OBJECTIVETo observe preventive and therapeutic effects of Tanshinone IIA (T II A) on oxaliplatin induced peripheral neuropathy (OlPN) and to explore its effects on the expression of calcitonin gene related peptide (CGRP) and never growth factor (NGF).

METHODSTotally 36 phase II - III patients with malignant tumor of digestive tract undergoing chemotherapy program with oxaliplatin, were equally assigned to the T II A group (using THA at 80 mg/day 1 day before oxaliplatin chemotherapy for 3 successive days) and the control group (using chemotherapy program with oxaliplatin alone) by segmented randomization. After 4 cycles of chemotherapy, the incidence degree and incidence of OlPN were evaluated. Sensory nerve conduction velocity (SNCV) and motor nerve conduction velocity ( MNCV) were tested by EMG evoked potential device. Serum levels of CGRP and NGF were also detected in the two groups before and after chemotherapy. The correlation of serum levels of CGRP and NGF to OIPN was assessed using linear correlation analysis.

RESULTSAfter chemotherapy the OlPN incidence was 27.8% (5/18 cases) in the T II A group, obviously lower than that in the control group (55.6%, 10/18 cases; P < 0.05). Compared with before treatment in the same group, SNCV and MNCV of common peroneal nerve were slowed down, serum NGF levels decreased, and serum CGRP levels obviously increased in the two groups (all P < 0.05). Compared with the control group after treatment, SNCV and MNCV of common peroneal nerve were obviously accelerated, serum NGF levels increased, and serum CGRP levels obviously decreased in the THA group (all P < 0.05). Results of linear correlation analysis indicated serum NGF level was negatively correlated with peripheral neuropathy (PN), serum CGRP expression was positively correlated with neurotoxicity (P < 0.05).

CONCLUSIONT II A could reduce the incidence of OlPN, which might be associated with inhibiting the expression of CGRP and up-regulating NGF activities.

Calcitonin Gene-Related Peptide ; blood ; Diterpenes, Abietane ; therapeutic use ; Gastrointestinal Neoplasms ; drug therapy ; Humans ; Nerve Growth Factor ; blood ; Neural Conduction ; drug effects ; Organoplatinum Compounds ; adverse effects ; Peripheral Nervous System Diseases ; chemically induced ; drug therapy ; Up-Regulation

Aim To establish the pharmacokinetic-pharmacodynamic(PK-PD) modeling to characterize the antipyretic effects of coptisine, an active component in coptis chinensis on rats.Methods Nine healthy male Sprague-Dawley(SD) rats were randomly divided into three groups, each with three.The rats in the first group were injected intravenously with lipopolysaccharide(LPS,100 μg·kg-1) alone.The second and third group rats were given coptisine high-dose(3.87 mg·kg-1) and coptisine low-dose(1.93 mg·kg-1) by tail vein injection at 30 min after LPS injection, respectively.Body temperature was measured at different time points, and blood samples from tail vein were collected simultaneously.The blood concentration of coptisine was determined by ultra performance liquid chromatography.Monolix software was used to model PK-PD of coptisine mean plasma concentration and temperature effects,by population computation with non-covariates.Besides.the model with advantage was selected by the fitting goodness.Results Coptisine could inhibit body temperature of endotoxin-induced fever in rats significantly.Two-compartment linear elimination model was used to describe the final PK model.Gaussian function, an input function of body temperature changes, which was used to depict PD model, the PK and PD models were connected by the Emax model.At last, the final model was fitted better;the fitting results indicated that the EC50 of antipyretic effect of coptisine was 89.7 μg·L-1, and the Emax was 1.88℃.Conclusions Coptisine has a powerful anti-pyretic effect on endotoxin-induced pyrexia of rats with high potency, Low in vivo distribution and quick clearance.

AIM: To prepare Nano-Liposome encapsulated MAGE3/HSP70(NL M3H) and study its character and antitumor immunity in mouse. METHODS: NL M3H was prepared by the thin film-dispersion ultrasonic. The shape and size of NL M3H were detected by electron microscope. The encapsulation rate, drug-carrying capacity, stability and the releasing character were tested by Sephedex-G100 gel filtration. The mouse was immunized by NL M3H, and the antitumor immunity was detected by ELISPOT and LDH release assay. RESULTS: The mean size of NL M3H was lower than 100 nm. The encapsulation rate was 38％.The drug content was 0.038 g/L. NL M3H has good stability after stored in 4℃ for 6 months. The releasing profile showed that 74 percent of proteins was released during the first 24 hours in saline. The results of ELISPOT and LDH release assay showed that NL M3H generated tumor specific cytotoxic T lymphocyte(CTL)to damage tumor cel1. CONCLUSION: NL M3H has novel characters, it can generate specific CTL to kill tumor cell, and can be used as new kind of vaccine agsinst tumor.

Aortic Aneurysm, Abdominal ; epidemiology ; Disease Susceptibility ; Humans ; Risk Factors

OBJECTIVETo investigate the mechanism of senescence delay of human diploid fibroblast (2BS) and protecting telomere length by epimedium flavonoids (EF).

METHODSThe drug sera of EF were used to treat the 2BS. The population doublings of 2BS cells were observed, the mRNA expression of p16 gene were determined by fluorescence real-time quantitative RT-PCR, the telomerase activation of 2BS cells were determined by TRAP-Hyb, the total retinoblastoma (Rb) and phosphorated Rb protein content were detected by ELISA, the telomere length of 2BS cells were determined by telomere restriction fragment (TRF) Southern blot assay.

RESULTSEF could significantly extend the population doublings of 2BS cells, the expression of p16 mRNA was decreased and the content of phosphorated Rb protein were increased by EF. The telomere lengthening of 2BS cells were improved by EF, but the telomerase was not activated.

CONCLUSIONIn senescence human fibroblasts 2BS cells, p16 gene mRNA expression increased, content of phosphorated Rb protein decreased and the telomere length of 2BS shortened, EF might delay the aging of cells through inhibiting the p16 gene expression, promoting the production of phosphorated Rb protein and to protect the length of telomere, but not activating the telomerase.

Animals ; Cells, Cultured ; Cellular Senescence ; genetics ; Cyclin-Dependent Kinase Inhibitor p16 ; biosynthesis ; genetics ; Epimedium ; chemistry ; Fibroblasts ; cytology ; Flavonoids ; pharmacology ; Male ; RNA, Messenger ; biosynthesis ; genetics ; Rats ; Rats, Sprague-Dawley ; Retinoblastoma Protein ; metabolism ; Telomerase ; biosynthesis ; Telomere ; genetics ; metabolism ; Transduction, Genetic

BACKGROUND/AIMS: Kruppel-like factor 4 (KLF4) is an epithelial-specific transcription factor primarily expressed in the gastrointestinal tract that mediates growth arrest in the colonic epithelium. We tried to find whether KLF4 expression is associated with the progression and differentiation of colorectal cancer. METHODS: We detected KLF4 expression in 109 colorectal specimens (40 normal appearing mucosa, 7 adenomas, and 62 carcinomas) by immunohistochemistry using a tissue microarray. Western blot and RT-PCR analyses were also performed. RESULTS: The upregulation of KLF4 expression in carcinoma tissue was statistically significant (p<0.05) when compared to normal appearing mucosa. The negative and weak positive staining rates in normal appearing mucosa, adenoma, and carcinoma were 42.5%, 71.4%, and 82.3%, respectively, indicating a decreased degree of KLF4 expression over the course of progressive transformation of normal cells into malignant derivatives. KLF4 protein levels showed no correlation with sex, age, or metastatic state (p>0.05), while KLF4 protein expression correlated with the diagnostic stage (p<0.05). Furthermore, strong KLF4 staining was detected in 22.9% (11/48) and 0% (0/14) of well/moderately and poorly differentiated colorectal cancers, respectively. Our results clearly indicate that KLF4 protein expression significantly correlates with the degree of differentiation in colorectal cancers (p<0.05). KLF4 expression in RKO cells is also upregulated by butyrate, an inducer of differentiation. CONCLUSIONS: Downregulation of KLF4 expression may lead to more poorly differentiated tumors.
Adenoma ; Blotting, Western ; Butyrates ; Colon ; Colorectal Neoplasms ; Down-Regulation ; Epithelium ; Gastrointestinal Tract ; Immunohistochemistry ; Kruppel-Like Transcription Factors ; Mucous Membrane ; Transcription Factors ; Up-Regulation

OBJECTIVETo study changes in the radiographic appearance during weight-bearing and non-weigh-bearing in hallux valgus, and to analyse the correlation between the elasticity of plantar soft tissue of hallux valgus and the pain under the metatarsal head.

METHODSFrom May 2012 to October 2012, 240 feet of 120 patients with hallux valgus were enrolled in the study. The degrees of the pian under the metatarsal head of all the patients were observed. AP and lateral X-ray films of feet were taken on the condition of weight-bearing and non-weight-bearing. So the hallux valgus angle (HVA), the inter-metatarsal angle between the first and second metatarsals (IM1-2), the inter-metatarsal angle between the first and fifth metatarsals (IM1-5), top angle of the medial longitudinal arch (TAOTMLA),and anterior angle of the medial longitudinal arch (AAOTMLA) were measured on the X-ray films. The differences of HVA, IM1-2, IM1-5, TAOTMLA and AAOTMLA between two groups were compared, and the correlation between the changes of IM1-2, IM 1-5, TAOTMLA, AAOTMLA and the degree of the pain under the metatarsal head were analysed.

RESULTSOne hundred and forty-eight feet had the pain under the metatarsal head. The IM1-2, IM1-5 and TAOTMLA increased on weight-bearing position compared with those on non-weight-bearing position, but the HVA and AAOTMLA decreased on weight-bearing position compared with those on non-weight-bearing position. There was a moderate relationship between the changes of IM 1-2,IM1-5 and the degree of the hallux valgus deformity, as well as the relationship between the different of IM1-5 and the degree of the pian under the metatarsal head.

CONCLUSIONThe degree of the collapse of the arch of foot with hallux valgus becomes serious with its deformity increasing. The pain under the metatarsal head of hallux valgus increases with the increased changes of IM 1-2,IM 1-5 and TAOTMLA. Analysis of the X-ray observation indexes of hallux valgus on weight-bearing position and non-weight-bearing position has important significance in evaluating the degree of the collapse of the arch of foot with hallux valgus,preventing and curing the the pain under the metatarsal head.

Adult ; Aged ; Female ; Hallux ; anatomy & histology ; diagnostic imaging ; physiopathology ; Hallux Valgus ; complications ; diagnostic imaging ; physiopathology ; Humans ; Metatarsalgia ; complications ; diagnostic imaging ; physiopathology ; Middle Aged ; Radiography ; Weight-Bearing ; Young Adult

Chuangxinmycin (CM) from Actinoplanes tsinanensis was an antibiotic discovered by Chinese scientists about 40 years ago. It contains a new heterocyclic system of indole fused with dihydrothiopyran, whose biosynthetic mechanism remains unclear. CM is used as an oral medicine in the treatment of bacterial infections in China. The simple structure makes CM as an attractive candidate of structure modification for improvement of antibacterial activity. Recently, we analyzed the secondary metabolites of Actinoplanes tsinanensis CPCC 200056, a CM producing strain, as a natural CM analogue. We discovered the first natural CM analogue 3-demethylchuangxinmycin (DCM) as a new natural product. Compared to CM, DCM exhibited a much weaker activity in the inhibition of the bacterial strains tested. The finding provides valuable information for the structure-activity relationship in the biosynthesis of CM.

Objective To explore the safety of collection of peripheral blood stem cells(PBSCs) from low-weight infants with osteopetrosis(OP) and its clinical significance. Methods One case of low-weight infants with OP received PBSCs collection using a continuous-flow blood cell separator,and the safety of collection process was observed.The amount of monocyte cell(MNC) and CD34+ cell were noted and its clinical significance was analyzed.Results Low-weight infants with OP could tolerate collection process,the number of collection MNC and CD34+ cells were 10.06?108/kg,2.74?106/kg.Conclusion Adequate PBSCs can be collected from OP who need not be mobilized,thus can offer backup for graft failure.PBSCs collection from low-weight infants is safe.

Objective To synthesize 18 F-DPA-714 and to study its labeling rate, radiochemical purity, stability and biological characteristics. Methods 18F-was reacted with K2CO3/K2.2.2 and then en-gaged in nucleophilic substitution with DPA-714. The crude product was purified by aluminum column and semi-preparation HPLC. The stability of 18 F-DPA-714 was identified in PBS and plasma. The lipid-water partition coefficient (LogP) was determined. Biodistribution analysis and microPET imaging were performed on mice and rats respectively. Results It took about 25 min for synthesizing 18 F-DPA-714, the radiochemi-cal yield was 31.6% (decay not corrected), and the radiochemical purity was ≥99%. The product re-mained stable within 4 h. The LogP of 18 F-DPA-714 was 2.71. Pharmacokinetics of 18 F-DPA-714 was more in line with the two compartment model, with the distribution half-life ( T1/2α) of 2.40 min and the elimina-tion half-life( T1/2β) of 69.15 min. 18 F-DPA-714 was quickly uptaken by tissues after the tail vein injection. It mainly distributed in the lungs, kidneys, and heart, with the radioactive uptake values of (17.85±7.52)%ID/g, (15.41±1.80) %ID/g and (10.56±0.94) %ID/g at 30 min post-injection, respectively. 18F-DPA-714 was mainly metabolized through the liver, and excreted by the kidneys. The uptake in bones was stable. PET dynamic scanning showed that 18 F-DPA-714 accumulated in the brain of aged rats and cleared slowly within 60 min. Conclusions 18 F-DPA-714 prepared in this study has high labeling rate, short synthesis time and small precursor dosage. It displays good biological distribution and blood-brain barrier permeability characteristics.