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A visible-light-induced cascade reaction is described for the one-pot synthesis of 6-hydroxyindoloquinazolinones using isatins (or isatins and isatoic anhydrides) and aliphatic carboxylic acids. The method provides 36 desired products in 33-96 % yield, exhibiting broad substrate scope and good functional group tolerance. This approach utilizes inexpensive and commercially available starting materials, enabling the direct construction of high-value complex structures under mild conditions without the need for photocatalyst, showcasing significant applicability and environmental friendliness.
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A photoredox-neutral radical-radical cross-coupling is described for the synthesis of 3-hydroxy-3-alkyloxindoles using isatins and benzyl carboxylic acids as substrates and 2,4,5,6-tetra(9H-carbazol-9-yl)isophthalonitrile (4CzIPN) as the photocatalyst. The method features a broad substrate scope and good functional group tolerance, providing 30 sterically hindered alcohols with moderate to excellent yields. This approach utilizes inexpensive and commercially available starting materials, avoiding the use of transition metals, extra oxidants/reductants, and harsh reaction conditions, showcasing significant applicability and environmental friendliness.
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BACKGROUND: Dental caries is a chronic oral disease caused by microbial infections, which result in erosion of the dental enamel and cause irreversible damage. Therefore, proper disease management techniques and the creation of an environment that prevents intraoral growth and biofilm formation of Streptococcus mutans in the early stages, are crucial to prevent the potential progression of dental plaque to disease. Here, we aimed to investigate antimicrobial and antibiofilm effects of the Bacillus velezensis ID-A01 supernatant (ID23029) against S. mutans, and its inhibitory effects on acidogenesis. RESULTS: A killing kinetics assay showed a peak lethality percentage of 94.5% after 6 h of exposure to ID23029. In sucrose-exposed conditions, ID23029 inhibited lactic acid formation, preventing the pH from falling below the threshold for enamel demineralization, and inhibited up to 96.6% of biofilm formation. This effect was maintained in the presence of lysozyme. Furthermore, ID23029 retained up to 92% lethality, even at an intraoral concentration at which lysozyme is ineffective against S. mutans. CONCLUSIONS: This study demonstrates the potential of the B. velezensis ID-A01 supernatant for the prevention and treatment of dental caries. Its eventual use in dental practice is encouraged, although further studies are required to confirm its beneficial effects.
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Anti-Infecciosos , Cárie Dentária , Humanos , Muramidase/farmacologia , Streptococcus mutans , Cárie Dentária/prevenção & controle , Anti-Infecciosos/farmacologia , BiofilmesRESUMO
Hidradenitis suppurativa (HS) is a chronic inflammatory follicular disease characterized by painful, recurrent, inflamed lesions most commonly occurring in the axillary, inguinal, and anogenital regions. HS can inflict immense physical and psychological impact on patients who suffer from this distressing disease. Management of HS generally requires combining various medical and procedural treatment modalities; however, the disease is often recalcitrant to conventional treatments. In light of recent evidence supporting the effectiveness of biologic agents in the treatment of HS, the Taiwanese Dermatological Association established an expert panel of nine dermatologists to develop consensus statements aimed to provide up-to-date evidence-based guidance in optimizing HS patient management in Taiwan. The recommendations described in the statements were summarized in a management algorithm in terms of general care, topical treatment, systemic treatment, and procedural treatment.
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With the expansion of user scale in LEO satellite networks, unbalanced regional load and bursty network traffic lead to the problem of load disequilibrium. A distributed hops-based back-pressure (DHBP) routing is proposed. DHBP theoretically derives a fast solution for the minimum end-to-end propagation hops between satellite nodes in inclined-orbit LEO satellite networks; hence, link weights are determined based on remaining hops between the next hop and destination satellites. In order to control the number of available retransmission paths, the permitted propagation region is restricted to a rectangular region consisting of source-destination nodes to reduce the propagation cost. Finally, DHBP is designed distributedly, to realize a dynamic selection of the shortest link with low congestion and balanced traffic distribution without obtaining the whole network topology. Network simulation results demonstrate that DHBP has higher throughput and lower delay under high load conditions compared with state-of-the-art routing protocols.
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Natural compounds bearing maleimide rings are a series of secondary metabolites derived from fungi/marine microorganisms, which are characterized by a general structure -CO-N(R)-CO-, and the R group is normally substituted with alkyl or aryl groups. Maleimide compounds show various biological activities such as antibacterial, antifungal, and anticancer activity. In this review, the broad-spectrum antimicrobial activities of 15 maleimide compounds from natural sources and 32 artificially synthesized maleimides were summarized, especially against Candida albicans, Sclerotinia sclerotiorum, and Staphylococcus aureus. It highlights that maleimide scaffold has tremendous potential to be utilized in the development of novel antimicrobial agents.
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Anti-Infecciosos , Antibacterianos/farmacologia , Anti-Infecciosos/farmacologia , Antifúngicos/farmacologia , Candida albicans , Maleimidas/farmacologia , Testes de Sensibilidade Microbiana , Estrutura Molecular , Relação Estrutura-AtividadeRESUMO
BACKGROUND/PURPOSE: Leukemia cutis (LC), by definition, is the infiltration of neoplastic leukocytes in the skin. The overall incidence of LC is rare. We aimed to investigate the association between clinical characteristics, classifications and prognosis among different types of LC in Taiwan. METHODS: We performed a retrospective analysis of forty-two patients with histopathology proven LC based on skin biopsies in a medical center in Southern Taiwan from 1997 to 2018. The study involved medical records of the patients, clinical manifestations, and outcomes according to different types of leukemia. RESULTS: This series consisted of 27 males and 15 females, and the mean age was 55.7 years old. The most common cutaneous features were papules (38%) and nodules (29%), followed by plaques (16%) and ulcers (10%). The most commonly affected sites were the trunk (33%) and extremities (31.5%), although generalized distribution (14%) was not rare. The prognosis of LC was very poor, 76.2% of patients (32/42) died during the follow-up, and the median survival time was 7.2 months (95% CI, 4.53-9.87 months). No statistical significance was found (P = 0.068 for survival curves) among different types of LC. CONCLUSION: This study was the first large-scale research in regarding to LC of Han Chinese. The commonest clinical presentations were papules and nodules, and the predilection sites were trunk and extremities. Besides, there was the high frequency of LC from AML and MDS in Taiwan. Clinicians should pay more attention to the leukemia patients with extramedullary manifestations due to poor survival outcomes.
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Leucemia , Neoplasias Cutâneas , Feminino , Humanos , Leucemia/epidemiologia , Infiltração Leucêmica , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Pele , Taiwan/epidemiologiaRESUMO
Previous studies have demonstrated that pioglitazone, a peroxisome proliferator-activated receptor gamma (PPARγ) agonist, inhibits ischemia-induced brain injury. The present study was conducted to examine whether pioglitazone can reduce impairment of behavioral deficits mediated by inflammatory-induced brain white matter injury in neonatal rats. Intraperitoneal (i.p.) injection of lipopolysaccharide (LPS, 2 mg/kg) was administered to Sprague-Dawley rat pups on postnatal day 5 (P5), and i.p. administration of pioglitazone (20 mg/kg) or vehicle was performed 5 min after LPS injection. Sensorimotor behavioral tests were performed 24 h after LPS exposure, and changes in biochemistry of the brain was examined after these tests. The results show that systemic LPS exposure resulted in impaired sensorimotor behavioral performance, reduction of oligodendrocytes and mitochondrial activity, and increases in lipid peroxidation and brain inflammation, as indicated by the increment of interleukin-1ß (IL-1ß) levels and number of activated microglia in the neonatal rat brain. Pioglitazone treatment significantly improved LPS-induced neurobehavioral and physiological disturbances including the loss of body weight, hypothermia, righting reflex, wire-hanging maneuver, negative geotaxis, and hind-limb suspension in neonatal rats. The neuroprotective effect of pioglitazone against the loss of oligodendrocytes and mitochondrial activity was associated with attenuation of LPS-induced increment of thiobarbituric acid reactive substances (TBARS) content, IL-1ß levels and number of activated microglia in neonatal rats. Our results show that pioglitazone prevents neurobehavioral disturbances induced by systemic LPS exposure in neonatal rats, and its neuroprotective effects are associated with its impact on microglial activation, IL-1ß induction, lipid peroxidation, oligodendrocyte production and mitochondrial activity.
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Comportamento Animal , Encefalite/tratamento farmacológico , Mitocôndrias/patologia , Pioglitazona/uso terapêutico , Substância Branca/patologia , Animais , Animais Recém-Nascidos , Comportamento Animal/efeitos dos fármacos , Citocinas/metabolismo , Complexo I de Transporte de Elétrons/metabolismo , Encefalite/patologia , Feminino , Hipotermia Induzida , Lipopolissacarídeos , Microglia/efeitos dos fármacos , Microglia/patologia , Mitocôndrias/efeitos dos fármacos , Oligodendroglia/efeitos dos fármacos , Oligodendroglia/patologia , Pioglitazona/farmacologia , Gravidez , Ratos Sprague-Dawley , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Redução de Peso/efeitos dos fármacos , Substância Branca/efeitos dos fármacosRESUMO
AIM: Glucagon-like peptide-1 receptor agonists (GLP-1Ras) have been reported to prevent non-alcoholic fatty liver disease (NAFLD), but the potential mechanisms are still debated. MicroRNAs (miRNAs) play a prominent role in the field of metabolic disorders, including NAFLD. Our study was designed to further evaluate the effect of GLP-1Ra liraglutide on NAFLD in terms of miRNAs. METHODS: MicroRNA expression was evaluated by clustering analysis of microRNA arrays in high fat diet-fed mice. The luciferase reporter assay was carried out to validate the cross-talk between adipose triglyceride lipase (ATGL) and miR-124a. MicroRNA-124a mimics and inhibitor plasmids were transfected to study the role of miR-124a in palmitate-treated normal human liver cell line (HL-7702). Liraglutide treatment was used to observe the effect of GLP-1Ra on the miR-124a/ATGL pathway. RESULTS: Expression of ATGL decreased and miR-124a expression increased in hepatosteatosis in vivo and in vitro. Mechanistically, miR-124a interacted with the 3'-untranslated region of ATGL mRNA and induced its degradation. MicroRNA-124a overexpression antagonized the effect of liraglutide on NAFLD by inhibiting ATGL expression, whereas miR-124a knockdown led to elevated ATGL and sirtuin 1 (Sirt1) expression, and subsequently decreased lipid accumulation and inflammation in cells. CONCLUSIONS: MicroRNA-124a overexpression contributes to the progression of NAFLD through reduction of ATGL expression, whereas miR-124a knockdown can reverse this trend, suggesting that miR-124a and its downstream target ATGL can be novel therapeutic targets of NAFLD. We reveal a novel mechanism by which liraglutide attenuates NAFLD by the miR-124a/ATGL/Sirt1 pathway.
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Pseudonocardia autotrophica was previously identified to produce a toxicity-reduced and solubility-improved disaccharide-containing anti-fungal compound belonging to the tetraene-family, Nystatin-like Pseudonocardia Polyene A1 (NPP A1). Subsequently NPP B1, a novel derivative harboring a heptaene core structure, was produced by a pathway-engineered Pseudonocardia strain through inactivation of the specific enoly reductase gene domain in the NPP biosynthetic gene cluster. Although in vitro and in vivo efficacy and toxicity studies indicate that NPP B1 is a promising lead antifungal compound, further improvement is required to increase the extremely low production yield in the pathway-engineered strain. To overcome this challenge, we performed the N-methyl-N'-nitro-N-nitrosoguanidine (NTG) iterative random mutagenesis, followed by zone-of-inhibition agar plug assay. After three rounds of the mutagenesis-and-screening protocol, the production yield of NPP B1 increased to 6.25 mg/L, which is more than an eightfold increase compared to the parental strain. The qRT-PCR analysis revealed that transcripts of the NPP B1 biosynthetic genes were increased in the mutant strain. Interestingly, an endogenous 125-kb plasmid was found to be eliminated through this mutagenesis. To further improve the NPP B1 production yield, the 32-kb NPP-specific regulatory gene cluster was cloned and overexpressed in the mutant strain. The chromosomal integration of the extra copy of the six NPP-specific regulatory genes led to an additional increase of NPP B1 yield to 31.6 mg/L, which is the highest production level of NPP B1 ever achieved by P. autotrophica strains. These results suggest that a synergistic combination of both the traditional and genetic strain improvement approaches is a very efficient strategy to stimulate the production of an extremely low-level metabolite (such as NPP B1) in a pathway-engineered rare actinomycetes strain.
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Actinobacteria/metabolismo , Nistatina/biossíntese , Polienos/metabolismo , Actinobacteria/genética , Actinomycetales/genética , Antifúngicos/química , Dissacarídeos/metabolismo , Genes Reguladores , Microbiologia Industrial , Família Multigênica , Mutagênese , Plasmídeos/metabolismo , Engenharia de Proteínas , AçúcaresRESUMO
As conjugated polymer nanoparticles (CPNs) have attracted growing interest as photoacoustic (PA) imaging contrast agents, revelation of the relationship between the molecular structure of conjugated polymers and PA property is highly in demand. Here, three donor-acceptor-structured conjugated polymer analogs are designed, where only a single heteroatom of acceptor units changes from oxygen to sulfur to selenium, allowing for systematic investigation of the molecular structure-PA property relationship. The absorption and PA spectra of these CPNs can be facilely tuned by changing the heteroatoms of the acceptor units. Moreover, the absorption coefficient, and in turn the PA signal intensity, decreases when the heteroatom changes from oxygen to sulfur to selenium. As these CPNs exhibit weak fluorescence and similar photothermal conversion efficiency (≈70%), their PA intensities are approximately proportional to their absorption coefficients. The in vivo brain vasculature imaging in this study also demonstrates this trend. This study provides a simple but efficient strategy to manipulate the PA properties of CPNs through changing the heteroatom at key positions.
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Nanopartículas/química , Técnicas Fotoacústicas/métodos , Polímeros/química , Animais , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , HumanosRESUMO
A new hexadecahedron assembled by core-shell CoS2 particles@N-doped carbon (CoS2 @NCH) is prepared successfully through the self-templating method. The CoS2 @NCH hybrid electrode delivers a high lithium-storage capacity of 778â mA h g-1 after 1000â cycles at a high current density of 1â A g-1 , which is the longest cycle lifespan among the reported CoS2 anode materials in lithium-ion batteries. Furthermore, the CoS2 @NCH hybrid electrode shows excellent rate capability with a discharge capacity of 220â mA h g-1 at an extremely high current density of 20â A g-1 , and a charge capacity of 649â mA h g-1 is restored upon returning the current density back to 2â A g-1 . The superior performance is attributed to the unique construction of CoS2 @NCH. The N-doped interconnected porous carbon shells form highly conductive skeletons for quick electron transfer and prevent the electrode from collapsing. Moreover, the porous characteristic of the materials plays a key role: as some effective channels, the mesopores on the porous carbon shells provide greater access for lithium, and the mesopores derived from the particle interspace enables the complete immersion of the electrodes in electrolyte, which alleviates the volume expansion and ensures the integrity of the electrode. In addition, the nanosized CoS2 particles, which shorten the ion-transport path and provide extra electroactive sites, also improve the reaction kinetics.
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In this study, polydimethylsiloxane (PDMS) and conductive carbon nanoparticles were combined to fabricate a conductive elastomer PDMS (CPDMS). A high sensitive and flexible CPDMS strain sensor is fabricated by using stamping-process based micro patterning. Compared with conventional sensors, flexible strain sensors are more suitable for medical applications but are usually fabricated by photolithography, which suffers from a large number of steps and difficult mass production. Hence, we fabricated flexible strain sensors using a stamping-process with fewer processes than photolithography. The piezoresistive coefficient and sensitivity of the flexible strain sensor were improved by sensor pattern design and thickness change. Micro-patterning is used to fabricate various CPDMS microstructure patterns. The effect of gauge pattern was evaluated with ANSYS simulations. The piezoresistance of the strain gauges was measured and the gauge factor determined. Experimental results show that the piezoresistive coefficient of CPDMS is approximately linear. Gauge factor measurement results show that the gauge factor of a 140.0 µm thick strain gauge with five grids is the highest.
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BACKGROUND: Gastrointestinal microbiota, particularly gut microbiota, is associated with human health. The biodiversity of gut microbiota is affected by ethnicities and environmental factors such as dietary habits or medicine intake, and three enterotypes of the human gut microbiome were announced in 2011. These enterotypes are not significantly correlated with gender, age, or body weight but are influenced by long-term dietary habits. However, to date, only two enterotypes (predominantly consisting of Bacteroides and Prevotella) have shown these characteristics in previous research; the third enterotype remains ambiguous. Understanding the enterotypes can improve the knowledge of the relationship between microbiota and human health. RESULTS: We obtained 181 human fecal samples from adults in Taiwan. Microbiota compositions were analyzed using next-generation sequencing (NGS) technology, which is a culture-independent method of constructing microbial community profiles by sequencing 16S ribosomal DNA (rDNA). In these samples, 17,675,898 sequencing reads were sequenced, and on average, 215 operational taxonomic units (OTUs) were identified for each sample. In this study, the major bacteria in the enterotypes identified from the fecal samples were Bacteroides, Prevotella, and Enterobacteriaceae, and their correlation with dietary habits was confirmed. A microbial interaction network in the gut was observed on the basis of the amount of short-chain fatty acids, pH value of the intestine, and composition of the bacterial community (enterotypes). Finally, a decision tree was derived to provide a predictive model for the three enterotypes. The accuracies of this model in training and independent testing sets were 97.2 and 84.0%, respectively. CONCLUSIONS: We used NGS technology to characterize the microbiota and constructed a predictive model. The most significant finding was that Enterobacteriaceae, the predominant subtype, could be a new subtype of enterotypes in the Asian population.
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Biodiversidade , Microbioma Gastrointestinal , Metagenoma , Metagenômica , Adulto , Análise por Conglomerados , Árvores de Decisões , Fezes/microbiologia , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Metagenômica/métodos , Fenótipo , RNA Ribossômico 16S/genética , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
Bimetallic transition-metal oxides, which exhibit superior electrochemical properties compared with pristine single-metal oxides, have recently become a topic of significant research interest for applications in lithium-ion batteries (LIBs). Herein, we report a simple and scalable electrospinning method to synthesize porous CoTiO3 nanofibers as the precursor for nanostructured bimetallic transition-metal oxides formed electrochemically in situ. This strategy ensures uniform mixing and perfect contact between two constituent transition-metal oxides during the lithiation/delithiation process. Furthermore, CoTiO3 nanofibers based on ultrafine CoTiO3 nanocrystals are interconnected to form a nano/microstructured 3D network, which ensures the high stability of the in situ formed structure composed of bimetallic transition-metal oxides, and also fast ion/electron transfer and electrolyte penetration into the electrode. Electrochemical measurements revealed the excellent lithium storage (647â mAh g-1 at 0.1â Ag-1 ) and retention properties (600â mAh g-1 at 1â Ag-1 after 1200â cycles) of the CoO/TiO2 electrode. Moreover, the electrochemical reaction mechanism was explored by using ex situ X-ray photoelectric spectroscopy and cyclic voltammetry tests, which confirmed the two-phase reaction processes in the electrodes. These results clearly validate the potential of CoTiO3 with a unique nano/microstructured morphology as the precursor for a bimetallic transition-metal oxide for use as the anode material for long-life LIBs.
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In this work, oxygen-deficient anatase TiO2 nanosheets (A-TiO2-x NSs) are proposed as a substrate to improve the electrochemical properties of sulfur electrodes for lithium-sulfur (Li-S) batteries. The A-TiO2-x NSs are prepared by partly reducing pristine TiO2 nanosheets (A-TiO2 NSs) in NaBH4 solution. With some oxygen vacancies on the surface of the TiO2 nanosheets, A-TiO2-x NSs not only promote electronic transfer, but also act as more effective polysulfide reservoirs to minimize the dissolution of lithium polysulfides (LiPSs) than the A-TiO2 NSs control. Hence, upon utilization as modifiers for cathodes of Li-S batteries, the A-TiO2-x NSs-modified sulfur (A-TiO2-x NSs-S) cathode exhibits a higher reversible specific capacity and greater cycling performance and rate capability than the A-TiO2 NSs-modified one (A-TiO2 NSs-S). For example, A-TiO2-x NSs-S delivers an initial specific capacity of 1277.1â mAh g-1 at 0.1â C and maintains a stable Coulombic efficiency of approximately 99.2 % after the first five cycles; these values are higher than those of 997.3â mAh g-1 and around 96.7 %, respectively, for A-TiO2 NSs-S. The enhanced electrochemical properties of the A-TiO2-x NSs-S cathode can be ascribed mainly to the more effective adsorption of dissolvable and diffused LiPSs by the oxygen vacancies. Therefore, utilization of the structure of oxygen vacancies in Li-S batteries demonstrates great prospects for practical application.
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One of the criteria used by the International Union for Conservation of Nature (IUCN) to assess threat status is the rate of decline in abundance over 3 generations or 10 years, whichever is longer. The traditional method for calculating generation length (T) uses age-specific survival and fecundity, but these data are rarely available. Consequently, proxies that require less information are often used, which introduces potential biases. The IUCN recommends 2 proxies based on adult mortality rate, TÌd = α + 1/d, and reproductive life span, TÌz = α + z* RL, where α is age at first reproduction, d is adult mortality rate, RL is reproductive life span, and z is a coefficient derived from data for comparable species. We used published life tables for 78 animal and plant populations to evaluate precision and bias of these proxies by comparing TÌd and TÌz with true generation length. Mean error rates in estimating T were 31% for TÌd and 20% for TÌz, but error rates for TÌd were 16% when we subtracted 1 year ( TÌd( adj )=TÌd-1 ), as suggested by theory; TÌd( adj ) also provided largely unbiased estimates regardless of the true generation length. Performance of TÌz depends on compilation of detailed data for comparable species, but our results suggest taxonomy is not a reliable indicator of comparability. All 3 proxies depend heavily on a reliable estimate of age at first reproduction, as we illustrated with 2 test species. The relatively large mean errors for all proxies emphasized the importance of collecting the detailed life-history information necessary to calculate true generation length. Unfortunately, publication of such data is less common than it was decades ago. We identified generic patterns of age-specific change in vital rates that can be used to predict expected patterns of bias from applying TÌd( adj ).
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Conservação dos Recursos Naturais , Tábuas de Vida , Reprodução , Animais , Fertilidade , Plantas , Dinâmica PopulacionalRESUMO
LW-213 is a derivative of Wogonin and the anticancer activities of Wogonin have been reported. To study whether LW-213 inhibits cancer cells and explore a possible mechanism, we investigate the compound in several cancer cell lines. We found LW-213 arrests G2/M cycle in breast cancer cells by suppression of Akt/Gsk3ß/ß-catenin signaling pathway. In compound treated cells, cell cycle-related proteins cyclin A, cyclin B1, p-CDK1, p-Cdc25C, and p-Chk2 (Thr68) were upregulated, and ß-catenin nuclear translocation was inhibited. Electrophoretic mobility shift assay revealed LW-213 inhibits binding of ß-catenin/LEF complex to DNA. GSK3ß inhibitor LiCl and siRNA against GSK3ß partially reversed G2/M arrest in breast cancer MCF-7 cells. These results suggest LW-213 triggered G2/M cell cycle arrest through suppression of ß-catenin signaling. In BALB/c mice, growth of xenotransplanted MCF-7 tumor was also inhibited after treatment of LW-213. Regulation of cyclin A, cyclin B1, and ß-catenin by LW-213 in vivo was the same as in vitro study. In conclusion, we found LW-213 exerts its anticancer effect on cell proliferation and cell cycle through repression of Akt/Gsk3ß/ß-catenin signaling pathway. LW-213 could be a potential candidate for anticancer drug development.
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Antineoplásicos/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Flavanonas/administração & dosagem , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Animais , Antineoplásicos/farmacologia , Apoptose , Neoplasias da Mama/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Feminino , Flavanonas/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Quinase 3 da Glicogênio Sintase/metabolismo , Glicogênio Sintase Quinase 3 beta , Humanos , Cloreto de Lítio/farmacologia , Células MCF-7 , Camundongos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto , beta Catenina/metabolismoRESUMO
D-serine is a coagonist of N-methyl-d-aspartate (NMDA) subtype of glutamate receptor and plays a role in regulating activity-dependent synaptic plasticity. In this study, we examined the mechanism by which extracellular ATP triggers the release of d-serine from astrocytes and discovered a novel Ca(2+) -independent release mechanism mediated by P2X7 receptors (P2X7 R). Using [(3) H] d-serine, which was loaded into astrocytes via the neutral amino acid transporter 2 (ASCT2), we observed that ATP and a potent P2X7 R agonist, 2'(3')-O-(4-benzoylbenzoyl)adenosine-5'-triphosphate (BzATP), stimulated [(3) H]D-serine release and that were abolished by P2X7 R selective antagonists and by shRNAs, whereas enhanced by removal of intracellular or extracellular Ca(2+) . The P2X7 R-mediated d-serine release was inhibited by pannexin-1 antagonists, such as carbenoxolone (CBX), probenecid (PBN), and (10) Panx-1 peptide, and shRNAs, and stimulation of P2X7 R induced P2X7 R-pannexin-1 complex formation. Simply incubating astrocytes in Ca(2+) /Mg(2+) -free buffer also induced the complex formation, and that enhanced basal d-serine release through pannexin-1. The P2X7 R-mediated d-serine release assayed in Ca(2+) /Mg(2+) -free buffer was enhanced as well, and that was inhibited by CBX. Treating astrocytes with general protein kinase C (PKC) inhibitors, such as chelerythrine, GF109203X, and staurosporine, but not Ca(2+) -dependent PKC inhibitor, Gö6976, inhibited the P2X7 R-mediated d-serine release. Thus, we conclude that in astrocytes, P2X7 R-pannexin-1 complex formation is crucial for P2X7 R-mediated d-serine release through pannexin-1 hemichannel. The release is Ca(2+) -independent and regulates by a Ca(2+) -independent PKC. The activated P2X7 R per se is also functioned as a permeation channel to release d-serine in part. This P2X7 R-mediated d-serine release represents an important mechanism for activity-dependent neuron-glia interaction.
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Astrócitos/metabolismo , Cálcio/metabolismo , Conexinas/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Receptores Purinérgicos P2X7/metabolismo , Serina/metabolismo , Trifosfato de Adenosina/análogos & derivados , Trifosfato de Adenosina/farmacologia , Sistema ASC de Transporte de Aminoácidos/metabolismo , Animais , Animais Recém-Nascidos , Astrócitos/efeitos dos fármacos , Células Cultivadas , Córtex Cerebral/citologia , Relação Dose-Resposta a Droga , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Masculino , Antígenos de Histocompatibilidade Menor , Purinérgicos/farmacologia , Ratos , Trítio/metabolismoRESUMO
The large-scale production of high-quality carbon nanomaterials is highly desirable for a variety of applications. We demonstrate a novel synthetic route to the production of fluorescent carbon nanoparticles (CNPs) in large quantities via a single-step reaction. The simple heating of a mixture of benzaldehyde, ethanol and graphite oxide (GO) with residual sulfuric acid in an autoclave produced 7 g of CNPs with a quantum yield of 20%. The CNPs can be dispersed in various organic solvents; hence, they are easily incorporated into polymer composites in forms such as nanofibers and thin films. Additionally, we observed that the GO present during the CNP synthesis was reduced. The reduced GO (RGO) was sufficiently conductive (σ ≈ 282 S m(-1)) such that it could be used as an electrode material in a supercapacitor; in addition, it can provide excellent capacitive behavior and high-rate capability. This work will contribute greatly to the development of efficient synthetic routes to diverse carbon nanomaterials, including CNPs and RGO, that are suitable for a wide range of applications.