Animals ; Gene Silencing ; physiology ; Gene Targeting ; Genetic Therapy ; methods ; Genomics ; Humans ; RNA Interference ; RNA, Small Interfering ; genetics ; therapeutic use ; RNA-Induced Silencing Complex

Albendazole ; adverse effects ; Child, Preschool ; Drug Eruptions ; etiology ; Humans ; Tablets

After binding to its ligand, epidermal growth factor receptor (EGFR) dimerizes and is autophosphorylated. These events initiate the signal transduction process, which regulates a plethora of biologic activity. The duration and strength of these signals are controlled by many regulatory mechanisms, including downregulating activated EGFR primarily via endocytosis and ubiquitination-dependent lysomal degradation. The interaction between EGFR and the ubiquitin ligase Cbl/adaptor protein CIN85, as well as ESCRT complex recruitment play important roles in the process of downregulating EGFR. Tumorigenesis results when the de-sensitization process of EGFR is halted by its own mutation or a mutation that abrogates Cbl E3 ligase activity.
Adaptor Proteins, Signal Transducing ; metabolism ; Animals ; Down-Regulation ; Endocytosis ; Epidermal Growth Factor ; pharmacology ; Humans ; Mutation ; Proto-Oncogene Proteins c-cbl ; metabolism ; Receptor, Epidermal Growth Factor ; genetics ; metabolism ; Signal Transduction ; Ubiquitin ; metabolism

BACKGROUNDStatins improve arterial stiffness in patients with coronary artery disease (CAD). Hypertension is a predominant contributor of arterial stiffening. However, the influence of hypertension on the effect of statins for improving arterial stiffness in CAD patients has seldom been investigated. Therefore, in this study, we investigated the relationships between statin use and arterial stiffness in normotensive and hypertensive CAD patients.

METHODSBrachial-ankle pulse wave velocity (ba-PWV) was measured in 437 patients, including 220 hypertensive CAD patients (121 used statins, 99 did not) and 217 normotensive CAD patients (105 used statins, 112 did not). The normotensive and hypertensive CAD patients were matched according to age, sex, and body mass index (BMI).

RESULTSIn the normotensive and hypertensive CAD patients, lipid profiles were significantly improved in the statin group compared with the non-statin group. No significant differences in the administered statins (i.e., atorvastatin, simvastatin, rosuvastatin, and pravastatin) and statin therapy duration were found between normotensive and hypertensive CAD patients (all P > 0.05). No significant correlation of ba-PWV and statin therapy duration was found in all CAD patients, normotensive CAD patients, or hypertensive CAD patients (all P > 0.05). ba-PWV in the statin group was significantly lower than that in the non-statin group in normotensive CAD patients ((1331.68 ± 167.52) cm/s vs. (1468.61 ± 244.54) cm/s, P = 0.002) but not in hypertensive CAD patients (P > 0.05). In multiple linear regression analyses, statin therapy was significantly associated with ba-PWV after adjusting for confounding variables in normotensive CAD patients (P = 0.018) but not in hypertensive CAD patients (P > 0.05).

CONCLUSIONSStatins may significantly improve arterial stiffness in CAD patients, and hypertension may probably influence the effectiveness of statin therapy in improving arterial stiffness in this population. Further studies are required to investigate the effect of statins on arterial stiffness in normotensive and hypertensive CAD patients.

Aged ; Ankle Brachial Index ; Coronary Artery Disease ; physiopathology ; Cross-Sectional Studies ; Female ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; pharmacology ; Hypertension ; physiopathology ; Male ; Middle Aged ; Pulse Wave Analysis ; Vascular Stiffness ; drug effects ; physiology

OBJECTIVETo observe the regularity of change in high mobility group protein box 1 (HMGB1) content in serum and spleen of mice with multiple organ dysfunction syndrome (MODS), to analyze the correlation between HMGB1 content and major histocompatibility complex (MHC)-II---I-A(b) expression on monocytes in blood and spleen, and to explore the effect of HMGB1 on immune function of circulating monocytes and splenocytes.

METHODSOne hundred 8-week-old male 57BL/6 mice were randomly divided into normal group and experimental group subdivided into 8 subgroups: 3, 8, 12 hours, 1, 2, 3, 5-7 days and 10-12 days post zymosan injection (PZI). MODS model was replicated by injecting zymosan into the peritoneal cavity. At each time point, blood and spleen were collected to detect HMGB1 content and the rate of I-A(b) positive monocytes.

RESULTSIn normal and PZI 3-hour, 8-hour mice, serum HMGB1 was not detected, but it significantly increased at PZI 12 hours. In spleen of normal mice, there was low level of HMGB1 expression. In zymosan-treated mice, HMGB1 started to rise in spleen at PZI 3 hours. Subsequently, HMGB1 content in both serum and spleen significantly increased, and it reached the peak level in 1-2 days, decreased in 5 days, and then increased in 10-12 days. The number of I-A(b) positive monocytes in circulating blood and spleen decreased at 1-2 days (t equal to 9.589, 4.432, P <0.01) and 10-12 days following the challenge, forming a two trough like decrease, just corresponding with two-peak increase of HMGB1. However, at 3 hours after zymosan challenge, I-A(b) expression on circulating monocytes was downregulated (t =5.977, P less than 0.01), while that in spleen upregulated (t equal to 4.814, P less than 0.01).

CONCLUSIONIn mice with MODS, up-regulated HMGB1 expression can regulate I-A(b)expression on monocytes to depress their ability of presenting antigen, which results in immune disturbance contributing development of MODS.

Animals ; HMGB1 Protein ; analysis ; Histocompatibility Antigens Class II ; analysis ; Male ; Mice ; Mice, Inbred C57BL ; Monocytes ; immunology ; Multiple Organ Failure ; immunology ; Spleen ; immunology ; Zymosan ; pharmacology

OBJECTIVETo investigate the role and significance of Wnt/beta-catenin signaling pathway regulating GSK-3beta, STAT3, Smad3 and TERT in hepatocellular carcinoma (HCC).

METHODSThe HCC cell line HepG2 was transfected with small interfering RNA (siRNA) directed against beta-catenin. Proteins were extracted and the expressions of beta-catenin, GSK-3beta, p-GSK-3beta, STAT3, Smad3 and TERT were detected by Western blot at 72 h and 96 h respectively after transfection.

RESULTSbeta-catenin expression was inhibited at both time points and the expression at 96 h was higher than that at 72 h (t = 4.43, P < 0.05). Interestingly, GSK-3beta and p-GSK-3beta expressions increased gradually at 72 and 96 h (tGSK-3beta= 4.98, tp-GSK-3beta= 29.83, P < 0.05) respectively, and STAT3 expression showed no alteration after transfection (F = 0.49, P > 0.05). Smad3 expression was increased at 72 h (t = 10.67, P < 0.05) and decreased to normal at 96 h (t = 1.26, P < 0.05), while TERT expression decreased at 72 h (t = 4.18, P is less than 0.05) and increased to normal at 96 h (t = 1.26, P > 0.05).

CONCLUSIONSWnt/beta-catenin signaling pathway is related to the expressions of GSK-3beta, Smad3 and TERT, but perhaps not related to STAT3 protein expression in HCC. It suggested that Wnt/beta-catenin signaling pathway might participate in HCC genesis and development through regulating the above three factors.

Carcinoma, Hepatocellular ; metabolism ; pathology ; Hep G2 Cells ; Humans ; Liver Neoplasms ; metabolism ; pathology ; RNA, Small Interfering ; Signal Transduction ; Wnt Proteins ; metabolism ; beta Catenin ; metabolism

OBJECTIVETo investigate the mRNA expression of matrix metalloproteinase 1 (MMP1) gene in oral squamous cell carcinoma (OSCC) and the paired normal tissues.

METHODSThe differential expression of MMP1 mRNA between 30 OSCC and paired normal tissues were detected with reverse transcription-PCR (RT-PCR).

RESULTSThe relative expression level of MMP1 mRNA in the OSCC tissues showed a 3.26-fold increase in comparison with that in the paired normal tissues (4.06-/+0.52 vs 1.24-/+0.17, P<0.0001). In the 30 OSCC tissues, the relative expression level of MMP1 mRNA was higher in histological grade II/III tissues (4.31-/+0.68) than in grade I (3.87-/+0.57) tissues, higher in OSCC in advanced stages (III/IV) than in tumors in early stages (I/II) (4.18-/+0.67 vs 3.65-/+0.53), and also higher in OSCC with cervical lymph node invasion than in those without cervical lymph node invasion (4.32-/+0.71 vs 3.91-/+0.51), but these differences were not statistically significant (P>0.05).

CONCLUSIONMMP1 gene may play a role in local invasion of OSCC, and can serve as a potential biomarker molecule for diagnosis, treatment and prognostic evaluation of OSCC, with also clinical value for OSCC classification.

Adult ; Aged ; Aged, 80 and over ; Carcinoma, Squamous Cell ; enzymology ; genetics ; pathology ; Female ; Gene Expression Regulation, Enzymologic ; Gene Expression Regulation, Neoplastic ; Humans ; Male ; Matrix Metalloproteinase 1 ; genetics ; Middle Aged ; Mouth Mucosa ; enzymology ; metabolism ; pathology ; Mouth Neoplasms ; enzymology ; genetics ; pathology ; RNA, Messenger ; genetics ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction

OBJECTIVETo investigate the method for reconstruction of large tissue defects following surgical resection of advanced oral cancer using pectoralis major myocutaneous flap.

METHODSFrom 2005 to 2009, 40 patients with advanced oral cancer received extensive surgical resection of oral cancer, and the intraoral defects were reconstructed using pectoralis major myocutaneous flaps.

RESULTSAll the flaps survived except one flap with partial necrosis.

CONCLUSIONPectoralis major myocutaneous flap is effective for reconstruction of large tissue defects after resection of advanced oral cancer.

Adult ; Aged ; Carcinoma, Squamous Cell ; surgery ; Female ; Humans ; Male ; Middle Aged ; Mouth Neoplasms ; surgery ; Pectoralis Muscles ; transplantation ; Postoperative Period ; Reconstructive Surgical Procedures ; methods ; Surgical Flaps

OBJECTIVETo explore the role of sorafenib in reversing multidrug resistance (MDR) in hepatoma BEL-7402/FU cells and its possible mechanisms.

METHODSMTT colorimetric assay was used to obtain the dose-response curve of sorafenib in BEL-7402/FU cells, and flow cytometry performed to assess the effect of sorafenib on Rho123 concentration in the cells. The optimal dose of sorafenib for cell treatment was determined according to the results of MTT assay and flow cytometry. MTT assay was employed to evaluate the effect of sorfenib on the cytotoxicity of the antitumor drugs, flow cytometry performed to determine the expression of cell membrane transport protein (P-gp), and RT-PCR used to detect mdr1 gene expression in the cells treated with sorafenib at the optimal dose.

RESULTSSorafenib at the concentration of 4 micromol/L, efficiently reversed the MDR of the cells with minimal side effects. At the concentration of 4 micromol/L, sorafenib partially reversed the drug resistance of BEL-7402/FU cells to ADM, 5-FU, GEM and DDP, with reversal indexes of 2.98, 7.16, 1.99 and 10.08, respectively. Treatment of the cells with 4 micromol/L, sorafenib also partially down-regulated P-gp expression in BEL-7402/FU cells, and caused a reduction of mdr1 gene expression by 27.3% in comparison with the control cells.

CONCLUSIONSorafenib can reverse MDR in human hepatoma cells probably in association with down-regulation of mdr1 gene expression and increased accumulation of the chemotherapeutic agents in the cells.

ATP-Binding Cassette, Sub-Family B, Member 1 ; genetics ; metabolism ; Antineoplastic Agents ; pharmacology ; Benzenesulfonates ; pharmacology ; Cell Line, Tumor ; Down-Regulation ; drug effects ; Drug Resistance, Multiple ; drug effects ; Drug Resistance, Neoplasm ; drug effects ; Humans ; Liver Neoplasms ; genetics ; Niacinamide ; analogs & derivatives ; Phenylurea Compounds ; Pyridines ; pharmacology

BACKGROUNDThe current diagnostic algorithms for chronic cough require the establishment of the primary presumptive causes followed by the confirmation of diagnosis with the specific therapies. The aim of the study was to investigate the discrepancy between presumptive and definite causes and its clinical implication.

METHODSA total of 109 patients with chronic cough underwent laboratory investigations to identify the cause of cough; including sinus computerized tomography (if needed), histamine bronchial provocation, induced sputum cytology and 24-hour esophageal pH or multi-channel intraluminal impedance combined with pH monitoring. The presumptive causes were confirmed by treating them sequentially. The difference between presumptive and definite causes of chronic cough was compared.

RESULTSSingle cause was more frequent in the definite diagnosis than in the presumptive diagnosis (78.9% vs. 54.1%, χ(2) = 15.01, P = 0.0001). In contrast, multiple causes were significantly fewer in definite diagnosis than in the presumptive diagnosis (15.6% vs. 37.6%, χ(2) = 13.53, P = 0.0002). There was a discrepancy between definite and presumptive causes in 30 patients (27.5%). Compared with the presumptive causes, definite upper airway cough syndrome (24.8% vs. 11.9%, χ(2) = 6.0, P = 0.01) and gastroesophageal reflux disease (6.4% vs. 0, χ(2) = 7.23, P = 0.007) was more frequent as a single cause of chronic cough while cough variant asthma plus gastroesophageal reflux disease (3.7% vs. 11.9%, χ(2) = 5.17, P = 0.02) and upper airway cough syndrome plus nonasthmatic eosinophilic bronchitis (0 vs. 9.2%, χ(2) = 10.48, P = 0.001) were fewer as multiple causes of chronic cough.

CONCLUSIONSA discrepancy was common between presumptive and definite causes of chronic cough. To treat presumptive causes sequentially may be a suitable solution for avoidance of erroneous multiple causes and possible over-treatment.

Adult ; Chronic Disease ; Cough ; etiology ; Female ; Humans ; Male ; Middle Aged