Changes of plasma fibroblast growth factor-21 (FGF-21) in oral glucose tolerance test and effects of metformin on FGF-21 levels in type 2 diabetes mellitus

Wstęp: Badanie przeprowadzono w celu ustalenia, czy czynnik wzrostu fibroblastów-21 (FGF-21) uczestniczy w regulacji stężenia glukozy i czy zastosowanie metforminy u chorych na cukrzycę wpływa na stężenie FGF-21. Materiał i metody: Do badania włączono 43 osoby, w tym 27 chorych z nowo rozpoznaną cukrzycą typu 2 (nT2DM). U wszystkich przeprowadzono test doustnego obciążenia 75 g glukozy (OGTT). Próbki krwi pobrano w 0., 60.,120. i 180. minucie testu. Osobom z nT2DM zaproponowano udział w dalszych badaniach; zastosowano u nich metforminę w dawce 1,0 g/dobę przez tydzień. Wyniki: Zmiany stężenia FGF-21 w osoczu podczas OGTT zaobserwowano tylko w grupie chorych na nT2DM; w grupie kontrolnej stężenie FGF-21 pozostało niezmienione. Nie stwierdzono, by stężenia FGF-21 w poszczególnych punktach czasowych różniły się w zależności od płci badanych (p < 0,05). Zastosowanie metforminy u osób z nT2DM spowodowało istotne zmniejszenie stężeń glukozy i FGF-21 we wszystkich punktach czasowych OGTT oraz zmniejszenie stężenia insuliny w 60. i 180. minucie, co wskazuje na obniżenie wskaźnika HOMA-IR. Wnioski: FGF-21 nie uczestniczy w krótkoterminowej regulacji glikemii u ludzi, a zmiany jego stężenia podczas OGTT są opóźnione w T2DM. Być może FGF-21 bierze udział w metabolizowaniu metforminy, zwiększając wrażliwość na glukozę i insulinę. (Endokrynol Pol 2013; 64 (3): 220&#8211;224)Introduction: The objectives of our study were to investigate whether fibroblast growth factor-21 (FGF-21) is involved in short-term regulation of glucose and the change of FGF-21 after metformin use in diabetic subjects. Material and methods: 43 subjects were recruited in the study, including 27 new-onset type 2 diabetes patients (nT2DM). A 75 g oral glucose tolerance test (OGTT) was administered to them. Blood samples were taken at 0, 60 ,120 and 180 minute of OGTT. nT2DM subjects were invited for further investigation, metformin was administered in a dose of 1.0 g every day for 1 week. Results: Plasma FGF-21 changed significantly in the nT2DM group during the OGTT administration but not in the control group. No gender differences were observed at different time points in FGF-21 levels (p < 0.05). Administration of metformin for nT2DM resulted in a significant decrease in both glucose and FGF-21 at all OGTT times and in insulin at 60 min and 180 min, indicative of a decrease in HOMA-IR. Conclusion: FGF-21 does not seem to be involved in short-term regulation of glycaemia in human subjects, and the change in OGTT delayed in T2DM. FGF-21 may participate in the processing of metformin, improving glucose and insulin sensitivity. (Pol J Endocrinol 2013; 64 (3): 220&#8211;224

Effect of JUNCAO-cultivated Ganoderma lucidum spent mushroom substrate-hot water extract on immune function in mice

Purpose: To evaluate the effect of JUNCAO-cultivated Ganoderma lucidum spent mushroom substratehot water extract (SMSG-HWE) on murine immunity.Methods: Five groups of mice (n = 10) received water with 0.00, 0.14, 0.28, 0.84, or 1.68 g/kg of SWSG-HWE, respectively, orally for 30 days. Various biochemical parameters of serum and tissues, including spleen and thymus indices, were determined were determined for the miceResults: The following markers were significantly higher in the 0.84 g/kg SMSG-HWE group than in the control group (all p &lt; 0.05): splenic lymphocyte proliferation, a marker of cell-mediate immunity; dinitrofluorobenzene-induced delayed hypersensitivity; and the number of haemolytic plaque-forming cells, as a marker of humoral immunity. Phagocytic rate, which evaluates mononuclear-macrophage function as a marker of innate immunity, was significantly higher in both the 0.84 g/kg HWE and 1.68 g/kg SWSG-HWE groups, while phagocytic index was significantly higher in the 0.28 g/kg SWSG-HWE group, compared to the control group (all p &lt; 0.05). Natural killer cell activity also was significantly enhanced in the 0.84 g/kg and 1.68 g/kg SWSG-HWE groups (p &lt; 0.05).Conclusion: These findings indicate that SWSG-HWE enhances murine immune function, and may be suitable as a potential additive in animal feed.Keywords: Hot water extract, Cell-mediated immune function, Concanavalin A, Mononuclearmacrophage function, Haemolytic plaque, Humoral immunity, Innate immunity, Animal feed additiv

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) interaction with 3' ends of Japanese encephalitis virus RNA and colocalization with the viral NS5 protein

Replication of the Japanese encephalitis virus (JEV) genome depends on host factors for successfully completing their life cycles; to do this, host factors have been recruited and/or relocated to the site of viral replication. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a cellular metabolic protein, was found to colocalize with viral RNA-dependent RNA polymerase (NS5) in JEV-infected cells. Subcellular fractionation further indicated that GAPDH remained relatively constant in the cytosol, while increasing at 12 to 24 hours postinfection (hpi) and decreasing at 36 hpi in the nuclear fraction of infected cells. In contrast, the redistribution patterns of GAPDH were not observed in the uninfected cells. Co-immunoprecipitation of GAPDH and JEV NS5 protein revealed no direct protein-protein interaction; instead, GAPDH binds to the 3' termini of plus- and minus-strand RNAs of JEV by electrophoretic mobility shift assays. Accordingly, GAPDH binds to the minus strand more efficiently than to the plus strand of JEV RNAs. This study highlights the findings that infection of JEV changes subcellular localization of GAPDH suggesting that this metabolic enzyme may play a role in JEV replication

3,6-Dibromo-9-(4-bromo­benz­yl)-9H-carbazole

The title compound, C19H12Br3N, was synthesized by N-alkyl­ation of 1-bromo-4-(bromo­meth­yl)benzene with 3,6-dibromo-9H-carbazole. There are two unique mol­ecules in the asymmetric unit. The carbazole ring system is essentially planar, with a mean deviation of 0.0402 Å for one mol­ecule and 0.0279 Å for the other. The carbazole planes are inclined to the benzene ring planes at dihedral angles of 58.3 (3) and 71.1 (3)° in the two mol­ecules

Periodic solutions for a kind of Liénard equation

Using inequality techniques and coincidence degree theory, new results are provided concerning the existence and uniqueness of T-periodic solutions for a Liénard equations with delay. An illustrative example is provided to demonstrate that the results in this paper hold under weaker conditions than existing results, and are more effective

Epileptiform discharge upregulates p-ERK1/2, growth-associated protein 43 and synaptophysin in cultured rat hippocampal neurons

AbstractExtracellular signal-regulated protein kinase, ERK1/2 is activated by phosphorylation (p-ERK1/2) during environmental stress such as epileptiform discharge. We investigated the role of ERK1/2 in abnormal axon growth and synapse reorganization in cultured neurons displaying epileptiform activity.The cultured neurons displaying epileptiform activity were treated with magnesium-free extracellular fluid for 3h and monitored epileptiform discharges using whole-cell patch clamp. Two study groups, neurons displaying epileptiform activity and the same neurons treated with ERK1/2 inhibitor U0126, were studied at six time points, 0min, 30min, 2h, 6h, 12h, and 24h following discharge. The expressions of p-ERK1/2, C-fos, growth-associated protein 43 (GAP-43) and synaptophysin (SYP), as markers of axon growth and synapse reorganization, were investigated by double-label immunofluorescence and western blotting.In the neurons displaying epileptiform activity, p-ERK1/2 was detected immediately following discharge, and expression peaked at 30min. The expression of C-fos, GAP-43 and SYP followed the same pattern as p-ERK1/2. In the treated group, p-ERK1/2 was inhibited completely, and C-fos, GAP-43 and SYP were reduced.These findings indicate that epileptiform discharge activates ERK1/2 which regulates C-fos in cultured neurons displaying epileptiform activity, and this cascade may upregulate GAP-43 and SYP to contribute to axon growth and synapse reorganization to potentiate epileptic activities

Identification and pharmacokinetics of saponins in Rhizoma Anemarrhenae after oral administration to rats by HPLC-Q-TOF/MS and HPLC-MS/MS

Rhizoma Anemarrhenae is a well-known herbal medicine with saponins as its commonly regarded major bioactive components. It is essential to classify the properties of saponins which are associated with their toxicity and efficacy. In this study, 25 compounds were identified by HPLC-Q-TOF/MS in the extract of Rhizoma Anemarrhenae and 8 saponins were detected in rat plasma by HPLC-MS/MS after oral administration of this extract. These were neomangiferin, mangiferin, timosaponin E1, timosaponin E, timosaponin B-II, timosaponin B-III, timosaponin A-III and timosaponin A-I. A sensitive and accurate HPLC-MS/MS method was developed and successfully applied to a pharmacokinetic study of the abovementioned eight saponins after oral administration of the Rhizoma Anemarrhenae extract to rats. The method validation, including specificity, linearity, precision, accuracy, recovery, matrix effect and robustness, met the requirements of the intended use. The pharmacokinetic parameter, Tmax value, ranged from 2 to 8 h for these eight saponins whereas their elimination half-life (t1/2) ranged from 4.06 to 9.77 h, indicating slow excretion. The plasma concentrations of these eight saponins were all very low, indicating a relatively low oral bioavailability. All these results provide support for further clinical studies

3,6-Dibromo-9-(4-chloro­benz­yl)-9H-carbazole

The title compound, C19H12Br2ClN, was synthesized by N-alkyl­ation of 1-chloro-4-(chloro­meth­yl)benzene with 3,6-dibromo-9H-carbazole. The carbazole ring system is essentially planar (mean deviation of 0.028 Å) and makes a dihedral angle of 74.6 (3)° with the plane of the benzene ring

Discrete-time BAM neural networks with variable delays

This Letter deals with the global exponential stability of discrete-time bidirectional associative memory (BAM) neural networks with variable delays. Using a Lyapunov functional, and linear matrix inequality techniques (LMI), we derive a new delay-dependent exponential stability criterion for BAM neural networks with variable delays. As this criterion has no extra constraints on the variable delay functions, it can be applied to quite general BAM neural networks with a broad range of time delay functions. It is also easy to use in practice. An example is provided to illustrate the theoretical development

STAT2 hypomorphic mutant mice display impaired dendritic cell development and antiviral response

Interferons (IFNs) are key regulators for both innate and adaptive immune responses. By screening ENU-mutagenized mice, we identified a pedigree- P117 which displayed impaired response to type I, but not type II, IFNs. Through inheritance test, genetic mapping and sequencing, we found a T to A point mutation in the 5' splice site of STAT2 intron 4–5, leading to cryptic splicing and frame shifting. As a result, the expression of STAT2 protein was greatly diminished in the mutant mice. Nonetheless, a trace amount of functional STAT2 protein was still detectable and was capable of inducing, though to a lesser extent, IFNα-downstream gene expressions, suggesting that P117 is a STAT2 hypomorphic mutant. The restoration of mouse or human STAT2 gene in P117 MEFs rescued the response to IFNα, suggesting that the mutation in STAT2 is most likely the cause of the phenotypes seen in the pedigree. Development of different subsets of lymphocytes appeared to be normal in the mutant mice except that the percentage and basal expression of CD86 in splenic pDC and cDC were reduced. In addition, in vitro Flt3L-dependent DC development and TLR ligand-mediated DC differentiation were also defective in mutant cells. These results suggest that STAT2 positively regulates DC development and differentiation. Interestingly, a severe impairment of antiviral state and increased susceptibility to EMCV infection were observed in the mutant MEFs and mice, respectively, suggesting that the remaining STAT2 is not sufficient to confer antiviral response. In sum, the new allele of STAT2 mutant reported here reveals a role of STAT2 for DC development and a threshold requirement for full functions of type I IFNs