Threohydroxyaspartate (THA) causes glutamate excitotoxicity in motor neurons in organotypic culture of rat spinal cord. Some drugs, including sulforaphane (SF) and riluzole, can protect motor neuron against excitotoxicity. It has been demonstrated that SF is a potent inducer of Phase II enzymes, while riluzole is a classic anti-glutamate agent. The objective of the current study is to investigate whether the combination of SF and riluzole is superior to either one used alone. In our study, the combination of SF with riluzole not only stimulates the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), reduced nicotinamide adenine dinucleotide phosphate (NADPH): quinone oxidoreductase 1 (NQO1) and heme oxygenase 1 (HO-1), but also reduces the extracellular accumulation of glutamate. When used at optimal doses, SF (10 microM) and riluzole (5 microM), either alone or in combination, all exert significant and similar neuroprotection, as measured by the number of motor neuron, medium malondialdehyde (MDA) level and lactate dehydrogenase (LDH) level. When used at low doses, the combination is better than each agent used alone. In conclusion, these results suggest the potential utility of combination use of SF and riluzole for protection of motor neuron against excitotoxicity.

OBJECTIVE: To detect content of bacterial endotoxin in Yuxingcao and Qingkailing injections by specific and nonspecific tachypleus amebocyte lysate technique for in order to investigate the feasibility of specific tachypleus amebocyte lysate technique for detecting bacterial endotoxin in traditional Chinese drug injections. METHOD: Different batches of Yuxingcao and Qingkailing injections were detected by specific and nonspecific tachypleus amebocyte lysate kits. RESULT: Yuxingcao injection could be detected by specific and nonspecific tachypleus amebocyte lysate technique, Whereas Qingkailing injection could be detected only by specific tachypleus amebocyte lysate. CONCLUSION: Using specific tachypleus amebocyte lysate as a substitute for nonspecific tachypleus amebocyte lysate is an effective method for detecting content of bacterial endotoxin in Qingkailing injection.

Mesoporous silica nanoparticles grafted with light-responsive polymer on the outer surface were developed as novel nanogated ensembles, which allow encapsulation and release of drug and biological molecules under light irradiation.

Background and Objective:The United States has experienced a large increase in the prevalence of obesity since the 1970s. Our objective was to describe recent trends in obesity and abdominal obesity among adults in the United States.Design:Trend study of cross-sectional studies.Subjects:We used data from up to 22 872 men and non-pregnant women aged >/=20 years from the National Health and Nutrition Examination Survey (NHANES) 1999-2008.Main Outcome Measures:Main outcome measures are mean body mass index and waist circumference, percentages of obesity and abdominal obesity. Obesity was defined as a body mass index >/=30 kg m(-2), and abdominal obesity was defined as a waist circumference >/=102 cm in men and >/=88 cm in women.Results:In men, the age-adjusted mean body mass index, mean waist circumference, and prevalence of obesity and abdominal obesity were 27.8 kg m(-2), 99.1 cm, and 26.9 and 37.8%, respectively, during 1999-2000 and 28.5 kg m(-2) (P (trend)=0.001), 100.8 cm (P (trend)=0.002), and 32.0 (P (trend)=0.001) and 43.7% (P (trend)=0.002), respectively, during 2007-2008. In women, the age-adjusted mean body mass index, mean waist circumference, and prevalence of obesity and abdominal obesity were 28.2 kg m(-2), 92.2 cm, and 33.2 and 55.8%, respectively, during 1999-2000 and 28.6 kg m(-2) (P (trend)=0.181), 94.9 cm (P (trend)=0.006), and 35.2 (P (trend)=0.180) and 61.8% (P (trend)=0.036), respectively, during 2007-2008. Significant linear trends for increasing prevalence of obesity were noted among men with the least and most education.Conclusion:Between 1999 and 2008, both obesity and abdominal obesity increased in men, and abdominal obesity increased in women.International Journal of Obesity advance online publication, 7 September 2010; doi:10.1038/ijo.2010.186.

BACKGROUND: The genioglossus (GG) is involved in the maintenance of an open airway for effective breathing. Although the pathogenesis of obstructive sleep apnea hypopnea syndrome (OSAHS) was closely associated with GG dysfunction, its causes and possible treatment have not been elucidated. The aim of the study was to investigate the effects of chronic intermittent hypoxia (CIH) on serum adiponectin levels, electromyograph (EMG) activity and ultrastructure of GG, as well as the effect of an adiponectin supplement in anesthetized rats. METHODS: Forty-two healthy male Wistar rats were randomly divided into normal control (A), CIH (B) and adiponectin treatment (C) groups, 14 rats in each group. CIH was performed eight hours per day for five weeks in both groups B and C. Group C received transvenous injection of adiponectin at the dosage of 10 microg per injection, twice a week for five weeks. At the end of the 5th week the GG EMG voltage was measured and compared among the three groups. Transmission electron microscope was used to observe the ultrastructure of the GG. RESULTS: CIH caused significant hypoadiponectinemia, weakened activity of GG EMG at both baseline and hypoxia stimulation, and induced ultrastructural pathological changes, such as, myofibril discontinuities, lysis of myofilament, edema of mitochondria and disruption of cristae, vacuolus and lysis of some mitochondria. Venous supplement of adiponectin improved the above pathological changes resulting from CIH. CONCLUSION: CIH resulted in pathological changes in GG's EMG and ultrastructure, which could be improved by supplement of adiponectin and be associated with hypoadiponectinemia caused by CIH.

Many types of cancer cells possess the ability to evade apoptosis, leading to their rapid and uncontrolled proliferation. As major regulators of apoptosis, Bcl-2 proteins serve as emerging targets for novel chemotherapeutic strategies. In this study, we examined the involvement of Bcl-2 proteins in apoptosis induced by the chemotherapeutic agent actinomycin D. A dramatic decrease in anti-apoptotic myeloid leukemia cell differentiation protein (Mcl-1) mRNA and protein expression was detected upon actinomycin D treatment. Further, Mcl-l overexpression caused resistance to cell death upon treatment with actinomycin D, implicating a role for the downregulation of Mcl-1 in actinomycin D-induced apoptosis. We also explored the therapeutic potential of actinomycin D in combination with ABT-737, an experimental agent that inhibits anti-apoptotic Bcl-2 proteins. Actinomycin D sensitized cells to ABT-737 treatment in a Bak- or Bax-dependent manner. Importantly, low concentrations of actinomycin D and ABT-737 were more effective in inducing cell death in transformed cells than their untransformed counterparts. A synergistic effect of actinomycin D and ABT-737 on cell death was observed in several human tumor cell lines. Like actinomycin D treatment, knocking down Mcl-1 expression greatly sensitized tumor cells to ABT-737 and Mcl-1 overexpression abrogated the cytotoxic effect induced by ABT-737 and actinomycin D. These results suggest that the downregulation of Mcl-1 by actinomycin D is likely responsible for the observed synergistic effect between the two drugs. Overall, our studies provide compelling evidence that the combination of actinomycin D and ABT-737 may lead to an effective cancer treatment strategy.

Hepatocellular carcinoma (HCC) is one of the most common human cancers and the patients' five-year survival rate is very low. Growing evidence indicates that interleukin-6 (IL-6) is a risk factor for HCC. High serum IL-6 may promote HCC development in hepatitis B patients. Therefore, IL-6 could be considered a HCC biomarker and blockade of IL-6 pathway may be a promising therapeutic alternative for HCC. STAT3 is major pathway to mediate signal from IL-6 to the nucleus, where different genes associated with proliferation and apoptosis are regulated. We previous reported that IL-6 induces cell survival upon drug treatment in HCC cells and inhibition of IL-6/STAT3 pathway using anti-IL-6 antibody or STAT3 small-molecule inhibitor LLL12 reduces this effect. Here we summarized the recent studies of IL-6 in HCC and showed another STAT3 small-molecule inhibitor FLLL32 also blocked IL-6-induced STAT3 activation in HCC cells. FLLL32 is a novel curcumin analogue, which has been described to suppress the constitutive activation of STAT3 in pancreatic and breast cancer cells in vitro and vivo. We demonstrated that FLLL32 blocked IL-6-induced STAT3 phosphorylation and nuclear translocation.

Objective To explore the effect of tanshinone IIA (TanIIA) on calcium current induced by beta-amyloid protein 25-35 (Abeta25-35) in neurons of nucleus basalis of Meynert (nbM). Methods Cell acute dissociated technique and the whole-cell recording model of patch-clamp technique of single-cell were used. The voltage-dependent calcium current in neurons of nbM was recorded in SD rats first. Then the effect of TanIIA on the voltage-dependent calcium current in the neurons was assayed. The change of calcium current induced by Abeta25-35 as well as the effect of TanIIA on the change of calcium current induced by Abeta25-35 in neurons of nbM were analyzed. Results Extracellular fluid containing different concentrations of TanIIA was irrigated, respectively. The peak current did not change obviously. There was no difference in current density between the TanIIA group and the control group at 0 mV (P>0.05). Extracellular fluid containing 200 nmol/L Abeta25-35 was irrigated after the normal calcium current recorded under whole patch clamp, and the peak current changed obviously. There was distinct difference in the current density between the Abeta group and the control group at 0 mV (P<0.05). Extracellular fluid containing Abeta25-35 and different concentrations of TanIIA were irrigated after the normal calcium current was recorded under whole patch clamp, respectively, and the peak current did not change. There was no difference in current density between the TanIIA +Abeta group and the control group at 0 mV (P>0.05). Conclusion In vitro, TanIIA could inhibit the calcium current amplification induced by Abeta25-35 in neurons of nbM. TanIIA may protect neurons against the toxicity of Abeta and decrease the inward flow of Ca(2+).

Objective To explore the role of phosphorylation of cAMP response element binding protein (CREB) in the incision-induced pain hypersensitivity. Methods A longitudinal incision was made in one plantar hind paw of isoflurane-anesthetized rats. Spinal cords were removed at various postoperative time after behavior test. Phosphorylation of CREB was determined by immunohistochemistry and double-labeling immunofluorescence. Morphine and gabapentin were intraperitoneally injected before the behavior test and were used to determine the interaction between phosphorylation of CREB and morphine and gabapentin. Results After the hind-paw incision, phosphorylation of CREB was enhanced in the ipsilateral lumbar spinal cord(P<0.05). The enhancement of p-CREB was mainly in the neurons in the dorsal horn of the spinal cord. All these were shown by double-labeling technique and p-CREB was mainly in the neurons. Intraperitoneal injection of morphine prevented the increased phosphorylation of CREB in the spinal cord and inhibited the mechanical allodynia induced by the incision(P>0.05). Gabapentin didn't inhibit the phosphorylation of CREB(P<0.05) but partly inhibited the mechanical allodynia. Conclusion Incision induces the phosphorylation of CREB in the spinal cord, and the increase of p-CREB is mainly in the neurons. Phosphorylation of CREB in the spinal cord contributes to the pain hypersensitivity induced by surgical incision.

We synthesized CdS nanorods through a conventional solvothermal method and studied their photoluminescence and electric transport properties before and after annealing. High-resolution transmission electron microscopy indicated that the surface layer of the annealed CdS nanorods was well crystallized, while that of the unannealed nanorods was amorphous. Energy-dispersive x-ray spectrography, x-ray photoelectron spectrography and thermogravimetric analysis were used to demonstrate that the amorphous layer at the surface of the as-prepared nanorods was pure CdS. The photoluminescence spectra showed that after annealing the intensity of the band-edge emission increased several times and the surface state emission at 548 nm disappeared. The unannealed CdS nanorods had approximately linear I-V characteristics and the conductance suddenly increased about 100 times upon visible light illumination by a halogen lamp. The annealed CdS nanorods exhibited nonlinear conductance with a turn-on voltage at about 2.2 V. These properties show that CdS nanorods have potential applications in nanophotoelectric or sensing devices.

By sputtering synthesis of cubic Cu(3)N, which decomposes at moderate temperatures, film growth proceeds with simultaneous nitrogen reemission from inside, leading to the formation of some unusual structures or morphology. We report a relief morphology comprising densely packed rosette-like features. The rosettes, typically 20 microm in size, show a radial furcation followed by successive bifurcation at approximately 74 degrees , resulting in a fivefold symmetric structure sometimes. The area expansion of the features can be as large as ten per cent with regard to the underlying bottom. Scanning electron micrographs reveal that it is the gliding of Cu(3)N nanocrystals along the Cu-rich {111}-planes that is responsible for the unusually large area expansion. The gliding and packing along the {111}-planes also explain the bifurcation angle of the ramified rosettes. Such a relief morphology can serve as a template for large-area fabrication of concave structures by inverse duplication, adding to the already abundant innovative applications of this material.

Trypsin-catalyzed (18)O labeling technique is increasingly used in shotgun proteomics for relative peptide/protein quantitation. However, precise quantitative measurements are often complicated by the instability of (18)O labeled peptides mainly caused by oxygen back-exchange. A number of attempts have been made to reduce or prevent oxygen back-exchange. Here, we demonstrate that the removal of immobilized trypsin by filtration using ZipTip can efficiently minimize oxygen back-exchange and enhance the stability of (18)O labeled peptides at various pH values. The approach presented here is more applicable to microscale samples. We also observed that IPG-IEF was applicable to separate the (18)O labeled peptides and the (18)O labeling rate of the peptides was no correlation with their molecular weight or pI. The ability to generate stably (18)O labeled samples without back-exchange should broaden the applications of (18)O labeling.

OBJECTIVE: To investigate the characteristics, sensitizin and the mechanism of pseudo allergic reaction induced by Yuxingcao injection. METHOD: Beagle dogs were randomly assigned to control group, 0.5% tween 80 group, Yuxingcao injection without tween 80 group, Yuxingcao injection included 0.5% tween 80 group. The animals in control group were intravenously injected with saline. The other group were intravenously injected with the corresponding test substances. Observe pseudo anaphylaxis of Beagle dogs within 30 min after administration. Blood pressure and respiration rate of Beagle dogs were measured before and after injection drugs 10 min and 30 min respectively. The pseudo allergic reactions were scored at same time points, and the sera of animals were collected to determine the HIS, CH50 and C5b-9 concentration using ELISA. RESULT: The scores of allergic reaction in 0.5% tween 80 group and Yuxingcao injection included 0.5% tween 80 group was evidently higher than that in control group in 2-5 min after administration. Animals of above two groups showed the symptoms of red swelling on ear part, pruritus, throwing the head, nausea, lapping the tongue, dysphoria and bradykinesia. Some of them had behaved with repose, urination, defecation, cyanosis, the frequency of breathes accelerating and blood pressure decreasing. The rate of pseudo allergic reactions was 100%. Serum CH50 concentration of 0.5% tween 80 group decreased 10 min after injection, while C5b-9 concentration increased. No obvious differences were observed 30 min after injection. There was no significant difference in HIS concentration between control group and treatment groups. CONCLUSION: The pseudo allergic reactions appeared after intravenous 0.5% tween 80 and Yuxingcao injection when mixed with tween 80. Furthermore, Yuxingcao injection without tween 80 did not induce pseudo allergic reactions. It was suggested that the pseudo allergic reactions of Yu Xing Cao Injection was related to the cosolvent tween 80. The pseudo allergic reactions of tween 80 may relate to the activation of complement.

This study examined the sterol compositions of 102 dinoflagellates using clustering and cluster validation techniques, as a means of determining the relatedness of the organisms. In addition, dinoflagellate sterol-based relationships were compared statistically to 18S rDNA-based phylogenetic relationships using the Mantel test. Our results indicated that the examined dinoflagellates formed six clusters based on sterol composition and that several, but not all, dinoflagellate genera, which formed discrete clusters in the 18S rDNA-based phylogeny, shared similar sterol compositions. This and other correspondences suggest that the sterol compositions of dinoflagellates are explained, to a certain extent, by the evolutionary history of this lineage.

Activation of NF-kappaB and MAPKs/AP-1 signaling pathways by receptor activator NF-kappaB ligand (RANKL) is essential for osteoclast activities. Targeting NF-kappaB and MAPKs/AP-1 signaling to modulate osteoclast activities has been a promising strategy for osteoclast related diseases. In this study, we examined the effects of maslinic acid (MA), a pentacyclic triterpene acid which is widely present in dietary plants, on RANKL-induced osteoclastogenesis, osteoclast function, and signaling pathways by in vitro and in vivo assay systems. In mouse bone marrow monocytes (BMMs) and RAW264.7 cells, MA inhibited RANKL-induced osteoclastogenesis in a dose-dependent manner within non-growth inhibitory concentration and MA decreased osteoclastogenesis-related marker gene expression, including TRAP, MMP-9, c-Src, CTR, and cathepsin K. Specifically, MA suppressed osteoclastogenesis and actin-ring formation at early stage. In ovariectomized mice, administration of MA prevented ovariectomy-induced bone loss by inhibiting osteoclast activities. At molecular levels, MA abrogated the phosphorylation of MAPKs and AP-1 activity, inhibited the IkappaBalpha phosphorylation and degradation, blocked NF-kappaB/p65 phosphorylation, nuclear translocation, and DNA binding activity by down-regulating RANK expression and blocking RANK interaction with TRAF6. Together, our data demonstrate that MA suppresses RANKL-induced osteoclastogenesis through NF-kappaB and MAPKs/AP-1 signaling pathways and MA is a promising agent in the treatment of osteoclast related diseases, such as osteoporosis. (c) 2010 American Society for Bone and Mineral Research.

Development of successful formulations for poorly water-soluble drugs remains a longstanding critical and challenging issue in cancer therapy. A beta-CD functionalized hyperbranched polyglycerol (HPG) as a potential water-insoluble drug carrier was prepared. The HPG-g-CD molecules could self-assemble into multimolecular spherical micelles in water, the size of which ranged from 200-300 nm with good dispersity. The high loading capacity and encapsulation efficiency of paclitaxel, as a model, were obtained and the release profiles with different copolymer composition showed a burst release followed by a continuous extended release. Furthermore, MTT analysis showed HPG-g-CD had good biocompatibility, indicating that HPG-g-CD may be considered as a promising hydrophobic drug delivery system.

A protecting group free and biomimetic total synthesis of (+)-ainsliadimer A has been accomplished in 14 steps from alpha-santonin. The synthesis relies on a hydrogen bonding promoted [4 + 2]-hetero-Diels-Alder dimerization to afford the key homodimer intermediate, which demonstrates the feasibility of using nonenzymatic conditions to achieve the proposed biosynthesis.

A method for the determination of trace organochlorine pesticides (OCPs) in soil using isotope dilution and high resolution gas chromatography-high resolution mass spectrometry (ID-HRGC-HRMS) was developed. The sample was extracted by accelerated solvent extractor (ASE) and cleaned-up by a Florisil solid phase extraction (SPE) cartridge. The analytes were separated by HRGC on a DB-5MS column (30 mx 0.25 mm x 0.25 microm) and determined by HRMS. The identifications of OCPs were based on the retention time of 13C-labelled standard and the abundance ratio of the two exact mass-to-charge ratios. The quantitative analysis was performed using the ratios of the integrated areas of the 13C-labelled standards. This method has the recoveries ranging from 77.3% to 114.5% and the relative standard deviations (RSD) less than 10.81% (n=5). The limits of detection (LODs) of this method for all OCPs were lower than 0.04 pg/g. The results indicated that the method is rapid, selective and sensitive for precise determination requirements of organochlorine pesticides at trace level in soil.

Five Anopheles marajoara Galvão and Damasceno populations, representing diverse ecological conditions, were sampled throughout Colombia and analyzed using nine hypervariable DNA microsatellite loci. The overall genetic diversity (H = 0.58) was lower than that determined for some Brazilian populations using the same markers. The Caquetá population (Colombia) had the lowest gene diversity (H = 0.48), and it was the only population at Hardy-Weinberg equilibrium. Hardy-Weinberg disequilibrium in the remaining four populations was probably caused by the Wahlund effect. The assignment analyses showed two incompletely isolated gene pools separated by the Eastern Andean cordillera. However, other possible geographical barriers (rivers and other mountains) did not play any role in the moderate genetic heterogeneity found among these populations (F(ST) = 0.069). These results are noteworthy, because this species is a putative malaria vector in Colombia.

DADH catalyzes the flavin-dependent oxidative deamination of D-amino acids to the corresponding alpha-keto acids and ammonia. Here we report the first X-ray crystal structures of DADH at 1.06 A resolution, and its complexes with iminoarginine (DADHred/iminoarginine) and iminohistidine (DADHred/iminohistidine) at 1.30 A resolution. The DADH crystal structure comprises an unliganded conformation and a product-bound conformation, which is almost identical to the DADHred/iminoarginine crystal structure. The active site of DADH was partially occupied with iminoarginine product (30% occupancy) that interacts with Tyr53 in the minor conformation of a surface loop. This flexible loop forms an "active site lid", similar to those seen in other enzymes, and may play an essential role in substrate recognition. The guanidinium side chain of iminoarginine forms a hydrogen bond interaction with the hydroxyl of Thr50 and an ionic interaction with Glu87. In the structure of DADH in complex with iminohistidine, two alternate conformations were observed for iminohistidine where the imidazole groups formed hydrogen bond interactions with the side chains of His48 and Thr50 and either Glu87 or Gln336. The different interactions and very distinct binding modes observed for iminoarginine and iminohistidine are consistent with the 1000-fold difference in kcat/Km values for D-arginine and D-histidine. Comparison of the kinetic data for the activity of DADH on different D-amino acids and the crystal structures in complex with iminoarginine and iminohistidine establishes that this enzyme is characterized by relatively broad substrate specificity, being able to oxidize positively charged and large hydrophobic D-amino acids bound within a flask-like cavity.