New stemona alkaloids from the roots of Stemona sessilifolia

From the roots of Stemona sessilifolia, three new stemona-type alkaloids, namely stemosessifoine (1), isooxymaistemonine (2), and isomaistemonine (3), along with eight known alkaloids (bisdehydrostemoninine, isobisdehydrostemoninine, tuberostemonine, bisdehydrotuberostemonine, bisdehydrostemoninine, isobisdehydrostemoninine, stemoninine, and protostemonine), were isolated. Their structures were determined on the basis of extensive 2D-NMR spectroscopic-data analysis and by comparison with reported values in the literature. Compound 1 is a structurally unprecedented alkaloid, and it is depicted to be bioconverted from tuberostemonine as the precursor. Isooxymaistemonine (2) showed a positive effect on the human high-density lipoprotein (HDL) receptor gene CD36 and LIMP II analogous-1 (CLA-1) at the dosage of 10 microg/ml.     

Association of matrix metalloproteinases-9 gene polymorphisms with genetic susceptibility to esophageal squamous cell carcinoma

Matrix metalloproteinases-9 (MMP-9) plays important roles in tumor invasion and metastasis by degrading extracellular matrix components. Variations in the DNA sequence in the MMP-9 gene may lead to altered MMP-9 production and/or activity, and so this may modulate an individual's susceptibility to esophageal squamous cell carcinoma (ESCC). To test this hypothesis, we investigated the association of the MMP-9 polymorphisms and their haplotypes with the risk of ESCC in a Chinese population. There were significant differences in the genotype and allele distribution of P574R polymorphism of the MMP-9 gene among cases and controls. The P574R GG genotypes were associated with a significantly increased risk of ESCC as compared with the CC genotypes (odds ratio [OR] = 4.08; 95% confidence interval [CI]: 1.58-10.52; p = 0.00). Compared with 279R-574P haplotype, 279R-574R (OR = 3.52; 95% CI: 1.99-6.25) and 279Q-574P (OR = 2.16; 95% CI: 1.07-4.35) haplotypes can increase the onset risk of ESCC statistically, but the role of 279R-574R haplotype is more obvious. MMP-9 P574R polymorphisms and P574R-R279Q haplotype are significantly associated with the risk of ESCC. Our study shows for the first time that MMP-9 gene P574R polymorphism may contribute to a genetic risk factor for ESCC in a Chinese population.     

Adiponectin and metabolic syndrome in middle-aged and elderly Chinese

Objective: Hypoadiponectinemia is an important risk factor for metabolic syndrome (MetS). However, little is known about its role in the Chinese population. The aim of this study was to investigate the association between plasma adiponectin levels and MetS in middle‐aged and elderly Chinese from both urban and rural areas of northern and southern China. Methods and Procedures: This population‐based cross‐sectional study included 3,193 subjects aged 50–70 from urban and rural areas of Beijing (northern China) and Shanghai (southern China). Plasma adiponectin concentrations were measured using a high‐throughput micro‐assay, Luminex. MetS was identified with the updated National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) criteria. Results: Adiponectin levels were significantly higher in female, and rural subjects than in male or urban residents (P < 0.001). The prevalence and the number of MetS components progressively increased with declined adiponectin levels (P for trend <0.001). The participants in the lowest adiponectin quartile had a significantly increased risk for acquiring MetS (odds ratio (OR) 3.38, 95% confidence interval (CI) 2.56–4.46) after adjustment for potential confounders. Subjects from Beijing or rural areas had a higher risk for MetS at the same given level of adiponectin than did their Shanghai or urban counterparts, respectively. Discussion: Adiponectin is negatively associated with MetS in the middle‐aged and elderly Chinese independent of known confounders such as BMI, physical activity and life habits. The urban–rural and northern–southern differences in susceptibility to MetS should be taken into consideration for the early detection and prevention of MetS.     

Aurora kinase A inhibitors: identification, SAR exploration and molecular modeling of 6,7-dihydro-4H-pyrazolo-[1,5-a]pyrrolo[3,4-d]pyrimidine-5,8-dione scaffold

Tricyclic 6,7-dihydro-4H-pyrazolo[1,5-a]pyrrolo[3,4-d]pyrimidine-5,8-dione was identified as a novel scaffold for Aurora kinase A inhibition through virtual screening. SAR exploration coupled with molecular modeling of 8a reveals the minimum pharmacophore requirements for Aurora kinase A inhibition.     

Design, synthesis, and studies of small molecule STAT3 inhibitors

A series of small molecule STAT3 inhibitors originally derived from our lead compound STA 21 were synthesized and evaluated. The most potent compound in this series, compound 1, exhibited the same anti-proliferative activities as STA 21 against prostate cancer cell lines that express constitutively active STAT3. Molecular docking showed compound 1 bound to the STAT3beta SH2 domain in a similar manner as STA 21.     

The 2-D double layer structures of indium–benzenemulticarboxylate coordination polymers with green fluorescence

Two coordination polymers, [In(btc)(2,2′-bpy)(H₂O)]_n · nH₂O (1) and [In₂(btec)(2,2′-bpy)₂Cl₂]_n (2) (H₃btc = 1,3,5-benzenetricarboxylic acid, H₄btec = 1,2,4,5-benzenetetracarboxylic acid, 2,2′-bpy = 2,2′-bipyridine), have been prepared under hydrothermal conditions. Single-crystal X-ray diffraction analyses reveal that compounds 1 and 2 consist of two-dimensional double layer structures with (3, 3) grids and (4, 2) grids, respectively. The grids along two different directions in 1 are of the opposite chirality, while the interactions of double-layer sheets in 2 create a three-dimensional supramolecular network with one-dimensional tunnels. The additional green luminescences for both 1 and 2 in the solid state at low temperature imply the red shift of emission energy in the compounds, which may derive from LMCT. Their X-ray powder diffractions and thermogravimetric analyses are also discussed.     

Population genetic characterisation of dominant Cryptosporidium parvum subtype IIaA15G2R1

The subtype IIaA15G2R1 at the 60 kDa glycoprotein (gp60) gene locus is the most dominant Cryptosporidium parvum infecting dairy cattle and humans in industrialised nations. The reasons for its high transmissibility are not clear, and it remains to be determined whether this subtype represents a homogeneous parasite population. In this study, we sequence-characterised 26 IIaA15G2R subtype specimens and 26 non-IIaA15G2R subtype specimens from the United States, Canada, United Kingdom and Spain at seven other known polymorphic loci, including CP47, CP56, DZ-HRGP, MSC6-5, MSC6-7, RPGR and ZPT. Extensive heterogeneity within IIaA15G2R1 and discordance in typing results between gp60 and other genetic markers were observed. Results of inter-locus and intra-ZPT linkage disequilibrium and recombination analyses indicated that the heterogeneity within IIaA15G2R1 and discordance in typing results among genetic loci were largely due to the occurrence of genetic recombination, mostly within the gp60 subtype IIaA15G2R1. Although there was no clear population diversion between IIaA15G2R and non-IIaA15G2R subtypes, results of STRUCTURE and F_ST analyses suggested the presence of at least two subpopulations; subpopulation 1 had an epidemic population structure and was widely distributed, whereas subpopulation 2 had a clonal population structure and consisted of geographically segregated multilocus subtypes. Genetic recombination between epidemic and geographically segregated C. parvum populations appeared to be a driving force in the emergence of a hyper-transmissible IIaA15G2R1 subtype. Genetic recombination was observed even between the zoonotic IIa subtype family and anthroponotic subtype family IIc at CP56, MSC6-7 and ZPT. Thus, the IIaA15G2R1 subtype at gp60 is likely a fitness marker for C. parvum and the wide spread of IIaA15G2R1 subtype around the world is probably independent of the sequence characteristics at other genetic loci.     

SLIDE, the Protein Interacting Domain of Imitation Switch Remodelers, Binds DDT-Domain Proteins of Different Subfamilies in Chromatin Remodeling Complexes

The Imitation Switch (ISWI) type adenosine triphosphate (ATP)-dependent chromatin remodeling factors are conserved proteins in eukaryotes, and some of them are known to form stable remodeling complexes...