In this study, we examined the effects of aspirin on the growth rates, subcellar distribution of beta-catenin protein, the expression of beta-catenin/TCF signaling pathway target gene cyclinD1 mRNA, and cell cycle of Jurkat cell line (Human T-acute lymphoblastic leukemia). Our results showed that the treatment with aspirin inhibited the growth of Jurkat cell line. Jurkat cells treated with 3 mmol/L of aspirin could significantly decrease nuclear localization of beta-catenin, and at 5 mmol/L of aspirin, the nuclear localization of beta-catenin was undetectable. QRT-PCR showed that the target gene cyclinD1 mRNA expression was gradually decreased with the dosage of aspirin. Aspirin induced G0/G1 cell cycle arrest in Jurkat cells. We are led to conclude that aspirin acts through beta-catenin-independent mechanisms. The effects of aspirin include down-regulation of beta-catenin nuclear localization and G0/G1 cell cycle arrest, which might serve as a means of growth inhibition in aspirin-treated human Jurkat cell line.

Dental Implants, Single-Tooth ; Dental Prosthesis, Implant-Supported ; Esthetics ; Humans ; Maxilla

Purpose To explore the expression of Toll-like receptor 4 (TLR4), PI3K, AKT and NF-κB in cervical lesions, and to in-vestigate their association with human papillomavirus ( HPV) 16 infection. Methods Immunohistochemical SP staining was performed to detect the expression of TLR4, PI3K, AKT, NF-κB in paraffin-embedded cervical tissue specimens from Uighur women with chroni-cal cervicitis, cervical intraepithelial neoplasia ( CIN) and cervical squamous cell carcinoma ( CSCC) . The HPV 16 DNA was detected by PCR. Results The positive expression rates of TLR4, PI3K, AKT, NF-κB in chronical cervicitis, CIN and cervical cancer were 32. 0%, 59. 4%, 77. 8%, 28. 0%, 56. 3%, 73. 0%, 24. 0%, 56. 3%, 79. 4%, and 8. 0%, 48. 4%, 81. 0%, respectively. The expression of them was higher in cervicitis than in CIN and cevical cancer ( P<0. 05 ) . The positive expression rates of HPV 16 in three groups were 8. 0%, 48. 4% and 81. 0% (P<0. 05). The expression of TLR4, PI3K, NF-κB and HPV 16 was related to cervi-cal cancer differentiation (P<0. 05). PI3K and AKT were significantly correlated with FIGOs’ stages (P<0. 05). NF-κB was corre-lated with lymph node metastasis. The expression of TLR4 was significantly associated with HPV 16 infection in CIN and CSCC ( r=0. 303, P=0. 015, r=0. 633, P=0. 000), and correlation with PI3K in CIN and CSCC (r=0. 254, P=0. 045, r=0. 386, P=0. 003). PI3K was associated with AKT only in CSCC (r=0. 298, P=0. 018). Conclusions The expression of TLR4 can be up-regulated by HPV 16 infection. High expression of PI3K/AKT signal pathway mediated by TLR4 may play important roles in the devel-opment and progression of CIN and CSCC, and HPV 16 infection may be a trigger factor affecting the molecular signal pathway.

OBJECTIVETo observe the clinical efficacy of Tongfu Mixture (TM) for post-ERCP pancreatitis (PEP).

METHODSTotally 54 PEP patients were randomly assigned to the control group (treated by routine therapy, 26 cases) and the TM treatment group (treated by TM, 28 cases). Clinical indices including the alleviation time of abdominal pain/distention, gastrointestinal function recovery time, and the post-surgical length of stay were observed. Blood amylase (AMY), C-reactive protein (CRP), plasma endotoxin (PLS), TNF-alpha, and IL-6 were detected before surgery, 12 h, 48 h, and 96 h after surgery.

RESULTSThe alleviation time of abdominal pain/distention, the gastrointestinal function recovery time, and the post-surgical length of stay were obviously shorter in the TM treatment group than those in the control group (P < 0.05). The recovery of AMY and CRP were better in the TM treatment group than in the control group at post-operative 48 h and 96 h (P < 0.05). The levels of LPS, TNF-alpha, and IL-6 were lower in the TM group than in the control group at post-operative 96 h (P < 0.05).

CONCLUSIONTM showed better clinical efficacy and could significantly decrease the post-surgical length of stay. post-ERCP pancreatitis; integrative medicine; Tongfu Mixture

Adult ; Cholangiopancreatography, Endoscopic Retrograde ; adverse effects ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Male ; Middle Aged ; Pancreatitis ; drug therapy ; etiology ; Phytotherapy

Objective To analyze the metabolic profile in serum between normal and orthotopic xenograft nude mice burdened with three human pancreatic cancer cell lines,which were differentiated differently.Methods Human pancreatic cancer lines SW1990,BxPC-3 and Panc-1 were subcutaneously injected into the nude mice,respectively.When the tumor volume reached 1.0 cm3,the nude mice were euthanized and the tumor tissues were removed and implanted to the pancreas to establish the orthotopic xenograft mice model.The serum from three orthotopic xenograft tumor nude mice and the normal controls were collected and then analyzed by 1H nuclear magnetic resonance spectroscopy.Results The three orthotopic xenograft nude mice models were successfully established.In SW1990,BxPC-3 and Panc-1 group,the orthotopic xenograft tumor formation rate was 79％ (11/14),93％ (13/14) and 86％ (12/14),while the mortality was 7％ (1/14),0 and 7％ (1/14),respectively.Compared with control group,the content of metabolites in the serum of orthotopic xenograft tumor nude mice was increased including creatine,alanine,glutamine,1-methylhistidine,isoleucine,lactate,phenylalanine,tryptophan and valine,but the glycerolphosphocholine (GPC) and glucose levels were reduced.As the tumors progressed to be more malignant,the content of valine and isoleucine tended to increase.Conclusions The establishment of the orthotopic implantation tumor nude mice model was stable and reliable with high tumor formation rate.Obvious metabolic differences of glucose,lipid and amino acids were observed between normal and human pancreatic cancer tumor burdening nude mice models.The common metabolic features identified in all three nude mice models burdened with human pancreatic cancer could be used as the potential markers for diagnosing human pancreatic cancer.

Relatively uniform-sized nanoparticles made of poly (lactic-co-glycolic acid) (PLGA) were prepared by premix membrane emulsification method. After the drug loading property was completed, the dynamic tissue distribution of nanoparticles was recorded. With the average particle size and span as indexes, membrane pore size, number of passing membrane times, membrane pressure, volume ratio of oil-water phase and the concentration of poly(vinyl alcohol) (PVA) in external water phase were investigated by single factor test, the optimum preparation technology of blank PLGA nanlparticles was as following: pore size of SPG membrane was 1 μm, membrane pressure was 1. 15 MPa, the number of passing membrane time was 3, the mass fraction of PVA of 2%, volume ratio of oil-water phase of 1 : 5. Prepared nanoparticles were round with smooth surface, the mean diameter was 332.6 nm, span was 0.010, the confocal laser scanning microscope (CLSM) concluded that fluorescent substance is uniform composizion in PLGA nanoparticle, and the in vivo imaging technology in mice include that the nanoparticles show good liver and spleen targeting property.
Animals ; Drug Carriers ; chemistry ; Drug Delivery Systems ; instrumentation ; Emulsions ; chemistry ; Fluorescent Dyes ; chemistry ; Lactic Acid ; chemistry ; Mice ; Mice, Nude ; Nanoparticles ; chemistry ; Particle Size ; Polyglycolic Acid ; chemistry

Objective：To evaluate bioequivalence and relative bioavailability of domestic and imported repaglinide tablets in healthy volunteers. Methods： Twenty two healthy male volunteers were randomized into A and B groups. A single dose (4 mg) of domestic and imported repaglinide tablets were given respectively according to an open 2-way crossover study design. The washout period was 1 week. Plasma concentrations of repaglinide were determined by HPLC method. Results：The pharmacokinetic parameters of domestic and imported drugs were as follows: t1/2 were(0.86±0.24) and (0.83±0.31) h；tmax were( 0.79±0.37) and (0.75±0.41) h；cmax were (52.43±20.92) and (53.32±24.94) μg/L. AUC0-t were (79.87±36.48) and (74.95±30.57) μg*h*L-1，respectively. The relative bioavailability of domestic formulation was (106.55±16.15)%. Conclusion： The results of variance analysis and two one-side t test show that 2 formulations are of bioequivalence.

Exosomes are a kind of endosomal vesicles that are secreted by most if not all living cells. Due to their capability of delivering a variety of cargos, such as tissue- or cell-specific proteins, lipids, and genetic materials, and their broad biological activities, exosomes have gained substantial attention as emerging therapeutics. Exosomes derived from mesenchymal stem cells (MSCs) and dendritic cells (DCs) are two types of exosomes that are widely studied. Many preclinical and clinical studies have shown that they have a satisfactory treatment effect in lung diseases, liver diseases, nervous system diseases, tumors, and other diseases. In addition, exosomes from macrophages, tumor cells, plant cells, and many other cells are getting more attention due to their therapeutic potential. Besides natural exosomes, research on engineered exosomes has also made plenty of progress. There have been several engineering methods of exosomes, such as targeting modification and loading of active ingredients. In this review, we summarize the research progress of therapeutic exosomes from different sources, and further discusses the application prospects of exosomes and possible challenges in the future.

Objective To screen fosfomycin-resistant genes in the clinical isolates of Enterococcus faecium Efm-HS0661 and verify their functions. MethodsAntimicrobial susceptibility and conjugation experiments were carried out to determine if the antimicrobial resistance in clinical strain was transferable.By Solexa high-throughput sequencing,the genes conferring fosfomycin resistance were screened. The function of resistance gene was identified by cloning.ResultsThe clinical isolates of Enterococcus faecium Efm-HS0661 were resistant to glycopeptide antibiotics and fosfomycin, and the fosfomycin resistance was found to be transferred by conjugation. Within the 2414 bp nucleotide sequence obtained by high-throughput sequencing, fosB, a plasmid-mediated fosfomycin resistance gene was found. The fosB gene was 420 bp in length, which shared 99. 8％ amino acid identity with other fosB from Staphylococcus spp. The minimal inhibitory concentration (MIC) of DH5α transformant containing fosB gene against fosfomycin was higher than that of DHSa transformant without fosB gene. ConclusionsThe high-throughput sequencing can be used to screen unknown resistance genes in clinical isolates. The plasmidmediated resistance gene fosB can confer fosfomycin resistance in Enterococcus faecium.

Objective To explore the relationship between NAT2 genetic polymorphism and the risk of colorectal cancer. Methods A hospital-based case-control study was conducted and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used to detect its genotypes.Results The frequency of NAT2 slow genotype was 19.58% in cases with colorectal cancer compared.with increased the risk for developing colorectal cancer and their OR were 2.16(95% CI:1.31～3.54).Conclusion The results suggest that NAT2 genetic polymorphism is associated with colorectal canoer susceptibility.People with NAT2 slow genotype have higher coloreetal cancer risk.