We reported the discovery of six novel coumarins, toddasirins A-F (1-6), each endowed with modified isoprenyl or geranyl side chains, derived from the roots of Toddalia asiatica. Comprehensive structural elucidation was achieved through multispectroscopic analyses, single-crystal X-ray diffraction experiments, and advanced quantum mechanical electronic circular dichroism (ECD) calculations. Furthermore, the anti-inflammatory activity of these compounds was assessed. Notably, compounds 1-3 and 6 demonstrated notable inhibitory effects on nitric oxide (NO) production in lipopolysaccharide (LPS)-induced RAW 264.7 cells, with 50% inhibitory concentration (IC₅₀) values of 3.22, 4.78, 8.90, and 4.31 μmol·L^-1, respectively.
Mice ; Animals ; Coumarins/chemistry* ; Rutaceae/chemistry* ; Anti-Inflammatory Agents/pharmacology* ; Plant Extracts/chemistry* ; RAW 264.7 Cells ; Nitric Oxide ; Molecular Structure

OBJECTIVE: The aim of this study was to investigate ziprasidone plasma concentration, daily dose and clinical efficacy and safety in Han Chinese and Mongolian patients with first-episode schizophrenia. METHODS: A total of 123 inpatients affected by schizophrenia were recruited from the Mental Health Center of Inner Mongolia in China. Ziprasidone plasma concentration, clinical efficacy and side effects were systematically evaluated at baseline, and at 1, 2, 4, and 6 weeks. Metabolic measures such as changes in weight, body mass index (BMI), fasting blood glucose (FBG), triglycerides, and cholesterol, were also recorded. RESULTS: 90 patients completed the study. Compared with Han patients, on average, Mongolian patients received a significantly higher ziprasidone dosage for adequate symptom control during the 6-week period and had a lower plasma concentration-to-dose ratio. The Mongolian patients also experienced greater increases in weight and BMI. No significant differences between the two ethnic groups were found in the rate of reduction in the Positive and Negative Syndrome Scale (PANSS) score, Treatment Emergent Symptom Scale (TESS) total score, FBG, triglycerides, cholesterol or Q-Tc interval. CONCLUSION: Compared to Han Chinese patients, Mongolian patients appeared to have increased ziprasidone clearance and require higher doses to achieve effective treatment for schizophrenia.
Asian Continental Ancestry Group ; Blood Glucose ; Body Weight ; China ; Cholesterol ; Ethnic Groups ; Fasting ; Humans ; Inpatients ; Mental Health ; Plasma* ; Schizophrenia* ; Treatment Outcome ; Triglycerides

Objective To investigate the expressions of Wnt-1 and FZD-1 in small cell lung cancer(SCLC) patients and their relations with chemotherapy resistance,clinical feature and prognosis.Methods Peripheral blood specimens were collected from 41 SCLC patients.The expression of Wnt-1 and FZD-1 in peripheral blood monouclear cells (PBMC) were detected.The relationship among the expression of Wnt-1 and FZD-1,clinicopathologic feature and prognosis was analyzed.Results The relative expression of Wnt-1 and FZD-1 in chemotherapy resistant group was significantly higher than that in chemotherapy sensitive group (all P ＜ 0.05).The expression of Wnt-1was positively correlated with that of FZD-1 (r =0.186,P ＜ 0.05).The FZD-1expression level was not correlated with patients' age,sex and smoking history (all P ＞ 0.05),but closely with clinic-staging (P =0.008).The Wnt-1 expression level was not correlated with patients' clinical features (all P ＞ 0.05).There was statistical difference in median survival time between Wnt-1 and FZD-1 high-expression group and low-expression group.Conclusions Wnt-1 and FZD-1relationships with chemotherapy resistance and prognosis.Wnt-1 and FZD-1 may act as an important role in chemotherapy resistance of SCLC and could be served as indicators for the chemotherapy resistance and outcome assessment of SCLC.

Objective: To investigate the efficacy and safety of the recombinant human tumor necrosis factor receptor Ⅱ-IgG Fc fusion protein (rhTNFR: Fc, etanercept) for the treatment of occupational medicamentosa-like dermatitis induced by trichloroethylene (OMLDT) . Methods: In September 2011 to February 2016, 12 patients with OMLDT were treated with etanercept 25 mg, subcutaneous injection, twice per week, doubling of first dose. The course of treatment was 6 weeks. The drug eruption area and severity index (DASI) score, the proportion of patients achieving a 50%, 75% and 90% reduction in DASI (DASI50, DASI75, DASI90) and the serum level of TNF-α were used to assess the efficacy at different times. Adverse reactions were also recorded and evaluated. The results were statistically analyzed by nonparametric Friedman test and repetitive measurement ANOVA using the software SPSS19.0. Results: After 4 weeks treatment, the DASI score decreased form 56.33±7.02 to 0.50±0.91 (P<0.01) . The DASI50, DASI75 and DASI90 were all increased to 12 (100%) . The serum level of TNF-α decreased form (43.74±41.62) pg/ml to (3.03±0.47) pg/ml (P<0.01) . Statistically significant difference was observed from the above indexes. There were no adverse reactions in clinical application. Conclusion Recombinant human tumor necrosis factor receptor Ⅱ-IgG Fc fusion protein may be a safe and effective drug in the treatment of OMLDT.

Objective To observe the effects of Fuzheng Huayu Capsule on the expressions of the main roles, Rock1 and Rock2, in RhoA/Rock signal transduction pathway in rats with myocardial infarction (MI);To explore the possible mechanism of Fuzheng Huayu Capsule to improve ventricular remodeling in myocardial fibrosis. Methods The MI model was induced by ligation of the left coronary artery. Rats with MI were randomly divided into the model group, Fuzheng Huayu group and Fasudil hydrochloride group. A sham-operation group threading without ligation was setting as a control group, with eight rats in each group. The rats were treated with corresponding medicine for 4 weeks from the second day after modeling. The expression of Rock1, Rock2 and its mRNA were detected by immunohistochemical and real-time PCR method. Results The protein expression of Rock1 and Rock2 in model group were significantly higher than those in the sham-operation group (P<0.05). The protein expression of Rock1 and Rock2 in the Fuzheng Huayu group and Fasudil hydrochloride group were lower than those in the model group. The mRNA expression of Rock2 was significantly higher in the model group than that in the sham-operation group (P<0.05). The mRNA expression of Rock1 in the Fasudil hydrochloride group was lower than that in the model group (P<0.05). The mRNA expression of Rock2 in the Fuzheng Huayu group and Fasudil hydrochloride group was lower than that in the model group (P<0.05). Conclusion Fuzheng Huayu Capsule can decrease the expression of Rock1, Rock2 and Rock2 in the marginal zone of myocardial infarction in rats with MI. The anti ventricular remodeling mechanism of Fuzheng Huayu Capsule maybe related with this.

G protein-coupled receptors (GPCRs) are involved in all human physiological systems where they are responsible for transducing extracellular signals into cells. GPCRs signal in response to a diverse array of stimuli including light, hormones, and lipids, where these signals affect downstream cascades to impact both health and disease states. Yet, despite their importance as therapeutic targets, detailed molecular structures of only 30 GPCRs have been determined to date. A key challenge to their structure determination is adequate protein expression. Here we report the quantification of protein expression in an insect cell expression system for all 826 human GPCRs using two different fusion constructs. Expression characteristics are analyzed in aggregate and among each of the five distinct subfamilies. These data can be used to identify trends related to GPCR expression between different fusion constructs and between different GPCR families, and to prioritize lead candidates for future structure determination feasibility.
Animals ; Computational Biology ; Crystallography, X-Ray ; Gene Expression ; Humans ; Plasmids ; genetics ; metabolism ; Protein Domains ; Receptors, Adrenergic, beta-1 ; Receptors, G-Protein-Coupled ; classification ; genetics ; metabolism ; Receptors, Odorant ; metabolism ; Receptors, Purinergic P1 ; genetics ; metabolism ; Sf9 Cells ; Spodoptera

Experimental course for integrative life science curriculum is designed for medical students ,which integrates basic knowledge and skills of cellular biology,biochemistry,genetics,molec-ular biology,molecular genetics,and immunology disciplines. Tongji University School of Medicine start-ed to implement integration-based new curriculum system since 2010. This article discussed on teaching philosophy,teaching content,teaching methods,teaching team construction and explored the effect and significance of experimental course for integrative life science curriculum.

According to content of ‘lipid metabolism’,we crafted a effective case for problem based learning (PBL) and practiced it in biochemistry course.In group discussion,students participated in discussion with great enthusiasm and initiative.During the discussion,students got a better understanding about lipid metabolism and clinical application of the knowledge.As teachers,we maily guided students during PBL,and at the same time,we also summed up the experience and explored how PBL be implemented for freshmen and sophomores who lack clinical practice.

Objective To investigate the relationship between the plasma adiponectin concentration and coronary arteriosclerosis change in patient with coronary heart disease(CHD).Method 142 patients were divided into CHD group and control group according to the Coronary Angiography(CAG).CHD group were further divided into stable angina pectoris(SAP)subgroup and acute coronary syndrome (ACS)subgroup according to the clinical property.According to the type of coronary change,CHD group wag divided into A type group, B type group and C type group,meanwhile according to the degree of coronary lesion,CHD group was divided into light stenosis group, moderate stenosis group and severe stenosis group.The plasma adiponectin concentration was measured by ELISA.Results The plasma adiponectin concentration in CHD group was significant lower than that in control group.The plasma adiponectin concentration in ACS subgroup was significant lower than that in SAP subgroup.The plasma adiponectin concentration decreased gradually from A type group to C type group and from light stenosis group to severe stenosis group(P＜0.001).Conclusions Adiponectin is a negative regulatory factor of coronary atherosclerosis,and Hypoadiponectin may be used to predict the change of coronary arteriosclerosis and the stability of plaque.

Objective To investigate the effect of pancreatic ? cell dysfunction on abnormal glucose tolerance during Graves hyperthyroidism. Methods We investigated 6 healthy people and 36 Graves disease patients with abnormal glucose tolerance, and determined blood sugar and insulin at 0, 60 and 120 minutes after breakfast respectively. Then the HOMA-IR, HOMA-? and ISI were compared between the two groups. Results The HOMA-IR in the Graves disease patients with abnormal glucose tolerance is evidently higher than in the healthy subjects (P