RESUMO
A series of metalloligands bearing homoleptic 2,2':6',2''-terpyridine (tpy)-CdII complexes has been successfully synthesized. The formation of ML1 was accomplished through a sequence of Suzuki-Miyaura coupling and complexation reactions, offering an alternative method to produce tpy-based metalloligands under relatively mild conditions. Moreover, the metallomacrocycle C1 and metallocatenane C2 were self-assembled from heteroleptic complexation reactions involving ML1 and suitable counterparts.
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Consensus on the cause of recent midlatitude circulation changes toward a wavier manner in the Northern Hemisphere has not been reached, albeit a number of studies collectively suggest that this phenomenon is driven by global warming and associated Arctic amplification. Here, through a fingerprint analysis of various global simulations and a tropical heating-imposed experiment, we suggest that the suppression of tropical convection along the Inter Tropical Convergence Zone induced by sea surface temperature (SST) cooling trends over the tropical Eastern Pacific contributed to the increased summertime midlatitude waviness in the past 40 years through the generation of a Rossby-wave-train propagating within the jet waveguide and the reduced north-south temperature gradient. This perspective indicates less of an influence from the Arctic amplification on the observed mid-latitude wave amplification than what was previously estimated. This study also emphasizes the need to better predict the tropical Pacific SST variability in order to project the summer jet waviness and consequent weather extremes.
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A range of bone abnormalities including short stature have been reported to be associated with the use of antiepileptic drugs (AEDs) in children. Exactly how AEDs impact skeletal growth, however, is not clear. In the present study, rat growth plate chondrocytes were cultured to study the effects of AEDs, including valproic acid (VPA), oxcarbazepine (OXA), levetiracetam (LEV), lamotrigine (LTG), and topiramate (TPM) on the skeletal growth. VPA markedly reduced the number of chondrocytes by apoptosiswhile other AEDs had no effect. The apoptosis associated noncleaved and cleaved caspase 3, and caspases were increased by exposure to VPA, which up-regulated cyclooxygenase 2 (COX-2) mRNA and protein levels likely through histone acetylation. The COX-2 inhibitor NS-398 attenuated the effects of VPA up-regulating COX-2 expression and decreased VPA-induced caspase 3 expression. The use of VPA in children should be closely monitored or replaced, where appropriate, by AEDs which do not apparently affect the growth plate chondrocytes.
Assuntos
Anticonvulsivantes , Lâmina de Crescimento , Ácido Valproico , Animais , Anticonvulsivantes/toxicidade , Células Cultivadas , Criança , Condrócitos/efeitos dos fármacos , Lâmina de Crescimento/efeitos dos fármacos , Humanos , Lamotrigina , Ratos , Ácido Valproico/toxicidadeRESUMO
A series of stellated metallosupramolecular architectures have been assembled through three-component integrative self-sorting. Building on the complementary ligand pairing, the initial attempts to synthesize the hexagram complex from a combination of X-shaped tetrakis- and V-shaped bis-terpyridine ligands, and CdII ions, resulted in an unprecedented mixture of stellated octanuclear and dodecanuclear metallocages, which were further isolated by column chromatography. To overcome the unexpected obstacle, the multivalent ligand design along with spontaneous heteroleptic complexation was applied to realization of the one-pot synthesis of the intricate topology. A centrally situated triangle served as a prop for quantitative formation of the six-pointed stellated complex. Notably, in the absence of the triangular prop, a four-pointed star was produced.
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Trachinocephalus gauguini Polanco, Acero Betancur, 2016 was described based on eighteen specimens collected from off the Marquesas Islands, the only location where this species has been recorded until now. Through morphological and molecular examination of Trachinocephalus specimens collected from an exploratory cruise conducted in June 2014 under the Tropical Deep-Sea Benthos program along the northern coast of the New Ireland Province, Papua New Guinea, we demonstrate the presence of this species in Papua New Guinea waters. This new record suggests a wide distribution for this rarely collected species in the western Pacific Ocean.
Assuntos
Nariz , Animais , Ilhas , Oceano Pacífico , Papua Nova GuinéRESUMO
Spontaneous formation of the heteroleptic cadmium(II) bis(terpyridine) complex under ambient conditions can be achieved by a combination of 6,6''-di(2,6-dimethoxylphenyl)-substituted and unsubstituted terpyridine-based ligands. Building on this dynamic heteroleptic complexation, diverse metallo-supramolecular macrocycles and cages were readily assembled in quantitative yields from the predesigned multicomponent systems. The complementary ligation reinforced self-recognition to facilitate the shape-dependent self-sorting of a four-component dynamic library into two well-defined parallelograms. In addition, the subtle lability difference between homoleptic and heteroleptic complexes led to the site-selective CdII -ZnII transmetalation in the Sierpinski triangle. Facile construction of a dodecanuclear tetrahedral metallocage was also realized by using two self-recognizable tritopic building blocks. The photophysical study of the metallo-supramolecules assembled from the d10 metal ions revealed intense ligand-based photoluminescence in solution. The self-assembly strategy described here provides an efficient methodology for building pre-programmable, sophisticated supramolecular architectures furnished with photoactivity.
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Predesigned complementary complexation of two 2,2':6',2â³-terpyridine-based ligands was established by installing 2,6-dimethoxyphenyl substituents at the terpyridyl 6,6â³-positions, which provided ancillary ion-dipole interactions in the coordination process and extra π-stacking stabilization in the resultant heteroleptic complex. The high-fidelity self-recognition ligation afforded facile access to the quantitative self-assembly of multicomponent triangle [Cd6L(3)3L(4)3] and ditrigon [Cd15L(3)6L(5)3] (that is, a hexagon with six 120° angles and two alternating edge lengths). It was found that the linear 6,6â³-substituted ditopic motif (L(3)) would be directed by the ligand geometry of L(5) to selectively incorporate into the parallel homoleptic connections in the bilayered framework.
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In addition to being the primary organ involved in redox cycling, the liver is one of the most highly innervated tissues in mammals. The interaction between hepatocytes and sympathetic, parasympathetic, and peptidergic nerve fibers through a variety of neurotransmitters and signaling pathways is recognized as being important in the regulation of hepatocyte function, liver regeneration, and hepatic fibrosis. However, less is known regarding the role of the sympathetic nervous system (SNS) in modulating the hepatic response to oxidative stress. Our aim was to investigate the role of the SNS in healthy and oxidatively stressed liver parenchyma. Mice treated with 6-hydroxydopamine hydrobromide were used to realize chemical sympathectomy. Carbon tetrachloride (CCl4) injection was used to induce oxidative liver injury. Sympathectomized animals were protected from CCl4 induced hepatic lipid peroxidation-mediated cytotoxicity and genotoxicity as assessed by 4-hydroxy-2-nonenal levels, morphological features of cell damage, and DNA oxidative damage. Furthermore, sympathectomy modulated hepatic inflammatory response induced by CCl4-mediated lipid peroxidation. CCl4 induced lipid peroxidation and hepatotoxicity were suppressed by administration of an α-adrenergic antagonist. We conclude that the SNS provides a permissive microenvironment for hepatic oxidative stress indicating the possibility that targeting the hepatic α-adrenergic signaling could be a viable strategy for improving outcomes in patients with acute hepatic injury.
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Fígado/metabolismo , Fígado/patologia , Estresse Oxidativo , Receptores Adrenérgicos alfa/metabolismo , Sistema Nervoso Simpático/patologia , Animais , Antioxidantes/farmacologia , Biomarcadores/metabolismo , Tetracloreto de Carbono , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/patologia , Forma Celular/efeitos dos fármacos , Quimiocinas/metabolismo , Dano ao DNA , Hepatócitos/efeitos dos fármacos , Hepatócitos/patologia , Hepatócitos/ultraestrutura , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Masculino , Camundongos Endogâmicos C57BL , Fármacos Neuroprotetores/farmacologia , Oxirredução/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Oxidopamina , Transdução de Sinais , Simpatectomia , Sistema Nervoso Simpático/efeitos dos fármacosRESUMO
Carbon tetrachloride (CCl4) is widely used as an animal model of hepatotoxicity and the mechanisms have been arduously studied, however, the contribution of the sympathetic nervous system (SNS) in CCl4-induced acute hepatotoxicity remains controversial. It is also known that either CCl4 or SNS can affect systemic inflammatory responses. The aim of this study was to establish the effect of chemical sympathectomy with 6-hydroxydopamine (6-OHDA) in a mouse model of CCl4-induced acute hepatotoxicity and systemic inflammatory response. Mice exposed to CCl4 or vehicle were pretreated with 6-OHDA or saline. The serum levels of aminotransferases and alkaline phosphatase in the CCl4-poisoning mice with sympathetic denervation were significantly lower than those without sympathetic denervation. With sympathetic denervation, hepatocellular necrosis and fat infiltration induced by CCl4 were greatly decreased. Sympathetic denervation significantly attenuated CCl4-induced lipid peroxidation in liver and serum. Acute CCl4 intoxication showed increased expression of inflammatory cytokines/chemokines [eotaxin-2/CCL24, Fas ligand, interleukin (IL)-1α, IL-6, IL-12p40p70, monocyte chemoattractant protein-1 (MCP-1/CCL2), and tumor necrosis factor-α (TNF-α)], as well as decreased expression of granulocyte colony-stimulating factor and keratinocyte-derived chemokine. The overexpressed levels of IL-1α, IL-6, IL-12p40p70, MCP-1/CCL2, and TNF-α were attenuated by sympathetic denervation. Pretreatment with dexamethasone significantly reduced CCl4-induced hepatic injury. Collectively, this study demonstrates that the SNS plays an important role in CCl4-induced acute hepatotoxicity and systemic inflammation and the effect may be connected with chemical- or drug-induced hepatotoxicity and circulating immune response.
Assuntos
Intoxicação por Tetracloreto de Carbono/fisiopatologia , Fígado/patologia , Sistema Nervoso Simpático/fisiopatologia , Síndrome de Resposta Inflamatória Sistêmica/fisiopatologia , Fosfatase Alcalina/sangue , Animais , Intoxicação por Tetracloreto de Carbono/sangue , Intoxicação por Tetracloreto de Carbono/complicações , Intoxicação por Tetracloreto de Carbono/tratamento farmacológico , Quimiocina CCL2/sangue , Quimiocinas/sangue , Citocinas/sangue , Dexametasona/uso terapêutico , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Síndrome de Resposta Inflamatória Sistêmica/sangue , Síndrome de Resposta Inflamatória Sistêmica/tratamento farmacológico , Síndrome de Resposta Inflamatória Sistêmica/etiologia , Transaminases/sangueRESUMO
BACKGROUND: This study investigated whether long-term treatment with antiepileptic drugs (AEDs) had negative effects on statural growth and serum calcium levels in children with epilepsy in Taiwan. METHODS: Children with epilepsy treated with one prescription of AEDs (monotherapy) for at least 1 year were selected. The AEDs included valproic acid (VPA; Deparkin) in 27 children (11 boys and 16 girls) aged 4-18 years, oxcarbazepine (Trileptal) in 30 children (15 boys and 15 girls) aged 5-18 years, topiramate (Topamax) in 19 children (10 boys and 9 girls) aged 6-18 years, and lamotrigine (Lamicta) in eight children (5 boys and 3 girls) aged 5-13 years. Patients with a history of febrile convulsions were selected as the controls. RESULTS: One year of VPA treatment significantly impaired the statural growth of pediatric patients with epilepsy (p < 0.005) compared with the control group. The underlying mechanism may have been due to the direct effect of VPA on the proliferation of growth plate chondrocytes rather than alterations of serum calcium. CONCLUSIONS: These results raise serious concerns about the growth of pediatric epilepsy patients who use AEDs, and potentially the need to closely monitor growth in children with epilepsy and adolescents under AED treatment, especially VPA.
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Anticonvulsivantes/efeitos adversos , Doenças do Desenvolvimento Ósseo/induzido quimicamente , Adolescente , Anticonvulsivantes/administração & dosagem , Anticonvulsivantes/uso terapêutico , Estatura/efeitos dos fármacos , Doenças do Desenvolvimento Ósseo/sangue , Doenças do Desenvolvimento Ósseo/epidemiologia , Doenças do Desenvolvimento Ósseo/etiologia , Cálcio/sangue , Carbamazepina/efeitos adversos , Carbamazepina/análogos & derivados , Carbamazepina/uso terapêutico , Tamanho Celular/efeitos dos fármacos , Células Cultivadas , Criança , Pré-Escolar , Condrócitos/efeitos dos fármacos , Epilepsia/sangue , Epilepsia/complicações , Epilepsia/tratamento farmacológico , Feminino , Frutose/administração & dosagem , Frutose/análogos & derivados , Frutose/uso terapêutico , Lâmina de Crescimento/patologia , Humanos , Lamotrigina , Masculino , Oxcarbazepina , Topiramato , Triazinas/administração & dosagem , Triazinas/uso terapêutico , Ácido Valproico/efeitos adversos , Ácido Valproico/uso terapêuticoRESUMO
The orchid floral organs represent novel and effective structures for attracting pollination vectors. In addition, to avoid inbreeding, the androecium and gynoecium are united in a single structure termed the gynostemium. Identification of C-class MADS-box genes regulating reproductive organ development could help determine the level of homology with the current ABC model of floral organ identity in orchids. In this study, we isolated and characterized two C-class AGAMOUS-like genes, denoted CeMADS1 and CeMADS2, from Cymbidium ensifolium. These two genes showed distinct spatial and temporal expression profiles, which suggests their functional diversification during gynostemium development. Furthermore, the expression of CeMADS1 but not CeMADS2 was eliminated in the multitepal mutant whose gynostemium is replaced by a newly emerged flower, and this ecotopic flower continues to produce sepals and petals centripetally. Protein interaction relationships among CeMADS1, CeMADS2 and E-class PeMADS8 proteins were assessed by yeast two-hybrid analysis. Both CeMADS1 and CeMADS2 formed homodimers and heterodimers with each other and the E-class PeMADS protein. Furthermore, transgenic Arabidopsis plants overexpressing CeMADS1 or CeMADS2 showed limited growth of primary inflorescence. Thus, CeMADS1 may have a pivotal C function in reproductive organ development in C. ensifolium.