Association of glucokinase regulatory protein polymorphism with type 2 diabetes and fasting plasma glucose: a meta-analysis.

Glucokinase regulatory protein (GCKR) which binds to glucokinase (GCK) in the nucleus and inhibits its activity in the presence of fructose-6-phosphate is critical for glucose metabolism. In the past few years, a number of case-control studies have been carried out to investigate the relationship between the GCKR polymorphism and type 2 diabetes (T2D) since it was first identified to be associated with fasting plasma glucose levels, insulin resistance through genome-wide association approach. After that, a number of studies reported that the rs780094 polymorphism in GCKR has been implicated in T2D risk. However, these studies have yielded contradictory results. To investigate this inconsistency, we performed a meta-analysis of 19 studies involving a total of 298,977 subjects for GCKR rs780094 to evaluate its effect on genetic susceptibility for T2D. In a combined analysis, the summary per-allele odds ratio for T2D of the rs780094 polymorphism was 1.11 (95 % CI: 1.07-1.14, P < 10(-5)). Significant results were also observed using dominant (OR = 1.18, 95 % CI: 1.05-1.34, P < 10(-5)) or recessive genetic model (OR = 1.20, 95 % CI: 1.12-1.28, P < 10(-5)). Significant results were found in Asians and Caucasians when stratified by ethnicity. Besides, the polymorphism was found to be significantly associated with increased fasting plasma glucose level. There was strong evidence of heterogeneity, which largely disappeared after stratification by ethnicity. This meta-analysis suggests that the rs780094 polymorphism in GCKR is associated with elevated T2D risk, but these associations vary in different ethnic populations.

Field observations and quantifications of atmospheric formaldehyde partitioning in gaseous and particulate phases.

Formaldehyde (HCHO) can possibly be taken by atmospheric particles due to its moderate solubility. Although previous model studies have proposed that uptake by particles was a large sink for HCHO, direct observation of HCHO partitioning and estimation of HCHO uptake coefficient (γ) for tropospheric conditions are still limited. In this work, online measurements of gaseous HCHO (HCHOg) and particulate HCHO (HCHOp) were carried out simultaneously at an urban site in Beijing in winter and spring. The results indicated that the average concentrations of HCHOp ranged from 0.15 to 0.4 µg m-3, accounting for 1.2% to 10% of the total HCHO (i.e., HCHOg + HCHOp). The median values of estimated γ based on the measured data were in the range of about 1.09 ∗ 10-5-2.42 ∗ 10-4, with lower values during PM2.5 pollution episodes. Besides, the pH and liquid water content of aerosols that are mainly determined by ambient relative humidity (RH) and inorganic salt composition were identified as the main influencing factors of γ. We propose that the HCHO uptake process was mainly driven by hydrone and hydrogen ions in particles.

miR­130b regulates PTEN to activate the PI3K/Akt signaling pathway and attenuate oxidative stress­induced injury in diabetic encephalopathy.

Diabetic encephalopathy (DE) is one of the main chronic complications of diabetes, and is characterized by cognitive defects. MicroRNAs (miRNAs/miRs) are widely involved in the development of diabetes­related complications. The present study evaluated the role of miR­130b in DE and investigated its mechanisms of action. PC12 cells and hippocampal cells were exposed to a high glucose environment to induce cell injuries to mimic the in vitro model of DE. Cells were transfected with miR­130b mimic, miR­130b inhibitor and small interfering RNA (si)­phosphatase and tensin homolog (PTEN) to evaluate the protective effect of the miR­130b/PTEN axis against oxidative stress in high glucose­stimulated cells involving Akt activity. Furthermore, the effect of agomir­130b was also assessed on rats with DE. The expression of miR­130b was reduced in the DE models in vivo and in vitro. The administration of miR­130b mimic increased the viability of high glucose­stimulated cells, prevented apoptosis, increased the activity of superoxide dismutase (SOD), decreased the malondialdehyde (MDA) content, activated Akt protein levels and inhibited the mitochondria­mediated apoptotic pathway. The administration of miR­130b inhibitor exerted opposite effects, while si­PTEN reversed the effects of miR­130b inhibitor. In vivo, the administration of agomir­130b attenuated cognitive disorders and neuronal damage, increased SOD activity, reduced the MDA content, activated Akt protein levels and inhibited the mitochondria­mediated apoptosis pathway in rats with DE. On the whole, these results suggest that miR­130b activates the PI3K/Akt signaling pathway to exert protective effects against oxidative stress injury via the regulation of PTEN in rats with DE.

[Correlative analysis of the parameters of eTRACKING detection of femoral artery and the syndrome types of traditional Chinese medicine in type 2 diabetic patients].

OBJECTIVE: To explore the correlation between the parameters of eTRACKING detection of femoral artery and the syndrome types of traditional Chinese medicine (TCM) in type 2 diabetic patients so as to provide clinical evidence for early prevention and treatment of diabetic lower extremity arterial disease. METHODS: A total of 147 cases of type 2 diabetic patients were included. Basic data and TCM clinical information were collected, and eTRACKING detection of common femoral arteries was performed. Differentiation of symptoms and signs for classification of TCM syndromes was performed in all patients. The correlations between TCM syndrome and pressure-strain elastic modulus (Ep), stiffness parameter beta, arterial compliance (AC), pulse wave velocity beta (PWVbeta), and augmentation index (AI) in common femoral arteries were observed. RESULTS: In the patients with deficiency of both yin and yang, the Ep value was higher than that in the patients with deficiency of both qi and yin, the stiffness parameter beta was higher than that in the other three syndrome types (deficiency of both qi and yin, excessive heat due to yin deficiency, accumulation of damp-beat in spleen), the AC value was lower than that in the patients with excessive heat due to yin deficiency, the PWVbeta value was higher than that in the patients with excessive heat due to yin deficiency and deficiency of both qi and yin, and the AI value was higher than that in the patients with excessive heat due to yin deficiency. The stiffness parameter beta in the patients with deficiency of both qi and yin was higher than that in the patients with accumulation of damp-heat in spleen. In the patients with blood stasis, the Ep value was higher and the AC value was lower than that in the patients without blood stasis. CONCLUSION: The decrease of elasticity in lower extremities can be detected by eTRACKING. This study reveals that type 2 diabetic patients with deficiency of both yin and yang, accumulation of damp-heat in spleen and blood stasis have more severe lower extremity arteriosclerosis. In eTRACKING parameters, stiffness parameter beta, AC and PWVbeta may become the objective indexes in evaluating early diabetic lower extremity arteriosclerosis.

Icariin Inhibits AMPK-Dependent Autophagy and Adipogenesis in Adipocytes In vitro and in a Model of Graves' Orbitopathy In vivo.

Graves' orbitopathy (GO), an extrathyroidal manifestation of Graves' disease, is an inflammatory autoimmune disorder of the orbit that involves the differentiation of precursor cells into mature adipocytes and retro-orbital adipose tissue accumulation. Here, we examined the involvement of autophagy in adipogenesis and explored the effects of icariin, a flavonoid isolated from the genus Epimedium with a wide range of biological and pharmacological effects, on autophagy and adipogenesis in 3T3-L1 preadipocytes and in a mouse model of GO. Microscopic examination of autophagosome formation and lipid droplet accumulation by Oil Red O staining, and western blot assessment of autophagic markers in the presence of the autophagy inhibitors Asn and 3-MA showed that autophagy is essential for adipogenesis. Icariin inhibited the differentiation of preadipocytes into mature adipocytes by suppressing autophagy, and these effects were mediated by the inhibition of AMPK/mTOR pathway activation. In a mouse model of thyroid stimulating hormone receptor induced GO, icariin reduced orbital muscle adipose tissue expansion and lipid droplet accumulation by inhibiting AMPK/mTOR mediated autophagy. Collectively, these results reveal a potential mechanism underlying the protective effects of icariin against autophagy induced adipogenesis and suggest that icariin could be developed as a new therapeutic candidate for the prevention and treatment of GO.

Celastrol inhibits IL-1ß-induced inflammation in orbital fibroblasts through the suppression of NF-κB activity.

Graves' disease is an autoimmune disease of the thyroid gland, which is characterized by hyperthyroidism, diffuse goiter and Graves' ophthalmopathy (GO). Although several therapeutic strategies for the treatment of GO have been developed, the effectiveness and the safety profile of these therapies remain to be fully elucidated. Therefore, examination of novel GO therapies remains an urgent requirement. Celastrol, a triterpenoid isolated from traditional Chinese medicine, is a promising drug for the treatment of various inflammatory and autoimmune diseases. CCK­8 and apoptosis assays were performed to investigate cytotoxicity of celastrol and effect on apoptosis on orbital fibroblasts. Reverse transcription­polymerase chain reaction, western blotting and ELISAs were performed to examine the effect of celastrol on interleukin (IL)­1ß­induced inflammation in orbital fibroblasts from patients with GO. The results demonstrated that celastrol significantly attenuated the expression of IL­6, IL­8, cyclooxygenase (COX)­2 and intercellular adhesion molecule­1 (ICAM­1), and inhibited IL­1ß­induced increases in the expression of IL­6, IL­8, ICAM­1 and COX­2. The levels of prostaglandin E2 in orbital fibroblasts induced by IL­1ß were also suppressed by celastrol. Further investigation revealed that celastrol suppressed the IL­1ß­induced inflammatory responses in orbital fibroblasts through inhibiting the activation of nuclear factor (NF)­κB. Taken together, these results suggested that celastrol attenuated the IL­1ß­induced pro­inflammatory pathway in orbital fibroblasts from patients with GO, which was associated with the suppression of NF-κB activation.

[Progress on painful diabetic peripheral neuropathy treated by integrative medicine].

The article reviewed clinical studies on painful diabetic peripheral neuropathy (PDPN) treated by integrative medicine. PDPN, a common complication of diabetes mellitus, which could severely influence patients' quality of life. The keystone and difficulty of PDPN treatment is to relieve pain. Tricyclic anti-depressants are the firstline agents for neuropathic pain but with obvious adverse reactions. Antiepileptic drugs and capsicin can relieve PDPN with less adverse reactions. In recent years, lots of report of clinical studies on DPN treated by TCM or integrative medicine were issued, but those pertinent to PDPN were seldom. Only the papers with independent statistical analysis on effect of pain relieving were selected to review in this article, and the authors presumed that it is feasible to treat PDPN with integrative medicine.

Effects of carbon-nitrogen ratio on nitrogen removal in a sequencing batch reactor enhanced with low-intensity ultrasound.

A sequencing batch reactor (SBR) enhanced with low-intensity ultrasound was designed to study the removal of nitrogen under different carbon-nitrogen (C/N) ratios. The results showed that the removal efficiencies of CODCr and nitrogen were inversely proportional to C/N ratios. The CODCr of the effluent in the control reactor (CR) and the low-intensity ultrasound-enhanced reactor (UER) were lower than 40 mg L(-1). With a decrease in C/N ratio, the NH4(+)-N removal load of the CR showed little change, while the NH4(+)-N removal load of UER increased from 21.2 to 56.1mg NH4(+)-N/g mixed liquid suspended solids per day. To further understand effects of low-intensity ultrasound, the denaturing gel gradient electrophoresis (DGGE) analysis showed that the similar coefficients of the community structures in the UER and CR were 86%, 52% and 29% when the C/N ratios were 15:1, 10:1, 5:1, respectively.

Pingmu decoction enhances apoptosis of orbital adipocytes derived from patients with Graves' ophthalmophathy.

Graves' ophthalmopathy (GO), an autoimmune disease, has been demonstrated to result from an increased volume of orbital contents, including adipose, connective and extraocular muscle tissues. In our previous study, we showed that Pingmu decoction is capable of alleviating GO progression. In this study, to further investigate the underlying mechanism(s), we examined the effects of Pingmu decoction-containing serum on the proliferation and apoptosis of preadipocytes and adipocytes derived from the orbital adipose tissue of GO patients. Our data demonstrate for the first time that Pingmu decoction-containing serum significantly reduces preadipocyte proliferation and increases adipocyte apoptosis as measured by MTT assay and Annexin V/FITC staining, respectively. Moreover, Pingmu decoction elevated the levels of cleaved caspase-3, 8 and 9 and decreased the levels of cell cycle-related genes compared to those of the control. In addition, cell cycle arrest at the G0/G1 phase was observed following Pingmu decoction treatment. This study shows a mechanism by which Pingmu decoction serves as an effective GO medicine by downregulating preadipocyte proliferation and increasing adipocyte apoptosis.

[Isolation and degrading characters of chlorpyrifos degrading bacteria XZ-3].

A strain of bacterium XZ-3 capable of highly degrading chlorpyrifos was screened from the soil sample collected from a pesticide plant after taming and enrichment. Based on analysis of phenotype, physiological and biochemical characters and 16S rDNA, XZ-3 was identified as Arthrobacter sp.. The effects of carbon source, pH, temperature and chlorpyrifos concentration on degradation were determined. The growth of bacteria in culture media were measured by visible absorption spectrophotometry under 400 nm. The residual chlorpyrifos in culture media was extracted with an equal volume of petroleum ether, and then determined by ultra-violet spectrophotometry. The results showed that the degradation rate of chlorpyrifos by XZ-3 was 86.8% in 24 h. The biodegradation rates were the highest when the additional carbon source was 0.3%, pH value was 9, chlorpyrifos concentration was 100 mg x L(-1), and cultivated temperature was 30 degrees C. The growth of bacteria increased with carbon source concentration, and was higher with pH from 8.0 to 10.0, and the highest when temperature was 30 degrees C, and chlorpyrifos concentration was 800 mg x L(-1). The strain could survive when chlorpyrifos concentration was 1000 mg x L(-1) and the removed amount of chlorpyrifos increased with chlorpyrifos concentration. The optimal conditions were proposed, which could provide theoretic basis for prevention and control of pesticides pollution.