In-vitro assay methods were established to evaluate transactivation and binding activity of compounds on peroxisome proliferator-activated receptor y (PPARγ). Firstly, plasmids were constructed for transactivation assay of PPARγ response element (PPRE) triggered reporter gene expression, and for cell-based binding activity assay of the chimeric receptor, which was fused with PPARγ ligand binding domain (LBD) and yeast transcriptional activator Gal4. Secondly, by using PPARy competitive binding assay based on time resolved-fluorescence resonance energy transfer (TR-FRET), affinities of compounds and drugs to PPARγ were evaluated. In application of these above methods, the PPARγ activating potency and characteristics of different compounds were evaluated, and a novel benzeneselfonamide derivative, ZLJ01, was found to have comparable binding activity and affinity with the well-known PPARy agonist, but lack of PPRE mediated transactivation activity. In preliminary study on in-vitro hypoglycemic activity, ZLJ1 was found to promote insulin-stimulated glucose uptake by liver cells. Therefore, we believe that combining transactivation and binding activity as well as affinity evaluation, the system could be used to screen non-agonist PPARγ ligand as anovel PPARγ modulator
Genes, Reporter ; Hepatocytes ; Hypoglycemic Agents ; chemistry ; Ligands ; PPAR gamma ; agonists ; chemistry ; Plasmids ; Response Elements ; Sulfonamides ; chemistry ; Transcriptional Activation

Medicine, Chinese Traditional ; methods

OBJECTIVETo explore the diagnosis and treatment of relapsing polychondritis (RP).

METHODSThe clinical manifestations, diagnosis, and treatment of 24 patients with RP were retrospectively analyzed. Twenty-four RP patients were examined for autoimmune antibody. Laryngoscopy was performed in 4 out of 6 RP patients with laryngeal involvement. Bronchoscopy was performed in 12 out of 19 RP patients with lower respiratory tract involvement. Biopsies were taken from the cartilage involved in 16 out of 24 patients.

RESULTSFive patients were ANA positive at present, 2 patients were SSA antibody positive, 2 patients were anti-RNP antibody positive, and 2 patients were anti-Sm antibody positive. Laryngoscopy revealed vocal fold edema and laryngeal stenosis. Bronchoscopy showed stenosis of trachea and both main bronchi and destruction of tracheobronchial cartilage. Histopathology revealed chronic inflammation of cartilage. Treatment included immunosuppressants (cyclophosphamide, methotrexate) together with prednisone. Eleven patients with respiratory tract involvement had laryngotracheostomy or airway stenting. Twenty-three patients alleviated after treatment, and 1 patients died.

CONCLUSIONSRP involves cartilage and connective tissue. Laryngotracheobronchial complications are the most severe manifestations of this disease. Corticosteroids and immunosuppressive drugs are effective treatment options. Patients with laryngotracheal stenosis and collapsed tracheobronchial wall should receive laryngostomy, tracheostomy, or airway stenting to improve airway obstruction symptoms.

Anti-Inflammatory Agents ; therapeutic use ; Cyclophosphamide ; therapeutic use ; Drug Therapy, Combination ; Humans ; Immunosuppressive Agents ; therapeutic use ; Methotrexate ; therapeutic use ; Polychondritis, Relapsing ; diagnosis ; drug therapy ; Prednisone ; therapeutic use ; Retrospective Studies

Imiquimod (R-837) and Resiquimod (R-838), two novel small-molecular-weight immune response modifiers, have similar structure. They have anti-virus and anti-tumor activities and can be used as B lymphocyte activators and adjuvants. They are widely used in dermatology to treat virus dermatoses and cutaneous benign or malignant tumors.
Adjuvants, Immunologic ; therapeutic use ; Aminoquinolines ; therapeutic use ; Antineoplastic Agents ; therapeutic use ; Condylomata Acuminata ; drug therapy ; Humans ; Imidazoles ; therapeutic use ; Skin Neoplasms ; drug therapy

Objective To study the value of DSA for hepatic vascular anatomy,and to evaluate the efficacy of portal vein occlusion in rabbits with hepatic VX2 tumor.Methods Twenty New Zealand white rabbits were randomly divided into two groups with 10 in each group,including test group A and positive control group B of ham operation.For the test group A,portal branch ligation(PBL)was performed for the left external branch after 3 weeks of the tumor implantation to the left external lobe.Two weeks later,the DSA of hepatic artery and portal vein were performed in all of the rabbits.Results The total displaying effectiveness of the branches of hepatic artery by DSA was better than that by vascular perfusion.There was hypovascular blood supply to hepatic artery implantation of the tumor in the test group A,comparing with that of the group B.Conclusion DSA can clearly display spacial details of the hepatic vascular anatomy in rabbits,and play an important role in post-procedual evaluation of the portal vein occlusion in rabbits.

OBJECTIVETo study the genotoxicity of components of diesel engine exhausts with ethanol-diesel blending fuel. To provide scientific arguments to find more economical and less polluted fuels.

METHODSAmes test, comet assay and GC-MS technique were used to test the genotoxicity and 16 kinds of PAHs on diesel engine exhausts with different proportions of ethanol (E0, E5, E10, E20).

RESULTSBoth Ames test and comet assay were positive. It shows that diesel engine exhausts can lead to mutation and DNA damage, especially in pure diesel oil. But the content of 16 kinds of PAHs and DNA damage level decreased in exhausts of E5. With the increase of ethanol proportion in diesel oil, the content of 16 kinds of PAHs and DNA damage level increased.

CONCLUSIONCompared with pure diesel oil and high proportion of ethanol fuel, E5 can reduce the genotoxicity and the brake specific exhausts of PAHs.

Air Pollutants ; toxicity ; Air Pollution ; Carbon Monoxide ; Comet Assay ; DNA Damage ; Ethanol ; toxicity ; Gasoline ; toxicity ; Mutagenicity Tests ; Particulate Matter ; Vehicle Emissions ; toxicity

OBJECTIVETo study the regulation of luteolin on spleen cells and sarcoma S180 cells in normal ICR mice.

METHODSSpleen cells and S180 cells were incubated with different concentrations of luteolin (50, 100, 200, and 400 μmol/L). The effect of luteolin on spleen cells and sarcoma S180 cells was determined by MTT assay. The apoptosis was detected using propidium iodide staining flow cytometry. Intracellular reactive oxygen species (ROS) was determined by flow cytometric analysis. Activities of free radicals scavenging were determined by hydroxyl radical and DPPH tests.

RESULTSCompared with the solvent control group, 200 and 400 μmol/L luteolin increased the spleen cells viability (P < 0.05). Luteolin at 100, 200, and 400 μmol/L decreased activities of S180 cells (P < 0.01). The proportion of sub-G1 phase spleen cells was reduced after treated with 200 and 400 μmol/L luteolin (P < 0.05). The proportion of sub-G1 phase S180 cells was elevated after treated with 200 and 400 μmol/L luteolin (P < 0.05). Compared with the solvent control group, levels of intracellular ROS in spleen cells of ICR mice all increased; levels of intracellular ROS in S180 cells all decreased after treated with 50, 100, 200, and 400 μmol/L luteolin (P < 0.05). Luteolin scavenged hydroxyl radical and DPPH in a dose dependent manner.

CONCLUSIONLuteolin had bilateral regulation on viability and apoptosis of spleen cells and S180 cells (promoting the viability of spleen cells, inhibiting apoptosis of spleen cells, inhibiting the viability of S180 cells, and promoting apoptosis of S180 cells), which was worth further study and exploration.

Animals ; Apoptosis ; Apoptosis Regulatory Proteins ; metabolism ; Cell Survival ; Luteolin ; metabolism ; Mice ; Mice, Inbred ICR ; Reactive Oxygen Species ; Sarcoma ; Spleen ; metabolism

OBJECTIVETo investigate the obstructive site and the dynamic change of the upper airway in patients with obstructive sleep apnea hypopnea syndrome (OSAHS) during sleep and wakefulness.

METHODSAfter being deprived of sleeping for 20 hours, sequential midline sagittal images of the upper airway were obtained in 21 patients during sleep and wakefulness with dynamic MRI. The obstructive state was studied according to hypopnea (< 10 s) and apnea (> or = 10 s). The length of obstruction site was measured and the dynamic characteristics of obstruction was observed. Statistical analysis was performed with paired t-test.

RESULTSThe obstruction at the level of the palatopharynx in patients with hypopnea during wakefulness was similar to that in patients with apnea during sleep. The maximal length [(6.61 +/- 1.23) cm], the minimal length [(0.95 +/- 0.22) cm] and maximal length difference [(5.66 +/- 1.27) cm] related to apnea during sleep were longer than those correlated with hypopnea [(2.99 +/- 0.51) cm, (0.72 +/- 0.23) cm, (2.27 +/- 0.67) cm, respectively] in wakefulness. (P < 0.01).

CONCLUSIONSThe obstruction of upper airway during sleep is dynamic and multilevel in patients with OSAHS. To a certain degree, hypopnea during wakefulness can give a clue to the obstructive state during sleep.

Adult ; Airway Obstruction ; diagnosis ; physiopathology ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Sleep Apnea, Obstructive ; diagnosis ; physiopathology

BACKGROUNDPeutz-Jeghers syndrome (PJS) is an autosomal dominantly inherited disease. STK11/LKB1 gene germline mutations have been identified as responsible for PJS. In our study, we investigated the molecular basis of PJS and evaluated correlation between the STK11 mutations and the Chinese population.

METHODSWe collected three pedigrees of PJS and screened the 9 exons and their flanking intronic sequences of STK11/LKB1 gene in the probands and normal individuals in the families using polymerase chain reaction (PCR) and direct sequencing.

RESULTSSequencing of the STK11 gene in the probands of 3 families revealed two novel mutations (c180C-->G and c998-1002delGCAGC) in exon 1 and exon 8, respectively. The mutation of c180C-->G resulted in a premature termination codon. The other mutation, a deletion of five nucleotides (998-1002delGCAGC) in exon 8, predicted to generate a translational frameshift and a termination at codon 1070.

CONCLUSIONSThe growing number of mutations in PJS pedigrees suggests the molecular basis of PJS. STK11 gene mutation can be detected in most patients with PJS.

Child ; Female ; Humans ; Male ; Mutation ; Pedigree ; Peutz-Jeghers Syndrome ; genetics ; Protein-Serine-Threonine Kinases ; genetics

Female ; Humans ; Leishmaniasis, Cutaneous ; diagnosis ; drug therapy ; pathology ; Male ; Middle Aged