Ataxia Telangiectasia Mutated Proteins ; Breast ; metabolism ; pathology ; Breast Neoplasms ; metabolism ; pathology ; Carcinoma, Ductal, Breast ; metabolism ; pathology ; Carcinoma, Intraductal, Noninfiltrating ; metabolism ; pathology ; Cell Cycle Proteins ; metabolism ; Checkpoint Kinase 2 ; DNA-Binding Proteins ; metabolism ; Female ; Humans ; Lymphatic Metastasis ; Neoplasm Grading ; Protein-Serine-Threonine Kinases ; metabolism ; Tumor Burden ; Tumor Suppressor Protein p53 ; metabolism ; Tumor Suppressor Proteins ; metabolism

To develop a cell-penetrating chimeric apoptotic peptide AVPI-LMWP/DNA co-delivery system for cancer therapy, we prepared the AVPI-LMWP/pTRAIL self-assembled complexes containing a therapeutic combination of peptide drug AVPI and DNA drug TRAIL. The chimeric apoptotic peptide AVPI-LMWP was synthesized using the standard solid-phase synthesis. The cationic AVPI-LMWP could condense pTRAIL by electrostatic interaction. The physical-chemical properties of the AVPI-LMWP/pTRAIL complexes were characterized. The cellular uptake efficiency and the inhibitory activity of the AVPI-LMWP/pTRAIL complexes on tumor cell were also performed. The results showed that the AVPI-LMWP/pTRAIL complexes were successfully prepared by co-incubation. With the increase of mass ratio (AVPI-LMWP/DNA), the particle size was decreased and the zeta potential had few change. Agarose gel electrophoresis showed that AVPI-LMWP could fully bind and condense pTRAIL at a mass ratio above 15:1. Cellular uptake efficiency was improved along with the increased ratio of W(AVPI-LMWP)/WpTRAIL. The in vitro cytotoxicity experiments demonstrated that the AVPI-LMWP/pTRAIL (W:W = 20:1) complexes was significantly more effective than the pTRAIL, AVPI-LMWP alone or LMWP/pTRAIL complexes on inhibition of HeLa cell growth. Our studies indicated that the AVPI-LMWP/pTRAIL co-delivery system could deliver plasmid into HeLa cell and induce tumor cell apoptosis efficiently, which showed its potential in cancer therapy using combination of apoptoic peptide and gene drugs.
Antineoplastic Agents ; chemistry ; Cell-Penetrating Peptides ; chemistry ; DNA ; chemistry ; Drug Delivery Systems ; HeLa Cells ; Humans ; Neoplasms ; drug therapy ; Particle Size ; Plasmids

BACKGROUNDGlaucoma is one of the leading causes of blindness in the world. Primary open-angle glaucoma (POAG) and primary congenital glaucoma (PCG) are subtypes of glaucoma. Myocillin is the first gene identified to be involved in POAG. Recently, myocillin mutation has been found in PCG. In this context, we reported a special glaucoma pedigree, which was composed of both PCG and POAG patients, and analyzed the mutation of myocillin in this pedigree.

METHODSThe family was composed of the parents, a son and a daughter. All members of the family underwent the complete ophthalmologic examinations. All coding exons 1 - 3 and flanking introns of myocilin gene were screened for sequence alterations by polymerase chain reaction and direct DNA sequencing.

RESULTSThe son was the proband, who was diagnosed as PCG in both eyes. The father was diagnosed as POAG in the right eye, the left eye was still normal. Both the sister and the mother of the proband had normal intraocular pressure without glaucomatous optic disc changes. The mutations in intron 2 of myocilin gene were detected in the family. While the proband and the father were homozygous, the mother and the sister were heterozygous for the mutation.

CONCLUSIONSHomozygous mutation in intron 2 of myocilin gene is involved in both POAG and PCG. It is suggested that the pathogenesis might be overlapping in POAG and PCG.

Cytoskeletal Proteins ; genetics ; Eye Proteins ; genetics ; Female ; Glaucoma ; congenital ; genetics ; Glaucoma, Open-Angle ; genetics ; Glycoproteins ; genetics ; Humans ; Introns ; Male ; Mutation ; Pedigree

OBJECTIVETo explore the correlations of circulating tumor cells (CTCs) and disseminated tumor cells (DTCs) with the clinicopathological characteristics, prognostic events, and survival outcomes in esophageal cancer (EC) patients.

METHODSThe PubMed, Web of Science, Embase database and Cochrane database were searched for studies reporting the outcomes of interest. The studies were selected according to established inclusion/exclusion criteria. Meta-analysis of the studies was performed using Review Manager 5.3 and Stata12.0 software with the odds ratio (OR), risk ratio (RR) , hazard ratio (HR) , and 95% confidence interval (95% CI) as the effect indexes.

RESULTSNineteen studies involving a total of 1766 patients were included in the analysis. Significant correlations of CTCs and DTCs were found with the clinicopathological parameters including the tumor stage (OR=1.95), depth of invasion (OR=1.99), lymph node metastasis (OR=2.44), distal metastasis (OR=5.98), histological differentiation (OR=1.67) and lymphovascular invasion (OR=4.48). CTCs and DTCs were also correlated with the prognostic events including relapse (RR=6.86) and metastasis (RR=3.22) and with the survival outcomes including the overall survival (OS) overall analysis (HR=3.46) and disease-free survival/progression-free survival (DFS/PFS) overall analysis (HR=3.00).

CONCLUSIONCTCs and DTCs are significantly associated with an advanced tumor stage, depth of tumor invasion, lymph node metastasis, distant metastasis before therapy, differentiation, lymphovascular invasion, relapse and metastasis in patients with EC. They are also significantly correlated with a poorer survival for OS and DFS/PFS to serve as clinical and prognostic predictors in patients with EC.

Disease-Free Survival ; Esophageal Neoplasms ; diagnosis ; Humans ; Lymphatic Metastasis ; Neoplasm Recurrence, Local ; Neoplastic Cells, Circulating ; Odds Ratio ; Prognosis ; Proportional Hazards Models ; Survival Analysis

OBJECTIVETo make an attempt at the multi-element speciation in the Chinese medicinal herbs by determining the concentrations of 25 elements in different extraction solutions.

METHODFirstly, five Chinese medicinal herbs (Buddleja officinalis, Dictamnus dasycarpus, Myristica fragrans, Albizia judibrissin and Inula japonica) from the same region of China were treated to obtain water-soluble phase, lipid-soluble phase and non-soluble phase by water extraction, organic solvent extraction and acid digestion, respectively. Secondly, Phytolacca acinosa, a Chinese medicinal herb collected from 9 regions of China, was extracted by 0% EtOH, 50% EtOH, 75% EtOH, 95% EtOH, respectively, referring the Chinese Pharmacopoeia. Finally, the concentrations of 25 elements, such as Be, Cr, Cu, Zn, Ge, Sr, Y, Mo, Cd, Tl, Pb and REEs, in the above three phases were determined by ICP-MS.

RESULTUnder the optimal conditions, all the 25 elements could be determined with detection limits ranged from 0.003 to 0.71 ng x g(-1). The average recoveries of the elements in P. acinosa were 88% approximately 119%, with the relative standard deviations 1.7% approximately 13.3%. It was observed that the determined 25 elements distributed in all the water-soluble, lipid-soluble and non-soluble phases, indicating that the inorganic species, organicspecies, as well as the protein bound species were coexisted in the herbs. Big differences of the element extraction rates could be found by using different ethanol solutions.

CONCLUSIONWith the aid of the obtained results, we may increase the extraction of necessary elements while decrease that of the toxic elements from the herbs by choosing a suitable solvent during the drug production.

Buddleja ; chemistry ; Cadmium ; analysis ; Copper ; analysis ; Dictamnus ; chemistry ; Drugs, Chinese Herbal ; chemistry ; isolation & purification ; Ecosystem ; Lead ; analysis ; Metals, Heavy ; analysis ; Molybdenum ; analysis ; Myristica fragrans ; chemistry ; Phytolacca ; chemistry ; Plants, Medicinal ; chemistry ; Solvents ; chemistry ; Trace Elements ; analysis ; Zinc ; analysis

Cells, Cultured ; Claudin-1 ; Dexamethasone ; pharmacology ; Electric Impedance ; Gene Expression Regulation ; drug effects ; Glaucoma ; chemically induced ; Humans ; Membrane Proteins ; genetics ; Trabecular Meshwork ; cytology ; drug effects ; metabolism

BACKGROUNDMany researchers studied the possibility of using stem cells as gene therapeutic vector. But few related reports on the adipose tissue-derived stem cells (ADSCs) are available. Therefore we intended to construct a lentiviral VEGF(165) expression vector and then infect the ADSCs to produce therapeutic seed cells.

METHODSEHS1001-68950485313912 clone was mutated by PCR method to produce consensus fragment of VEGF(165) transcript (NM_001025368). Lentivirus was enveloped with pGC-FU, pHelper 1.0 and pHelper 2.0 plasmids in 293T cells. And then the ADSCs (multiplicity of infection = 20) were transfected with the vectors after titer determination. Stable expression of VEGF(165) in ADSCs was confirmed by immunofluorescence staining, enzyme-linked immunosorbent assay (ELISA) and Western blotting analysis.

RESULTSDNA sequencing and 293T transfection verified VEGF(165) was linked to the GFP fused vector. The virus titer is up to 2 × 10(8) determined by quantitative PCR. VEGF(165) transduced cells could show green fluorescence confirmed by immunofluorescence staining (almost 95%). ELISA analyses could detect out the density of VEGF was 850.86 - 1202.13 pg/ml (mean (923.00 ± 31.22) pg/ml) in the supernatant of VEGF(165)-transduced cells but not detected in the GFP-transduced cells (P < 0.001) and the Western blotting analyses also confirmed VEGF(165) expression in VEGF(165)-transduced cells.

CONCLUSIONSThe VEGF(165) over-expression ADSCs were obtained and may be used as a cell therapeutic tool and may be applied for vascular regeneration, especially in the treatment of erectile dysfunction.

Adipose Tissue ; cytology ; Animals ; Enzyme-Linked Immunosorbent Assay ; Genetic Vectors ; Lentivirus ; genetics ; Rats ; Stem Cells ; chemistry ; Vascular Endothelial Growth Factor A ; analysis

Objective To investigate the relationship between children's body mass index (BMI)at 5 to 6 years old and glucose concentrations of mothers without pre-existing diabetes or a gestational diabetes mellitus(GDM) diagnosis during pregnancy.Methods A prospective observational study was performed in offspring whose mother had no pre-existing diabetes or a GDM diagnosis during pregnancy in the First Affiliated Hospital of Kunming Medical Uni versity from Jan.2006 to Dec.2007.The data of maternal glucose concentrations of oral glucose tolerance test(OGTT)were acquired through referring to clinical records.Weight and height at 5 to 6 years old were measured and used to calculate BMI.Multivariable linear regression models were used to examine the association between children's BMI and maternal glucose concentrations.The influence of maternal glucose concentrations on the risk of overweight of offspring was analyzed by Logistic regression.Results There were 860 cases of children were followed-up,including 459 male cases and 401 female cases.The average BMI of children was(15.6 ± 2.7) kg/m2.There were 78 cases of overweight (9.06％) and 50 cases of obesity(5.81％).The mean maternal fasting glucose level of the OGTT was (3.8 ± 0.6) mmol/L and 2 h glucose level of the OGTT was (6.0 ± 0.9) mmol/L.After adjusting for progestation BMI,maternal weight gain during pregnancy,sex,birth weight,age and paternal weight,at the 5 to 6 years old,BMI of offspring of mothers whose fasting glucose level of the OGTT≥5.51 mmol/L were significantly higher than those of mothers whose average blood glucose level ＜5.51 mmol/L(β =0.45,95％ CI:0.15-0.80).Maternal fasting glucose level of the OGTT≥5.51 mmoL/L was associated with an greater risk of children's overweight(OR =2.32,95％ CI:1.30-3.96).Conclusions Even though the mother was in the absence of pre-existing diabetes or GDM during pregnancy,fetal exposure to high maternal glucose concentration may also promote the development of overweight in the offspring at 5 to 6 years old.

Aim To explore the effect of cuminaldehyde in cumin fruit on gastric ulcer and the protective mechanism via establishing the gastric ulcer model of rats was by ethanol injury. Methods Thirty-six male R. norregicus were divided into six groups: control group, model group, omeprazole positive control group and cuminaldehyde low, medium and high dosage groups. After seven days of continuous intragastric administration, the acute gastric ulcer of R. norregicus was tested by absolute alcohol. Gastric ulcer area, inhibition rate, gastric tissue antioxidant activity, serum inflammatory factors and gastric mucosal protective factors were detected in different groups. Results The results showed that cuminaldehyde significantly reduced the area of gastric ulcer and increased the inhibition rate of gastric ulcer. The inhibition rate of cuminaldehyde at high dose group was up to 74.65%, the activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH) in gastric tissue significantly increased, and the contents of serum prolandin E

OBJECTIVETo evaluate the chromium (Cr) levels in blood and urine among general population in China between 2009 and 2010, and thereby to analyze its prevalent features.

METHODSFrom year 2009 to 2010, a total of 11 983 subjects of general population aged between 6 and 60 year-old were recruited from 24 districts in 8 provinces in eastern, central and western China mainland, by cluster random sampling method. The information about their living environment and health status were collected by questionnaire, and 11 983 blood samples and 11 853 urine samples were also collected. Inductively coupled plasma mass spectrometry (ICP-MS) was applied to test the Cr level both in blood and urine; and the Cr distribution in blood and urine among groups of population in different ages, genders and districts, were then analyzed.

RESULTSAmong general population in China, the geometric mean (GM) of Cr concentration in blood was 1.19 µg/L, with median at 1.74 µg /L and 95% percentile at 5.59 µg/L. The Cr concentration in blood among males and females were separately 1.18 µg/L and 1.20 µg/L(P > 0.05); while its GM in the groups of population aged 6 - 12, 12 - 16, 16 - 20, 20 - 30, 30 - 45 and 45 - 60 years old were 1.00, 1.22, 1.01, 1.40, 1.27 and 1.30 µg/L (P < 0.01), respectively; and the figures in populations from eastern, central and western China were 1.00, 1.70 and 1.98 µg/L (P < 0.01), respectively. Among general population, the GM of Cr concentration in urine was 0.53 µg/L, with median was lower than 0.42 µg/L and 95% percentile at 3.53 µg/L. The Cr concentration in urine among males and females were separately 0.52 µg/L and 0.53 µg/L (P > 0.05);while its GM in the groups of population aged 6 - 12, 12 - 16, 16 - 20, 20 - 30, 30 - 45 and 45 - 60 years old were 0.56, 0.60, 0.52, 0.50, 0.52 and 0.46 µg/L (P < 0.01), respectively;and the figures in populations from eastern, central and western China were 0.58, < 0.42 and 0.60 µg/L (P < 0.01), respectively.

CONCLUSIONThe study reported the Cr levels in blood and urine among general population in China, and thereby provided basic data evidence for the following Cr biological monitoring studies in near future.

Adolescent ; Adult ; Child ; China ; Chromium ; blood ; urine ; Female ; Humans ; Male ; Middle Aged ; Population Surveillance ; Young Adult