hGAD65 group respectively. The diabetes incidence in the PBS group was higher than that in hGAD65 group (P = 0.008). (2) At 12 weeks of age, the insulitis scores in hGAD65 group was lower than that in PBS group (P = 0.001) and pcDNA group (P = 0.027) respectively. (3) The apoptotic beta cell rates in hGAD65 group was lower than that in PBS group (P = 0.014) and pcDNA group (P = 0.023). (4) IL-4 levels in sera, spleen IL-4 and NF-ATc mRNA level in hGAD65 group were higher than those in PBS group (all P < 0.05) and pcDNA group (all P < 0.05) respectively, NF-ATp mRNA level in hGAD65 group was lower than that in PBS group (P < 0.05). CONCLUSION: Human GAD65 DNA vaccine via downregulating NF-ATp and upregulating NF-ATc and IL-4, makes Th cells deviate to Th2, and sequently prevents insulitis, beta-cell apoptosis and diabetes onset in NOD mice.

Animals↗
PubMed2004

Purification and characterization of an acid deoxyribonuclease from the cultured mycelia of Cordyceps sinensis.

A new acid deoxyribonuclease (DNase) was purified from the cultured mycelia of Cordyceps sinensis, and designated CSDNase. CSDNase was purified by (NH(4))(2)SO(4) precipitation, Sephacryl S-100 HR gel filtration, weak anion-exchange HPLC, and gel filtration HPLC. The protein was single-chained, with an apparent molecular mass of ca. 34 kDa, as revealed by SDS-PAGE, and an isoelectric point of 7.05, as estimated by isoelectric focusing. CSDNase acted on both double-stranded (ds) and single- stranded (ss) DNA, but preferentially on dsDNA. The optimum pH of CSDNase was pH 5.5 and its optimum temperature 55. The activity of CSDNase was not dependent on divalent cations, but its enzymic activity was inhibited by high concentration of the cation: MgCl(2) above 150 mM, MnCl(2) above 200 mM, ZnCl(2) above 150 mM, CaCl(2) above 200 mM, NaCl above 300 mM, and KCl above 300 mM. CSDNase was found to hydrolyze DNA, and to generate 3-phosphate and 5-OH termini. These results indicate that the nucleolytic properties of CSDNase are essentially the same as those of other well-characterized acid DNases, and that CSDNase is a member of the acid DNase family. To our knowledge, this is the first report of an acid DNase in a fungus.

Cations↗
PubMed2004

Ruthenium(II) porphyrin-catalyzed amidation of aromatic heterocycles.

[reaction: see text] Ruthenium(II) porphyrin-catalyzed amidation of aromatic heterocycles with iminoiodanes under mild conditions (CH(2)Cl(2), 4 A molecular sieves, ultrasound, 40 degrees C) was achieved in moderate to good yields (up to 84%) and conversions (up to 99%). Only the N,N-ditosylamidated product was obtained for reactions involving heteroarenes, where X = O, S, or NTs. N-Alkyl- and N-aryl-substituted pyrroles, on the other hand, were shown to give the 3,4-diaminated adduct.

Journal Article↗
PubMed2004

Two novel antibiotics, Sch 419558 and Sch 419559, produced by Pseudomonas fluorescens: effect on activity by overexpression of RpoE.

Two new secondary metabolites designated as Sch 419558 (1) and Sch 419559 (2), were isolated from the fermentation broth of Pseudomonas fluorescens. Structure elucidation of 1 and 2 was accomplished by spectroscopic data analyses including MS and NMR experiments. Both compounds were identified as lipopeptides containing valine and threonine linked with 1-amino-1-hydroxy-heptadec-9-en-2-one or 1-amino-1-hydroxy-pentadecan-2-one carbon chains, respectively. Characterization of the amino acids was further confirmed by amino acid analysis. Compounds 1 and 2 exhibited antibacterial activity against a sensitized E. coli strain with minimum inhibitory concentration of 0.3 and 0.6 microg/mL, respectively. Overexpression of RpoE in the E. coli strain increased the MIC over 60-fold for compounds 1 and 2.

Anti-Bacterial Agents↗
PubMed2004

Post-transcriptional regulation of sterol regulatory element-binding protein-1 by ethanol induces class I alcohol dehydrogenase in rat liver.

Members of the sterol regulatory element-binding protein (SREBP) family of transcription factors control the synthesis and uptake of cholesterol, fatty acids, triglycerides, and phospholipids. Continuous intragastric infusion of ethanol-containing diets as part of total enteral nutrition generates well defined 6-day cycles (pulses) of urine ethanol concentrations (UECs) in rats. Pulsatile UECs are the result of cyclical expression and activity of the principal alcohol-metabolizing enzyme, hepatic Class I alcohol dehydrogenase (ADH), and this mechanism involves regulated CCAAT/enhancer-binding protein-beta expression and binding to the ADH promoter. In this study, we further explore the molecular mechanism for ethanol-induced ADH expression during the UEC pulse in adult male rats fed ethanol by total enteral nutrition for 21-30 days. In hypophysectomized rats, in which the ADH protein increased by approximately 6-fold, the nuclear form of SREBP-1 decreased by approximately 7-fold. Because the ADH promoter contains two canonical sterol response element (SRE) sites (-63 to -53 and -52 to -40 relative to the transcription start site), electrophoretic mobility shift assays were conducted using an ADH-specific SRE site. Hepatic nuclear protein binding decreased by 2.4-fold on the ascending limbs and by 3.6-fold on the descending limbs of UEC pulses (p < 0.05). The specificity of nuclear protein binding to the ADH-SRE site was confirmed using antibody and UV cross-link assays. The in vivo binding status of SREBP-1 to ADH-SRE sites, as measured by the chromatin immunoprecipitation assay, had a pattern very similar to the electrophoretic mobility shift assay results. Functional analysis of the ADH-SREs demonstrated these sites to be essential for ADH transcription. In vitro transcription assays demonstrated that depletion of the SREBP-1 protein from nuclear extracts increased transcription activity by approximately 5-fold and that the liver X receptor agonist T0901317 (a known activator of SREBP-1c transcription) reduced in vitro expression of ADH mRNA by 2-fold. We conclude that SREBP-1 is a negative regulator of the ADH gene and may work in concert with the CCAAT/enhancer-binding proteins to mediate ethanol induction of ADH in vivo.

Alcohol Dehydrogenase↗
PubMed2004

[Preventive effects of pioglitazone on diabetes and relevant mechanisms, experimental study on non-obese diabetic mice].

OBJECTIVE: To explore the effects of pioglitazone on insulitis and diabetes and relevant mechanism. METHODS: Seventy-three female non-obese diabetic (NOD)/Lt mice aged 4 weeks were randomly divided into 3 groups, control group (n = 25, fed with regular diet), low dosage pioglitazone group (n = 23, pioglitazone of the concentration of 0.01% was added into the feed) and high dosage pioglitazone group (n = 25, pioglitazone of the concentration of 0.04% was added into the feed). The mice were killed when diabetes developed or they reached the age of 30 weeks. The body weight and amount of food intake were measured every week and the amount of drug intake was calculated. Urine glucose was checked weekly from week 10 to week 30. When urine glucose was positive and relevant symptoms appeared, blood glucose was measured. The criterion of diagnosis of diabetes was the consecutive blood glucose level > or = 16.7 mmol/L for 2 times. At the 12th week 4-7 mice from the 3 groups respectively were killed and their pancreases were removed to be scored on insulitis by HE staining, the spleen cells were cultured. The IL-4 and IFN-r levels in serum and supernatants of spleen cell cultures were measured by ELISA. The pancreatic IFN-r mRNA level was tested using RT-PCR method. RESULTS: (1) At the age of 30 weeks, the diabetes incidence rates was 80% (20/25) in the control group, 60.9% (14/23) in the low dose group, and 60% (15/25) in the high dose group (P > 0.05). At the following time points the diabetes incidence rates of the 2 treated groups were lower than that of the control group (all P < 0.05): (1) 0% in the low dose group vs 16%: of the control group at the age of 100 days, and 39% vs 68% at the age of 185 days; and (2) 0% in the high dose group vs 16% in the control group at the age of 110 days, 4% vs 24% at the age of 120 days, and 12%vs 36% at the age of 135 days. (2) There was no difference in insulitis scores between the control group and low dose or high dose groups at the age of 12 weeks (1.99 +/- 0.75 vs 1.01 +/- 0.68 and 1.19 +/- 0.84, both P > 0.05), however, the score of the combined pioglitazone group (low dose group + high dos group) was significantly higher than that of the control group (1.12 +/- 0.75 vs 1.99 +/- 0.75, P < 0.05). (3) There was no differences in the IL-4/IFN-r ratios in serum and splenocyte culture supernatant and pancreatic IFN-r mRNA levels among the three groups (all P > 0.05). CONCLUSION: Pioglitazone, to some extent, lessens the insulitis severity and delays the diabetes onset. Its mechanism may be unrelated to immune deviation of Th1 to a Th2.

Animals↗
PubMed2003

Structure elucidation of Sch 538415, a novel acyl carrier protein synthase inhibitor from a microorganism.

A novel acyl carrier protein synthase inhibitor, Sch 538415 (1), was isolated from an unidentified bacterial microbe. Structure elucidation of 1 was accomplished based on analysis of spectroscopic data including UV, MS and 2D-NMR spectra. Compound 1 exhibited inhibitory activity in the acyl carrier protein synthase (AcpS) assay with an IC(50) value of 4.19 microM and showed antibacterial activity against Staphylococcus aureus in the agar diffusion assay.

Aza Compounds↗