Aim The kinetics of nicotinic acetylcholine receptor (N-AChR) was stadied. MethodsThe saturation experiments of Torpedo electric organ N-AChR were taken with125I-?-BuTX. The results were calculated by Scatfit program. Experiments were thenperformed to study the kinetics of dissociation of ?-BuTX and nicotine from N-AChR,respectively. When their binding reached saturation, an excess of 1000 times ?-BuTX ornicotine was added. The saturation binding properties of the N-AChR extracted fromleg muscles of the 13th day chick embroys and optic lobes of the 20th day chick em-broys were studied. The results were calculated by Scatfit program. The othe experi-ments were taken to observe the competition between mcotine and 125I-?-BuTX forbinding with Torpedo, optic lobe and skeletal muscle of the chick N-AChRs. ResultsThe saturation experiments of Torpedo electric organ N-AChR resulted in a Scatchardplot of hyperbola which responded to the model of two kinds of receptor with on eli-gand.The difference of and B max between high affinity binding site and low affnitybineing site was significant. The dissaciation experiment showed that the fast dissocia-tion rate of tow ligands was 500 times more than that of the slow dissociation rate. Thisresult suggested that there may be two subtype N-AChRs.The saturation bindingproperties of N-AChR of leg muscles and optic lobe of the chick embroys revealed aScatchard plot of two kinds of N-AChR indicating a single type of site. The bindingaffinity of receptor of optic lobe was 100 times more than that of muscles. In competi-tion for Torpedo receptor by nicotine and 125I-?-BuTX, the values of IC50 were different:which suggested that two kinds of receptor sites were existent. In competition ofNicotine and 125I-?-BuTX for optic lobe and skeletal muscles of the chick N-AChR, thevalue IC50 of skeletal muscles N-AChR was 7. 7 times higher than that of optic lobe. Itindicated that two kinds of N-AChR subtype existed in the optic lobe and in theskeletal muscles of chick respectively. Conclusion N-AChR of Torpedo electric organcontains two kinds of subtype receptors. N-AChR of optic lobe of chick embroys is onesubtype receptor, and N-AChR of skeletal muscles of chick embroy is another subtypereceptor.

BACKGROUNDRosiglitazone is known as the most potent and specific peroxisome proliferators-activated receptor gamma (PPAR-gamma) ligand. It has potentially far-reaching effects on pathophysiological processes, from cancer to atherosclerosis and diabetes. However, it is not clear whether rosiglitazone affects the protein expression of transforming growth factor beta3 (TGF-beta3) and the cell proliferation in human uterine leiomyoma cells in vitro.

METHODSHuman uterine leiomyoma tissues were dissected and cultured. Cells were divided into 5 groups: one control group and other four groups with different concentrations of rosiglitazone (10(-7), 10(-8), 10(-9) and 10(-10) mol/L). Cells were cultured for 72 hours in serum-free Dulbecco's modified Eagle's medium. MTT reduction assay was used to detect the cell proliferation. Reverse transcription polymerase chain reaction (RT-PCR) was used to detect the mRNA expression of PPAR-gamma and TGF-beta3. Immunofluorescence staining was used to detect the expressions of PPAR-gamma and TGF-beta3 proteins.

RESULTSMTT reduction assay indicated that the treatment with rosiglitazone (from 10(-7) to 10(-9) mol/L) resulted in an inhibition of the cell growths after 72 hours (P < 0.01). RT-PCR analysis revealed that 10(-7) mol/L rosiglitazone significantly affected the gene expression at 72-hour: PPAR-gamma mRNA expression was up-regulated and TGF-beta3 mRNA was down-regulated and rosiglitazone at the concentration of 10(-7) mol/L affected these most effectively (P < 0.01). Immunofluorescence staining demonstrated that treatment with 10(-7) mol/L rosiglitazone resulted in the significant changes of PPAR-gamma and TGF-beta3 protein expressions compared with the other treatment groups and the control group at 72-hour (P < 0.01). All the effects of rosiglitazone on uterine leiomyoma cells were dose- and time-dependent in vitro.

CONCLUSIONSThe present study demonstrates that the PPAR-gamma activator, rosiglitazone, inhibits the cell proliferation partly through the regulations of PPAR-gamma and TGF-beta3 expressions. The cross-talk between the signal pathways of PPAR-gamma and TGF-beta3 may be involved in the process.

Cell Line, Tumor ; Cell Proliferation ; drug effects ; Female ; Gene Expression Regulation, Neoplastic ; drug effects ; Humans ; Leiomyoma ; drug therapy ; pathology ; PPAR gamma ; agonists ; analysis ; genetics ; RNA, Messenger ; analysis ; Thiazolidinediones ; pharmacology ; Transforming Growth Factor beta3 ; analysis ; genetics ; Uterine Neoplasms ; drug therapy ; pathology

Objective To investigate whether elevated baseline levels of high sensitivity C-Reactive Protein (hsCRP) and neutrophil (NE) are associated with an increased risk of breast cancer in Kailuan female cohort. Methods Females from Kailuan cohort (2006-2007) were included in this study. Information on check-up, hsCRP and NE were collected at baseline for all subjects. Multivariable Cox proportional hazards regression models were used to calculate hazard ratios (HR) and 95% confidence intervals (95%CI) of association between baseline hsCRP and NE values and breast cancer risk. Results By December 31, 2015, a total of 18 866 participants were enrolled in this study. During the follow-up, 183 new cases of breast cancer were observed. All participants were divided into three groups according to the level of hsCRP (<1 mg/L, 1-3 mg/L and >3 mg/L). The cumulative incidence of breast cancer were 829/105, 1 211/105 and 1 495/105 in these 3 groups, respectively ( 2=12.08， P=0.002). Compared with participants with lower hsCRP levels (<1 mg/L), individuals with the highest hsCRP (>3 mg/L) levels had significantly increased risk of breast cancer (HR=1.71,95%CI: 1.18-2.47, P=0.005), howerver, we didn’t find the statistically significant association between NE level (<3.70×109/Lvs. ≥3.70×109/L) and the risk of brease cancer (P>0.05). Conclusions Elevated levels of hsCRP at baseline might increase the risk of breast cancer in females.

OBJECTIVETo evaluate the safety of recombinant human interferon alpha-2b for nasal spray for the prevention of SARS and other upper respiratory viral infections.

METHODSField epidemiologic evaluation was conducted, the design was randomized and had a synchronously parallel control group. In the study, the drugs were given for five days and all subjects were followed up for ten days.

RESULTSDuring the period of using interferon, body temperature of the experimental group was normal compared to the control group. Experimental group had more influenza-like symptoms than the control group (P < 0.05), such as headache (4.83%-7.09%), dizziness (7.17%-11.63%), lassitude (8.55%-15.06%), muscular soreness (4.43%-7.09%), pharynx dryness (12.10%-17.85%), angina (6.25%-8.72%), abdominal pain (2.30%-5.50%) and diarrhea (2.45%-5.66%). Most of side effects reached their peak with in the first 3 days. Except for pharynx dryness, the incidences of all other side effects declined after completion of the use of the trial drug, and incidences of some symptoms in experimental group were lower than those of the control group. There were no significant differences in the symptoms of cough and expectoration between the experimental group and the control group. The incidence of exanthem in the control group was significantly higher than that in the experimental group. The side effect of bloody nasal mucus was not observed in experimental group, which had been reported by other authors in several volunteer studies.

CONCLUSIONUsing recombinant human interferon alpha-2b for nasal spray could lead to some influenza-like symptoms, however, all those symptoms were mild , reversible, and relieved after completion of the use of the trial drug. No serious side effects were found during the period of following up. The authors conclude that the drug is safe.

Abdominal Pain ; chemically induced ; Adolescent ; Adult ; Antiviral Agents ; administration & dosage ; adverse effects ; therapeutic use ; Dizziness ; chemically induced ; Female ; Follow-Up Studies ; Headache ; chemically induced ; Humans ; Interferon-alpha ; administration & dosage ; adverse effects ; therapeutic use ; Male ; Recombinant Proteins ; SARS Virus ; drug effects ; Severe Acute Respiratory Syndrome ; prevention & control ; virology ; Treatment Outcome ; Young Adult

Objective: Several COVID-19 patients have overlapping comorbidities. The independent role of each component contributing to the risk of COVID-19 is unknown, and how some non-cardiometabolic comorbidities affect the risk of COVID-19 remains unclear. Methods: A retrospective follow-up design was adopted. A total of 1,160 laboratory-confirmed patients were enrolled from nine provinces in China. Data on comorbidities were obtained from the patients' medical records. Multivariable logistic regression models were used to estimate the odds ratio ( Results: Overall, 158 (13.6%) patients were diagnosed with severe illness and 32 (2.7%) had unfavorable outcomes. Hypertension (2.87, 1.30-6.32), type 2 diabetes (T2DM) (3.57, 2.32-5.49), cardiovascular disease (CVD) (3.78, 1.81-7.89), fatty liver disease (7.53, 1.96-28.96), hyperlipidemia (2.15, 1.26-3.67), other lung diseases (6.00, 3.01-11.96), and electrolyte imbalance (10.40, 3.00-26.10) were independently linked to increased odds of being severely ill. T2DM (6.07, 2.89-12.75), CVD (8.47, 6.03-11.89), and electrolyte imbalance (19.44, 11.47-32.96) were also strong predictors of unfavorable outcomes. Women with comorbidities were more likely to have severe disease on admission (5.46, 3.25-9.19), while men with comorbidities were more likely to have unfavorable treatment outcomes (6.58, 1.46-29.64) within two weeks. Conclusion Besides hypertension, diabetes, and CVD, fatty liver disease, hyperlipidemia, other lung diseases, and electrolyte imbalance were independent risk factors for COVID-19 severity and poor treatment outcome. Women with comorbidities were more likely to have severe disease, while men with comorbidities were more likely to have unfavorable treatment outcomes.
Adult ; Aged ; COVID-19/virology* ; China/epidemiology* ; Comorbidity ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Severity of Illness Index ; Treatment Outcome