Cyclic adenosine monophosphate(cAMP)is a “second messenger” that regulates cell signal transduction. Adenylyl cyclases(ACs)and phosphodiesterases(PDEs)can directly regulate cAMP level in cells and then regulate the downstream signaling pathways. Increasing intracellular cAMP level can inhibit inflammation and enhance smooth muscle relaxation, which is an effective strategy for the prevention and treatment of chronic obstructive pulmonary disease(COPD). This paper briefly summarizes the signaling pathways regulating cAMP and their mechanisms and related drugs in COPD therapy, hoping to provide references for further research and development of new target drugs which regulate cAMP for the prevention and treatment of COPD.

The purpose of this research is to investigate the effects and mechanisms of paeonol (PL), a phenolic compound found in many traditional Chinese formulations, on reversing drug resistance in the ovarian cancer resistant SKOV3/DDP cells. The results showed that PL had significant drug-resistant reversal effect on SKOV3/DDP cells. Flow cytometry showed that PL could inhibit P-glycoprotein (P-gp) function in a concentration-dependent manner. Fluorescent quantitative PCR and cell immunofluorescence techniques were used to detect mechanisms of action. Results revealed that both the inhibitory effect on MDR1/P-gp and metadherin (MTDH) expression and the induction effect on phosphatase and tensin homolog (PTEN), by 15, 30, and 60 μmol·L^-1 PL, were increased with increased concentrations of PL (P < 0.01, P < 0.05). The inhibitory effect on MTDH mRNA and the induction effect on PTEN mRNA, by PI3K inhibitor LY294002, were stronger or equivalent to that of the 60 μmol·L^-1 PL treated group; however, the inhibition or induction effect on MTDH or PTEN protein were only comparable to the 15 μmol·L^-1 PL treated group. The present study shows that the effect of PL on SKOV3/DDP cells may be related to the inhibition of P-gp function and expression, the inhibition of MDR1, MTDH expression, and the induction of PTEN expression, all which can provide a theoretical foundation for PL as a drug resistance reversal agent on the treatment of ovarian cancer chemotherapy resistance.

OBJECTIVE To detect the reversal effect of Guizhi Fuling Wan on cisplatin-resistant ovarian cancer SKOV3/DDP cells and its relationship with protein expression of phosphatase and tensin homolog (PTEN) and metadherin (MTDH). METHODS Guizhi Fuling Wan (GFW) concentrated solution was prepared according to the Chinese Pharmacopoeia 2015 edition, Wistar rats were given GFW viagavage at 4 g·kg-1·d-1,8 g·kg-1·d-1,16 g·kg-1·d-1,or given saline as blank control for 5 days.Blood samples were taken and the corresponding drug-containing low-dose sera, medium-dose sear, high-dose sera and blank sera were prepared.The XCELLigence RTCA S16 real-time label-free cell analyzer was used to detect the reversal effect by the sera combined with cisplatin or paclitaxel in SKOV3/DDP cells. Annexin V-FITC and PI double-staining were used to detect the apoptosis-inducing effect of the sera in the cells. RT-qPCR and western blot were used to detect the mRNA and protein expression of PTEN and MTDH after the cells treated with the sera. RESULTS The inhibition rate of low-dose sera against SKOV3/DDP cells was less than 5%.After the low-dose sera combined with cisplatin or pacli-taxel, the IC50 of SKOV3/DDP cells against cisplatin and paclitaxel decreased by 3.01 and 1.79-fold, respectively.The total apoptosis rates induced by the low-dose sera,medium-dose sear,high-dose sera and blank sera in SKOV3/DDP cells were 11.08±0.13,19.42±0.30,24.23±0.31,and 3.21±0.24,respec-tively; there was a significant difference between the groups (P<0.01). RT-qPCR results showed that, compared with the blank serum, the sera can up-regulate the expression of PTEN mRNA and down-regulate the expression of MTDH mRNA in a dose-dependent manner. Western blot results showed that the induction effect to PTEN protein and the inhibition effect to MTDH protein by the sera were gradually enhanced with thesera dose increasement. CONCLUSION The resistance reversal effect of Guizhi Fuling Wan on ovarian cancer SKOV3/DDP cells may be related to the inhibition of MTDH, up-regulation of PTEN and induction of apoptosis, providing with an experiment basis for the applica-tion of Guizhi Fuling Wan as a reversal agent for chemotherapy resistance of ovarian cancer.

Objective To observe the changes in subfoveal choroidal thickness (SFCT) and peripapillary choroidal thickness (pCT) in nonarteritic anterior ischemic optic neuropathy (NAION). Methods Nineteen newly occurred NAION patients were included. The patients were divided into group A (20 affected eyes of 19 patients) and B (18 fellow eyes of 18 patients). Twenty eyes of 20 age, gender, intraocular pressure and axial length-matched healthy volunteers (group C) were enrolled in this study. The differences of age (t=1.58), gender ratios (χ2=0.107), intraocular pressure (t=0.092) and axial length (t=0.148) between 3 groups were not significant (P>0.05). SFCT, pCT were measured at first visit, 1 month and 3 months after treatment using enhanced deep imaging technique of spectral domain optical coherence tomography. The correlation of best corrected visual acuity (BCVA) and the choroidal thickness was investigated. Results At the first visit, the mean SFCT and pCT in group A were significant thicker than group C (t=2.957, 2.844; P=0.006, 0.009). There was no difference of SFCT and pCT between group B and C (t=2.019, 2.024; P=0.053, 0.057). There was no correlation between BCVA and SFCT, pCT (F=0.161, 0.033; P=0.695, 0.859). One month after treatment, SFCT in group A was still thicker than group C (t=2.803, P=0.009); while pCT was decreased in group A when compared to group C, but the difference was not significant (t=1.871, P=0.084). Three months after treatment, the differences of SFCT and pCT were not significant between group A and C (t=1.223, 1.105; P=0.236, 0.282). Conclusions At first visit, SFCT and pCT in NAION eyes showed a significant increase when compared to normal eyes. One month later, pCT in NAION eyes decreased to normal. Three months later, both SFCT and pCT decreased. These findings may suggest that a thickened choroid is a clinical characteristic at acute stage in NAION eyes.

Objective To study the clinical significance of EGFR mutation in patients with advanced non -small cell lung cancer combined with malignant pleural effusion,and to provide reliable theoretical basis for clinical treatment .Methods 3 0 patients of advanced non -small -cell lung cancer complicated with malignant pleural effusion in Zhoushan island area were selected.DNA was extracted in the pleural effusion and EGFR 19,21 two loci of gene mutation was detected by sequencing PCR.EGFR and clinical characteristics of the patients (gender,age,smoking history,disease types of cases and in the level of CEA level)was compared.Results Among the 30 cases,4 cases of gene mutation,1 case of male patient,3 cases of female patients,4 cases of adenocarcinoma,4 cases of non smokers, 2 cases of EGFR19 deletion,2 cases of EGFR21 mutation.Among them,3 patients were treated by biological target therapy,the survival time was more than 1 year,and there were no obvious adverse reactions,and the effective rate was 75.00%.Conclusion The gene mutations of EGFR were detected in the patients with advanced non -small cell lung cancer combined with malignant pleural effusion,and the mutation rate 13.30%,which was high in female,non smoker and adenocarcinoma,and it could be used to treat the tumor.

OBJECTIVETo investigate whether inhalable particulate matters can cause the damage of chromosome or mitotic apparatus to produce micronucleus, and to evaluate genetic toxicology of moxa smoke on chromosome.

METHODSBy MTT method, the 24 h half maximal inhibitory concentration (IC50) of moxa smoke condensation (MSC) on Chinese hamster ovary (CHO) cells was 0.087 mg/mL. CHO cells, which were cultured in vitro, were divided into a solvent control group, a positive control group (cyclophosphamide as solvent), a low concentration group, a moderate concentration group and a high concentration group. The low concentration group, moderate concentration group and high concentration group were set approximately 1/8, 1/4, 1/2 of IC50, respectively. Whether micronucleus had dose-effect response induced by the damage of chromosome or mitotic apparatus was observed after CHO cells were contaminated by MSC in the low concentration group, moderate concentration group and high concentration group.

RESULTSThe rate of micronucleus induced by MSC in the low concentration group, moderate concentration group and high concentration group was higher than that in the solvent control group (all P < 0.05), which presented dosage-effect response. The experiment was repeated 3 times, indicating it was repeatable with statistical significance.

CONCLUSIONHigh concentration of MSC shows toxicity to induce chromosome damage, which disappears at low concentration. The genetic toxicology is also dependent on concentration, and the concentration of moxa smoke is essential. In clinical treatment, it is noted to control the level of moxa smoke, while the clinical safety standard of moxa smoke concentration is in need of further study.

Air Pollutants ; adverse effects ; Animals ; CHO Cells ; Cell Nucleus ; drug effects ; genetics ; Cricetinae ; Cricetulus ; Inhalation Exposure ; adverse effects ; analysis ; Micronucleus Tests ; Moxibustion ; adverse effects ; Particulate Matter ; adverse effects ; Smoke ; adverse effects ; analysis

OBJECTIVETo observe the effects of intervention of moxa smoke with different concentrations on superoxide dismutase (SOD) and malondialdehyde (MDA) in serum and lung of male rats, so as to explore the safety concentration of moxa smoke.

METHODSA total of 32 Wistar male rats were randomly divided into a control group, a low-concentration group, a moderate-concentration group and a high-concentration group, 8 rats in each one. All the rats were exposed in the full-automatic toxicant exposure cabinet, and the overshadow of moxa smoke was set at 0%, 10%, 40% and 70%, respectively. Each rat was exposed for 20 min per day. After 26 weeks, the activities of SOD and content of MDA in serum, lung organ and bronchoalveolar lavage fluid were tested.

RESULTSCompared with the control group, the activities of serum SOD in the high-concentration group were reduced (P< 0. 05), but those in the low-concentration group and moderate-concentration group were not significantly different (both P>0. 05). Compared with the control group, the content of serum MDA in the low-concentration group, moderate-concentration group and high-concentration group was increased insignificantly (all P>0. 05). There were no significant differences regarding activities of SOD and content of MDA in lung organ and bronchoalveolar lavage fluid among each moxa smoke group (all P>0. 05).

CONCLUSIONThere is no obvious toxic reaction in the low-concentration group and moderate-concentration group; in the high-concentration group the antioxidant ability is damaged due to long-term exposure.

Animals ; Artemisia ; chemistry ; Lung ; enzymology ; metabolism ; Male ; Malondialdehyde ; blood ; metabolism ; Moxibustion ; Rats ; Rats, Wistar ; Smoke ; analysis ; Superoxide Dismutase ; blood ; metabolism

OBJECTIVETo evaluate the cost-effectiveness of combining Chinese medicine (CM) with Western medicine (WM) for ischemic stroke patients.

METHODSHospitalization summary reports between 2006 and 2010 from eight hospitals in Beijing were used to analyze the length of stay (LOS), cost per stay (CPS), and outcomes at discharge.

RESULTSAmong 12,009 patients (female, 36.44%; mean age, 69.98±13.06 years old), a substantial number of patients were treated by the WM_Chinese patent medicine (CPM)_Chinese herbal medicine (CHM) (38.90%); followed by the WM_CPM (32.55%), the WM (24.26%), and the WM_CHM (4.15%). With adjustment for confounding variables, LOS of the WM_CPM_CHM group was about 10 days longer than that of the WM group, and about 6 days longer than that of the WM_CPM group or the WM_CHM group (P<0.01); CPS of the WM_CPM_CHM group was United States dollar (USD) 1,288 more than that of the WM group, and about USD 600 more than that of the WM_CPM group or the WM_CHM group (P<0.01). Compared with the WM group, odd ratio (OR) of recovered and improved outcome of the WM_CPM_CHM group was the highest [OR: 12.76, 95% confidence intervals (CI): 9.23, 17.64, P<0.01], OR of death outcome of the WM_CPM_CHM group was the lowest (OR: 0.08, 95% CI: 0.05, 0.12, P<0.01). There was no significant difference between LOS, CPS and OR of the WM_CPM group and those of the WM_CHM group (P>0.05). Cost/effectiveness and incremental cost-effectiveness ratio of the WM_CPM_CHM group were robustly higher than those of the WM group.

CONCLUSIONCompared with WM alone, supplementing CPM and CHM to WM provides significant health benefits of improving the chance of recovered and improved outcome, and reducing the death rate, at an expense of longer LOS and higher CPS.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Brain Ischemia ; complications ; drug therapy ; economics ; Child ; Child, Preschool ; Cost-Benefit Analysis ; Decision Trees ; Drug Therapy, Combination ; Female ; Hospitalization ; economics ; Humans ; Infant ; Infant, Newborn ; Length of Stay ; Linear Models ; Male ; Medicine, Chinese Traditional ; economics ; Middle Aged ; Patents as Topic ; Risk Factors ; Stroke ; complications ; drug therapy ; economics ; Treatment Outcome ; Young Adult

Ornithine decarboxylase (ODC) is the rate-limiting enzyme in polyamine biosynthesis and a target for chemoprevention. Hydroxydibenzoylmethane (HDB), a derivative of dibenzoylmethane of licorice, is a promising chemopreventive agent. In this paper, we investigated whether HDB would inhibit the ODC pathway to enhance apoptosis in human promyelocytic leukemia HL-60 cells. We found ODC enzyme activity was reduced during HDB treatment. Overexpression of ODC in HL-60 parental cells could reduce HDB-induced apoptosis, which leads to loss of mitochondrial membrane potential (Deltapsim), through lessening intracellular ROS. Furthermore, ODC overexpression protected cytochrome c release and the activation of caspase-3 following HDB treatment. The results demonstrated HDB-induced apoptosis was through a mechanism of down-regulation of ODC and occurred along a ROS-dependent mitochondria-mediated pathway.
Apoptosis/*drug effects ; Caspase 3/metabolism ; Chalcones/metabolism/*pharmacology ; Chemoprevention ; Cytochromes c/biosynthesis/secretion ; Down-Regulation ; Gene Expression ; HL-60 Cells ; Humans ; Immunoblotting ; Leukemia, Myeloid/*enzymology/pathology ; Membrane Potential, Mitochondrial/drug effects ; Mitochondria/enzymology ; Ornithine Decarboxylase/antagonists & inhibitors/genetics/*metabolism ; Reactive Oxygen Species/analysis/metabolism ; Reverse Transcriptase Polymerase Chain Reaction

OBJECTIVETo reveal the relationship of chronic pulmonary heart disease (CPHD) with the chemotactic factor Fractalkine (FKN) and tumor necrosis factor-alpha (TNF-alpha), and to explore the action mechanism of tetramethylpyrazine (TMP) for suppressing pulmonary hypertension.

METHODSPatients with CPHD were randomly assigned to two groups, 19 in Group A and 16 in Group B, and a control group (group C) consisting of 18 healthy adults was setup. Conventional treatment were given to all patients, which consisted of Piperacillin 3. 375 g iv dripping twice a day, Levofloxacin 0.6 g + Ambroxol 60 mg + Doxofylline 0.2 g iv dripping once a day, all for 10-14 days, and acid-base and electrolytes balance in patients were monitored and corrected. At the same time, TMP (trade name: Chuanqing, containing 120 mg of TMP in a 2 mL ampoule) was given additionally to patients in Group B at the dosage of 240 mg/d by adding in 250 mL of normal saline via iv dripping. Serum levels of FKN and TNF-alpha were detected before and after treatment by enzyme-linked immunoassay, and the change of mean pulmonary arterial pressure (mPAP) was measured as well.

RESULTSBefore treatment, difference of FKN and TNF-alpha levels between the two patients' groups were insignificant (P > 0.05), but all higher than those in Group C respectively (P < 0.01). While after treatment, the two indices and mPAP levels in Group B were statistically lower than those before treatment, also than those in Group A. Regression analysis showed a positive correlation between TNF-alpha and FKN (r = 0.662, P < 0.001).

CONCLUSIONSA high blood FKN and TNF-alpha expression state exists in CPHD patients, which could be suppressed by TMP, and these suppressive effects may be one of the important mechanisms responsible for the pulmonary arterial pressure lowering action of TMP.

Aged ; Aged, 80 and over ; Chemokine CX3CL1 ; metabolism ; Female ; Humans ; Male ; Middle Aged ; Pulmonary Heart Disease ; drug therapy ; metabolism ; Pyrazines ; pharmacology ; therapeutic use ; Tumor Necrosis Factor-alpha ; metabolism