Diagnosis, Differential ; Humans ; Immunohistochemistry ; Keratins ; analysis ; Male ; Prostatic Hyperplasia ; diagnosis ; Prostatic Intraepithelial Neoplasia ; diagnosis ; Prostatic Neoplasms ; diagnosis ; Racemases and Epimerases ; analysis ; Staining and Labeling ; methods

Ceramics ; Ergonomics ; Female ; Humans ; Male ; Occupational Exposure ; Workload

Animals ; Arginine Vasopressin ; metabolism ; Female ; Hippocampus ; drug effects ; metabolism ; Lead ; toxicity ; Learning ; drug effects ; Memory ; drug effects ; Pregnancy ; Prenatal Exposure Delayed Effects ; Rats ; Rats, Sprague-Dawley

Adult ; Female ; Granulomatosis with Polyangiitis ; complications ; Humans ; Nasal Obstruction ; etiology

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

OBJECTIVETo explore the pattern of abnormal skeletal development in girls with idiopathic precocious puberty (IPP) and the therapeutic effect of Chinese herbs for nourishing yin and purging fire (CH).

METHODSMeasurement of bone age, bone mineral content (BMC) and bone density (BD) were performed and levels of serum gla-protein (BGP), insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein 3 (IGFBP3) were determined in girls with IPP at various stages of pubertal development. Data were compared with those collected from matched girls, and the correlativity between various parameters and the extent of the disease were analyzed to explore the pattern. Thirty-eight girls out of them were treated with CH and the therapeutic effect was observed.

RESULTSThe bone age of the IPP girls was ahead of time obviously (P < 0.05), levels of BMC, BD and serum BGP, IGF-1 were significantly higher than the levels in the healthy girls of matched age (P < 0.05). And the degree of these changes were markedly positive correlated with the severity of disease (P < 0.05). After being remitted with CH treatment, the advanced bone age was apparently alleviated, and above-mentioned abnormal criteria were lowered significantly (P < 0.05).

CONCLUSIONThe skeletal development of the girls with IPP was accelerated and the skeletal maturity were ahead of time, the more serious the condition of disease, the more obvious the acceleration and the advanced bone age. CH could decelerate skeletal development and delay the skeletal maturity of IPP patients.

Age Determination by Skeleton ; Bone Development ; Child ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Insulin-Like Growth Factor I ; metabolism ; Osteocalcin ; blood ; Phytotherapy ; Puberty, Precocious ; blood ; drug therapy

Objective To investigate the effect of swimming exercise on insulin sensitivity and interleukin-1 beta(IL-1β)mRNA expression in muscle tissue of insulin-resistant (IR) rats induced by high-fat diet.Methods The IR rat model was induced by high-fat diet feeding for 10 weeks and assessed by hyperinsulinemic-euglycemic clamp technique (HEC). The rats were divided into the fllowing three groups: normal group without exercise, IR groups with and without swimming exercise. After 4 weeks swimming excersie, insulin sensitivity and serum IL-1β levels were measured.Results Glucose infusion rate (GIR) of the IR rats was significantly elevated than that of non-exercise IR rats (P<0.01). Moreover, serum IL-1β levels were reduced markedly in IR rats (P<0.01). Conclusion High-fat diet feeding can partly reverse IR of rats to normal value. Swimming exercise improves insulin sensitivity and reduces the levels of IL-1β in IR rats induced by high-fat diet.

Epiberberine, one of the most important isoquinoline alkaloid in Coptidis Rhizoma, possesses extensive pharmacological activities. In this paper, the liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to study phase I and phase II metabolites. A Thermo HPLC system (including Surveyor AS, Surveyor LC Pump, Surveyor PDA. USA) was used. The cocktail probe drugs method was imposed to determine the content change of metoprolol, dapsone, phenacetin, chlorzoxazone and tolbutamide simultaneously for evaluating the activity of CYP2D6, CYP3A4, CYP1A2, CYP2E1 and CYP2C9 under different concentrations of epiberberine in rat liver microsomes. The result showed that epiberberine may have phase I and phase II metabolism in the rat liver and two metabolites in phase I and three metabolites in phase II are identified in the temperature incubation system of in vitro liver microsomes. Epiberberine showed significant inhibition on CYP2D6 with IC50 value of 35.22 μmol L(-1), but had no obvious inhibiting effect on the activities of CYP3A4, CYP1A2, CYP2E1 and CYP2C9. The results indicated that epiberberine may be caused drug interactions based on CYP2D6 enzyme. This study aims to provide a reliable experimental basis for its further research and development of epiberberine.
Animals ; Berberine ; analogs & derivatives ; chemistry ; metabolism ; Chromatography, High Pressure Liquid ; Cytochrome P-450 CYP2D6 ; metabolism ; Cytochrome P-450 CYP2D6 Inhibitors ; chemistry ; metabolism ; Drugs, Chinese Herbal ; chemistry ; metabolism ; Male ; Microsomes, Liver ; drug effects ; enzymology ; metabolism ; Molecular Structure ; Rats ; Rats, Sprague-Dawley ; Tandem Mass Spectrometry

To figure out the stability and intestinal bacteria metabolites of rats in vitro of astragaloside IV ( AST), this research was done to explore the stability of AST in the artificial gastric juice. artificial intestinal juice and rat liver homogenate and the metabolism in rat intestinal in vitro. HPLC was used to calculate the remaining rate of AST in biological samples by measuring the content of AST, while metabolites were determined by combining the methods of TLC, HPLC and LC-MS/MS. It turned out that AST was difficult to metabolize in the artificial gastric juice, artificial intestinal juice and rat liver. Also, the metabolic pathway of AST was stepped by deglycosylation. Firstly, AST was converted to its secondary etabolites (6-O-β-D-glucopyranosyl- cycloastragenol, CMG) by removal of xylose moiety at C-3, then transformed into cycloastragenol (CAG) after hydrolytic removal of the glucose moiety at C-6. All the results suggested that the metabolism of AST in vivo occurs mainly in the intestinal by hydrolysis of glycosyl. In conclusion, hydrolysis of intestinal flora is the main reason that AST metabolizes.
Animals ; Bacteria ; metabolism ; Chromatography, High Pressure Liquid ; Drug Stability ; Intestines ; microbiology ; Liver ; metabolism ; Rats ; Rats, Sprague-Dawley ; Saponins ; chemistry ; metabolism ; Tandem Mass Spectrometry ; Triterpenes ; chemistry ; metabolism

Transcriptions are regulated by transcription factors. Natural transcription factors usually consist of at least two functional domains: a DNA-binding domain and an effector domain. According to this, novel artificial transcription factors are designed to up or down regulate transcription and expression of a target gene. The Cys2-His2 zinc finger domain is a DNA-binding module that has been widely used as the DNA-binding domain in artificial transcription factors. Each zinc finger domain, which comprises about 30 amino acids that adopt a compact structure by chelating a zinc ion, typically functions by binding 3 base pairs of DNA sequence. Several zinc fingers linked together would bind proportionally longer DNA sequences. According to the "bipartite complementary" library strategy, a pair of zinc finger phage display libraries were constructed. After construction of the libraries, a 9bp sequence (5'-GCAGAGGCC-3') on the promoter of SV40 was chosen as a target for next step. After parallel selection, PCR amplification, desired fragments recovery, re-ligation, and additional rounds of selection, phage enzyme-linked ELISA experiments were performed to identify specific binding clones displaying the zinc fingers with predetermined sequence-specificity to our target sequence. Then two clones with strong ELISA signals were chosen to be tested for binding both to its full target site (5'-GCAGAGGCC-3') and to sites containing single transition mutations. The binding specificity of one of the two clones (clone 3) was shown to be fairly good. The three-finger DNA-binding domain targeted to SV40 promoter, that is, zinc finger sequences on clone 3, was fused to KOX1 suppression domain KRAB and cloned into pcDNA3.1 (+) (which expression product was artificial transcription factor). The zinc fingers (which expression product was the DNA-binding domain of artificial transcription factor) and KRAB domain only (which expression product was effector domain of artificial transcription factor) were also cloned separately into the same expression vector. All constructs contained an N-terminal nuclear localization signal. Every of the vectors (including pcDNA3.1 (+) without inserting sequences) were cotransfected with pGL3-Control and pRL-TK and the activity of luciferase was used to indicate the function of product from transfected expression vectors. Our artificial transcription factor was proved to repress the expression of reporter gene efficiently,while with only DNA-binding domain or effector domain the repression was not remarkable. By adding different effector domains and changing the DNA-binding domain, artificial transcription factor would have a wide range of potential applications.
Enzyme-Linked Immunosorbent Assay ; Genes, Synthetic ; genetics ; physiology ; Models, Theoretical ; Peptide Library ; Polymerase Chain Reaction ; Promoter Regions, Genetic ; genetics ; Transcription Factors ; chemical synthesis ; chemistry ; metabolism ; Zinc Fingers ; genetics ; physiology