Astragalus membranaceus Inhibits Peritoneal Fibrosis via Monocyte Chemoattractant Protein (MCP)-1 and the Transforming Growth Factor-β1 (TGF-β1) Pathway in Rats Submitted to Peritoneal Dialysis

Inflammation and transforming growth factor-β1 (TGF-β1) contribute to the development of peritoneal fibrosis (PF), which is associated with peritoneal dialysis (PD). Astragalus membranaceus (Astragalus) has anti-inflammatory and anti-fibrotic effects in many diseases. The goal of this study was to determine the anti-fibrotic effects of Astragalus on the PF response to PD. A rat model of PD was induced using standard PD fluid, and PF was verified by HE and Masson’s staining, as well as through the expression of fibroblast surface protein (FSP) and collagen III. The expression levels of monocyte chemoattractant protein (MCP)-1, F4/80 (macrophage/monocyte marker in rat), TGF-β1 and the downstream proteins phospho-SMAD 2/3 in dialyzed peritoneal tissue treated with or without Astragalus was evaluated using immunohistochemistry analysis. Overall correlations between MCP-1 and TGF-β1 staining were analyzed using both the Spearman and Pearson methods. The results showed that Astragalus could inhibit the recruitment and activation of monocytes/macrophages, thereby reducing the production of TGF-β1 in the dialyzed peritoneal membrane. PF was also significantly decreased following treatment with Astragalus. MCP-1 expression had a strong positive correlation with TGF-β1 sensitivity, suggesting that the anti-fibrotic function of Astragalus was mediated by MCP-1 and the TGF-β1 pathway. Our results indicate that Astragalus could be a useful agent against PD-induced PF.     

β-Ketoacyl-acyl Carrier Protein Synthase I (KASI) Plays Crucial Roles in the Plant Growth and Fatty Acids Synthesis in Tobacco

Fatty acids serve many functions in plants, but the effects of some key genes involved in fatty acids biosynthesis on plants growth and development are not well understood yet. To understand the functions of 3-ketoacyl-acyl-carrier protein synthase I (KASI) in tobacco, we isolated two KASI homologs, which we have designated NtKASI-1 and NtKASI-2. Expression analysis showed that these two KASI genes were transcribed constitutively in all tissues examined. Over-expression of NtKASI-1 in tobacco changed the fatty acid content in leaves, whereas over-expressed lines of NtKASI-2 exhibited distinct phenotypic features such as slightly variegated leaves and reduction of the fatty acid content in leaves, similar to the silencing plants of NtKASI-1 gene. Interestingly, the silencing of NtKASI-2 gene had no discernibly altered phenotypes compared to wild type. The double silencing plants of these two genes enhanced the phenotypic changes during vegetative and reproductive growth compared to wild type. These results uncovered that these two KASI genes had the partially functional redundancy, and that the KASI genes played a key role in regulating fatty acids synthesis and in mediating plant growth and development in tobacco.     

Poly(β-3-methylmalic acid): A new degradable functional polyester with two stereogenic centers in the main chain

Summary Racemic ((3S,4R)-(3R,4S))-3-methyl-4-benzyloxycarbonyl-2-oxetanone has been prepared by a simple and reproductible method starting from a racemic mixture of threo-((2S,3S)-(2R,3R))-3-methylaspartic acid as chiral precursor. This , substituted -lactone has been polymerized anionically, using tetraethylammonium benzoate as initiator, to yield high molecular weight and amorphous racemic threo-poly(-benzyl-3-methylmalate). The catalytic cleavage of protecting benzyl ester groups has been conducted in different solvents and racemic threo-poly(-3-methylmalic acid) has been obtained in N-methylpyrrolidone at room temperature. Racemic threo-poly(-3-methylmalic acid-co-benzyl--3-methylmalate) has been prepared by heterogeneous H₂/Pd charchoal catalyzed partial hydrogenolysis of the polymer precursor. Solubility of these different materials has been considered. Hydrolysis of threo-poly(-3-methylmalic acid) has conducted to racemic threo-3-methylmalic acid. High resolution ¹³C NMR and selective INEPT NMR have been used for resonances assignment of polymers and copolymers. This new poly(-hydroxy acid) type polyester expands the family of poly(-malic acid) derivatives by opening the route for tailor making functional polystereoisomers with two stereogenic centers in the main chain and with the presence of an hydrophobic alkyl group and an hydrophilic carboxylic acid group in the macromolecule.     

Enhanced Inhibition of Prostate Tumor Growth by Dual Targeting the Androgen Receptor and the Regulatory Subunit Type Iα of Protein Kinase A in Vivo

Progression to castration resistance is a major problem in the treatment of advanced prostate cancer and is likely to be driven by activation of several molecular pathways, including androgen receptor (AR) and cyclic AMP-dependent protein kinase A (PKA). In this study, we examined the therapeutic efficacy of a combined inhibition of the AR and the regulatory subunit type Iα (RIα) of protein kinase A with second generation antisense oligonucleotides (ODNs) in androgen-sensitive LNCaP and castration-resistant LNCaPabl tumors in vivo. We found that targeting the AR alone inhibited LNCaP, as well as LNCaPabl tumors. Combined inhibition resulted in an improved response over single targeting and even a complete tumor remission in LNCaPabl. Western blot analysis revealed that both ODNs were effective in reducing their target proteins when administered alone or in combination. In addition, treatment with the ODNs was associated with an induction of apoptosis. Our data suggest that dual targeting of the AR and PKARIα is more effective in inhibiting LNCaP and LNCaPabl tumor growth than single treatment and may give a treatment benefit, especially in castration-resistant prostate cancers.     

Inositol (1,4,5)-Trisphosphate Receptors in Invasive Breast Cancer: A New Prognostic Tool?

Simple SummaryThe inositol-trisphosphate receptor (IP₃R) is a key player in physiological and pathological intracellular calcium signaling. The objective of the present study was to assess the putative value of the three IP₃R subtypes as prognostic biomarkers in breast cancer. We found that IP₃R3 is the most strongly expressed subtype in breast cancer tissue. Furthermore, IP₃R3 and IP₃R1 are significantly more expressed in invasive breast cancer tissue than in non-tumor tissue. In contrast to IP₃R1 and IP₃R2, the expression of IP₃R3 was positively correlated with prognostic factors including tumor size, regional node invasion, histologic grade, proliferation index, and hormonal status. By analyzing public databases, we found that the expression of all IP₃R subtypes is significantly correlated with the overall survival and disease-free survival of patients with breast cancer. We conclude that relative to the other two IP₃R subtypes, IP₃R3 expression is upregulated in breast cancer and is correlated with prognostic factors. We strongly believe that our results will open up new perspectives with regard to the link between IP₃Rs and breast cancer aggressiveness.AbstractBreast cancer is the leading cause of cancer death among women in worldwide and France. The disease prognosis and treatment differ from one breast cancer subtype to another, and the disease outcome depends on many prognostic factors. Deregulation of ion flux (especially Ca²⁺ flux) is involved in many pathophysiology processes, including carcinogenesis. Inside the cell, the inositol-trisphosphate receptor (IP₃R) is a major player in the regulation of the Ca²⁺ flux from the endoplasmic reticulum to the cytoplasm. The IP₃Rs (and particularly the IP₃R3 subtype) are known to be involved in proliferation, migration, and invasion processes in breast cancer cell lines. The objective of the present study was to evaluate the potential value of IP₃Rs as prognostic biomarkers in breast cancer. We found that expression levels of IP₃R3 and IP₃R1 (but not IP₃R2) were significantly higher in invasive breast cancer of no special type than in non-tumor tissue from the same patient. However, the IP₃R3 subtype was expressed more strongly than the IP₃R1 and IP₃R2 subtypes. Furthermore, the expression of IP₃R3 (but not of IP₃R1 or IP₃R2) was positively correlated with prognostic factors such as tumor size, regional node invasion, histologic grade, proliferation index, and hormone receptor status. In an analysis of public databases, we found that all IP₃Rs types are significantly associated with overall survival and progression-free survival in patients with breast cancer. We conclude that relative to the other two IP₃R subtypes, IP₃R3 expression is upregulated in breast cancer and is correlated with prognostic factors.     

Dihydroaustrasulfone Alcohol (WA-25) Impedes Macrophage Foam Cell Formation by Regulating the Transforming Growth Factor-β1 Pathway

Atherosclerosis is considered an inflammatory disease. However, clinically used anti-atherosclerotic drugs, such as simvastatin, have many side effects. Recently, several unique marine compounds have been isolated that possess a variety of bioactivities. In a previous study, we found a synthetic precursor of the marine compound (austrasulfone), which is dihydroaustrasulfone alcohol (WA-25), has anti-atherosclerotic effects in vivo. However, the detailed mechanisms remain unclear. Therefore, to clarify the mechanisms through which WA-25 exerts anti-atherosclerotic activity, we used RAW 264.7 macrophages as an in vitro model to evaluate the effects of WA-25. In lipopolysaccharide (LPS)-stimulated RAW 264.7 cells, WA-25 significantly inhibited expression of the pro-inflammatory proteins, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). In contrast, simvastatin increased the COX-2 expression compared to WA-25. In addition, WA-25 impedes foam cell formation and up-regulated the lysosomal and cyclic adenosine monophosphate (cAMP) signaling pathway. We also observed that transforming growth factor β1 (TGF-β1) was up-regulated by WA-25 and simvastatin in LPS-induced RAW 264.7 cells, and the promising anti-atherosclerosis effects of WA-25 were disrupted by blockade of TGF-β1 signaling. Besides, WA-25 might act through increasing lipolysis than through alteration of lipid export. Taken together, these data demonstrate that WA-25 may have potential as an anti-atherosclerotic drug with anti-inflammatory effects.     

Unraveling the Early Events of Amyloid-β Protein (Aβ) Aggregation: Techniques for the Determination of Aβ Aggregate Size

The aggregation of proteins into insoluble amyloid fibrils coincides with the onset of numerous diseases. An array of techniques is available to study the different stages of the amyloid aggregation process. Recently, emphasis has been placed upon the analysis of oligomeric amyloid species, which have been hypothesized to play a key role in disease progression. This paper reviews techniques utilized to study aggregation of the amyloid-β protein (Aβ) associated with Alzheimer's disease. In particular, the review focuses on techniques that provide information about the size or quantity of oligomeric Aβ species formed during the early stages of aggregation, including native-PAGE, SDS-PAGE, Western blotting, capillary electrophoresis, mass spectrometry, fluorescence correlation spectroscopy, light scattering, size exclusion chromatography, centrifugation, enzyme-linked immunosorbent assay, and dot blotting.     

仁兴集团(展位号:E3A01)

正仁兴集团成员内仁兴机器厂有限公司是历史最悠久的,该公司二十世纪五十年代成立于香港,致力研制注塑成型机,是香港该行始创者之一。创业至今都以质量及信誉奉为经营之道,六十年多来所研制的各系列注塑成型机均以质量优越而享誉国际。仁兴集团九十年代初自资在深圳兴建厂房及购置进口生产设备,并成立了仁兴机械(深圳)有限公司;获得英国BSI ISO9001质量管理证书。2011年引入了管理更全面、分析能力更优化的ERP企业资源规划系统;2013年获《香港星级品牌大奖2013》-企业     

Competitive Binding of Off-Flavor Compounds with Soy Protein and β-Cyclodextrin in a Ternary System: A Model Study

Removal of soy protein (SP)-bound 2-nonanone by β-cyclodextrin (βCD) was studied using an equilibrium dialysis technique. It was observed that in the presence of βCD, a significant (p < 0.05) amount of SP-bound 2-nonanone could be removed in a concentration-dependent manner. Up to 94% of SP-bound 2-nonanone was stripped from SP when 6 mM βCD was present in the system. However, in thermodynamic terms, the net standard free energy change for transfer of 2-nonanone from SP to βCD, i.e., \( \Updelta \Updelta G^\circ_{{{\text{SP}} \to \beta {\text{CD}}}} \), was essentially zero, implying that the apparent equilibrium binding constant for the formation of βCD–2-nonanone complex was essentially same as that for the SP–2-nonanone complex formation in the ternary system. This indicated that stripping-off of 2-nonanone from SP by βCD was driven by the mass action ratio. Based on these results, it is shown that βCD can be used effectively for removing SP-bound off-flavor carbonyl compounds.     

A Novel Human TGF-β1 Fusion Protein in Combination with rhBMP-2 Increases Chondro-Osteogenic Differentiation of Bone Marrow Mesenchymal Stem Cells

Transforming growth factor-beta (TGF-β) is involved in processes related to the differentiation and maturation of osteoprogenitor cells into osteoblasts. Rat bone marrow (BM) cells were cultured in a collagen-gel containing 0.5% fetal bovine serum (FBS) for 10 days in the presence of rhTGF (recombinant human TGF)-β1-F2, a fusion protein engineered to include a high-affinity collagen-binding decapeptide derived from von Willebrand factor. Subsequently, cells were moderately expanded in medium with 10% FBS for 4 days and treated with a short pulse of rhBMP (recombinant human bone morphogenetic protein)-2 for 4 h. During the last 2 days, dexamethasone and β-glycerophosphate were added to potentiate osteoinduction. Concomitant with an up-regulation of cell proliferation, DNA synthesis levels were determined. Polymerase chain reaction was performed to reveal the possible stemness of these cells. Osteogenic differentiation was evaluated in terms of alkaline phosphatase activity and mineralized matrix formation as well as by mRNA expression of osteogenic marker genes. Moreover, cells were placed inside diffusion chambers and implanted subcutaneously into the backs of adult rats for 4 weeks. Histological study provided evidence of cartilage and bone-like tissue formation. This experimental procedure is capable of selecting cell populations from BM that, in the presence of rhTGF-β1-F2 and rhBMP-2, achieve skeletogenic potential in vitro and in vivo.     

Enhancement of scaffolding properties for poly(3-hydroxybutyrate): blending with poly-β-alanine and wet electrospinning

Poly-β-alanine (PBA), and its derivatives poly(α-methyl-β-alanine) and poly[N-(3-methoxypropyl-β-alanine) were synthesized by hydrogen transfer polymerization (HTP). Porous 3?D matrices of poly(3-hydroxybutyrate) (P3HB) reinforced with PBA/its derivatives were obtained via lyophilization and wet electrospinning. However, mechanical properties of the porous matrices prepared by wet electrospinning were found to present superior performance for tissue engineering applications. Cell culture study was performed by using wet electrospun P3HB matrices doped with 10% (w/w) PBA which show better manipulation ability, chemical and mechanical properties. Scaffolds of P3HB-PBA (10% w/w) blend was determined to demonstrate better cell attachment and proliferation compared to the scaffolds of pure P3HB.     

A novel Zn(II) framework with 3-fold interpenetrating α-polonium topology

A novel coordination polymer [Zn₂(dbi)(m-BDC)₂]_n (1), where dbi = 1,1′-(1,10-decanediyl)bis(imidazole) and m-BDC = 1,3-benzenedicarboxylate anion, has been isolated under hydrothermal condition and characterized by single-crystal X-ray diffraction. The compound 1 displays a 3-fold interpenetrated α-polonium-type network, which is built from bimetallic cores as six-connected nodes. Thermal gravimetric analysis (TGA) and luminescent property for 1 are discussed in detail.     

LaCr1-xFexO3 (0≤x≤0.7): A novel NTC ceramic with high stability

Perovskite-phase LaCr_1-xFe_xO₃ (0 ≤ x ≤ 0.7) ceramics were fabricated by two-step sintering of powders synthesized by conventional solid-state reaction. XRD patterns reveals that the ceramics are single-phased LaCr_1-xFe_xO₃ solid solution at lower Fe contents, but form a biphasic mixture of LaCrO₃-LaFeO₃ at higher Fe contents. SEM analysis indicates that Fe doping causes a reduction in porosity, and a corresponding increase in density. The effects of Fe doping on electrical properties have also been investigated. The electrical resistivity ρ_25°C decreases initially and then increases within a wide range of 634.4–83915.9 Ω·cm with increasing Fe content, whereas B varies within a relatively narrow range of 3651−4301 K. Such combination enables it to be a potential candidate for NTC thermistors. An investigation of elevated-temperature aging behavior shows that the resistance shifts at 25 °C were less than 0.65 % after annealing at 125 °C in air for 1000 h, revealing that the material exhibits excellent stability.     

Atomic Force Microscopy Study of Protein–Protein Interactions in the Cytochrome CYP11A1 (P450scc)-Containing Steroid Hydroxylase System

Atomic force microscopy (AFM) and photon correlation spectroscopy (PCS) were used for monitoring of the procedure for cytochrome CYP11A1 monomerization in solution without phospholipids. It was shown that the incubation of 100 μM CYP11A1 with 12% Emulgen 913 in 50 mM KP, pH 7.4, for 10 min at T = 22°C leads to dissociation of hemoprotein aggregates to monomers with the monomerization degree of (82 ± 4)%. Following the monomerization procedure, CYP11A1 remained functionally active. AFM was employed to detect and visualize the isolated proteins as well as complexes formed between the components of the cytochrome CYP11A1-dependent steroid hydroxylase system. Both Ad and AdR were present in solution as monomers. The typical heights of the monomeric AdR, Ad and CYP11A1 images were measured by AFM and were found to correspond to the sizes 1.6 ± 0.2 nm, 1.0 ± 0.2 nm and 1.8 ± 0.2 nm, respectively. The binary Ad/AdR and AdR/CYP11A1_mon complexes with the heights 2.2 ± 0.2 nm and 2.8 ± 0.2 nm, respectively, were registered by use of AFM. The Ad/CYP11A1_mon complex formation reaction was kinetically characterized based on optical biosensor data. In addition, the ternary AdR/Ad/CYP11A1 complexes with a typical height of 4 ± 1 nm were AFM registered.     

A randomly branched poly(hydroxyl-β-amino amide): synthesis and complexation

A novel type of polycation with high density of discrete charge, diversified amino group type and abundant hydrophilic short-chains was synthesized from tetraethylenepentamine (TEPA) and glycidol acrylate. The obtained polycation was abbreviated as PTGA. The structure and protonation property of PTGA was characterized by ¹H NMR, FTIR, GPC and acid-base titration. ¹H NMR of PTGA indicated that there were not only Michael addition and ring-opening but also high degree of amidation during polymerization. Only 12% ester group was left after polymerization. So PTGA is a kind of poly(hydroxyl-β-amino amide). Acid base titration indicated that the protonation of PTGA has wide protonation range and shows obvious proton sponge effect. The complexation of PTGA with polyanion was studied by using poly(acrylic acid) (PAA) as a model polyanion. The complex was characterized by dynamic light scattering and UV-Vis spectroscopy. It was found that the size of complex particle size first increased and then decreased as the charge ratio of PTGA to PAA.     

The -308G/A of Tumor Necrosis Factor (TNF)-α and 825C/T of Guanidine Nucleotide Binding Protein 3 (GNB3) are Associated with the Onset of Acute Myocardial Infarction and Obesity in Taiwan

Acute myocardial infarction is a highly prevalent cardiovascular disease in Taiwan. Among several etiological risk factors, obesity and inflammation are strongly associated with the frequency of hypertension, cardiovascular disease, diabetes, and myocardial infarction. To discriminate obesity- and inflammation-related genes and the onset of acute myocardial infarction (AMI), a case-control study was conducted to investigate the association of the -308G/A polymorphisms of tumor necrosis factor (TNF)-α and the C825T polymorphism of guanidine nucleotide binding protein 3 (GNB3) with the onset of AMI among Taiwanese cohorts. A total of 103 AMI patients and 163 matched normal control samples were enrolled in the present study. The genomic DNA was extracted and subjected into polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) analysis. An association between the A homozygosity of the TNF-α-308G/A polymorphism and the onset of AMI was observed among the male subjects (p = 0.026; Spearman index = 0.200, p = 0.008). An association between the T homozygosity of GNB3 C825T polymorphism and obesity was also observed (Fisher's exact, p = 0.009). The TT genotype has a protective effect against acquiring AMI among the obese female population in Taiwan (Fisher's exact, p = 0.032). In conclusion, TNF-α-308G/A and the GNB3 C825T polymorphisms are associated with obesity and AMI in the Taiwanese population.     

Unexpected fragmentation of the Fe3(CO)9(μ3-Se)(μ3-AsCH3) cluster core in the reaction with CpCo(CO)2: synthesis and structure of Fe3(CO)6(μ3-Se)(μ-AsCH3{CpFe(CO)2})2(μ-CO)

The [Fe₃(CO)₆(μ₃-Se)(μ-AsCH₃{CpFe(CO)₂})₂(μ-CO)] (Cp=η⁵-C₅H₅) cluster has been obtained by the reaction of [Fe₃(CO)₉(μ₃-Se)(μ₃-AsCH₃)] with [CpCo(CO)₂]. Its crystal and molecular structures have been determined by X-ray analysis.     

[Y2(H2O)(BDC)3(DMF)]·(DMF)3: A rare 2-D (42.6)(45.6)2(48.62)(49.65.8) net with multi-helical-array and opened windows

In this work, we present a rare earth metal–organic framework, Y₂(H₂O)(BDC)₃(DMF)]·(DMF)₃ (BDC = 1,3-benzenedicarboxylate) 1, with a rare 2D (4².6)(4⁵.6)₂(4⁸.6²)(4⁹.6⁵.8) net, helical tubes with opposite chirality interweaving of triple-helical chains, opened windows and high thermal stability.