RESUMO
In the development of nanomaterial electrodes for improved electrocatalytic activity, much attention is paid to the compositions, lattice, and surface morphologies. In this study, a new concept to enhance electrocatalytic activity is proposed by reducing impedance inside nanomaterial electrodes. Gold nanodendrites (AuNDs) are grown along silver nanowires (AgNWs) on flexible polydimethylsiloxane (PDMS) support. The AuNDs/AgNWs/PDMS electrode affords an oxidative peak current density of 50 mA cm-2 for ethanol electrooxidation, a value ≈20 times higher than those in the literature do. Electrochemical impedance spectroscopy (EIS) demonstrates the significant contribution of the AgNWs to reduce impedance. The peak current densities for ethanol electrooxidation are decreased 7.5-fold when the AgNWs are electrolytically corroded. By in situ surface-enhanced Raman spectroscopy (SERS) and density functional theory (DFT) simulation, it is validated that the ethanol electrooxidation favors the production of acetic acid with undetectable CO, resulting in a more complete oxidation and long-term stability, while the AgNWs corrosion greatly decreases acetic acid production. This novel strategy for fabricating nanomaterial electrodes using AgNWs as a charge transfer conduit may stimulate insights into the design of nanomaterial electrodes.
RESUMO
The soil microbial carbon pump (MCP) is increasingly acknowledged as being directly linked to soil organic carbon (SOC) accumulation and stability. Given the close coupling of carbon (C) and nitrogen (N) cycles and the constraints imposed by their stoichiometry on microbial growth, N addition might affect microbial growth strategies with potential consequences for necromass formation and carbon stability. However, this topic remains largely unexplored. Based on two multi-level N fertilizer experiments over 10 years in two soils with contrasting soil fertility located in the North (Cambisol, carbon-poor) and Southwest (Luvisol, carbon-rich), we hypothesized that different resource demands of microorganism elicit a trade-off in microbial growth potential (Y-strategy) and resource-acquisition (A-strategy) in response to N addition, and consequently on necromass formation and soil carbon stability. We combined measurements of necromass metrics (MCP efficacy) and soil carbon stability (chemical composition and mineral associated organic carbon) with potential changes in microbial life history strategies (assessed via soil metagenomes and enzymatic activity analyses). The contribution of microbial necromass to SOC decreased with N addition in the Cambisol, but increased in the Luvisol. Soil microbial life strategies displayed two distinct responses in two soils after N amendment: shift toward A-strategy (Cambisol) or Y-strategy (Luvisol). These divergent responses are owing to the stoichiometric imbalance between microbial demands and resource availability for C and N, which presented very distinct patterns in the two soils. The partial correlation analysis further confirmed that high N addition aggravated stoichiometric carbon demand, shifting the microbial community strategy toward resource-acquisition which reduced carbon stability in Cambisol. In contrast, the microbial Y-strategy had the positive direct effect on MCP efficacy in Luvisol, which greatly enhanced carbon stability. Such findings provide mechanistic insights into the stoichiometric regulation of MCP efficacy, and how this is mediated by site-specific trade-offs in microbial life strategies, which contribute to improving our comprehension of soil microbial C sequestration and potential optimization of agricultural N management.
Assuntos
Carbono , Fertilizantes , Nitrogênio , Microbiologia do Solo , Solo , Solo/química , Carbono/metabolismo , Carbono/análise , Nitrogênio/metabolismo , Nitrogênio/análise , Fertilizantes/análise , Ciclo do Carbono , MicrobiotaRESUMO
A base promoted oxidative [4+2] annulation of pyrrole-2-carbaldehyde derivatives with o-hydroxyphenyl propargylamines for the synthesis of highly substituted indolizines has been developed. Using DBN as base, a broad range of 5,6,7-trisubstituted indolizines have been prepared in good to excellent yields under mild conditions, and many useful functional groups can be tolerated.
RESUMO
A series of novel sulfonyl hydrazide based ß-carboline derivatives (SX1-SX32) were designed and synthesized, and their structures were characterized on NMR and HRMS. Their α-glucosidase inhibitory screening results found that compounds (SX1-SX32) presented potential α-glucosidase inhibitory: IC50 values being 2.12 ± 0.33-19.37 ± 1.49 µM. Compound SX29 with a para-phenyl (IC50: 2.12 ± 0.33 µM) presented the strongest activity and was confirmed as a noncompetitive inhibitor. Fluorescence spectra, CD spectra and molecular docking were conducted to describe the inhibition mechanism of SX29 against α-glucosidase. Cells cytotoxicity indicated SX29 (0-32 µM) had no cytotoxicity on 293T cells. In particular, in vivo experiments revealed that oral administration of SX29 could regulate hyperglycemia and glucose tolerance of diabetic mice. These achieved findings indicated that sulfonyl hydrazide based ß-carboline derivatives bore promising potential for discovering new α-glucosidase inhibitors with hypoglycemic activity.
RESUMO
Orthosiphon aristatus is a well-known folkloric medicine and herb for Guangdong soup for the treatment of rheumatism in China. Eight isopimarane-type and migrated pimarane-type diterpenoids (1-8), including a new one with a rarely occurring α,ß-unsaturated diketone C-ring, were isolated from O. aristatus. Their structures were determined by spectroscopic methods and quantum chemical calculations. Furthermore, the most abundant compound, orthosiphol K, was structurally modified by modern synthetic techniques to give seven new derivatives (9-15). The anti-rheumatoid arthritis activity of these diterpenoids were evaluated on a TNF-α induced MH7A human rheumatoid fibroblast-like synoviocyte model. Compound 10 showed the most potent activity among these compounds. Based on their inhibitory effects on the release levels of IL-1ß, the preliminary structure-activity relationships were concluded. Furthermore, western blot analysis revealed that 10 could increase the expression of IκBα and decrease the expression of NF-κB p65, and the expression levels of COX-2 and NLRP3 proteins were consequently down-regulated.
Assuntos
Artrite Reumatoide , Diterpenos , Orthosiphon , Humanos , Orthosiphon/química , Orthosiphon/metabolismo , Abietanos , Artrite Reumatoide/tratamento farmacológico , Fator de Necrose Tumoral alfa , Diterpenos/farmacologia , Diterpenos/química , NF-kappa B/metabolismoRESUMO
The roadblocks for the planar silver/silver chloride (Ag/AgCl) quasi-reference electrode (qRE) development are the potential stability and long-term reliability as potentiometric sensors. Although there is a significant amount of work on potentiometric screen-printed and inkjet-printed sensors, none of the REs has comparable performance to that of the conventional glass RE and knowledge on reliable planar Ag/AgCl qREs is still limited. Here, a novel fishbone-structured flexible Ag/AgCl qRE (Fishbone-Ag/AgCl qRE) was developed and its stability and long-term reliability were significantly improved. The stability of the Fishbone-Ag/AgCl qRE was comparable to that of a commercial glass Ag/AgCl RE. In a long-term stability test, the Fishbone-Ag/AgCl qRE could continuously and stably operate for more than 4 h. Shelf-life testing revealed a 6 month life span. The conductivity and diameter of the nanowires in the fishbone structure of the Ag/AgCl qRE had important influences on electrochemical properties. The conductivity of the qRE influenced the charge-transfer rate in the electrode so that it affected the potential stability. Thicker diameter and slight chlorination on the surface of the AgNWs resulted in enhanced long-term reliability of the qRE. The capabilities of this new nanostructured material were applied in vivo for noninvasive monitoring of electrocardiogram. The discovery is elementary and substantially informs improved nanostructure RE design for testing and commercial medical device applications.
Assuntos
Nanofios , Prata , Prata/química , Reprodutibilidade dos Testes , Eletrodos , EletrocardiografiaRESUMO
An N-heterocyclic carbene (NHC)-catalyzed [3 + 3] cycloaddition of α-bromoenals with nitroketene aminals or nitroketene N,S-acetals has been developed. This methodology provides an efficient strategy for the construction of valuable nitro-containing heterocyclic compounds. This protocol features mild reaction conditions, easily available starting materials, broad substrate scope and easy scalability.
RESUMO
The reaction of vinylsulfonamides with donor-acceptor carbenes derived from α-aryldiazoesters, catalyzed by the tert-butyl glycine-derived dirhodium complex Rh2(S-4-Br-NTTL)4, has been reported. This method provides a variety of α-aryl-ß-aminocyclopropane carboxylic acid derivatives bearing one quaternary carbon stereogenic center vicinal to the amino-substituted carbon in high yields with excellent diastereo- and enantioselectivities. Vinylsulfonamides showed complementary advantages over the well-developed vinylamides or vinylcarbamates for this Rh(II)-catalyzed cyclopropanation strategy. Moreover, these conformationally restricted α-aryl-ß-aminocyclopropyl carboxylic acid derivatives can be readily incorporated into dipeptides.
Assuntos
Ácidos Carboxílicos , Glicina , Catálise , Estrutura Molecular , EstereoisomerismoRESUMO
A phenyliodine(III) diacetate-promoted/1,1,1,3,3,3-hexafluoroisopropanol-controlled dearomative spirocyclization of phenolic ketones was reported, providing two libraries of structurally interesting scaffolds, spirocyclohexadienonic ketals and their acetoxylated counterparts, in moderate to excellent yields under mild conditions. Control experiments unravel that the reaction proceeds through a spirocyclohexadienone-oxocarbenium cation species. In addition, an in situ-generated hypervalent iodine(III)-catalyzed version, as well as the late-stage transformation of products via conjugate additions, was also realized.
Assuntos
Iodo , Cetonas , Cátions , FenóisRESUMO
An unprecedented copper-catalyzed tandem reaction of 1,6-enynes with diazo compounds via a cross-coupling/[2 + 2] cycloaddition sequence was reported. A library of methylenecyclobutane-fused ring systems including cyclobuta[b]indolines, cyclobuta[b]benzofuran, benzo[b]cyclobuta[d]thiophene, and bicyclo[3.2.0] structures were obtained in moderate to excellent yields under very mild reaction conditions. The reaction exhibited high proximal-regioselectivity and diastereoselectivity. Moreover, 1,6-allenene has proven to be the key intermediate and proceeds via a thermally promoted [2 + 2] cycloaddition in the absence of copper catalyst.
RESUMO
A copper-catalyzed cascade reaction of diazo compounds with 1,n-allenynes (n = 6,7) was reported, which provides efficient access to various functionalized 3-azabicyclo[m.2.0] frameworks (m = 5,6) in moderate to excellent yields under mild reaction conditions. The reaction proceeds through intermolecular cross-coupling to form bisallene intermediates, followed by subsequent intramolecular [2+2] cycloaddition.
RESUMO
Argininosuccinate synthetase 1 (ASS1) is a rate-limited enzyme in arginine biosynthesis. The oncogenic potential of ASS1 in terms of prognosis and cancer metastasis in arginine prototrophic gastric cancer (GC) remains unclear at present. We identify differentially expressed proteins in microdissected GC tumor cells relative to adjacent nontumor epithelia by isobaric mass tag for relative and absolute quantitation proteomics analysis. GC cells with stable expression or depletion of ASS1 were further analyzed to identify downstream molecules. We investigated their effects on chemoresistance and cell invasion in the presence or absence of arginine. ASS1 was highly expressed in GC and positively correlated with GC aggressiveness and poor outcome. Depletion of ASS1 led to inhibition of tumor growth and decreased cell invasion via induction of autophagy-lysosome machinery, resulting in degradation of active ß-catenin, Snail, and Twist. Ectopic expression of ASS1 in GC cells reversed these effects and protected cancer cells from chemotherapy drug-induced apoptosis via activation of the AKT-mammalian target of rapamycin signaling pathway. ASS1 contributes to GC progression by enhancing aggressive potential resulting from active ß-catenin, Snail, and Twist accumulation. Our results propose that ASS1 might contribute to GC metastasis and support its utility as a prognostic predictor of GC.-Tsai, C.-Y., Chi, H.-C., Chi, L.-M., Yang, H.-Y., Tsai, M.-M., Lee, K.-F., Huang, H.-W., Chou, L.-F., Cheng, A.-J., Yang, C.-W., Wang, C.-S., Lin, K.-H. Argininosuccinate synthetase 1 contributes to gastric cancer invasion and progression by modulating autophagy.
Assuntos
Argininossuccinato Sintase/biossíntese , Autofagia , Regulação Enzimológica da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Transdução de Sinais , Neoplasias Gástricas/enzimologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Argininossuccinato Sintase/genética , Linhagem Celular Tumoral , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Metástase Neoplásica , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Taxa de Sobrevida , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismoRESUMO
Oral cancer is one of the most common cancers worldwide, and there are currently no biomarkers approved for aiding its management. Although many potential oral cancer biomarkers have been discovered, very few have been verified in body fluid specimens in parallel to evaluate their clinical utility. The lack of appropriate multiplexed assays for chosen targets represents one of the bottlenecks to achieving this goal. In the present study, we develop a peptide immunoaffinity enrichment-coupled multiple reaction monitoring-mass spectrometry (SISCAPA-MRM) assay for verifying multiple reported oral cancer biomarkers in saliva. We successfully produced 363 clones of mouse anti-peptide monoclonal antibodies (mAbs) against 36 of 49 selected targets, and characterized useful mAbs against 24 targets in terms of their binding affinity for peptide antigens and immuno-capture ability. Comparative analyses revealed that an equilibrium dissociation constant (KD ) cut-off value < 2.82 × 10-9 m could identify most clones with an immuno-capture recovery rate >5%. Using these mAbs, we assembled a 24-plex SISCAPA-MRM assay and optimized assay conditions in a 25-µg saliva matrix background. This multiplexed assay showed reasonable precision (median coefficient of variation, 7.16 to 32.09%), with lower limits of quantitation (LLOQ) of <10, 10-50, and >50 ng/ml for 14, 7 and 3 targets, respectively. When applied to a model saliva sample pooled from oral cancer patients, this assay could detect 19 targets at higher salivary levels than their LLOQs. Finally, we demonstrated the utility of this assay for quantification of multiple targets in individual saliva samples (20 healthy donors and 21 oral cancer patients), showing that levels of six targets were significantly altered in cancer compared with the control group. We propose that this assay could be used in future studies to compare the clinical utility of multiple oral cancer biomarker candidates in a large cohort of saliva samples.
Assuntos
Biomarcadores Tumorais/análise , Carcinoma de Células Escamosas/diagnóstico , Espectrometria de Massas/métodos , Neoplasias Bucais/diagnóstico , Proteômica/métodos , Saliva/química , Animais , Anticorpos Monoclonais/química , Anticorpos Monoclonais/imunologia , Afinidade de Anticorpos/imunologia , Biomarcadores Tumorais/metabolismo , Simulação por Computador , Humanos , Imunoensaio , Limite de Detecção , Camundongos , Peptídeos/imunologiaRESUMO
BACKGROUND: In humans, the presence of antiphospholipid antibodies (aPL) is frequently found in immune thrombocytopenia. The present study investigated whether aPL and any aPL subtypes are associated with canine thrombocytopenia, in particular, immune-mediated thrombocytopenia (immune thrombocytopenia) that usually manifests with severe thrombocytopenia. RESULTS: Sera were collected from 64 outpatient dogs with thrombocytopenia (Group I, platelet count 0 - 80 × 10(3)/uL), and 38 of which having severe thrombocytopenia (platelet count < 30 × 10(3)/uL) were further divided into subgroups based on the presence of positive antiplatelet antibodies (aPLT) (subgroup IA, immune thrombocytopenia, n =20) or the absence of aPLT (subgroup IB, severe thrombocytopenia negative for aPLT, n =18). In addition, sera of 30 outpatient dogs without thrombocytopenia (Group II), and 80 healthy dogs (Group III) were analyzed for comparison. Indirect ELISAs were performed to compare serum levels of aPL subtypes, including anticardiolipin antibodies (aCL), antiphosphatidylserine antibodies (aPS), antiphosphatidylcholine (aPC), and anti-ß2 glycoprotein I antibodies (aß2GPI), and antiphosphatidylinositol antibodies (aPI), among different groups or subgroups of dogs. Among outpatient dogs, aCL, being highly prevalent in outpatient dogs with thrombocytopenia (63/64, 98 %), is an important risk factor for thrombocytopenia (with a high relative risk of 8.3), immune thrombocytopenia (relative risk 5.3), or severe thrombocytopenia negative for aPLT (relative risk ∞, odds ratio 19). In addition, aPS is a risk factor for immune thrombocytopenia or severe thrombocytopenia negative for aPLT (moderate relative risks around 2), whereas aPC and aß2GPI are risk factors for immune thrombocytopenia (relative risks around 2). CONCLUSIONS: Of all the aPL subtypes tested here, aCL is highly associated with canine thrombocytopenia, including immune thrombocytopenia, severe thrombocytopenia negative for aPLT, and less severe thrombocytopenia. Furthermore, aPS is moderately associated with both canine immune thrombocytopenia and severe thrombocytopenia negative for aPLT, whereas aß2GPI, and aPC are moderately relevant to canine immune thrombocytopenia. In contrast, aPI is not significantly associated with canine immune thrombocytopenia.
Assuntos
Anticorpos Antifosfolipídeos/sangue , Doenças do Cão/imunologia , Fosfatidilcolinas/imunologia , Fosfatidilserinas/imunologia , Trombocitopenia/veterinária , beta 2-Glicoproteína I/imunologia , Animais , Anticorpos Anticardiolipina , Doenças do Cão/sangue , Cães , Ensaio de Imunoadsorção Enzimática/veterinária , Feminino , Humanos , Masculino , Especificidade da Espécie , Trombocitopenia/sangue , Trombocitopenia/imunologiaRESUMO
The mammalian bladder urothelium classified as basal, intermediate, and terminally differentiated umbrella cells offers one of the most effective permeability barrier functions known to exist in nature because of the formation of apical uroplakin plaques and tight junctions. To improve our understanding of urothelial differentiation, we analyzed the microRNA (miRNA) expression profiles of mouse urinary tissues and by TaqMan miRNA analysis of microdissected urothelial layers and in situ miRNA-specific hybridization to determine the dependence of these miRNAs on the differentiation stage. Our in situ hybridization studies revealed that miR-205 was enriched in the undifferentiated basal and intermediate cell layers. We then used a quantitative proteomics approach to identify miR-205 target genes in primary cultured urothelial cells subjected to antagomir-mediated knockdown of specific miRNAs. Twenty-four genes were reproducibly regulated by miR-205; eleven of them were annotated as cell junction- and tight junction-related molecules. Western blot analysis demonstrated that antagomir-induced silencing of miR-205 in primary cultured urothelial cells elevated the expression levels of Tjp1, Cgnl1, and Cdc42. Ectopic expression of miR-205 in MDCK cells inhibited the expression of tight junction proteins and the formation of tight junctions. miR-205- knockdown urothelial cells showed alterations in keratin synthesis and increases of uroplakin Ia and Ib, which are the urothelial differentiation products. These results suggest that miR-205 may contribute a role in regulation of urothelial differentiation by modulating the expression of tight junction-related molecules.
Assuntos
Diferenciação Celular/fisiologia , MicroRNAs/metabolismo , Proteínas de Junções Íntimas/metabolismo , Animais , Células Cultivadas , Cães , Células Epiteliais/metabolismo , Células Madin Darby de Rim Canino , Camundongos Endogâmicos ICR , Análise de Sequência com Séries de Oligonucleotídeos , Proteômica , RNA Mensageiro/metabolismo , Proteínas de Junções Íntimas/genética , Junções Íntimas/metabolismo , Urotélio/citologia , Urotélio/metabolismoRESUMO
Carboxylesterases are mainly involved in the mediation of metabolic resistance of many insects to organophosphate (OP) insecticides. Carboxylesterases underwent two divergent evolutionary events: (1) quantitative mechanism characterized by the overproduction of carboxylesterase protein; and (2) qualitative mechanism caused by changes in enzymatic properties because of mutation from glycine/alanine to aspartate at the 151 site (G/A151D) or from tryptophan to leucine at the 271 site (W271L), following the numbering of Drosophila melanogaster AChE. Qualitative mechanism has been observed in few species. However, whether this carboxylesterase mutation mechanism is prevalent in insects remains unclear. In this study, wild-type, G/A151D and W271L mutant carboxylesterases from Culex pipiens and Aphis gossypii were subjected to germline transformation and then transferred to D. melanogaster. These germlines were ubiquitously expressed as induced by tub-Gal4. In carboxylesterase activity assay, the introduced mutant carboxylesterase did not enhance the overall carboxylesterase activity of flies. This result indicated that G/A151D or W271L mutation disrupted the original activities of the enzyme. Less than 1.5-fold OP resistance was only observed in flies expressing A. gossypii mutant carboxylesterases compared with those expressing A. gossypii wild-type carboxylesterase. However, transgenic flies universally showed low resistance to OP insecticides compared with non-transgenic flies. The flies expressing A. gossypii W271L mutant esterase exhibited 1.5-fold resistance to deltamethrin, a pyrethroid insecticide compared with non-transgenic flies. The present transgenic Drosophila system potentially showed that a quantitative increase in carboxylesterases induced broader resistance of insects to insecticides than a qualitative change.
Assuntos
Afídeos/enzimologia , Carboxilesterase , Culex/enzimologia , Drosophila melanogaster , Resistência a Inseticidas , Inseticidas/farmacologia , Animais , Animais Geneticamente Modificados , Afídeos/genética , Carboxilesterase/genética , Carboxilesterase/metabolismo , Culex/genética , Drosophila melanogaster/efeitos dos fármacos , Drosophila melanogaster/enzimologia , Drosophila melanogaster/genética , Feminino , Expressão Gênica , Resistência a Inseticidas/genética , Resistência a Inseticidas/fisiologia , Masculino , Mutação , Nitrilas/farmacologia , Compostos Organofosforados/farmacologia , Piretrinas/farmacologiaRESUMO
Cyclin A1 belongs to the type-A cyclins and participates in cell cycle regulation. Since its discovery, cyclin A1 has been shown mostly in testis. It plays important roles in spermatogenesis. However, there were also reports on ovary expression of cyclin A1. Therefore, we intended to revisit the expression of cyclin A1 in mouse ovary. Our study showed that cyclin A1 was expressed at the mRNA level and the protein level in mouse ovary. Tissue staining revealed that cyclin A1 was expressed in maturating oocytes. With the recent data on the functions of cyclins in somatic and stem cells, we also discussed the possibilities of further studies of cyclin A1 in mouse oocytes and perhaps in the oogonial stem cells. Our findings not only add to the supportive evidence of cyclin A1 expression in oocytes, but also may promote more interest in exploring cyclin A1 functions in ovary.
Assuntos
Ciclina A1/biossíntese , Regulação da Expressão Gênica no Desenvolvimento , Oócitos/metabolismo , Ovário/metabolismo , Animais , Ciclina A1/genética , Feminino , Humanos , Camundongos , Ovário/crescimento & desenvolvimento , RNA Mensageiro/biossínteseRESUMO
The thyroid hormone, 3, 3',5-triiodo-l-thyronine (T(3)), regulates cell growth, development, differentiation, and metabolism via interactions with thyroid hormone receptors (TRs). However, the secreted proteins that are regulated by T(3) are yet to be characterized. In this study, we used the quantitative proteomic approach of stable isotope labeling with amino acids in cell culture coupled with nano-liquid chromatography-tandem MS performed on a LTQ-Orbitrap instrument to identify and characterize the T(3)-regulated proteins secreted in human hepatocellular carcinoma cell lines overexpressing TRα1 (HepG2-TRα1). In total, 1742 and 1714 proteins were identified and quantified, respectively, in three independent experiments. Among these, 61 up-regulated twofold and 11 down-regulated twofold proteins were identified. Eight proteins displaying increased expression and one with decreased expression in conditioned media were validated using Western blotting. Real-time quantitative RT-PCR further disclosed induction of plasminogen activator inhibitor-1 (PAI-1), a T(3) target, in a time-course and dose-dependent manner. Serial deletions of the PAI-1 promoter region and subsequent chromatin immunoprecipitation assays revealed that the thyroid hormone response element on the promoter is localized at positions -327/-312. PAI-1 overexpression enhanced tumor growth and migration in a manner similar to what was seen when T(3) induced PAI-1 expression in J7-TRα1 cells, both in vitro and in vivo. An in vitro neutralizing assay further supported a crucial role of secreted PAI-1 in T(3)/TR-regulated cell migration. To our knowledge, these results demonstrate for the first time that proteins involved in the urokinase plasminogen activator system, including PAI-1, uPAR, and BSSP4, are augmented in the extra- and intracellular space of T(3)-treated HepG2-TRα1 cells. The T(3)-regulated secretome generated in the current study may provide an opportunity to establish the mechanisms underlying T(3)-associated tumor progression and prognosis.
Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , Inibidor 1 de Ativador de Plasminogênio/metabolismo , Proteoma/metabolismo , Tri-Iodotironina/metabolismo , Aminoácidos , Animais , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Movimento Celular , Cromatografia Líquida , Humanos , Marcação por Isótopo , Neoplasias Hepáticas/patologia , Masculino , Camundongos , Camundongos Nus , Camundongos SCID , Invasividade Neoplásica , Proteínas de Neoplasias/metabolismo , Inibidor 1 de Ativador de Plasminogênio/genética , Ratos , Ratos Sprague-Dawley , Espectrometria de Massas em Tandem , Carga TumoralRESUMO
BACKGROUND/PURPOSE: Autoimmune thyroiditis can be diagnosed by measuring patients' serum levels of thyroid stimulating hormone (TSH), anti-thyroglobulin antibody (TGA), and anti-thyroid microsomal antibody (TMA). This study evaluated whether there were hematinic deficiencies, high blood homocysteine levels, and serum gastric parietal cell antibody (GPCA) positivity in patients with TGA or TMA. METHODS: The blood hemoglobin (Hb), iron, vitamin B12, folic acid, homocysteine and TSH concentrations and the serum GPCA level in 190 TGA- or TMA-positive patients were measured and compared with the corresponding levels in 190 age- and sex-matched healthy control subjects. RESULTS: We found that 31 (16.3%), 27 (14.2%), 12 (6.3%), and 2 (1.1%) TGA- or TMA-positive patients had deficiencies of Hb (Men<13g/dL, Women<12g/dL), iron (< 60µg/dL), vitamin B12 (< 200pg/mL), and folic acid (< 4ng/mL), respectively. Moreover, 25 (13.2%) and 48 (25.3%) TGA- or TMA-positive patients had abnormally high blood homocysteine level and serum GPCA positivity, respectively. TGA- or TMA-positive patients had a significantly higher frequency of Hb (p<0.001), iron (p<0.001), or vitamin B12 deficiency (p=0.001), of abnormally elevated blood homocysteine level (p=0.001), or of serum GPCA positivity (p<0.001) than healthy control subjects. Of 190 TGA- or TMA-positive patients, 8 (4.2%) had lower serum TSH level (< 0.1µIU/mL, suggestive of hyperthyroidism), 163 (85.8%) had serum TSH level within normal range (0.1-4.5µIU/mL), and 19 (10%) had higher serum TSH level (>4.5µIU/mL, suggestive of hypothyroidis). CONCLUSION: There are significant deficiencies of hemoglobin, iron, and vitamin B12, abnormally high blood homocysteine levels, and serum GPCA positivity in TGA- or TMA-positive patients. In addition, the majority (85.8%) of TGA- or TMA-positive patients had euthyroid and only a small portion (14.2%) of TGA- or TMA-positive patients had either hypothyroidism or hyperthyroidism.
Assuntos
Deficiência de Ácido Fólico/etiologia , Hemoglobinas/deficiência , Homocisteína/sangue , Deficiências de Ferro , Tireoidite Autoimune/complicações , Deficiência de Vitamina B 12/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Autoanticorpos/sangue , Biomarcadores/sangue , Estudos de Casos e Controles , Feminino , Ácido Fólico/sangue , Deficiência de Ácido Fólico/sangue , Deficiência de Ácido Fólico/diagnóstico , Hemoglobinas/metabolismo , Humanos , Hipertireoidismo/sangue , Hipertireoidismo/diagnóstico , Hipertireoidismo/etiologia , Hipotireoidismo/sangue , Hipotireoidismo/diagnóstico , Hipotireoidismo/etiologia , Ferro/sangue , Masculino , Pessoa de Meia-Idade , Células Parietais Gástricas/imunologia , Tireoidite Autoimune/sangue , Tireoidite Autoimune/imunologia , Vitamina B 12/sangue , Deficiência de Vitamina B 12/sangue , Deficiência de Vitamina B 12/diagnósticoRESUMO
Herein, a B(C6F5)3-catalyzed formal (n + 3) (n = 5 and 6) cycloaddition of bicyclo[1.1.0]butanes (BCBs) with imidazolidines/hexahydropyrimidines is described. The reaction provides a modular, atom-economical, and efficient strategy to two libraries of synthetically challenging medium-bridged rings, 2,5-diazabicyclo[5.1.1]nonanes and 2,6-diazabicyclo[6.1.1]decanes, in moderate to excellent yields. This reaction also features simple operation, mild reaction conditions, and broad substrate scope. A scale-up experiment and various synthetic transformations of products further highlight the synthetic utility.