This study aims to clarify out the anti-inflammatory mechanism of Qingfei Xiaoyan Wan. Chemical constituents of Qingfei Xiaoyan Wan identified by UPLC Q-TOF, were submit to Molinspiration, PharmMapper and KEGG bioinformatics softwares for predicting their absorption parameters, target proteins and related pathways respectively; and the gene chip and real time-PCR were carried out to investigate the expression of inflammatory genes on lung tissue of guinea pigs or human bronchial epithelial cell lines. The predicted results showed that 19 of the 24 absorbable constituents affected at 9 inflammation-related pathways through 11 protein targets; Qingfei Xiaoyan Wan treatment can significantly reduce the infiltration of cytokines through ERK1 gene and 5 inflammatory pathways (Focal adhesion, Fc epsilon RI, Toll-like receptors, NK cell-mediated cytotoxic, and ERK/MAPK). The results of real time-PCR further confirmed that the anti-inflammatory effects of Qingfei Xiaoyan Wan were due to active ingredients such as arctigenin, cholic acid and sinapic acid intervened focal adhesion, Fc epsilon RI signaling and ERK/MAPK pathways. The novel approach of 'drug-target-pathway' will present an effective strategy for the study of traditional Chinese medicines.
Animals ; Anti-Inflammatory Agents ; pharmacology ; Asthma ; metabolism ; pathology ; Cell Line ; Cholic Acid ; pharmacology ; Coumaric Acids ; pharmacology ; Cytokines ; metabolism ; Drug Combinations ; Drugs, Chinese Herbal ; pharmacology ; Epithelial Cells ; drug effects ; Female ; Furans ; pharmacology ; Guinea Pigs ; Humans ; Inflammation ; metabolism ; Lignans ; pharmacology ; Lung ; pathology ; MAP Kinase Signaling System ; Male ; Random Allocation ; Receptors, IgE ; metabolism ; Toll-Like Receptors ; metabolism

OBJECTIVETo explore the relationship of beta-catenin and sensitivity to Bortezomib of myeloma cell lines.

METHODSMyeloma cell lines RPMI8226, CZ-1 and NCI-H929 were treated with Bortezomib and 2ME2, alone or in combination. Typan blue dye exclusion and modified MTT were used to assess the cell viability with or without treatment. Annexin V-FITC and PI staining was performed to detect apoptosis rate. RT-PCR was used to detect beta-catenin mRNA and western blot to analyze beta-catenin protein.

RESULTSThe basic expression level of beta-catenin was different in tested myeloma cell lines: RPMI8226 was the most while NCI-H929 the least and CZ-1 the intermediate. IC50 of RPMI8226, CZ-1 and NCI-H929 were (49.8 +/- 0.6), (24.7 +/- 0.4) and (8.4 +/- 0.2) nmol/L, respectively. After the treatment of Bortezomib (at 0, 1, 5, 10 nmol/L), beta-catenin level of tested cell lines accumulated in a time and dose dependent manner for western blot, while no significant change was observed in the result of RT-PCR. The beta-catenin protein levels in the Bortezomib (5 nmol/L) and 2ME2 (1 micromol/L) treated cell group were much lower than that in Bortezomib (5 nmol/L) group, the decrease of the gray scale of beta-catenin/beta-actin was 64.03% for RPMI8226, 52.56% for CZ-1, 51.48% for NCI-H929, and the apoptosis rates were 8.00, 1.86 and 1.19 times increase compared to untreated group.

CONCLUSIONMyeloma cell lines with higher beta-catenin level are less sensitive to Bortezomib, and combination treatment of low dose 2ME2 and Bortezomib can reduce beta-catenin accumulation and enhance the sensitivity to Bortezomib.

Apoptosis ; drug effects ; Boronic Acids ; pharmacology ; Bortezomib ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Humans ; Multiple Myeloma ; metabolism ; pathology ; Pyrazines ; pharmacology ; RNA, Messenger ; genetics ; beta Catenin ; genetics ; metabolism

OBJECTIVETo evaluate the effect of polymorphism at the -238 and -308 position of the TNF-alpha promotor region on the clinical outcome of thalidomide (Thal)-based regimens for the treatment of multiple myeloma (MM).

METHODSThe polymorphism at the -238 and -308 position of the TNF-alpha promotor region of 168 MM patients treated with Thal-based regimens were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Genotypes were tested for association with overall response by logistic regression, and survival was evaluated by univariate and multivariate analysis.

RESULTSIn TNF-alpha -238 position, 11 (6.5%) patients had GA genotype and 1 (0.6%) AA genotype. In TNF-alpha -308 position, 19 (11.3%) had GA genotype and 1 (0.6%) AA genotype. In univariate analysis, the TNF-alpha -238 GA + AA genotypes were associated with a significantly prolonged progression free survival (PFS) (P = 0.017), and a better overall survival (OS) (P = 0.150). Multivariate COX regression analysis showed that TNF-alpha -238 polymorphic status was an independent prognostic factor for prolonged PFS (P = 0.049).

CONCLUSIONThe TNF-alpha -238 polymorphic status is associated with a favorable clinical outcome in MM patients treated with thalidomide-based regimen. The polymorphism status of TNF-alpha gene might be of promise for developing a more informative stratification system for MM.

Adult ; Aged ; Aged, 80 and over ; Female ; Genotype ; Humans ; Male ; Middle Aged ; Multiple Myeloma ; drug therapy ; genetics ; Polymorphism, Genetic ; Prognosis ; Promoter Regions, Genetic ; Thalidomide ; therapeutic use ; Treatment Outcome ; Tumor Necrosis Factor-alpha ; genetics

OBJECTIVETo explore the clinical significance of serum free light chain (sFLC) levels in nonsecretory multiple myeloma (NSMM).

METHODSNine NSMM patients were hospitalized in our department from Feb 2002 to Sep 2006 and no M-components was found in their serum and urine by immunofixation electrophoresis (IFE). sFLC was assayed by immuno-nephelometry. The clonality of sFLC was estimated by serum kappa:lambda sFLC ratio. Meanwhile, serum immunoglobulin, total kappa and lambda light chain level were also determined in these patients.

RESULTSIncreased serum concentrations of either kappa or lambda sFLC (and abnormal kappa/lambda ratios) were detected in 6 of 9 patients with NSMM although their serum immunoglobulin levels were not elevated and total kappa:lambda light chain ratios (1.32 - 2.20) were in the reference range. All the 9 patients had clonal IgH gene rearrangements.

CONCLUSIONQuantification of sFLC by immuno-nephelometry is more sensitive than that of serum total light chain measurement and is helpful in estimating the clonality of the light chain in patients with NSMM.

Adult ; Female ; Humans ; Immunoglobulin Light Chains ; blood ; Male ; Middle Aged ; Multiple Myeloma ; blood ; Nephelometry and Turbidimetry ; Sensitivity and Specificity

OBJECTIVETo analyze the clinical and laboratory features and risk factors of multiple myeloma (MM) with extramedullary disease (EM) and its extraosseous localizations at diagnosis and during the course of MM.

METHODSThe clinical features, survival rate and prognostic factors were retrospectively analyzed in 40 patients having EM from a total of 418 MM patients hospitalized in Changzheng Hospital from 1993 to 2006.

RESULTSAmong the 40 patients, the first three localizations of EM involved soft tissue, pleura or peritoneum and central nervous system (CNS). Median duration of follow-up was 30 months. The median overall survival (OS) was 28 months. Twenty-five patients (6%) were found to have EM at diagnosis (group A), and their median OS was 16 months and 15 patients (3.6%) developed EM during the course of the disease (group B), and their expected median OS was 72 months. There was a significant difference between group A and B (P = 0.0045) for OS. Compared with those in group A, patients in group B had a higher percentage of plasmacytes (P = 0.022) and plasmablasts (P = 0.029) in bone marrow, and less advanced stage for international staging system (ISS) (P = 0.027). Log-rank univariate analysis showed that higher CRP level, higher serum LDH, Stage II and III for ISS, Hb < 110 g/L at diagnosis were poor prognostic factors. However, multivariate analysis with COX model showed none of them were statistically significant.

CONCLUSIONEM tumors are not a rare manifestation of MM. Soft tissue in the commonest area involved. Higher serum CRP and LDH level, more advanced stage for ISS, anemia and having EM are poor prognostic factors of MM.

Adult ; Aged ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Multiple Myeloma ; complications ; pathology ; therapy ; Prognosis ; Retrospective Studies ; Risk Factors ; Survival Analysis

OBJECTIVETo investigate the relationship between the contour of articular eminence and traces of the condylar kinematic center during jaw opening movement in healthy subjects, and compare trace characteristics of condylar kinematic center and MRI findings in TMD patients.

METHODSIn 10 healthy subjects, jaw-opening motion was recorded. The kinematic center and terminal hinge axis point of the condyle were used as trace reference points. The contour of articular eminence was examined by MRI. Seven patients with TMD signs and/or symptoms (disk displacement) were selected for this study. The condylar trace was recorded during jaw protrusion and opening-closing. The internal derangement in temporomandibular joints was detected by MRI and defined as: (1). normal disk position, (2). disk displacement with reduction, (3). disk displacement without reduction.

RESULTSIn healthy subjects, most of the opening traces of the kinematic center coincided with the contour of articular eminence (8/10 joints in left, 9/10 joints in right). For terminal hinge axis point, no trace coincided with the contour of articular eminence (0/20 joints in left and right). In TMD patients, according to MRI findings, the condylar traces of kinematic center in 3 normal disk position joints showed normal shape. However, in 6 disk displacements with reduction joints and 5 disk displacement without reduction joints, the condylar traces of kinematic center showed irregular patterns except 1 disk displacement with reduction joint.

CONCLUSIONSIn comparison with the terminal hinge axis point, the opening traces of the kinematic center can be interpreted as the translatory movement of the condyle/disc along the articular eminence. The study suggests the use of kinematic center in condylar movement studies.

Adolescent ; Adult ; Humans ; Magnetic Resonance Imaging ; Mandibular Condyle ; physiology ; Temporomandibular Joint ; physiology ; Temporomandibular Joint Disorders ; physiopathology

The aim of this study was to investigate the effect of arsenic trioxide (As(2)O(3)) combined with bortezomib on the proliferation, apoptosis and beta-catenin level in myeloma cell lines. Myeloma cell lines RPMI8226, CZ-1 and NCI-H929 were treated with As(2)O(3) and bortezomib alone or in combination for 48 hours. Trypan blue dye exclusion and modified MTT were used to assess the cell viability. Flow cytometry with Annexin V-FITC and PI staining was used to detect the apoptosis rate. The beta-catenin level was analyzed by Western blot. The results showed that IC(50) of bortezomib to RPMI8226, CZ-1 and NCI-H929 were 46.9, 20.7 and 6.8 nmol/L, respectively. After the combination treatment with bortezomib (5 nmol/L) and As(2)O(3) (1 micromol/L), the cell viability of RPMI8226, CZ-1 and NCI-H929 decreased from 88.99%, 72.23%, 51.06% to 54.01%, 39.59%, 25.00%(p<0.05), the apoptosis rate increased from 11.1+/-0.1%, 26.8+/-1.7%, 46.8+/-5.5% to 36.1+/-2.2%, 60.4+/-3.8%, 76+/-5.6% (p<0.01) respectively. The Q value of two groups lies between enhancement and significant enhancement (1.198 - 3.75). Besides, beta-catenin levels in tested cell lines were decreased to 24.15%, 31.85%, 33.72% of their basic constitutions respectively (p<0.05). It is concluded that combination treatment of As(2)O(3) and bortezomib can enhance the proliferation inhibition and apoptosis induction of bortezomib to myeloma cell lines, reduce beta-catenin level, and increase the sensitivity of myeloma cell lines to bortezomib.
Antineoplastic Agents ; pharmacology ; Apoptosis ; drug effects ; Arsenicals ; pharmacology ; Boronic Acids ; pharmacology ; Bortezomib ; Cell Proliferation ; drug effects ; Drug Synergism ; Humans ; Multiple Myeloma ; metabolism ; pathology ; Oxides ; pharmacology ; Pyrazines ; pharmacology ; Tumor Cells, Cultured ; beta Catenin ; metabolism

The article investigates the feasibility of delivering drugs to brain via inner ear, and provides a novel route for delivering drugs to the brain tissues. Dexamethasone acetate (DA)-loaded solid lipid nanoparticles (SLN) was prepared by using Compritol 888 ATO as material. HPLC assays for the determination of DA, dexamethasone sodium phosphate (DSP) and dexamethasone (Dex) were developed, separately. DA-loaded SLN and DSP solution were administered after intratympanic injection (IT) or intravenous injection (IV). Perilymph ( PL) and cerebrospinal fluid (CSF) were collected periodically. The concentrations in PL and CSF were measured by HPLC, and used to estimate pharmacokinetic parameters of Dex in CSF. The AUC of Dex in CSF following IT DA-loaded SLN or DSP solution were respectively 2.5 and 4.3-fold higher than those following IV. After IT, DA-loaded SLN increased the AUC by 13 times and extended the MRT by 19 times, compared with the solution. Moreover, the AUC of Dex in PL following IT the SLN was 76% lower than that following IT the solution. Intra-cochlear administration shows great potential and offers a promising alternative to brain-targeted drug delivery.
Animals ; Anti-Inflammatory Agents ; administration & dosage ; pharmacokinetics ; Brain ; metabolism ; Cerebrospinal Fluid ; metabolism ; Dexamethasone ; administration & dosage ; analogs & derivatives ; metabolism ; pharmacokinetics ; Drug Delivery Systems ; Ear, Inner ; metabolism ; Fatty Acids ; chemistry ; Female ; Guinea Pigs ; Lecithins ; Male ; Nanoparticles ; Particle Size ; Perilymph ; metabolism ; Random Allocation ; Surface-Active Agents ; chemistry ; Tissue Distribution

OBJECTIVETo investigate the value of serum cystatin C (Cys-C), urinary Cys-C, urinary retinol binding protein (RBP) and urinary neutrophil gelatinase-associated lipocalin (NGAL) in the early assessment of multiple myeloma (MM) and their characteristic changes in different pathological types of renal impairment.

METHODSAccording to glomerular filtration rate (eGFR), the patients were divided into two groups, of which marked group A with normal renal function, the other marked group B with abnormal renal function. Sixty healthy subjects were chosen as control. Detection of the serum Cys-C, urinary RBP, urinary Cys-C, urinary NGAL, serum creatinine (Scr), urinary microalbumin (MAU) and urinary α1-microglobulin (α1-MG) were performed. Renal biopsy was carried out for patients who had abnormal serum Cys-C, urinary Cys-C, urinary RBP, urinary NGAL and were willing to accept further test.

RESULTSCompared with healthy controls, the serum Cys-C, urinary RBP, urinary Cys-C, urinary NGAL of group A were significantly higher than that of healthy controls. Six group A patients received renal biopsy, and varying degrees of renal damage were discovered. The serum Cys-C, urinary RBP, urinary Cys-C and urinary NGAL positive rate were 66.7%, 66.7%, 66.7% and 83.3%, respectively. Of twenty-four cases received biopsy after abnormal examination results were shown, six turned out to be amyloidosis, twelve cast nephropathy (CN) and 6 monoclonal immunoglobulin deposition disease (MIDD). Compared with MIDD and amyloidosis, the urinary Cys-C and NGAL of the CN group are significantly higher (P < 0.05). Compared with CN and amyloidosis, urinary RBP of MIDD is significantly higher (P = 0.043). Compared with MIDD and CN, the MAU of amyloidosis is significantly higher (P = 0.006).

CONCLUSIONCompared with the conventional indicators, serum Cys-C, urinary Cys-C, RBP and NGAL are more sensitive in early assessment of MM patients with renal damage. The MAU is higher in amyloid, the urinary Cys-C and urinary NGAL are significantly elevated in CN, the urinary RBP is significantly elevated in MIDD.

Acute-Phase Proteins ; urine ; Adult ; Aged ; Case-Control Studies ; Cystatin C ; blood ; urine ; Female ; Humans ; Kidney ; pathology ; Kidney Diseases ; blood ; diagnosis ; urine ; Kidney Function Tests ; Lipocalin-2 ; Lipocalins ; urine ; Male ; Middle Aged ; Multiple Myeloma ; blood ; pathology ; urine ; Proto-Oncogene Proteins ; urine ; Retinol-Binding Proteins ; urine

In this paper the contents of rosmarinic acid, salvianolic acid B, crytotanshinone, tanshinone II(A) in samples of different original processed Salvia Miltiorrhizae Radix et Rhizoma were determined by HPLC. Different processing methods have varied influences on four active ingredients in Salvia Miltiorrhizae Radix et Rhizoma. Sun-drying reduced the content of crytotanshinone, tanshi-none II(A) and rosmarinic acid, integralsamples were better than those cut into segments. Oven dry method had great influence on water--soluble ingredients, high temperature (80-100 degrees C) could easily cause big loss of rosmarinic acid and salvianolic acid B. The role of traditional processing method "fahan: was complicated, the content of rosmarinic acid decreased, crytotanshinone and tanshinone II(A) increased, and salvianolic acid B showed no difference after "fahan". Drying in the shade and oven dry under low temperatrure (40-60 degrees C) were all effective to keep active ingredients of Salvia Miltiorrhizae Radix et Rhizoma, and, there was no difference between integral samples and samples cut into segments. Therefore, considering comprehensively the content of active ingredients in Salvia Miltiorrhizae Radix et Rhizoma, and processing costing etc., shade-drying or oven dry underlow temperature (40-60 degrees C) should be the most suitable original processing method.
Chemistry, Pharmaceutical ; methods ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal ; chemistry ; Hot Temperature ; Quality Control ; Rhizome ; chemistry ; Salvia miltiorrhiza ; chemistry ; Temperature