Pseudo-random Single Photon Counting: a High-speed Implementation

Biomedical Optics Express. 2010  |  Pubmed ID: 21258444

Pseudo-random single photon counting (PRSPC) is a new time-resolved optical measurement method which combines the spread spectrum time-resolved method with single photon counting. A pseudo-random bit sequence is used to modulate a continuous wave laser diode, while single photon counting is used to build up the optical signal in response to the modulated excitation. Periodic cross-correlation is performed to obtain the temporal profile of the subject of interest. Compared with conventional time-correlated single photon counting (TCSPC), PRSPC enjoys many advantages such as low cost and high count rate without compromising the sensitivity and time-resolution. In this paper, we report a PRSPC system that can be used for high-speed acquisition of the temporal point spread function of diffuse photons. It can reach a photon count rate as high as 3 Mcps (counts per second). Phantom experiments have been conducted to demonstrate the system performance.

[Surveys on the Nutrition Literacy of 802 Adults in Jiangxi Province]

Wei Sheng Yan Jiu = Journal of Hygiene Research. Nov, 2010  |  Pubmed ID: 21351643

To investigate the nutrition literacy status of adults in Jiangxi province and afford support for nutrition education.

[Progress on the Study of Estimating Influenza-associated Deaths Under Regression Models.]

Zhonghua Liu Xing Bing Xue Za Zhi = Zhonghua Liuxingbingxue Zazhi. Jun, 2010  |  Pubmed ID: 21163110

Genetic Analysis of IREB2, FAM13A and XRCC5 Variants in Chinese Han Patients with Chronic Obstructive Pulmonary Disease

Biochemical and Biophysical Research Communications. Nov, 2011  |  Pubmed ID: 22027142

Recently, variants (rs2568494, rs2869967 and rs3821104) in the IREB2, FAM13A and XRCC5 genes were found to be associated with chronic obstructive pulmonary disease (COPD) in non-Asian populations by genome-wide association study (GWAS) analysis. To evaluate whether variants in these genes are related to COPD in Chinese Han population, we investigated COPD patients of Chinese Han ethnicity from Mainland China. Significant differences in genotypic distributions (χ(2)=6.319, p=0.042 for rs2869967; χ(2)=6.062, p=0.048 for rs3821104) and allele distributions (χ(2)=4.014, p=0.045 for rs2869967; χ(2)=5.607, p=0.018 for rs3821104) were observed between patients and control subjects for variants rs2869967 and rs3821104, whereas no statistically significant associations for genotypic and allelic distribution between IREB2 rs2568494 and COPD phenotype (p>0.05) were identified. Our results support that FAM13A rs2869967 and XRCC5 rs3821104 are associated with COPD in Chinese Han population.

Genome Sequencing Reveals Insights into Physiology and Longevity of the Naked Mole Rat

Nature. Nov, 2011  |  Pubmed ID: 21993625

The naked mole rat (Heterocephalus glaber) is a strictly subterranean, extraordinarily long-lived eusocial mammal. Although it is the size of a mouse, its maximum lifespan exceeds 30 years, making this animal the longest-living rodent. Naked mole rats show negligible senescence, no age-related increase in mortality, and high fecundity until death. In addition to delayed ageing, they are resistant to both spontaneous cancer and experimentally induced tumorigenesis. Naked mole rats pose a challenge to the theories that link ageing, cancer and redox homeostasis. Although characterized by significant oxidative stress, the naked mole rat proteome does not show age-related susceptibility to oxidative damage or increased ubiquitination. Naked mole rats naturally reside in large colonies with a single breeding female, the 'queen', who suppresses the sexual maturity of her subordinates. They also live in full darkness, at low oxygen and high carbon dioxide concentrations, and are unable to sustain thermogenesis nor feel certain types of pain. Here we report the sequencing and analysis of the naked mole rat genome, which reveals unique genome features and molecular adaptations consistent with cancer resistance, poikilothermy, hairlessness and insensitivity to low oxygen, and altered visual function, circadian rythms and taste sensing. This information provides insights into the naked mole rat's exceptional longevity and ability to live in hostile conditions, in the dark and at low oxygen. The extreme traits of the naked mole rat, together with the reported genome and transcriptome information, offer opportunities for understanding ageing and advancing other areas of biological and biomedical research.

The Role of Dileucine in the Expression and Function of Human Organic Anion Transporter 1 (hOAT1)

International Journal of Biochemistry and Molecular Biology. 2011  |  Pubmed ID: 21494320

Human organic anion transporter hOAT1 plays a critical role in the body disposition of environmental toxins and clinically important drugs including anti-HIV therapeutics, anti-tumor drugs, antibiotics, anti-hypertensives, and anti-inflammatories. In the current study, we investigated the role of dileucine (L6L7) at the amino terminus of hOAT1 in the expression and function of the transporter. We substituted L6L7 with alanine (A) simultaneously. The resulting mutant transporter L6A/L7A showed no transport activity due to its complete loss of expression at the cell surface. Such loss of surface expression of L6A/L7A was consistent with a complete loss of an 80 kDa mature form and a dramatic decrease in a 60 kDa immature form of the mutant transporter in the total cell lysates. Treatment of L6A/L7A-expressing cells with proteasomal inhibitor resulted in a significant increase in the immature form of hOAT1, but not its mature form, whereas treatment of these cells with lysosomal inhibitor had no effect on the expression of the mutant transporters, suggesting that the mutant transporter was degraded through proteasomal pathway. The accumulation of mutant transporter in the endoplasmic reticulum (ER) was confirmed by coimmunolocalization of L6L7 with calnexin, an ER marker. Furthermore, treatment of L6A/L7A-expressing cells with sodium 4-phenylbutyrate (4PBA) and glycerol, two chemical chaperones, could not promote the exit of the immature form of the mutant transporter from the ER. Our data suggest that L6L7 are critical for the stability and ER export of hOAT1.

Uniform Mesoporous Carbon As a Carrier for Poorly Water Soluble Drug and Its Cytotoxicity Study

European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Fur Pharmazeutische Verfahrenstechnik E.V. Dec, 2011  |  Pubmed ID: 22193360

In this study, uniform mesoporous carbon spheres (UMCS) with 3-D pore system and fibrous ordered mesoporous carbon (FOMC) with 2-dimensional hexagonal mesoporous structure were studied as drug carriers for oral drug delivery system. Lovastatin (LOV), which has low water solubility, was chosen as a model drug. Drug release rate and degree of drug loading of UMCS and FOMC were compared. The effects of different pore channel structures and pore sizes on LOV uptake and release were systematically investigated. Cytotoxicity of UMCS and FOMC on human colon carcinoma (Caco-2) cells were also studied. The results indicate that UMCS has a higher degree of drug loading (up to 36.26% drug weight/total weight) compared with FOMC. The dissolution rate of LOV from UMCS was found to be markedly increased compared with pure crystalline LOV, and the dissolution rate of LOV from FOMC was relatively sustained compared with UMCS, and both UMCS and FOMC exhibited a weak cytotoxicity at tested concentrations (10-800μg/ml).

An Outbreak of Sheep Pox Associated with Goat Poxvirus in Gansu Province of China

Veterinary Microbiology. Nov, 2011  |  Pubmed ID: 22169434

Three strains of Capripoxviruses (CaPVs) were isolated from an outbreak of sheep pox in Gansu province of China. They were analyzed by P32 gene-based molecular methods and a species-specific PCR based on the RPO30 gene. Two bands which are specific to goat poxvirus (GTPV) were observed after the PCR products of P32 gene were digested with the endonuclease of Hinf I. Moreover, an amplicon of 172bp, which is specific to GTPV, was amplified from the viruses by using the RPO30 gene-based PCR. Sequence analysis of the P32 genes showed that three nucleotide bases for coding residue of aspartic acid which are located at 163-165 position of P32 gene of sheep poxvirus (SPPV) were absent, and six single nucleotide substitutions which are characteristic of GTPV were present. The viruses were genetically closer to GTPV strains and clustered into the GTPV branch of the phylogenetic tree constructed on the basis of the P32 gene. The results characterized the isolated viruses as GTPV. It is the first report of an outbreak of sheep pox associated with GTPV in China.

Liposome Formulated with TAT-modified Cholesterol for Improving Brain Delivery and Therapeutic Efficacy on Brain Glioma in Animals

International Journal of Pharmaceutics. Nov, 2011  |  Pubmed ID: 21945185

The treatment of central nervous system diseases such as brain glioma is a major challenge due to the presence of the blood-brain barrier (BBB). A cell-penetrating peptide TAT (AYGRKKRRQRRR), which appears to enter cells with alacrity, was employed to enhance the delivery efficiency of normal drug formulation to the brain. Targeting liposomal formulations often apply modified phospholipids as anchors. However, cholesterol, another liposomal component more stable and cheaper, has not been fully investigated as an alternative anchor. In our study, TAT was covalently conjugated with cholesterol for preparing doxorubicin-loaded liposome for brain glioma therapy. Cellular uptake by brain capillary endothelial cells (BCECs) and C6 glioma cells was explored. The anti-proliferative activity against C6s confirmed strong inhibitory effect of the liposomes modified with doxorubicin-loaded TAT. The bio-distribution findings in brains and hearts were evident of higher efficiency of brain delivery and lower cardiotoxic risk. The results on survival of the brain glioma-bearing animals indicate that survival time of the glioma-bearing rats treated with TAT-modified liposome was much longer than in the other groups. In conclusion, the potency of the TAT-modified liposome to enter the BBB appears to be related with the TAT on the liposome's surface. The TAT-modified liposome may improve the therapeutic efficacy on brain glioma in vitro and in vivo.

N-Trimethyl Chitosan Nanoparticle-encapsulated Lactosyl-Norcantharidin for Liver Cancer Therapy with High Targeting Efficacy

Nanomedicine : Nanotechnology, Biology, and Medicine. Feb, 2012  |  Pubmed ID: 22321383

N-Trimethyl chitosan (TMC) was synthesized and used to prepare lactosyl-norcantharidin TMC nanoparticles (Lac-NCTD-TMC-Nps) using an ionic cross-linkage process. Lac-NCTD-TMC-Nps particles with an average particle size of 120.6 ± 1.7 nm were obtained, with an entrapment efficiency of 69.29% ± 0.76%, and drug-loading amount of 9.1% ± 0.07%. The release of Lac-NCTD-TMC-Nps in vitro was investigated through a dialysis method, and its sustained effect was evident. In the human liver cancer cell line HepG2, the half-maximum inhibiting concentration (IC(50)) of TMC-encapsulated Lac-NCTD (Lac-NCTD-TMC-Nps) was only 24.2% that of free Lac-NCTD at 24 h. Lac-NCTD induced HepG2 cell death by triggering apoptosis. In vitro cellular uptake and in vivo NIR fluorescence real-time imaging both indicated a high targeting efficacy. Compared with Lac-NCTD and Lac-NCTD chitosan nanoparticles ( Lac-NCTD-CS-Nps ), Lac-NCTD-TMC-Nps had the strongest antitumor activity on the murine hepatocarcinoma 22 subcutaneous model.

Chaetoglobosin Vb from Endophytic Chaetomium Globosum: Absolute Configuration of Chaetoglobosins

Chirality. May, 2012  |  Pubmed ID: 22593034

One new cytochalasan alkaloid, chaetoglobosin V(b) (1), together with two structurally related known compounds, chaetoglobosin V (2) and chaetoglobosin G (3), was isolated from the ethyl acetate extract of a culture of the endophytic fungus Chaetomium globosum, associated with the leaves of Ginkgo biloba tree. The structures of the isolated compounds were elucidated by spectroscopic methods including 1D and 2D NMR and mass spectrometry. The absolute configuration of chaetoglobosin V(b) (1) was established by means of electronic circular dichroism (CD) spectroscopy, on the basis of the comparison between the CD spectrum of (+)-1 with that calculated with time-dependent density functional theory method for a simplified model. The correlation between compounds 1-3 was demonstrated by a biomimetic transformation of chaetoglobosin G (3) under mild conditions in chaetoglobosins V and V(b) (1 and 2). The isolated metabolites were tested against some phytopathogens.

Measurements of Secondary Organic Aerosol Formed from OH-initiated Photo-oxidation of Isoprene Using On-line Photoionization Aerosol Mass Spectrometry

Environmental Science & Technology. Mar, 2012  |  Pubmed ID: 22397593

Isoprene is a significant source of atmospheric organic aerosol; however, the secondary organic aerosol (SOA) formation and involved chemical reaction pathways have remained to be elucidated. Recent works have shown that the photo-oxidation of isoprene leads to form SOA. In this study, the chemical composition of SOA from the OH-initiated photo-oxidation of isoprene, in the absence of seed aerosols, was investigated through the controlled laboratory chamber experiments. Thermal desorption/tunable vacuum-ultraviolet photoionization time-of-flight aerosol mass spectrometry (TD-VUV-TOF-PIAMS) was used in conjunction with the environmental chamber to study SOA formation. The mass spectra obtained at different photon energies and the photoionization efficiency (PIE) spectra of the SOA products can be obtained in real time. Aided by the ionization energies (IE) either from the ab initio calculations or the literatures, a number of SOA products were proposed. In addition to methacrolein, methyl vinyl ketone, and 3-methyl-furan, carbonyls, hydroxycarbonyls, nitrates, hydroxynitrates, and other oxygenated compounds in SOA formed in laboratory photo-oxiadation experiments were identified, some of them were investigated for the first time. Detailed chemical identification of SOA is crucial for understanding the photo-oxidation mechanisms of VOCs and the eventual formation of SOA. Possible reaction mechanisms will be discussed.

A Novel Lanreotide-encoded Micelle System Targets Paclitaxel to the Tumors with Overexpression of Somatostatin Receptors

Molecular Pharmaceutics. May, 2012  |  Pubmed ID: 22435704

Many tumor cells specifically overexpress somatostatin receptors, in particular, subtype 2 (SSTR2). Lanreotide, a somatostatin analogue with high affinity for SSTR2, can be exploited as a ligand for tumor targeted therapy. In this study, lanreotide was first conjugated to poly(ethylene glycol)-b-poly(ε-caprolactone) (PEG-b-PCL) copolymer, and the active targeting micelles with paclitaxel (lanreotide-PM-PTX) or fluorescent agent were constructed and characterized with various analytical methods. Lanreotide-PM-PTX micelles were spherical in shape with a hydrodynamic diameter of 43.2 ± 0.4 nm, high drug encapsulation (87.1 ± 2.8%) and slow drug release rate. Two cancer cell lines (human lung cancer H446 and human breast cancer MCF-7 cells) with different expression levels of SSTR2 were used in this study. As observed by flow cytometry, confocal microscopy and cytotoxicity studies, lanreotide-encoded PEG-b-PCL micelles demonstrated more specific cell uptake and cytotoxicity in SSTR2-positive tumor cells via a receptor-mediated mechanism over the passive targeting micelles. The active targeting micelles showed higher accumulation in tumor tissue and tumor cells in tumor-bearing mice in vivo by near-infrared fluorescence (NIRF) imaging, high-performance liquid chromatography and confocal microscopy, respectively. Furthermore, treatment with lanreotide-PM-PTX micelles resulted in stronger tumor inhibition, increased life span and enhanced tumor cell apoptosis in SSTR2-overexpressing tumor model in athymic nude mice. The in vivo efficacy test with both H446 and MCF-7 tumor models further demonstrated the involvement of receptor-mediated interaction. Finally, the active targeting micelles exhibited less body weight loss, lower hemolysis and lower myelosuppression, as compared with the control groups. In conclusion, lanreotide can serve as an effective homing peptide, and the lanreotide-modified PEG-b-PCL micelles hold considerable promise in the treatment of SSTR2-overexpressing solid tumors.

Preparation of Uniaxial Multichannel Silk Fibroin Scaffolds for Guiding Primary Neurons

Acta Biomaterialia. Jul, 2012  |  Pubmed ID: 22465574

Physical guidance cues have been exploited to stimulate neuron adhesion and neurite outgrowth. In the present study, three-dimensional (3-D) silk fibroin scaffolds with uniaxial multichannels (42-142μm in diameter) were prepared by a directional temperature field freezing technique, followed by lyophilization. By varying the initial silk fibroin concentration, the chemical potential and quantity of free water around cylindrical ice crystals could be controlled to control the cross-section morphology of the scaffold channels. Aligned ridges also formed on the inner surface of the multichannels in parallel to the direction of the channels. In vitro, primary hippocampal neurons were seeded in these 3-D silk fibroin scaffolds with uniaxial multichannels of ∼120μm in diameter. The morphology of the neurons was multipolar and alignment along the scaffold channels was observed. Cell-cell networks and cell-matrix interactions established by newly formed axons were observed after 7days in culture. These neurons expressed β-III-tubulin, nerve filament and microtubule-associated protein, while glial fibrillary acidic protein immunofluorescence was barely above background. The ridges on the inner surface of the channels played a critical role in the adhesion and extension of neurons by providing continuous contact guidance. These new 3-D silk scaffolds with uniaxial multichannels provided a favorable microenvironment for the development of hippocampal neurons by guiding axonal elongation and cell migration.

The Eradication of Breast Cancer and Cancer Stem Cells Using Octreotide Modified Paclitaxel Active Targeting Micelles and Salinomycin Passive Targeting Micelles

Biomaterials. Jan, 2012  |  Pubmed ID: 22019123

Tumor stem cells have emerged as the new targets for anti-cancer therapy, besides tumor cells themselves. To eradicate both breast cancer cells and breast cancer stem cells which can not be eliminated by the conventional chemotherapy, octreotide (Oct)-modified paclitaxel (PTX)-loaded PEG-b-PCL polymeric micelles (Oct-M-PTX) and salinomycin (SAL)-loaded PEG-b-PCL polymeric micelles (M-SAL) were developed and investigated in combination. In this study, Oct that targets somatostatin receptors (SSTR) overexpressed in tumors including breast cancer, was coupled to the PEG end of PEG-b-PCL, and all the micelles were prepared using thin film hydration method. Results showed that the particle size of all the micelles was approximately 25-30 nm, and the encapsulation efficiency was >90%. Quantitative and qualitative analysis demonstrated that Oct facilitates the uptake of micelles in SSTR overexpressed breast cancer MCF-7 cells while free Oct inhibited cellular uptake of Oct-modified micelles, revealing the mechanism of receptor-mediated endocytosis. Breast cancer stem cells (side population cells, SP cells) were sorted from MCF-7 cells and identified with the CD44+/CD24- phenotype. M-SAL was capable of decreasing the proportion of SP cells, and its suppression was more potent in SP cells than that in cancer cells. As compared to PTX-loaded micelles (M-PTX), the inhibition of Oct-M-PTX against MCF-7 cells was stronger while such effect significantly increased when applying Oct-M-PTX in combination with M-SAL. In the MCF-7 xenografts, the combination therapy with Oct-M-PTX plus M-SAL produced the strongest antitumor efficacy, in accord with the combination treatment in vitro. Compared with free SAL, M-SAL was found to be more effective in suppressing breast cancer stem cells in vivo. Thus, this combination therapy may provide a strategy to improve treatment of breast cancers for eradication of breast cancer cells together with breast cancer stem cells.