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A phytochemical investigation on the 70% EtOH extract of the bark of Dysoxylum hainanense resulted in the isolation of four new triterpenoids, dysoxyhaines A–D ( 1–4 ). Structural elucidation of all the compounds were performed by spectral methods such as 1D and 2D ( 1 H 1 H COSY, HMQC, and HMBC) NMR spectroscopy, in addition to high resolution mass spectrometry. The isolated components were evaluated in vitro for anti-inflammatory activities for Cox-1 and Cox-2, and radical scavenging potential using ABTS ·+ and DPPH test. As a result, nor seco-olean type triterpenoid 1 exhibited significant anti-inflammatory potential, while tirucallane triterpenoids 3 and 4 showed radical scavenging activities. [ABSTRACT FROM AUTHOR]

Due to the existence of cancer stem cells (CSCs), persistence and relapse of human hepatocellular carcinoma (HCC) are common after treatment with existing anti-cancer therapies. Emerging evidence indicates that lipopolysaccharide (LPS) plays a crucial role in aggravating HCC, but information about the effect of LPS on CSCs of HCC remains scant. Here, we report that the stemness of CD133(+) CSCs sorted from the human HCC cell line Huh7 was maintained well when cells were cultured with LPS. The reduction of CD133 expression was much lesser in cultured CSCs in the presence of LPS. In response to LPS stimulation, CSCs showed an increase in their activity of clonogenesis and tumorigenesis. LPS also supported maintaining CSC abilities of migration, invasion, and chemo-resistance. Treatment with HIF-1α-specific siRNA significantly reduced CD133 expression by CSCs at both mRNA and protein levels. Further, the expression of HIF-1α and CD133 was reduced in LPS-stimulated CSCs when the NF-κB inhibitor was added to the cell culture. HIF-1α-specific siRNA also effectively counteracted the effect of LPS on maintaining CSC abilities of migration and invasion. These data indicate that LPS, an important mediator in the liver tumor microenvironment, supports the maintenance of CSC stemness through signaling of the NF-κB/HIF-1α pathway. Our current study highlights LPS as a potential target for developing new therapeutic approaches to eliminate CSCs during the treatment of HCC. [ABSTRACT FROM AUTHOR]

Aims: The aim of this research was to investigate the effects of cyclopropanyldehydrocostunolide (also named LJ), a derivative of sesquiterpene lactones (SLs), on high glucose (HG)-induced podocyte injury and the associated molecular mechanisms.Methods: Differentiated mouse podocytes were incubated in different treatments. The migration and albumin filtration of podocytes were examined by Transwell filters. The protein and mRNA levels of MCP-1 were measured using enzyme-linked immunosorbent assay (ELISA) and quantitative real-time PCR (q-PCR). Protein expression and phosphorylation were detected by western blot, and the nuclear translocation of NF-κB was performed with a confocal microscope. The gene expression of the receptor activator for NF-κB (RANK) was silenced by small interfering RNA (siRNA).Results: Our results showed that HG enhanced migration, albumin filtration and MCP-1 expression in podocytes. At the molecular level, HG promoted the phosphorylation of NF-κB/p65, IKKβ, IκBα, mitogen-activated protein kinase (MAPK) and the nuclear translocation of p65. LJ reversed the effects of HG in a dose-dependent manner. Furthermore, our data provided the first demonstration that the receptor activator for NF-κB ligand (RANKL) and its cognate receptor RANK were overexpressed in HG-induced podocytes and were downregulated by LJ. RANK siRNA also attenuated HG-induced podocyte injury and markedly inhibited the activation of NF-κB and MAPK signaling pathways.Conclusions: LJ attenuates HG-induced podocyte injury by suppressing RANKL/RANK-mediated NF-κB and MAPK signaling pathways. [ABSTRACT FROM AUTHOR]

Abstract: Using the first-principles density-functional theory within the generalized gradient approximation (GGA), we have investigated the structural, elastic, mechanical, electronic, and optical properties and phase transition of CuInO2. Structural parameters including lattice constants and internal parameter, pressure effects and phase transition pressure were calculated. We have obtained the elastic coefficients, bulk modulus, shear modulus, Young''s modulus and Poisson''s ratio. We find that two phases of CuInO2 are indirect band gap semiconductors (F–Γ and H–Γ for 3R and 2H, respectively). Optical properties, including the dielectric function, refractive index, extinction coefficient, reflectivity, absorption coefficient, loss function and optical conductivity have been obtained for radiations of up to 30eV. [Copyright &y& Elsevier]

The BTB (broad-complex, tram track, and bric-abrac) proteins are involved in developmental processes, biotic, and abiotic stress responses in various plants, but the molecular basis of protein interactions is yet to be investiagted in rice. In this study, the identified BTB proteins were divided into BTB-TAZ, MATH-BTB, BTB-NPH, BTB-ANK, BTB-Skp, BTB-DUF, and BTB-TPR subfamilies based on the additional functional domains found together with the BTB domain at N- and C-terminal as well. This suggesting that the extension region at both terminal sites could play a vital role in the BTB gene family expansion in plants. The yeast two-hybrid system, firefly luciferase complementation imaging (LCI) assay and bimolecular fluorescence complementation (BiFC) assay further confirmed that BTB proteins interact with several other proteins to perform a certain developmental process in plants. The overexpression of BTB genes of each subfamily in Arabidopsis revealed that BTB genes including OsBTB4 , OsBTB8 , OsBTB64 , OsBTB62 , OsBTB138 , and OsBTB147 , containing certain additional functional domains, could play a potential role in the early flowering, branching, leaf, and silique development. Thus we concluded that the presence of other functional domains such as TAZ, SKP, DUF, ANK, NPH, BACK, PQQ, and MATH could be the factor driving the diverse functions of BTB proteins in plant biology. [ABSTRACT FROM AUTHOR]

Metastasis and recurrence severely impact the treatment effect of hepatocellular carcinoma (HCC). HCC complicated with cholestasis is more prone to recurrence and metastasis. Previous studies have implicated pathogenesis of HCC by bile acid; however, the underlying mechanism is unknown yet. Glycochenodeoxycholate (GCDC) is one of most important component of bile acid (BA). In the present study, the role of GCDC in HCC cells invasion was detected by in vitro and in vivo assays. GCDC was found to significantly enhance the invasive potential of HCC cells; Further studies showed that GCDC could induce autophagy activation and higher invasive capability in HCC cells. Interestingly, inhibition of autophagy by chloroquine (CQ) reversed this phenomenon. Subsequently, the correlation between TBA expression level and clinicopathological characteristics was analyzed in HCC patients. Clinically, high TBA level in HCC tissue was found to be associated with more invasive and poor survival in HCC patients. Mechanistic study showed that bile acid induced autophagy by targeting the AMPK/mTOR pathway in HCC cells. Therefore, our results suggest that bile acid may promote HCC invasion via activation of autophagy and the level of bile acid may serve as a potential useful indicator for prognosis of HCC patients. • GCDC enhanced the metastasis of HCC which was mediated by autophagy. • AMPK/mTOR pathway contributed to the metastatic potential of HCC cells mediated by autophagy. • TBA level was correlated to autophagy activation and HCC prognosis in clinically specimens. [ABSTRACT FROM AUTHOR]

Abstract The GASA (GA- stimulated Arabidopsis) gene family is highly specific to plants, signifying a crucial role in plant growth and development. Herein, we retrieved 119 GASA genes in 10 different plant species in two major lineages (monocots and eudicots). Further, in the phylogenetic tree we classified these genes into four well-conserved subgroups. All the proteins contain a conserved GASA domain with similar characteristics and a highly specific 12-cysteine residue of the C-terminus position. According to the global microarray data and qRT-PCR based analysis, the OsGASA gene family was dominantly expressed in the seedling and transition phase of floral stages. Despite this, OsGASA genes profoundly contribute to rice grain size and length, whereas the highest abundance of transcript level was noticed in stage-2 (Inf 6, 3.0-cm-long spikelet) and stage-3 (Inf 7, 5.0-cm-long spikelet) under GA treatment during panicle formation. Additionally, the maximum expression level of these genes was recorded in response to GA and ABA in young seedlings. Further, in response to abiotic stresses, OsGASA1/8/10 was up- regulated by salt, OsGASA2/5/7 by drought, OsGASA3/6 by cold, and OsGASA4/9 by heat stress. With the exception of OsGASA4 , the higher transcription levels of all the other GASA genes were induced by Cd and Cr metal stresses (8–10 fold changes) at various time points. Finally, the GO ontology analysis of GASAs revealed the biological involvement in the GA-mediated signaling pathway and abiotic stresses. Prominently, most of these proteins are localized in cellular components such as the cell wall and extracellular region, where the molecular functions such as ATP binding and protein binding were observed. These results imply that GASAs are significantly involved in rice panicle developmental stages, responses to external stimuli, and hormones. [ABSTRACT FROM AUTHOR]

Owing to the triazene groups in the channel, Cd-MOF exhibits a good fluorescent response to Hg2+, which make it as a promising sensor for toxic ions. [Display omitted] A new cadmium metal–organic framework (Cd-MOF) has been synthesized by one-pot reaction between 5,5′-(triaz-1-ene-1,3-diyl)diisophthalic acid (H 4 TEDA) and cadmium acetate. Interestingly, the uncoordinated triazene groups locate in the channel of Cd-MOF. Moreover, the compound exhibits good luminescent property. Benefitting from the porosity, uncoordinated triazene group and luminescence property, Cd-MOF displays high selective response for Hg2+, which makes it as a potential sensor for detecting the toxic metal ions. [ABSTRACT FROM AUTHOR]

Abstract: Mutation-based molecular diagnostics of autosomal dominant polycystic kidney disease (ADPKD) is complicated by genetic and allelic heterogeneity, large multi-exon genes, and duplication sequences of PKD1. Recently, targeted resequencing by pooling long-range polymerase chain reaction (LR-PCR) amplicons has been used in the identification of mutations in ADPKD. Despite its high sensitivity, specificity and accuracy, LR-PCR is still complicated. We performed whole-exome sequencing on two unrelated typical Chinese ADPKD probands and evaluated the effectiveness of this approach compared with Sanger sequencing. Meanwhile, we performed targeted gene and next-generation sequencing (targeted DNA-HiSeq) on 8 individuals (1 patient from one family, 5 patients and 2 normal individuals from another family). Both whole-exome sequencing and targeted DNA-HiSeq confirmed c.11364delC (p.H3788QfsX37) within the unduplicated region of PKD1 in one proband; in the other family, targeted DNA-HiSeq identified a small insertion, c.401_402insG (p.V134VfsX79), in PKD2. These methods do not overcome the screening complexity of homology. However, the true positives of variants confirmed by targeted gene and next-generation sequencing were 69.4%, 50% and 100% without a false positive in the whole coding region and the duplicated and unduplicated regions, which indicated that the screening accuracy of PKD1 and PKD2 can be largely improved by using a greater sequencing depth and elaborate design of the capture probe. [Copyright &y& Elsevier]

Abstract: Danon disease is a rare X-linked lysosomal storage disease characterized by hypertrophic cardiomyopathy, myopathy and mental retardation, and is due to a primary defect in lysosome-associated membrane protein-2 (LAMP 2). More than 26 mutations in the LAMP2 gene have been described, including a small number of de novo mutations, some of which are suspected to be caused by germline mosaicism. Here, we describe the first molecularly documented evidence of somatic mosaicism for a LAMP2 mutation, identified in the asymptomatic mother of a boy with Danon disease caused by the frameshift mutation c.808dupG (p.A270Gfx3) within exon 6. In addition, in order to gain insight into the possible explanation for the mother''s lack of phenotype, the level of somatic mosaicism and the X-chromosome inactivation pattern were investigated. This study provides new insight into the causes of phenotypic variability in female mutation-carriers and underlines the importance of parental molecular testing for accurate genetic counseling for Danon disease. [Copyright &y& Elsevier]

Abstract: Structural, mechanical and thermodynamic properties of seven phases of SrHfO3 were studied using the plane-wave ultrasoft pseudopotential technique based on the first-principles density functional theory. Seven phases of SrHfO3 are found to be elastically stable with the cubic, tetragonal and orthorhombic structures and the most stable phase is orthorhombic (Pnma) structure. Moreover, we have obtained bulk and shear modulus using Voigt–Reuss–Hill approach, mechanical properties using anisotropy and ductility calculations, Dedye temperature using Debye–Grüneisen model. The calculated results show that atomic bonding along the z-axis is stronger (weaker) than that along the x-axis for P4/mbm, I4/mcm, Pnma (P4mm, Cmcm, Imma) phases. [Copyright &y& Elsevier]