Adiponectin attenuates the osteoblastic differentiation of vascular smooth muscle cells through the AMPK/mTOR pathway.

Vascular calcification is common in patients with peripheral artery diseases and coronary artery diseases. The osteoblastic differentiation of vascular smooth muscle cells (VSMCs) contributes significantly to vascular calcification. Adiponectin has been demonstrated to exert a protective effect in osteoblastic differentiation of VSMCs through regulating mTOR activity. However, the upstream and downstream signaling molecules of adiponectin-regulated mTOR signaling have not been identified in VSMCs with osteoblastic differentiation. In this study, the VSMC differentiation model was established by beta-glycerophosphate (ß-GP) induction. The mineralization was identified by Alizarin Red S staining. Protein expression and phosphorylation were detected by Western blot or immunofluorescence. Adiponectin attenuated osteoblastic differentiation and mineralization of ß-GP-treated VSMCs. Adiponectin inhibited osteoblastic differentiation of VSMCs through increasing the level of p-AMPKα. Pretreatment of VSMCs with AMPK inhibitor blocked while AMPK activator enhanced the effect of adiponectin on osteoblastic differentiation of VSMCs. Adiponectin upregulated TSC2 expression and downregulated mTOR and S6K1 phosphorylation in ß-GP-treated VSMCs. Adiponectin treatment significantly attenuates the osteoblastic differentiation and calcification of VSMCs through modulation of AMPK-TSC2-mTOR-S6K1 signal pathway.

Exenatide can inhibit calcification of human VSMCs through the NF-kappaB/RANKL signaling pathway.

BACKGROUND: Arterial calcification is an important pathological change of diabetic vascular complication. Osteoblastic differentiation of vascular smooth muscle cells (VSMCs) plays an important cytopathologic role in arterial calcification. The glucagon-like peptide-1 receptor agonists (GLP-1RA), a novel type of antidiabetic drugs, exert cardioprotective effects through the GLP-1 receptor (GLP-1R). However, the question of whether or not GLP-1RA regulates osteoblastic differentiation and calcification of VSMCs has not been answered, and the associated molecular mechanisms have not been examined. METHODS: Calcifying VSMCs (CVSMCs) were isolated from cultured human arterial smooth muscle cells through limiting dilution and cloning. The extent of matrix mineralization was measured by Alizarin Red S staining. Protein expression and phosphorylation were detected by Western blot. Gene expression of receptor activator of nuclear factor-κB ligand (RANKL) was silenced by small interference RNA (siRNA). RESULTS: Exenatide, an agonist of GLP-1 receptor, attenuated ß-glycerol phosphate (ß-GP) induced osteoblastic differentiation and calcification of human CVSMCs in a dose- and time-dependent manner. RANKL siRNA also inhibited osteoblastic differentiation and calcification. Exenatide decreased the expression of RANKL in a dose-dependent manner. 1,25 vitD3 (an activator of RANKL) upregulated, whereas BAY11-7082 (an inhibitor of NF-κB) downregulated RANKL, alkaline phosphatase (ALP), osteocalcin (OC), and core binding factor α1 (Runx2) protein levels and reduced mineralization in human CVSMCs. Exenatide decreased p-NF-κB and increased p-AMPKα levels in human CVSMCs 48 h after treatment. Significant decrease in p-NF-κB (p-Ser(276), p-Ser(536)) level was observed in cells treated with exenatide or exenatide + BAY11-7082. CONCLUSION: GLP-1RA exenatide can inhibit human VSMCs calcification through NF-κB/RANKL signaling.

Potential for layered double hydroxides-based, innovative drug delivery systems.

Layered Double Hydroxides (LDHs)-based drug delivery systems have, for many years, shown great promises for the delivery of chemical therapeutics and bioactive molecules to mammalian cells in vitro and in vivo. This system offers high efficiency and drug loading density, as well as excellent protection of loaded molecules from undesired degradation. Toxicological studies have also found LDHs to be biocompatible compared with other widely used nanoparticles, such as iron oxide, silica, and single-walled carbon nanotubes. A plethora of bio-molecules have been reported to either attach to the surface of or intercalate into LDH materials through co-precipitation or anion-exchange reaction, including amino acid and peptides, ATPs, vitamins, and even polysaccharides. Recently, LDHs have been used for gene delivery of small molecular nucleic acids, such as antisense, oligonucleotides, PCR fragments, siRNA molecules or sheared genomic DNA. These nano-medicines have been applied to target cells or organs in gene therapeutic approaches. This review summarizes current progress of the development of LDHs nanoparticle drug carriers for nucleotides, anti-inflammatory, anti-cancer drugs and recent LDH application in medical research. Ground breaking studies will be highlighted and an outlook of the possible future progress proposed. It is hoped that the layered inorganic material will open up new frontier of research, leading to new nano-drugs in clinical applications.

Surface-enhanced Raman scattering substrates of high-density and high-homogeneity hot spots by magneto-metal nanoprobe assembling.

Binary naoparticles composed of a superparamagnetic Fe(3)O(4) core and an Au nanoshell were prepared via a high-temperature hydrolysis reaction followed by seed-mediated growth. The nanoprobes render simultaneous dual functions of both fast magnetic response and local surface plasmon resonance. Using these nanoprobes, analyte molecules can be easily biologically captured, magnetically concentrated, and analyzed by surface-enhanced Raman scattering (SERS). Particularly, the complex particles were assembled under magnetic force direction into a SERS substrate. It was found to possess both a high enhancement factor (10(6)) and high homogeneity of "hot spot" distribution (fluctuation less than 20% for a 1 µm(2) area) with 4-aminothiophenol as the analyte.

Facile synthesis of homochiral compounds integrating circularly polarized luminescence and two-photon excited fluorescence.

A pair of novel chiral one-dimensional compounds with the general formula [Cd(NO3)2L2]·THF (where L is R- or S-2,2'-bis(methoxymethoxy)-6,6'-bis(4-pyridyl)-1,1'-binaphthyl) for the first time show circularly polarized luminescence, two-photon excited fluorescence, and second harmonic generation activity.

[Determination of Cd in sediment samples by flow injection on-line anion exchange combined with vapour generation-atomic fluorescence spectrometry].

In the present work, a method was developed for the determination of ultra-trace levels of Cd in sediment samples by atomic fluorescence spectrometry (AFS). A flow injection on-line separation and preconcentration technique coupled with an intermittent injection vapor generation technique was employed in the study. The instrument operating parameters and chemical conditions were optimized. In a 2.0 mol x L(-1) HCl solution, Cd (II) was adsorbed on 717-strong alkaline anion exchange resin, while Cu (II) and Pb (II) passed throngh. Then Cd (II) was eluted by 0.5 mol x L(-1) HNO3. The eluting solution was determined directly by intermittent injection vapor generation atomic fluorescence spectrometry. It was showed that Cd (II) can be preconcentrated effectively and the interference can be completely eliminated by this improved method. The Cd atomic vapor generation efficiency could be greatly enhanced in the presence of Co (II) and 1, 10-phenanthroline. The linear range of the determination was 0-12 microg x L(-1) with a detection limit of 0.058 microg x L(-1). The RSD (5 microg x L(-1), n=7) was 1.09%. The method was convenient, rapid and successfully validated by using national water sediment standard reference materials.

[Enrichment of triphenyltin in water samples by beta-cyclodextrin cross-linking polymer and determination by hydride-generation atomic fluorescence spectrometry].

A new method was proposed for the enrichment of triphenyltin in water samples by beta-cyclodextrin cross-linking polymer and the quantitative determination of tin in triphenyltin by hydride-generation atomic fluorescence spectrometry. The chemical conditions and instrumental conditions were investigated and optimized. The method is sensitive and precise. The detection limit is 0.1 ng x mL(-1) and the RSD 2.64% (for 0.04 microg x mL(-1)). The proposed method has been successfully applied to the determination of triphenyltin in various water samples.

[Determination of trace beryllium in geological samples by oxygen doped air-acetylene flame atomic absorption spectrometry].

A new method for the determination of trace beryllium in geological samples by oxygen-air-acetylene flame atomic absorption spectrometry is reported in the present paper. The optimum determination conditions were selected. When suitable amounts of 8-hydroxyquinoline are added, the interference effect from the coexisting elements can be minimized and the sensitivity for the determination of beryllium can be increased. The detection limit (k = 3) is 0.006 microg x mL(-1) for beryllium. The method has been applied to the determination of trace beryllium in geological standard samples, and the results are in good agreement with the certified values with a precision of 4.69% RSD( n = 8).

The protective effect of GLP-1 analogue in arterial calcification through attenuating osteoblastic differentiation of human VSMCs.

BACKGROUND: Arterial calcification is a common event in cardiovascular pathogenesis. Osteoblastic differentiation of vascular smooth muscle cells (VSMCs) is the most important cytopathologic foundation of arterial calcification. Glucagon-like peptide-1 (GLP-1) exerts multiple cardioprotective actions beyond insulinotropic effects through GLP-1 receptor (GLP-1R). However, whether GLP-1 regulates osteoblastic differentiation of VSMCs and associated molecular mechanisms has not been clarified. METHODS: The human VSMC differentiation model was established by beta-glycerophosphate (ß-GP) induction. The mineralization was measured by Alizarin Red S staining. Protein expression and phosphorylation were detected by Western blot or immunofluorescence. GLP-1R gene expression was silenced by siRNA. RESULTS: The GLP-1 analogue liraglutide dose- and time-dependently inhibited the protein expression of osteoblastic differentiation markers alkaline phosphatase (ALP), osteocalcin (OC), and Runt-related transcription factor 2 (Runx2), phosphorylation of PI3K, Akt, mTOR, and S6K1. Silencing of GLP-1R gene expression by siRNA significantly blocked the effects of liraglutide in ALP protein expression and PI3K/Akt phosphorylation. CONCLUSION: GLP-1 analogue liraglutide attenuates the osteoblastic differentiation and calcification of human VSMCs through its receptor and subsequent activation of PI3K/Akt/mTOR/S6K1 signaling. GLP-1 analogues may be potential agents for the treatment of cardiovascular diseases.

Sarco-Osteoporosis: Prevalence and Association with Frailty in Chinese Community-Dwelling Older Adults.

The aim was to apply AWGS criteria to estimate the prevalence of sarco-osteoporosis and investigate its relationship with frailty, in a sample of 316 community-dwelling Chinese older people. Regression analysis was performed using frailty as the dependent variable. The results showed that the prevalence rate of sarco-osteoporosis was 10.4% in older men and 15.1% in older women. ≧80 years old (OR 4.8; 95% CI, 3.05-10.76; P = 0.027), women (OR 2.6; 95% CI, 1.18-2.76; P = 0.036), and higher level of comorbidity (OR 3.71; 95% CI, 1.61-10.43; P = 0.021) were independently associated with the likelihood of being sarco-osteoporosis. In the frail group, sarco-osteoporosis occurred in 26.3% of men, in 38.5% of women, and in lower proportion in the prefrail (13.6% of men; 16.2% of women) and nonfrail group (1.6% of men; 1.9% of women) (P < 0.05, resp.). Furthermore, the likelihood of being frail/prefrail was substantially higher in the presence of sarco-osteoporosis (OR 4.16; 95% CI, 2.17-17.65; P = 0.019 in men; and OR 4.67; 95% CI, 2.42-18.86; P = 0.007 in women). The results indicate that patients with sarco-osteoporosis are more likely to be ≧80 yrs with higher burden of comorbidities and to have frailty/prefrailty, especially for women.

Artery calcification, osteoporosis, and plasma adiponectin levels in Chinese elderly.

OBJECTIVES: The purpose of this study is to investigate the plasma adiponectin level and thoracic aortic calcification (TAC) in Chinese elderly. BACKGROUND: The association of serum adiponectin levels and thoracic aortic calcification has not been reported. METHODS: Total plasma adiponectin level was measured by ELISA. TAC was evaluated by posterior-anterior chest radiographs. Osteoporosis was diagnosed using dual energy X-ray absorptiometry. RESULTS: The mean plasma adiponectin level was 6.3 ± 3.7 µg/ml, TAC was detected in 58% of subjects, and comorbidities of TAC and osteoporosis were observed in 33.6% subjects. The percentages of TAC or comorbidities of TAC and osteoporosis were higher in subjects with low adiponectin tertile level than that in patients with intermediate or high adiponectin tertile level. Multivariable logistic regression analysis showed that adiponectin level was negatively associated with TAC prevalence. CONCLUSIONS: Plasma adiponectin level is associated with TAC and lower plasma adiponectin level may be a useful indicator of artery calcification in the elderly.

Occurrence and volatility of several trace elements in pulverized coal boiler.

The contents of eight trace elements(Mn, Cr, Pb, As, Se, Zn, Cd, Hg) in raw coal, bottom ash and fly ash were measured in a 220 t/h pulverized coal boiler. Factors affecting distribution of trace elements were investigated, including fly ash diameter, furnace temperature, oxygen content and trace elements' characters. One coefficient of Meij was also improved to more directly show element enrichment in combustion products. These elements may be classified into three groups according to their distribution: Group 1: Hg, which is very volatile. Group 2: Pb, Zn, Cd, which are partially volatile. Group 3: Mn, which is hardly volatile. Se may be located between groups 1 and 2. Cr has properties of both group 1 and 3. In addition, the smaller diameter of fly ash, the more relative enrichment of trace elements (except Mn). The fly ash showed different adsorption mechanisms of trace elements and the volatilization of trace elements rises with furnace temperature. Relative enrichments of trace elements(except Mn and Cr) in fly ash are larger than that in bottom ash. Low oxygen content can not always improve the volatilization of trace elements. Pb is easier to form chloride than Cd during coal combustion. Trace elements should be classified in accordance with factors.

[Study and application of flow injection liquid-liquid extraction non-aqueous media mercury reduction atomic fluorescence spectrometry].

A new method for on-line solvent extraction covalent hydride generation in a non-aqueous media was proposed. Flow injection techniques were used to develop an efficient on-line solvent extraction pre-concentration and pre-separation system. The hydride generation is carried out in an aliquot of metal-complex extraction solution by sodium tetrahydroborate(III) in N,N-dimethyl formamide solution and anhydrons acetic acid. Hg is extracted by KI + HNO3 + (NH2)2CS into TBP and hydride generation by proposed method. A improved u-type gas-liguid separator was used. The working conditions and manifolds scheme of flow injection had been optimized. The method is applied to the determination of mercury in GSD-4 and GSD-6 geological reference materials with good accuracy and precision.

[Determination of zinc in mineral by FAAS after phase separation and extraction].

Non-ion surface active agent can be separated from its solution of water by heating to its cloud point. A new method for the determination of zinc in mineral samples by flame atomic absorption spectrophotometer after phase separation and extraction making use of its cloud point was studied in this paper. The conditions of phase separation and extraction such as using Triton X-100 as phase separation agent, and octanol to drop the cloud point, and the influence of acidity and the number of times for oscillating were discussed. The detection limit was 0.005 microg x mL(-1). This method has been applied to the determination of zinc in ores with satisfactory results.

[Determination of available as (III) and as (V) in soils by flow injection hydride generation atomic fluorescence spectrometry].

A method for the determination of available As (III) and As (V) in soils by flow injection hydride generation atomic fluorescence spectrometry (FI-HG-AFS) was presented. As the concentration of As (III) in extract was determined by HG-AFS in the medium of 0.1 mol.L-1 citric acid solution and the total arsenic was determined after FI on-line reduction of As (V) by L-cysteine, the concentration of As (V) was calculated by the difference. The manifolds for FI on-line reduction of As (V) were designed. The chemical conditions and the operating parameters were optimized. The detection limits (3 sigma) of As (III) and As (V) are 0.11 and 0.07 ng.mL-1, respectively, and the relative standard deviation is 1.43 for 7 determinations of 10 ng.mL-1 As (III) solution. The developed method was applied to the determination of available As (III) and As (V) in real soils and the recovery was 82%-104%.

Vitamin D Binding Protein Affects the Correlation of 25(OH)D and Frailty in the Older Men.

Vitamin D binding protein (DBP) may alter the biologic activity of 25-hydroxyvitamin D [25(OH)D]. The objective of our present study was to determine the joint effect of serum 25(OH)D and DBP on the risk of frailty. Five hundred sixteen male participants aged 70 years or older were recruited in Changsha city and its surrounding area in Hunan province of China. Frailty was defined as the presence of at least three of the five following criteria: weakness, low physical activity, slow walking speed, exhaustion, and weight loss. Multivariate linear regression analysis was performed to assess the relationship between 25(OH)D and DBP levels. Odds ratios (ORs) for frailty were evaluated across quartiles of 25(OH)D and DBP levels, adjusted age, education, and body mass index. The results showed that participants in the lowest quartile of 25(OH)D and the highest quartile of DBP levels, the lowest quartile of 25(OH)D and the lowest quartile of DBP levels, and those in the the lower quartile of 25(OH)D and lowest quartile of DBP levels had significantly higher OR of being frail compared with those in the highest quartile of 25(OH)D and lowest quartile of DBP, with OR of 3.18 (95% CI: 1.46-4.56, P < 0.05), 2.63 (95% CI: 1.31-3.68, P < 0.01), and 2.52 (95% CI: 1.22-3.52, P < 0.05), respectively. The results indicate that the joint effect of serum 25(OH)D and DBP levels is associated with the risk of frailty, and serum DBP levels affects 25(OH)D-frailty relationship in the older men.

Effects of low-dose testosterone undecanoate treatment on bone mineral density and bone turnover markers in elderly male osteoporosis with low serum testosterone.

This prospective 2-year, single-center, randomized, placebo-controlled, open-label clinical trial was performed to evaluate the efficacy of low-dose testosterone undecanoate (TU) treatment on bone mineral density (BMD) and biochemical markers of bone turnover in elderly male osteoporosis with low serum testosterone. A total of 186 elderly male osteoporosis patients with low serum testosterone were randomized into three groups: low-dose TU (20 mg, per day), standard-dose TU (40 mg, per day), and placebo group with a 24-month followup. Since the 6th month in standard-dose TU group or since the 12th month followup in low-dose TU group and throughout the study, lumbar spine and femoral neck BMD and serum levels of free testosterone, estradiol, and bone alkaline phosphatase significantly increased. There were no significant differences between groups of low-dose TU and standard dose TU in the percentage of changes of these data since the 18th month followup and throughout the study. No side effects on prostate glands including prostate specific antigen were found. In conclusion, low-dose TU (20 mg, per day) may be a cost effective and safe protocol for treating elderly male osteoporosis with low serum testosterone.

Supramolecular gelatin nanoparticles as matrix metalloproteinase responsive cancer cell imaging probes.

We demonstrate the on-chip preparation of size-controllable supramolecular gelatin nanoparticles (SGNs) with a quantum dot (QD) payload as matrix metalloproteinase (MMP) responsive cancer cell imaging probes.