Interaction of sodium and potassium ions withκ-carrageenan

Summary NMR and potentiometric methods revealed at least two types of interactions of Na⁺ and K⁺ ions with -carrageenan, viz., Coulombic interaction with polysaccharide sulfate groups, and a coordination one, leading, in the case of the Na⁺ ions, to formation of nonstoichiometric complexes. The absence of any correlation between the coordination binding density of the cations and their promoting effect on gelation process was demonstrated.     

Hairless and NFκB Form a Positive Feedback Loop After UVB and TNFα Stimulation(†)

Hairless (HR) is a nuclear protein with corepressor activity whose exact function in the skin remains to be determined. Mutations in both human and mouse Hairless lead to hair loss accompanied by the appearance of papules, a disorder called atrichia with papular lesions. Furthermore, mice with mutations in HR are known to have a higher susceptibility to ultraviolet radiation-induced tumorigenesis, suggesting that HR plays a crucial role in the epidermal UVB response. Using normal human keratinocytes (NHKs) and keratinocytes containing a mutation in HR, we found that HR is an early UVB response gene that negatively regulates NFκB mRNA expression. HR mutant keratinocytes have a dysregulated UVB response that includes increased proliferation and the aberrant activation of NFκB effector genes. Additionally, we show that another UVB response gene, TNFα, negatively regulates HR mRNA expression. TNFα-induced negative regulation of HR occurs through a direct interaction of the p65 subunit with a single NFκB-binding domain located in the HR promoter region. Therefore, we show for the first time that HR and NFκB participate in a positive feedback loop that can be initiated either by UVB or TNFα.     

Heat shock protein 90 regulates IκB kinase complex and NF-κB activation in angiotensin II-induced cardiac cell hypertrophy

Heat shock protein 90 (HSP90), one of the most abundant proteins in the cardiac cells is essential for cell survival. Previous studies have shown that angiotensin II induces cardiac cell hypertrophy. However, the role of HSP90 in the angiotensin II-induced cardiac hypertrophy is unclear. In this study, we showed that HSP90 regulated angiotensin II-induced hypertrophy via maintenance of the IκB kinase (IKK) complex stability in cardiac cells. An HSP90 inhibitor, geldanamycin (GA), significantly suppressed angiotensin II-induced [3H]leucine incorporation and atrial natriuretic factor expression in cardiac cells. GA also inhibited the NF-κB activation induced by angiotensin II. Importantly, treatment with GA caused a degradation of IKKα/β; on the other hand, a proteasome-specific inhibitor restored the level of IKKα/β. We also found that GA prevented HSP90-IKKs complex induced by angiotensin II in cardiac cells. The small interfering RNA (siRNA)-mediated knockdown of HSP90 expression significantly inhibited angiotensin II-induced cell hypertrophy and NF-κB activation. These results suggest that angiotensin II-induced cardiac hypertrophy requires HSP90 that regulates the stability and complex of IKK.     

Structural and magnetic studies of Schiff base complexes of nickel(II) nitrite: change in crystalline state, ligand rearrangement and a very rare μ-nitrito-1κO:2κN:3κO' bridging mode

Four new nickel(II) complexes, [Ni(2)L(2)(NO(2))(2)]·CH(2)Cl(2)·C(2)H(5)OH, 2H(2)O (1), [Ni(2)L(2)(DMF)(2)(μ-NO(2))]ClO(4)·DMF (2a), [Ni(2)L(2)(DMF)(2)(μ-NO(2))]ClO(4) (2b) and [Ni(3)L'(2)(μ(3)-NO(2))(2)(CH(2)Cl(2))](n)·1.5H(2)O (3) where HL = 2-[(3-amino-propylimino)-methyl]-phenol, H(2)L(') = 2-({3-[(2-hydroxy-benzylidene)-amino]-propylimino}-methyl)-phenol and DMF = N,N-dimethylformamide, have been synthesized starting with the precursor complex [NiL(2)]·2H(2)O, nickel(ii) perchlorate and sodium nitrite and characterized structurally and magnetically. The structural analyses reveal that in all the complexes, Ni(II) ions possess a distorted octahedral geometry. Complex 1 is a dinuclear di-μ(2)-phenoxo bridged species in which nitrite ion acts as chelating co-ligand. Complexes 2a and 2b also consist of dinuclear entities, but in these two compounds a cis-(μ-nitrito-1κO:2κN) bridge is present in addition to the di-μ(2)-phenoxo bridge. The molecular structures of 2a and 2b are equivalent; they differ only in that 2a contains an additional solvated DMF molecule. Complex 3 is formed by ligand rearrangement and is a one-dimensional polymer in which double phenoxo as well as μ-nitrito-1κO:2κN bridged trinuclear units are linked through a very rare μ(3)-nitrito-1κO:2κN:3κO' bridge. Analysis of variable-temperature magnetic susceptibility data indicates that there is a global weak antiferromagnetic interaction between the nickel(ii) ions in four complexes, with exchange parameters J of -5.26, -11.45, -10.66 and -5.99 cm(-1) for 1, 2a, 2b and 3, respectively.     

New biphenantherene and nervogenic acid derivatives from Liparis regnieri Finet and their inhibitory activities against NF-κB activation

A phytochemical investigation of the whole plant of Liparis regnieri Finet led to the isolation of one new biphenantherene (1) and ten new nervogenic acid derivatives (2–11), together with nine known compounds. Their structures were elucidated mainly by extensive analyses of 1D and 2D NMR spectroscopic data and chemical reactions. Additionally, for the first time a previously unreported biphenantherene was discovered to effectively suppress TNF-α induced expression of NF-κB-Luc in Hela cells with the IC₅₀ value of 1.80 μM and the structure-activity relationshipwas also discussed.     

Pomegranate fruit extract inhibits UVB-induced inflammation and proliferation by modulating NF-κB and MAPK signaling pathways in mouse skin

There is considerable interest in the identification of natural agents capable of affording protection to skin from the adverse effects of solar ultraviolet B (UVB) radiation. Pomegranate (Punica granatum L.) fruit possesses as strong antioxidant, anti-inflammatory and antiproliferative properties. Recently, we have shown that oral feeding of pomegranate fruit extract (PFE) to mice afforded substantial protection from the adverse effects of single UVB radiation via modulation in early biomarkers of photocarcinogenesis. This study was designed to investigate the photochemopreventive effects of PFE (0.2%, wt/vol) after multiple UVB irradiations (180 mJ cm(-2), on alternative day, for a total of seven treatments) to the skin of SKH-1 hairless mice. Oral feeding of PFE to SKH-1 mice inhibited UVB-induced epidermal hyperplasia, infiltration of leukocytes, protein oxidation and lipid peroxidation. Immunoblot analysis demonstrated that oral feeding of PFE to mice inhibited UVB-induced (1) nuclear translocation and phosphorylation of nuclear factor kappa B/p65, (2) phosphorylation and degradation of IκBα, (3) activation of IKKα/ΙΚΚβ and (4) phosphorylation of mitogen-activated protein kinase proteins and c-Jun. PFE consumption also inhibited UVB-induced protein expression of (1) COX-2 and iNOS, (2) PCNA and cyclin D1 and (3) matrix metalloproteinases-2,-3 and -9 in mouse skin. Taken together, these data show that PFE consumption afforded protection to mouse skin against the adverse effects of UVB radiation by modulating UVB-induced signaling pathways.     

κ-卡拉胶研究进展

结合作者的研究工作，综述了κ-卡拉胶(KC)的化学结构、性质、应用及热可逆凝胶化机理及金属离子促凝胶化的研究进展。     

Heterolytic CH-bond activation in the synthesis of Ni{(2-aryl-κC)pyridine-κN}2 and derivatives

Thermolysis of Ni(OTf)₂ in 2-phenyl-pyridine or 2-tolyl-pyridine afforded the cationic chelate derivatives, [bis(2-aryl-pyridine)Ni{(2-aryl-κC²)pyridine-κN}]OTf (aryl = phenyl, 1a; tolyl, 1b). Addition of KBr to 1a and LiBr to 1b provided the bromides, (2-aryl-pyridine)BrNi{(2-aryl-κC²)pyridine-κN} (aryl = phenyl, 2a; tolyl, 2b). When subjected to KO^tBu in Et₂O, the bromides generated the entitled bis-cyclometalated compounds, Ni{(2-aryl-κC²)pyridine-κN}₂ (aryl = phenyl, 3a; tolyl, 3b). These compounds insert diphenylacetylene into one cyclometalate arm to produce [(2-aryl-κC²)pyridine-κN]Ni[2-(2-(1,2-diphenylethenyl-κC²)aryl)pyridine-κN] (aryl = phenyl, 4a; p-tolyl, 4b). X-ray crystallographic studies were conducted on 1a, 2a, 3a and 4a, and a brief DFT study of 3a confirmed its low spin configuration and rippled geometry.     

Design,synthesis and biological evaluation of novel quinazoline derivatives as potential NF-κb inhibitors

A series of novel 4-aminoquinazoline derivatives were designed, synthesized and biological properties on nuclear factor-kappaB (NF-κb) pathway inhibitory and potential in vitro anti-proliferation against breast cancer lines were also evaluated. Among them, LU1501 exhibited potent inhibition with IC₅₀ values in SK-BR-3 (10.16 ± 0.86 µM) and HCC1806 (10.66 ± 1.01 µM) cell lines. In vivo studies in breast cancer tumor model proved the correlation between anticancer activity of LU1501 and proliferation inhibition through the NF-κb signal pathway. The molecular docking studies also portrayed the potential binding mechanism between LU1501 and the key proteins of p65 and IkBα in NF-κb pathway. Accordingly, compound LU1501 could serve as a potent agent against breast cancer for further investigation.     

Synthesis and crystal structure of bis[(μ-κO:κO′-acetato)(μ-κO:κ2O′-acetato)][(η5-Cp)tris(dimethylphosphito-P)cobalt-O,O′,O″]yttrium(III)

The [η⁵-CpCo{P(O)(OMe)₂}₃Y(O₂CCH₃)₂]₂, yttrium(III) complex has been synthesized by the stoichiometric mixture of YCl₃, NaL_OMe and NaAc in a 1:1:2 molecular ratio in dry THF solvent and we have determined the structure by X-ray diffraction. The molecule is a dimeric compound, which consists of one tripodal ligand (L_OMe=CpCo[P(O)(OMe)₂]₃) and two bridging acetato (Ac) ligands on each yttrium atom. The acetate ligands of this complex have two different coordination modes, which are μ-κO:κO′-acetato and μ-κO:κ²O′-acetato bound to each yttrium atom.     

Pyridinium tetrakis(nitrato-κ2O,O′)(2,2′:6′,2′′-terpyridine-κ3N)cerate(III) pyridine solvate and bis(methanol-κO)tris(nitrato-κ2O,O′)(2,2′:6′,2′′-terpyridine-κ3N)cerium(III)

The title complexes, (C₅H₆N)[Ce(NO₃)₄(C₁₅H₁₁N₃)]·C₅H₅N or (Hpy)­[Ce(NO₃)₄(terpy)]·py, (I) (py is pyridine, C₅H₅N, and terpy is ter­pyridine, C₁₅H₁₁N₃), and [Ce(NO₃)₃­(C₁₅H₁₁N₃)(CH₄O)₂] or [Ce(NO₃)₃(terpy)(OHCH₃)₂], (II), are 11-coordinate. The coordination polyhedron of the Ce atom in (I) is irregular, while that in (II) can be described as an icosahedron with two vertices replaced by one.     

Synthesis and characterization of chloro-bis(quinoline-2-carboxylato-κ2N,O)gallium(III)

The preparation and characterization of a new gallium(III) complex with quinoline-2-carboxylate, of formula [Ga(quin-2-c)₂Cl], are described. The crystal structure of the complex has been determined by X-ray diffraction, crystallizing in monoclinic space group P2₁/n with Ga(III) adopting a distorted tetragonal pyramid. Gallium(III) coordinates two quinoline-2-carboxylates and one chloride with a Cl,N₂,O₂ donor set. In the crystal the 2-D supramolecular structure is generated by weak intermolecular interactions, C–H?···?O, C–H?···?Cl, and C–H?···?π. The cytotoxicity assays against several human cancer cell lines (Du145, A549, MCF-7, A498, HT-29) and against mouse fibroblasts (BALB/3T3) revealed moderate antiproliferative activity of the complex.     

miR-9 and let-7g enhance the sensitivity to ionizing radiation by suppression of NFκB1

The activation of nuclear factor-kappa B1 (NFkB1) in cancer cells may confer resistance to ionizing radiation (IR). To enhance the therapeutic efficiency of IR in lung cancer, we screened for microRNAs (miRNAs) that suppress NFkB1 and observed their effects on radiosensitivity in a human lung cancer cell line. From time series data of miRNA expression in γ-irradiated H1299 human lung cancer cells, we found that the expression of miR-9 was inversely correlated with that of NFκB1. Overexpression of miR-9 down-regulated the level of NFκB1 in H1299 cells, and the surviving fraction of γ-irradiated cells was decreased. Interestingly, let-7g also suppressed the expression of NFκB1, although there was no canonical target site for let-7g in the NFκB1 3' untranslated region. From these results, we conclude that the expression of miR-9 and let-7g could enhance the efficiency of radiotherapy for lung cancer treatment through the inhibition of NFκB1.     

Inhibition of NF-κB prevents high glucose-induced proliferation and plasminogen activator inhibitor-1 expression in vascular smooth muscle cells

Recent epidemiologic studies clearly showed that early intensive glucose control has a legacy effect for preventing diabetic macrovascular complications. However, the cellular and molecular processes by which high glucose leads to macrovascular complications are poorly understood. Vascular smooth muscle cell (VSMC) dysfunction due to high glucose is a characteristic of diabetic vascular complications. Activation of nuclear factor-κB (NF-κB) may play a key role in the regulation of inflammation and proliferation of VSMCs. We examined whether VSMC proliferation and plasminogen activator inhibitor-1 (PAI-1) expression induced by high glucose were mediated by NF-κB activation. Also, we determined whether selective inhibition of NF-κB would inhibit proliferation and PAI-1 expression in VSMCs. VSMCs of the aorta of male SD rats were treated with various concentrations of glucose (5.6, 11.1, 16.7, and 22.2 mM) with or without an inhibitor of NF-κB or expression of a recombinant adenovirus vector encoding an IκB-α mutant (Ad-IκBαM). VSMC proliferation was examined using an MTT assay. PAI-1 expression was assayed by real-time PCR and PAI-1 protein in the media was measured by ELISA. NF-κB activation was determined by immunohistochemical staining, NF-κB reporter assay, and immunoblotting. We found that glucose stimulated VSMC proliferation and PAI-1 expression in a dose-dependent manner up to 22.2 mM. High glucose (22.2 mM) alone induced an increase in NF-κB activity. Treatment with inhibitors of NF-κB such as MG132, PDTC or expression of Ad-IκB-αM in VSMCs prevented VSMC proliferation and PAI-1 expression induced by high glucose. In conclusion, inhibition of NF-κB activity prevented high glucose-induced VSMC proliferation and PAI-1 expression.     

N- vs O-Coordination in cyclomanganation of 1,5-diaryl-3-(2-pyridyl)pentane-1,5-diones and 3-(2-pyridyl)chalcones; cyclomanganation at saturated carbon and the crystal structure of [1,5-diphenyl-κC-3-(2-pyridyl- κN)pentan-2-yl-κC-1,5-dione-κOκO]tetracarbonylmanganesetricarbonylmanganese

Reaction of 1,5-diphenyl-3-(2-pyridyl)pentane-1,5-dione (5a) with 2.5 moles of benzylpentacarbonylmanganese in petroleum spirit under reflux gives a small amount of the symmetric di-aryl-manganated product [1,5-diphenyl-κC²-3-(2-pyridyl)pentane-1,5-dione-κO¹κO⁵]bis-(tetracarbonylmanganese) (7a), but mostly [1,5-diphenyl-κC²-3-(2-pyridyl-κN)pentan-2-yl- κC²-1,5-dione-κO¹κO⁵]tetracarbonylmanganesetricarbonylmanganese (6a) which is manganated at only one aryl carbon [by Mn(CO)₄] but also [by Mn(CO)₃ with N and O coordination] at the methylene carbon adjacent to the Mn(CO)₄-coordinated ketone carbonyl. The latter is a rare example of direct cyclomanganation at a saturated carbon and the only known case adjacent to a carbonyl group; the X-ray crystal structure of 6a is reported. With 3 moles of benzylpentacarbonylmanganese the yield of 6a remains unchanged but some trimanganation product [1,5-diphenyl-κC^2′κC^2?-3-(2-pyridyl-κN)pentan-2-yl-κC²-1,5-dione-κO¹κO⁵]tris-(tetracarbonylmanganese) (8a) is formed, presumably from 7a. Routes to products are proposed and activating factors considered. 1,5-Di-(2-thienyl)-3-(2-pyridyl)pentane-1,5-dione (5b) and its 3-thienyl isomer (5c) similarly give 6a analogues [1,5-di-(2-thienyl-κC³)-3-(2-pyridyl-κN)pentan-2-yl-κC²-1,5-dione-κO¹κO⁵]tetracarbonylmanganesetricarbonylmanganese (6b) and [1,5-di-(3-thienyl-κC²)-3-(2-pyridyl-κN)pentan-2-yl-κC²-1,5-dione-κO¹κO⁵]tetracarbonylmanganesetricarbonylmanganese (6c).Also reported are the mono-cyclomanganation product [1-(2,6-dimethoxyphenyl)-3-(2-pyridyl-κN)prop-2-en-2-yl-κC²-1-one]tetracarbonylmanganese (16) and dicyclomanganation product [1-(2,5-dimethyl-3-thienyl-κC⁴)-3-(2-pyridyl-κN)prop-2-en-2-yl- κC²-1-one-κO ]bis-(tetracarbonylmanganese) (17) from reaction of the respective (E)-1-aryl-3-(2-pyridyl)prop-2-en-1-ones (3-(2-pyridyl)chalcones), the first reported examples of enone metallation at the α-carbon via N-coordination by a β-2-pyridyl group.