Aqua­(dicyanamido){μ-6,6′-dimeth­oxy-2,2′-[ethane-1,2-diylbis(nitrilo­methyl­idyne)]diphenolato}nickel(II)sodium

The mol­ecule of the title compound, [NaNi(C18H18N2O4)(C2N3)(H2O)], is approximately planar, with a maximum deviation from the mol­ecular plane of 0.770 (5) Å. The coordination environment of the Ni2+ ion is distorted square-planar and it is N2O2 coordinated by the 6,6′-dimeth­oxy-2,2′-[ethane-1,2-diylbis(nitrilo­methyl­idyne)]diphenolate Schiff base ligand. The Na+ atom is chelated by the four O atoms of the Schiff base ligand, a water ligand and a dicyanamide anion. The structure displays inter­molecular O—H⋯N hydrogen bonding

Aqua­(dicyanamido)­{μ-6,6′-dimeth­oxy-2,2′-[ethane-1,2-diylbis(nitrilo­methyl­i­dyne)]diphenolato}copper(II)sodium(I)

The mol­ecule of the title compound, [CuNa(C18H18N2O4)(C2N3)(H2O)], is almost planar, the maximum deviation from the mol­ecular plane being 0.48 (4) Å. The coordination environment of the Cu2+ ion is distorted square-planar and it is N 2 O 2-chelated by the Schiff base ligand. The Na+ cation has a distorted octahedral environment defined by the four O atoms of the 6,6′-dimeth­oxy-2,2′-[ethane-1,2-diylbis(nitrilo­methyl­idyne)]diphenolate ligand, a water ligand and a dicyanamide anion

{6,6′-Dieth­oxy-2,2′-[ethane-1,2-diylbis(nitrilo­methyl­idyne)]diphenolato}zinc(II) monohydrate

The mol­ecule of the title compound, [Zn(C20H22N2O4)]·H2O, deviates from planarity with a dihedral angle between the two benzene rings is 18.3 (1)°. The four-coordinate ZnII ion has a distorted square-planar coordination and is N2O2-chelated by the Schiff base ligand. The ZnII ion and solvent water mol­ecule are located on a twofold rotation axis. The structure displays inter­molecular O—H⋯O hydrogen bonding

Accumulation of the Mutations in Basal Core Promoter of Hepatitis B Virus Subgenotype C1 Increase the Risk of Hepatocellular Carcinoma in Southern China

Background: Hepatitis B virus (HBV) genotype C is associated with the development of hepatocellular carcinoma (HCC). In addition, HBV subgenotype C1 is the major subgenotype in Southern China. The aim of this study was to investigate whether there were the specific mutation patterns in HBV/C1 associated with Southern Chinese patients with HCC. Methods: Mutations in HBV basal core promoter (BCP) and their association with HCC were assessed in a matched cross-sectional control study of 102 HCC and 105 chronic hepatitis (CH) patients (from Guangdong, China) infected with HBV/C1. Functional analysis of HBx mutants was performed by the colony formation assay and the luciferase assays. Results: T1762/A1764 double mutations was frequently found in patients infected with HBV/C1, regardless of clinical status (64.7% in HCC and 51.4% in CH, P0.05). Unexpectedly, the adjacent V1753 or A1768 mutation significantly increased the risk of HCC (P0.05). Moreover, the prevalence of triple or quadruple mutations in BCP was significantly higher in patients with HCC than those with CH, particularly for HBeAg-positive-carriers (P0.05). Functional analysis revealed that T1762/A1764 mutation alone did not alter the transcriptional activity and the inhibitory effects on cell proliferation of HBx, but triple or quadruple mutations largely abrogated this effect.Conclusions: Accumulation of mutations involving V1753 or/and A1768 in addition to T1762/A1764 in BCP region were closely related to HCC among the patients infected with HBV/C1, particularly for HBeAg-positive-carriers. The increased risk of HCC caused by BCP variants may be attributable partially to modifying the biological functions of HBx

A novel FBN2 mutation in a Chinese family with congenital contractural arachnodactyly

AbstractCongenital contractural arachnodactyly (CCA, OMIM: 121050) is an autosomal dominant condition that shares skeletal features with Marfan syndrome (MFS, OMIM: 154700), including contractures, arachnodactyly, dolichostenomelia, scoliosis, crumpled ears and pectus deformities but excluding the ocular and cardiovascular complications that characterize MFS. These two similar syndromes result from mutations in two genes belonging to the fibrillin family, FBN1 and FBN2, respectively. We successfully identified a novel FBN2 mutation (C1406R) in a Chinese family with CCA for over five generations. This mutation was detected in the patients of this family but not in the seven unaffected family members or 100 normal individuals. SIFT and PolyPhen analyses suggested that the mutation was pathogenic. We identified a missense mutation in the calcium binding-epidermal growth factor (cbEGF)-like domain. Our study extends the mutation spectrum of CCA and confirms a relationship between mutations in the FBN2 gene and the clinical findings of CCA

Beneficial effects of silibinin on serum lipids, bile acids, and gut microbiota in methionine-choline-deficient diet-induced mice

Background and purposeSilibinin (SIL) is a flavonoid lignin isolated from the fruit and seeds of silybum marianum that exhibits good therapeutic potential for NASH. However, the effects of SIL on serum lipids, bile acids (BAs), and gut microbiota (GM) in NASH mice remain unknown. The present work aimed to explore the beneficial effects of SIL supplementation on serum lipids, bile acids, and gut microbiota in MCD mice.Experimental approachAfter male C57BL/6 mice were fed with a methionine-choline deficient (MCD) diet and simultaneously gavaged with SIL (20 mg/kg. d) for 8 weeks, the pathological changes of liver tissue were observed by oil red O, haematoxylin-eosin, and Masson tricolor staining; the levels of serum AST and ALT, and liver TG and MDA were detected by assay kits; metabonomics and 16S rDNA sequencing were used to analyze the composition of serum lipids and BAs and the abundance of GM; and the mRNA expression levels of hepatic genes related to BAs homeostasis were detected by RT-qPCR.ResultsThe results indicated that SIL treatment decreased the levels of 26 lipids (including four arachidonic acids, seven FFAs, 12 acyl carnitines, and three GPs) and two BAs (23-DCA, GLCA), while Dubosiella increased the levels of 10 lipids (including TxB3, PG16:0_18:1, Cer t18:0/24:0 and 7 TGs), five BAs (β-MCA, α-MCA, UDCA, 3-oxo-DCA and HCA), and two GMs (Verrucomicrobiota and Akkermansiaceae) of MCD mice, but had no significant effect on the mRNA expression of CYP7A1, CYP27A1, Bsep, Mrp2, Ntcp, or Oatp1b2. Therefore, influencing GM composition and then regulating the levels of serum lipids and BAs through enterohepatic axis should be an important mechanism of SIL-induced alleviative effect on MCD mice. More importantly, we found that SIL had a good coordination in regulating the abundance of GM and the contents of serum lipids and BAs in MCD mice, that is, when the abundance of probiotics was up-regulated, the content of beneficial unsaturated fatty acids in serum was up-regulated, while the serum levels of harmful lipids and BAs were down-regulated.ConclusionThe alleviating effect of SIL on NASH may be closely related to the correction of intestinal bacteria disorder, serum bile acid, and lipid metabolic disturbance in mice

Use of serial analysis of gene expression to reveal the specific regulation of gene expression profile in asthmatic rats treated by acupuncture

<p>Abstract</p> <p>Background</p> <p>Asthma has become an important public health issue and approximately 300 million people have suffered from the disease worldwide. Nowadays, the use of acupuncture in asthma is increasing. This study intended to systematically analyze and compare the gene expression profiles between the asthmatic and acupuncture-treated asthmatic rat lung, and tried to gain insight into the molecular mechanism underlying the early airway response (EAR) phase of asthma treated by acupuncture.</p> <p>Methods</p> <p>Four tag libraries of serial analysis of gene expression (SAGE) were established from lung tissues of control rats (CK), asthmatic rats (AS), asthmatic rats treated by acupuncture (ASAC), and control rats treated by acupuncture (CKAC). Bioinformatic analyses were carried out by using the methods including unsupervised hierarchical clustering, functional annotation tool of the database for annotation, visualization, and integrated discovery (DAVID), gene ontology (GO) tree machine, and Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis.</p> <p>Results</p> <p>There were totally 186 differentially expressed tags (P < 0.05, P_CK/AS) between the libraries of CK and AS, 130 differentially expressed tags between libraries of AS/ASAC (P < 0.05, P_AS/ASAC), and 144 differentially expressed tags between libraries of CK/CKAC (P < 0.05, P_CK/CKAC). The gene expression profiles of AS and ASAC were more similar than other libraries via unsupervised SAGE clustering. By comparison of P_CK/ASand P_AS/ASAC, the DAVID genes functional classification was found to be changed from "immune response" to "response to steroid hormone stimulus", and the GO term "antigen processing and presentation of peptide antigen" disappeared in P_AS/ASAC. Totally 3 same KEGG pathways were found among the three groups. Moreover, 21 specific tags of the acupuncture in treating asthma were detected using Venn diagrams.</p> <p>Conclusion</p> <p>Our SAGE research indicates that the gene expression profile of the EAR phase of asthma could be effectively and specifically regulated by acupuncture, which suggests that the gene expression of immune response and steroid hormone may play an important role in the treatment.</p

Proliferation-Attenuating and Apoptosis-Inducing Effects of Tryptanthrin on Human Chronic Myeloid Leukemia K562 Cell Line in Vitro

Tryptanthrin, a kind of indole quinazoline alkaloid, has been shown to exhibit anti-microbial, anti-inflammation and anti-tumor effects both in vivo and in vitro. However, its biological activity on human chronic myeloid leukemia cell line K562 is not fully understood. In the present study, we investigated the proliferation-attenuating and apoptosis-inducing effects of tryptanthrin on leukemia K562 cells in vitro and explored the underlying mechanisms. The results showed that tryptanthrin could significantly inhibit K562 cells proliferation in a time- and dose-dependent manner as evidenced by MTT assay and flow cytometry analysis. We also observed pyknosis, chromatin margination and the formation of apoptotic bodies in the presence of tryptanthrin under the electron microscope. Nuclei fragmentation and condensation by Hoechst 33258 staining were detected as well. The amount of apoptotic cells significantly increased whereas the mitochondrial membrane potential decreased dramatically after tryptanthrin exposure. K562 cells in the tryptanthrin treated group exhibited an increase in cytosol cyt-c, Bax and activated caspase-3 expression while a decrease in Bcl-2, mito cyt-c and pro-caspase-3 contents. However, the changes of pro-caspase-3 and activated caspase-3 could be abolished by a pan-caspase inhibitor ZVAD-FMK. These results suggest that tryptanthrin has proliferation-attenuating and apoptosis-inducing effects on K562 cells. The underlying mechanism is probably attributed to the reduction in mitochondria membrane potential, the release of mito cyt-c and pro-caspase-3 activation