Anti-inflammatory ent-cleistanthane-type diterpenoids from Phyllanthus rheophyticus.

A bioactivity-guided isolation from the aerial parts of Phyllanthus rheophyticus obtained 17 undescribed ent-cleistanthane-type diterpenoids, namely phyllarheophols A-Q, as well as 12 known analogs. Their structures were characterized by a combination of spectroscopic data interpretation, single-crystal X-ray diffraction and ECD analysis. The anti-inflammatory activities of these compounds were evaluated by measuring their inhibitory effects on NO production in LPS-stimulated RAW264.7 macrophages, and their preliminary structure-activity relationships were also discussed. Further study showed that promising compounds phyllarheophol D and phyacioid B significantly suppressed the expressions of cytokines and nitric oxide synthase through the NF-κB signaling pathway.

Diterpenoids with an unusual tricyclo[10.3.0.02,9]pentadecane skeleton from Pedilanthus tithymaloides as multidrug resistance modulators.

Three new diterpenoids with an unusual carbon skeleton, pedilanins A-C (1-3), and nine new jatrophane diterpenoids, pedilanins D-L (4-12), along with five known ones (13-17), were isolated from Pedilanthus tithymaloides. Compounds 1-3 characterize an unprecedented tricyclo[10.3.0.02,9]pentadecane skeleton. Compounds 4-8 are rare examples of the jatrophanes bearing a cyclic hemiketal substructure. Their structures were determined by an extensive analysis of HRESIMS, NMR, quantum-chemical calculation, DP4+ probability, and X-ray crystallographic data. In the bioassay, compounds 1-12 dramatically reversed multidrug resistance in cancer cells with the fold-reversals ranging from 17.9 to 396.8 at the noncytotoxic concentration of 10 µM. The mechanism results indicated that compounds 2 and 3 inhibited the P-glycoprotein (Pgp) transporter function, thus reversing the drug resistance.

Synthesis and discovery of Baylis-Hillman adducts as potent and selective thioredoxin reductase inhibitors for cancer treatment.

The selenoprotein thioredoxin reductase (TrxR) is of paramount importance in maintaining cellular redox homeostasis, and aberrant upregulation of TrxR is frequently observed in various cancers due to their elevated oxidative stress in cells. Thus, it seems promising and feasible to target the ablation of intracellular TrxR for the treatment of cancers. We report herein the design and synthesis of a series of Baylis-Hillman adducts, and identified a typical adduct that possesses the superior cytotoxicity against HepG2 cells over other types of cancer cells. The biological investigation shows the selected typical adduct selectively targets TrxR in HepG2 cells, which thereafter results in the collapse of intracellular redox homeostasis. Further mechanistic studies reveal that the selected typical adduct arrests the cell cycle in G1/G0 phase. Importantly, the malignant metastasis of HepG2 cells is significantly restrained by the selected typical adduct. With well-defined molecular target and mechanism of action, the selected typical adduct, even other Baylis-Hillman skeleton-bearing compounds, merits further development as candidate or ancillary agent for the treatment of various cancers.

Cardiac glycosides from Digitalis lanata and their cytotoxic activities.

Cardiac glycosides (CGs) are good candidates as drug leads in the treatment of cancer because of their structural diversities and potent biological activities. In this study, fifteen CGs including three new ones (1-3) were isolated from Digitalis lanata Ehrh. Their structures were elucidated by HRESIMS, NMR spectroscopic methods, including homonuclear and heteronuclear coupling constant analysis, and acid-catalyzed hydrolysis and derivatization analysis of the sugar chain. The cytotoxic activities of these CGs were evaluated against three human cancer cell lines (A549, HeLa and MCF-7 cell lines), and all of them showed strong activities at nanomolar scale. The flow cytometric analysis indicated that compound 1 induced cell cycle arrest in the G2/M phase. Transcriptome analysis revealed a panel of possible targets for compound 1. RT-PCR and western blot experiments showed that 1 significantly inhibited the expression of vasohibin-2 (VASH2). Moreover, compound 1 restrained angiogenesis in a concentration-dependent manner in the chick embryo chorioallantoic membrane (CAM) model.

Jatrolignans C and D: New Neolignan Epimers from Jatropha curcas.

Two new neolignans jatrolignans, C (1) and D (2), a pair of epimers, were isolated from the whole plants of Jatropha curcas L. (Euphorbiaceae). Their structures were determined with HRESIMS, IR, and NMR data analysis, and electronic circular dichroism (ECD) experiments via a comparison of the experimental and the calculated ECD spectra. Their antichlamydial activity was evaluated in Chlamydia abortus. They both showed dose-dependent antichlamydial effects. Significant growth inhibitory effects were observed at a minimum concentration of 40 µM.

Structural characterization of lignin and lignin-carbohydrate complex (LCC) of sesame hull.

In the present study, lignin and lignin-carbohydrate complex (LCC) constituting the cell wall structure of sesame hulls were investigated to explore novel techniques of dehulling. Milled wood lignin (MWL), Björkman LCC, and acid-soluble LCC (LCC-AcOH) were extracted from sesame hulls and characterized by carbohydrate composition analysis, molecular weight analysis, UV-vis spectroscopy, FT-IR, thermal analysis, Py-GC/MS, 2D HSQC NMR, and 31P NMR. The results showed that rhamnose accounted for the largest proportion of the lignin and LCC fractions, followed by glucose. Björkman LCC had the largest molecular weight, MWL had the smallest molecular weight, and LCC-AcOH had the largest polydispersity index. The lignin of sesame hulls consisted of syringyl (S), guaiacyl (G), p-hydroxyphenyl (H), and caffeyl alcohol (C) units. The most abundant monomer was guaiacyl (G), followed by caffeyl alcohol (C). C-type lignin is a new type of lignin that is different from the three traditional lignin monomers. The major lignin-linked bonds in the MWL and LCC-AcOH were ß-O-4' and ß-ß', and ß-5' bonds were present in the Björkman LCC. The major LCC chemical bonds in the three fractions were PhGly. These findings will provide the factual basis for exploring different dehulling methods to enhance the quality of sesame products.

Cytotoxic cardenolides from Calotropis gigantea.

Sixteen cardiac glycosides, including five previously undescribed compounds, were extracted and purified from whole plants of Calotropis gigantea (L.). Spectroscopic data and electronic circular dichroism (ECD) analyses were used to determine their structures. Calogiganin C is the first naturally occurring example of a cardenolide containing a 7-membered lactone in ring A. The cytotoxic activities of these compounds against A172, U251, AGS, PANC-1, HepG2, HCT116 and NCI-H226 cell lines were evaluated. Four of them exhibited the most potent growth inhibitory activity against a panel of human cancer cell lines, including A172, U251, AGS, PANC-1 and HCT116. Notably, uscharidin and calotropin showed pronounced cytotoxicities at low nanomolar concentrations against A172 and U251 cells, and possible cell death mechanism studies manifested that these two compounds induced G2/M cell cycle arrest, which demonstrated promising anticancer potential.

[Progress on wheat A genome illustration and its evolutional analysis].

Wheat is one of the main food crops and widely grown in the world. It feeds more than 35% of the world's population. Obtaining high-quality genome sequences of wheat is important for its basic and breeding researches. However, the large and complex genome of wheat once led to its genome sequencing as an "impossible task". Recently, with the development of high-throughput sequencing and assembly technology, many wheat genome sequences have been released, and their sequencing and assembly quality is being improved continuously. In the last two years, five wheat reference genomes with different ploidy levels have been published, including two diploid ancestors Triticum urartu (AA) and Aegilops tauschii (DD), wild and cultivated tetraploid wheat T. turgidum ssp. dicoccoides (BBAA) and hexaploid wheat T. aestivum (BBAADD). Among them, the sequencing and analysis of the T. urartu genome, a donor of polyploid wheat A subgenome, was led by the Institute of Genetics and Developmental Biology of the Chinese Academy of Sciences. In this review, we summarize the research progress on structure and evolution analyses of the T. urartu genome to provide some valuable information for promoting the basic and applied researches of wheat.

[Liver histological changes in chronic hepatitis B patients with elevated ALT less than 2 x ULN].

OBJECTIVE: To investigate the relevant factors of liver histological changes in chronic hepatitis B (CHB) patients with mildly elevated ALT and to explore the clinical values of these factors on anti-viral treatment. METHODS: A total of 152 CHB patients with mildly elevated ALT (less than 2 x ULN) who underwent liver biopsy were included in the study. Correlations between routine laboratory markers, liver histological inflammation grade and fibrosis stage were statistically assessed by Spearman correlation analysis, one-way ANOVA, area under the curve (AUC) of the receiver operating characteristic curves (ROC) and Logistic regression statistical analysis. RESULTS: All patients in the study showed various hepatic histological damages. Among the 152 patients 50 (32.9%) were found with inflammation grade 1 (G1), 42 (27.6%) with G2, 46 (30.3%) with G3 and 14 (9.2%) with G4. 16 patients (10.5%) were found with fibrosis stage 2 (S2), 25 (16.5%) with S3 and 41 (27.0%) with S4. Routine laboratory markers Alb, BPC and WBC were significantly correlated with hepatic histological inflammation grade and fibrosis stage. Marked liver fibrosis and moderate to severe liver damage were significantly higher in patients aged more than 40 years as compared to those less than 40 years of age (P = 0.002, P = 0.010). The regression equation P = 1/[1+e-(9.36250-1625Alb-0.0234BPC)] was established with sensitivity and specificity of 83.3% and 65.0%, respectively. CONCLUSION: 67.8% of CHB patients with mildly elevated ALT have significant injury to the liver tissue. CHB patients aged more than 40 years have a significant increase of marked liver fibrosis and moderate to severe liver damage. The regression equation is valuable to predict whether CHB patients need antiviral therapy or not.

[Analysis on detection of enterovirus nucleotides in feces samples of hand-foot-mouth disease patients after recovery].

OBJECTIVE: To explore the duration of enterovirus (EV) nucleotides positive in feces samples of hand-foot-mouth disease (HFMD) patients after recovery. METHODS: A consecutive 6-week follow up were carried out towards 49 cases of laboratory-diagnosed HFMD patients. A total of 5 - 8 g feces sample was collected from each patient once a week. The common EV nucleotides of HFMD were detected by RT-PCR method and analyzed by Kaplan-Meier Survival Analysis Method. RESULTS: The subtypes of the 49 HFMD patients included 16 enterovirus 71 (EV71), 15 coxsackievirus A16 (CoxA16) and 18 EV; a six-week follow up was carried out among all of them. In the first week, one EV71 patient and two EV patients were lost; in the fourth week, one CoxA16 were lost; and in the fifth week, one EV71 patient was lost. During the consecutive 6-week follow-up, the positive rates of EV nucleotides among EV71 patients were 81.3%, 60.9%, 47.4%, 33.9%, 27.1% and 18.1% separately; and the positive rates in CoxA16 group were 93.3%, 73.3%, 53.3%, 33.3%, 16.7% and 8.3% respectively. In EV group, the positive rates of EV nucleotides were 44.4% and 7.4% in the first two weeks and then turned to negative in the next 4 weeks. There was significant statistical difference in positive rates of EV nucleotides among different patients (χ(2) = 11.78, P = 0.001); however, each group of HFMD patients showed a declined trend with the extension of time. CONCLUSION: The duration of EV nucleotides positive in feces samples of HFMD patients lasted for a long period since their recovery; and the positive results in EV71 and CoxA16 patients might last for 6 weeks.

[Study on the quality of life and social support among people living with HIV/AIDS and their family members].

OBJECTIVE: To explore the quality of life and related social support among people living with HIV/AIDS with related factors. METHODS: 331 people living with HIV/AIDS and 148 of their family members were selected using a typical sampling method. Questionnaires on general conditions, tables on history of infection, generic quality of life inventory-74 (GQOLI-74) and social support scale (SSS) were used. RESULTS: Data from one-way analysis suggested that people living with HIV/AIDS and their family members with the different sexs, different villages and different cultural backgrounds had differences in GQOLI-74 scores (P < 0.05) while people living with HIV/AIDS with the different villages had differences in SSS scores (P < 0.05). Results from Multiple linear regression analysis revealed that being elderly and negative life events were negatively associated with social support (P < 0.05), while factors as more advanced educational background, harmonious neighborhood relationship and having bother pouring nature were the predictive factors (P < 0.05). CONCLUSION: Many factors might affect dimensions of quality of life among people living with HIV/AIDS and their family members in rural areas of northern Anhui. Community care and social support of HIV/AIDS should still be greatly enhanced in the countryside of China. A community care mode based on family and neighborhood was expected to be developed.

[Study on the equity of rural health service in the experimental region of new rural cooperative medical scheme, Yuexi county, Anhui province].

OBJECTIVE: To explore the situation of equity in health service delivery in the experimental region of new rural cooperative medical scheme (NRCMS). METHODS: A household questionnaire survey was conducted to 2112 residents in the experimental county of NRCMS in Yuexi county with a stratified-cluster sampling on the situation of health service delivery, from July 1-15,2005. Data was analyzed with Epi Info 6.04 and SPSS 11.0 software and indices as rate, ratio, Gini coefficient, concentration index (CI) and chi-square test etc. RESULTS: There was no significante difference of the treatment-seeking rate during two weeks among five groups economic condition residents (chi2 = 5.52, P > 0.05) and the rates were 48.14 per thousand, 82.90 per thousand, 65.88 per thousand, 48.72 per thousand and 50.66 per thousand respectively with CI = -0.026. Similarly, the hospitalization rates were 59.08 per thousand, 67.36 per thousand, 51.76 per thousand, 58.97 per thousand and 52.86 per thousand respectively in the last year and the CI = - 0.017. But there was a significante difference of rates on chronic disease among the five groups of residents with different economic conditions in the last six months (chi2 = 18.42, P < 0.01) and the rates were 295.40 per thousand, 243.52 per thousand, 230.59 per thousand, 225.64 per thousand and 176.21 per thousand and the CI = -0.055. When income reduced, the prevalence had been increasing among residents. Meanwhile, the collection funds showed unfair in residents with various income and the compensating fund of new rural cooperative medical scheme had not reduced the gap between rich and poor. CONCLUSION: There was an unequity of medicine expenditure and compensating fund in residents with various income in the experimental region. The low income residents had a high health service need and the government should improve NRCMS greatly to change the situation.