Background The terrifying undiagnosed rate and high prevalence of diabetes have become a public emergency. A high efficiency and cost-effective early recognition method is urgently needed. We aimed to generate innovative, user-friendly nomograms that can be applied for diabetes screening in different ethnic groups in China using the non-lab or noninvasive semi-lab data. Methods This multicenter, multi-ethnic, population-based, cross-sectional study was conducted in eight sites in China by enrolling subjects aged 20–70. Sociodemographic and anthropometric characteristics were collected. Blood and urine samples were obtained 2 h following a standard 75 g glucose solution. In the final analysis, 10,794 participants were included and randomized into model development (n = 8096) and model validation (n = 2698) group with a ratio of 3:1. Nomograms were developed by the stepwise binary logistic regression. The nomograms were validated internally by a bootstrap sampling method in the model development set and externally in the model validation set. The area under the receiver operating characteristic curve (AUC) was used to assess the screening performance of the nomograms. Decision curve analysis was applied to calculate the net benefit of the screening model. Results The overall prevalence of undiagnosed diabetes was 9.8% (1059/10794) according to ADA criteria. The non-lab model revealed that gender, age, body mass index, waist circumference, hypertension, ethnicities, vegetable daily consumption and family history of diabetes were independent risk factors for diabetes. By adding 2 h post meal glycosuria qualitative to the non-lab model, the semi-lab model showed an improved Akaike information criterion (AIC: 4506 to 3580). The AUC of the semi-lab model was statistically larger than the non-lab model (0.868 vs 0.763, P < 0.001). The optimal cutoff probability in semi-lab and non-lab nomograms were 0.088 and 0.098, respectively. The sensitivity and specificity were 76.3% and 81.6%, respectively in semi-lab nomogram, and 72.1% and 67.3% in non-lab nomogram at the optimal cut off point. The decision curve analysis also revealed a bigger decrease of avoidable OGTT test (52 per 100 subjects) in the semi-lab model compared to the non-lab model (36 per 100 subjects) and the existed New Chinese Diabetes Risk Score (NCDRS, 35 per 100 subjects). Conclusion The non-lab and semi-lab nomograms appear to be reliable tools for diabetes screening, especially in developing countries. However, the semi-lab model outperformed the non-lab model and NCDRS prediction systems and might be worth being adopted as decision support in diabetes screening in China.
Quantitative real time RT-PCR has been described as the most sensitive method for the detection of low abundance mRNA. To date, no reference genes have been screened in the half-smooth tongue sole (Cynoglossus semilaevis). The aim of this study was to select the most stable genes for quantitative real-time RT-PCR. Eight housekeeping genes (18S, TUBA, B2M, ACTB, EF1A, GAPDH, RPL17 and UBCE) were tested at different developmental stages, in different tissues, and following exposure to the drug SB-431542. Using geNorm, BestKeeper and NormFinder software, GAPDH/B2M, GAPDH/18S and UBCE/GAPDH were identified as the most suitable genes from samples taken of different developmental stages while 18S/RPL17 were consistently ranked as the best reference genes for different tissue types. Furthermore, TUBA/B2M, TUBA/UBCE and B2M/TUBA were found to be the most suitable genes in samples treated with the drug, SB-431542 by geNorm, BestKeeper and NormFinder respectively. Across both different developmental stages and tissue types, the combination of 18S and GAPDH was the most stable reference gene analyzed by Ref-Finder. To test and verify the screened reference genes, the expression profiles of LEFTY-normalized to the combination of GAPDH/18S and ACTB were presented. These results will be useful for future gene-expression studies in the half-smooth tongue sole.
Lycium barbarum (L. barbarum) fruit or extract has been regarded as a superior-grade Chinese medicine, used to modulate body immunity and for anti-aging purposes. However, the underlying molecular mechanisms behind these effects remain unclear. In the present study, L. barbarum polysaccharides (LBPs), considered a major contributor of L. barbarum effects, were used to elucidate its mechanism of action by phenotypic and senescence associated-β-galactosidase (SA-β-gal) assays, evaluation of survival rates in vivo and expression profiling of genes related to the p53 signaling pathway in a zebrafish model. Zebrafish embryos were continuously exposed to various concentrations of LBPs (1.0, 2.0, 3.0 and 4.0 mg/ml) for 3 days. The results of fluorescent acridine orange and SA-β-gal staining indicated that cell apoptosis and senescence mainly occur in the head at 24 hours post fertilization (hpf) and 72 hpf. In addition, resistance to replicative senescence was observed at low doses of LBPs, especially at the 3.0 mg/ml concentration. Furthermore, the expression of genes that relate to aging, such as p53, p21 and Bax, was decreased, while that of Mdm2 and TERT genes was increased after treatment with LBPs. The results demonstrated that the effects of LBPs on cell apoptosis and aging might be mediated by the p53-mediated pathway.
In this study, we report the cellular uptake studies of novel LX loaded nanoliposomes in H2O2 stress SH-SY5Y Cells synthesized by thin film evaporation method. We have isolated the smallest size nanoliposomes after 90 min ultrasonification, keeping Polydisperse Index as 0.259. The morphology, size, zepta potential and drug efficiency of prepared nanoliposomes are characterized by using Transmission Electron Microscope (TEM), particle size analyzer and High Pressure Liquid Chromatography (HPLC). The particle size analyzer have confirmed the particle size of nanoluposomes measured in range of 100-250 nm, whereas the shape of these nanoliposomes is almost spherical. The zeta potential of small size nanoliposomes was measured as -49.62 and encapsulation efficiency of the LX loaded nanoliposomes was 87%. The oxidative stress response in SH-SY5Y Cells for various doses of drug with and without nanoliposomes has affectively improved the cell-stress response up to 20% after 24 h of incubation at 37 degrees C. The results indicated that LX loaded nanoliposomes were taken by the cells effectively which ultimately improved the cell-stress response. Thus, this study confirmed that synthesized nanoliposomes are not only effective drug carriers but could be potentially used for delivery of genes, antibodies, and proteins in future.
Dragon's blood is a bright red resin obtained from Dracaena cochinchinensis. It is a traditional medicinal that is used for wound healing and to stop bleeding. Its main biological activity appears to be from phenolic compounds found in Dragon's blood. In this study, the radioprotective effects of Dragon's blood were examined after whole brain irradiation of rats with either 100 MeV/u Carbon (12)C(6+) heavy ions or (60)Co γ-rays. The amounts of radiation-induced oxidative stress, inflammatory cytokines and apoptosis in irradiated rat brains were compared with and without Dragon's blood treatment. Compared to the "irradiation only" control group, the Dragon's blood treatment group significantly decreased malondialdehyde and hydrogen peroxide levels, and increased superoxide dismutase activity and glutathione levels induced by oxidative stress in radiation exposed rats (P < 0.05). Dragon's blood also significantly reduced radiation-induced inflammatory cytokines of tumor necrosis factor-α, interferon-γ and interleukin-6 levels (P < 0.05) and inhibited hippocampal neuronal apoptosis in (60)Co γ-ray irradiated rats. Furthermore, Dragon's blood significantly increased expression of brain-derived neurophic factor and inhibited the expression of pro-apoptotic caspase 3 (P < 0.05-0.01). Finally, Dragon's blood significantly inhibited expression of the AP-1 transcription factor family members c-fos and c-jun proteins (P < 0.05-0.01). The results obtained here suggest that Dragon's blood has radioprotective properties in rat brains after both heavy ions and (60)Co γ-ray exposure.
Abstract. There are statistical data indicating that diabetes is a risk factor for Parkinson's disease (PD). Methylglyoxal (MG), a biologically reactive byproduct of glucose metabolism, the levels of which have been shown to be increase in diabetes, reacts with dopamine to form 1-acetyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (ADTIQ); this formation may provide further insight into the connection between PD and diabetes. In this study, we investigated the role of ADTIQ in these two diseases to determine in an aim to enhance our understanding of the link between PD and diabetes. To this end, a cell model of hyperglycemia and a rat model of diabetes were established. In the cell model of hyperglycemia, compared with the control group, the elevated glucose levels promoted free hydroxyl radical formation (p<0.01). An ADTIQ assay was successfully developed and ADTIQ levels were detected and quantified. The levels of its precursors, MG and dopamine (DA), were determined in both the cell model of hyperglycemia and the rat model of diabetes. The proteins related to glucose metabolism were also assayed. Compared with the control group, ADTIQ and MG levels were significantly elevated not only in the cell model of hyperglycemia, but also in the brains of rats with diabetes (p<0.01). Seven key enzymes from the glycolytic pathway were found to be significantly more abundant in the brains of rats with diabetes. Moreover, it was found that adenosine triphosphate (ATP) synthase and superoxide dismutase (SOD) expression levels were markedly decreased in the rats with diabetes compared with the control group. Therefore, ADTIQ expression levels were found to be elevated under hyperglycemic conditions. The results reported herein demonstrate that ADTIQ, which is derived from MG, the levels of which areincreased in diabetes, may serve as a neurotoxin to dopaminergic neurons, eventually leading to PD. IntroductionDiabetes mellitus (DM), as a state of chronic hyperglycemia, and Parkinson's disease (PD) are diseases which consist a global health threat. In recent years, there have been increasing data indicating that hyperglycemia is associated with an increased risk of developing PD (1,2). However, the mechanisms underlying the association between hyperglycemia and PD have not yet been elucidated.Deng and Rajput (6) were the first to report, in 2001, that 1-acetyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (ADTIQ), a salsolinol-like compound, is found at highly concentrated levels in the brains of patients who suffer from PD (3). When the brains of deceased patients with PD were compared to those of normal subjects, it was found that patients with PD presented elevated levels of ADTIQ in all the examined brain areas. This finding indicated that elevated ADTIQ expression levels may be one of the mechanisms involved in the increased risk patients with diabetes have of developing PD (4).Formation of a salsolinol-like compound, the neurotoxin, 1-acetyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline, in a cellular model of hyperglycem...
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