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1.
J Am Chem Soc ; 146(31): 21999-22007, 2024 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-39044627

RESUMO

Persulfides (RSS-) are ubiquitous source of sulfides (S2-) in biology, and interactions between RSS- and bioinorganic metal centers play critical roles in biological hydrogen sulfide (H2S) biogenesis, signaling, and catabolism. Here, we report the use of contact-ion stabilized [Na(15-crown-5)][tBuSS] (1) as a simple synthon to access rare metal alkyl persulfide complexes and to investigate the reactivity of RSS- with transition metal centers to provide insights into metal thiolate persulfidation, including the fundamental difference between alkyl persulfides and alkyl thiolates. Reaction of 1 with [CoII(TPA)(OTf)]+ afforded the η1-alkyl persulfide complex [CoII(TPA)(SStBu)]+ (2), which was characterized by X-ray crystallography, UV-vis spectroscopy, and Raman spectroscopy. RSS- coordination to the Lewis acidic Co2+ center provided additional stability to the S-S bond, as evidenced by a significant increase in the Raman stretching frequency for 2 (vS-S = 522 cm-1, ΔvS-S = 66 cm-1). The effect of persulfidation on metal center redox potentials was further elucidated using cyclic voltammetry, in which the Co2+ → Co3+ oxidation potential of 2 (Ep,a = +89 mV vs SCE) is lowered by nearly 700 mV when compared to the corresponding thiolate complex [CoII(TPA)(StBu)]+ (3) (Ep,a = +818 mV vs SCE), despite persulfidation being generally seen as an oxidative post-translational modification. The reactivity of 2 toward reducing agents including PPh3, BH4-, and biologically relevant thiol reductant DTT led to different S2- output pathways, including formation of a dinuclear 2Co-2SH complex [CoII2(TPA)2(µ2-SH)2]2+(4).

2.
J Am Chem Soc ; 145(24): 13435-13443, 2023 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-37294127

RESUMO

Reactive sulfur species (RSS) and reactive selenium species (RSeS) play integral roles in hydrogen sulfide (H2S) and hydrogen selenide (H2Se) biological signaling pathways, and dichalcogenide anions are proposed transient intermediates that facilitate a variety of biochemical transformations. Herein we report the selective synthesis, isolation, spectroscopic and structural characterization, and fundamental reactivity of persulfide (RSS-), perselenide (RSeSe-), thioselenide (RSSe-), and selenosulfide (RSeS-) anions. The isolated chalcogenides do not rely on steric protection for stability and have steric profiles analogous to cysteine (Cys). Simple reduction of S8 or Se by potassium benzyl thiolate (KSBn) or selenolate (KSeBn) in the presence of 18-crown-6 afforded [K(18-crown-6)][BnSS] (1), [K(18-crown-6)][BnSeSe] (2), [K(18-crown-6][BnSSe] (3), and [K(18-crown-6][BnSeS] (4). The chemical structure of each dichalcogenide was confirmed by X-ray crystallography and solution-state 1H, 13C, and 77Se NMR spectroscopy. To advance our understanding of the reactivity of these species, we demonstrated that reduction of 1-4 by PPh3 readily generates E═PPh3 (E: S, Se), and reduction of 1, 3, and 4 by DTT readily produces HE-/H2E. Furthermore, 1-4 react with CN- to produce ECN-, which is consistent with the detoxifying effects of dichalcogenide intermediates in the Rhodanese enzyme. Taken together, this work provides new insights into the inherent structural and reactivity characteristics of dichalcogenides relevant to biology and advances our understanding of the fundamental properties of these reactive anions.

3.
Arch Biochem Biophys ; 728: 109352, 2022 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-35863479

RESUMO

Esophageal carcinoma (ESCA) is one of the most prevalent and aggressive malignancies of the gastrointestinal tract and constitutes sixth primary cause of cancer-related death worldwide. It is urgently needed to identify effective therapeutic targets. Differentially expressed genes (DEGs) involved in ESCA were identified via bioinformatics analysis. Four DEGs were selected for further analysis using Gene Expression Profiling Interactive Analysis, Human Protein Atlas, UALCAN web portal, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. 5-ethynyl-2'-deoxyuridine incorporation and cell counting kit-8 assays were used to evaluate cell proliferation. Western blot analysis was used to detect the protein levels of lysosomal-associated transmembrane protein 4B (LAPTM4B), Notch1, hairy and enhancer of split 1 (Hes1), and hairy and enhancer of split-related with YRPW motif 1 (Hey1). Results showed that LAPTM4B, Bcl-2 homology domain 3 (BH3)-interacting domain death agonist (BID), epithelial cell transforming sequence 2 (ECT2), and aurora kinase A (AURKA) were upregulated in several types of tumors including ESCA and correlated with tumor stage and tumor histology based on bioinformatics analysis. KEGG pathway analysis suggested that LAPTM4B-associated genes were significantly enriched in Notch pathway. Meanwhile, BID-, ECT2-, and AURKA-correlated genes were particularly enriched in p53 signaling pathway. Additionally, we found that LAPTM4B silencing inhibited cell proliferation and Notch pathway in ESCA cells. Notch1 overexpression abrogated LAPTM4B knockdown-induced proliferation reduction in ESCA cells. In conclusion, LAPTM4B silencing inhibited proliferation in ESCA cells by inactivating the Notch pathway.


Assuntos
Carcinoma , Neoplasias Esofágicas , Aurora Quinase A , Biologia Computacional , Regulação Neoplásica da Expressão Gênica , Humanos , Proteínas de Membrana , Proteínas Oncogênicas , Fatores de Transcrição
4.
Environ Res ; 205: 112539, 2022 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-34896322

RESUMO

In this work, we prepared Cu2FeSnS4 (CFTS) microspheres via solvothermal method and studied their photocatalytic performance towards the degradation of organic pollutants. With increasing solvothermal temperature from 160 °C to 180 °C, the morphology of CFTS changes from irregular 2D to hierarchical 3D shapes. Hierarchical 3D CFTS microspheres packed with 2D nanosheets were successfully prepared at 180 °C. During the solvothermal process, octadecyl amine (ODA) acts as a capping agent to prevent the aggregation of particles, while L-cystine functions as an environmentally friendly sulfur source and complexing reagent. The large surface area and mesoporous structure of the as-prepared 3D hierarchical CFTS microspheres provide more active sites, enhance visible light absorption and promote charge separation and transfer, leading to the improved photodegradation performance for RhB and MB compared to the samples prepared at the temperature lower than 180 °C. This work provides a simple and low-cost method for the synthesis of 3D hierarchical CFTS towards photocatalytic applications.

5.
Appl Microbiol Biotechnol ; 106(7): 2415-2431, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35352151

RESUMO

Squalene, as an important terpenoid, is extensively used in the medicine and health care fields owing to its functions of anti-oxidation, blood lipid regulation and cancer prevention. The marine microalgae, Schizochytrium sp., which acts as an excellent strain with potential of high squalene production was selected as the starting strain. The overexpressed strain with sqs gene got the reduced biomass and lipid, while the squalene titer was increased by 79.6% ± 4.7% to 12.8 ± 0.2 mg/L. In order to further increase squalene production, the recombinant strain (HS strain) with sqs and hmgr gene co-overexpression was further constructed. The biomass and squalene titer of the HS strain were increased by 13.6% ± 1.2% and 88.8% ± 5.3%, respectively, which indicated the carbon flux of the mevalonate pathway was enhanced for squalene accumulation. Regarding the squalene synthesis is completely coupled with cell growth, fermentation strategy to prolong the logarithmic growth phase was conducive to improve squalene production. Under the condition of optimal composition and concentrated medium, the squalene titer of HS strain was 27.0 ± 1.3 mg/L, which was 2.0 times that of the basal medium condition (13.5 ± 0.4 mg/L). This study which combined the metabolic engineering and fermentation strategy provides a new strategy for squalene production in Schizochytrium sp. KEY POINTS: •The overexpression of sqs and hmgr genes promoted carbon metabolism for squalene. •The optimal and concentrated media can increase squalene yield.


Assuntos
Microalgas , Estramenópilas , Biomassa , Fermentação , Microalgas/metabolismo , Esqualeno/metabolismo , Estramenópilas/genética , Estramenópilas/metabolismo
6.
Sensors (Basel) ; 22(10)2022 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-35632049

RESUMO

To achieve high-precision vector measurement values in a geomagnetic field, it is necessary to develop methods for overcoming alternating magnetic interference (AMI), which is generated by electrical equipment. This paper proposes the adaptive alternating magnetic interference suppression (AAIS) algorithm. In this algorithm, first, only a triaxial fluxgate sensor measures the magnetic field data. The time-frequency diagram of the total magnetic field is obtained quickly through short-time Fourier transform and wavelet transform. Additionally, the time and frequency of AMI appearance are analyzed. Then, the triaxial adaptive notch filter suppresses the three-component related magnetic interference. Herein, simulation and actual experiments are performed to verify the effectiveness of AAIS. The results indicate that the algorithm can quickly detect the frequencies of AMI from the total magnetic field and adaptively fit their amplitude and phase on the vector magnetic field. Finally, AAIS can suppress the interference effectively. The AAIS algorithm realizes error compensation for the vector measurement values by the total magnetic field, which effectively improves the vector measurement accuracy of the geomagnetic field. We highlight that the AAIS algorithm is effective for AMIs of different frequencies, numbers, and intensities without reference sensors. Our work has practical implications in airborne, vehicle-mounted, and shipborne geomagnetic vector detection.

7.
J Environ Manage ; 316: 115230, 2022 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-35537269

RESUMO

Excess sludge management is a restrictive factor for the development of municipal wastewater treatment plants. The addition of metabolic uncouplers has been proven to be effective in sludge reduction. However, the long-term effect of metabolic uncoupler o-chlorophenol (oCP) on the biological wastewater treatment system operated in anaerobic-oxic mode is still unclear. To this end, two parallel reactors operated in anaerobic-oxic mode with and without 10 mg/L of oCP addition were investigated for 91 days. The results showed that 56.1 ± 2.3% of sludge reduction was achieved in the oCP-added system, and the nitrogen and phosphorus removal ability were negatively affected. Dosing oCP stimulated the formation of microbial products and increased the DNA concentration, but resulted in a decrease in the electronic transport activity of activated sludge. Microbial community analysis further demonstrated that a significant reduction of bacterial richness and diversity occurred after oCP dosing. However, after stopping oCP addition, the pollutant removal ability of activated sludge was gradually increased, but the sludge yield, as well as species richness and diversity, did not recover to the previous level. This study will provide insightful guidance on the long-term application of metabolic uncouplers in the activated sludge system.


Assuntos
Clorofenóis , Microbiota , Anaerobiose , Reatores Biológicos , Nitrogênio , Esgotos/microbiologia , Eliminação de Resíduos Líquidos/métodos
8.
Molecules ; 27(15)2022 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-35897914

RESUMO

Allobetulin is structurally similar tobetulinic acid, inducing the apoptosis of cancer cells with low toxicity. However, both of them exhibited weak antiproliferation against several tumor cell lines. Therefore, the new series of allobetulon/allobetulin-nucleoside conjugates 9a-10i were designed and synthesized for potency improvement. Compounds 9b, 9e, 10a, and 10d showed promising antiproliferative activity toward six tested cell lines, compared to zidovudine, cisplatin, and oxaliplatin based on their antitumor activity results. Among them, compound 10d exhibited much more potent antiproliferative activity against SMMC-7721, HepG2, MNK-45, SW620, and A549 human cancer cell lines than cisplatin and oxaliplatin. In the preliminary study for the mechanism of action, compound 10d induced cell apoptosis and autophagy in SMMC cells, resulting in antiproliferation and G0/G1 cell cycle arrest by regulating protein expression levels of Bax, Bcl-2, and LC3. Consequently, the nucleoside-conjugated allobetulin (10d) evidenced that nucleoside substitution was a viable strategy to improve allobetulin/allobetulon's antitumor activity based on our present study.


Assuntos
Antineoplásicos , Cisplatino , Antineoplásicos/farmacologia , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Cisplatino/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Estrutura Molecular , Nucleosídeos/farmacologia , Oxaliplatina/farmacologia , Relação Estrutura-Atividade
9.
Chemistry ; 25(19): 5028-5035, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30710376

RESUMO

Fundamental photocatalytic limitations of solar CO2 reduction remain due to low efficiency, serious charge recombination, and short lifetime of catalysts. Herein, two-dimensional graphitic carbon nitride nanosheets with nitrogen vacancies (g-C3 Nx ) located at both three-coordinate N atoms and uncondensed terminal NHx species were prepared by one-step tartaric acid-assistant thermal polymerization of dicyandiamide. Transient absorption spectra revealed that the defects in g-C3 N4 act as trapped states of charges to result in prolonged lifetimes of photoexcited charge carriers. Time-resolved photoluminescence spectroscopy revealed that the faster decay of charges is due to the decreased interlayer stacking distance in g-C3 Nx in favor of hopping transition and mobility of charge carriers to the surface of the material. Owing to the synergic virtues of strong visible-light absorption, large surface area, and efficient charge separation, the g-C3 Nx nanosheets with negligible loss after 15 h of photocatalysis exhibited a CO evolution rate of 56.9 µmol g-1 h-1 under visible-light irradiation, which is roughly eight times higher than that of pristine g-C3 N4 . This work presents the role of defects in modulating light absorption and charge separation, which opens an avenue to robust solar-energy conversion performance.

10.
Int J Med Sci ; 16(4): 529-536, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31171904

RESUMO

Epithelial-mesenchymal transition (EMT), which involves the dramatic reorganization of the cytoskeleton, is a crucial initiating step in tumor invasion and metastasis. Protein 4.1B is a membrane-cytoskeleton cross-linker that plays an important role in tumor progression and metastasis; however, the functional roles of 4.1B in melanoma remain unclear. In this study, we aimed to investigate the effect and underlying mechanism of 4.1B on melanoma cells. Our results demonstrated that 4.1B expression was downregulated in murine B16 and B16-F10 melanoma cell lines. Ectopic 4.1B expression significantly inhibited the migration of melanoma cells and pulmonary metastasis. We further investigated the possible mechanism underlying the effect of 4.1B on EMT. The results showed that ectopic 4.1B expression altered the expression of representative EMT markers (E-cadherin, vimentin and N-cadherin), and inhibited the expression of three important transcription factors (Slug, Snail, and Twist) related to EMT in melanoma cells. Moreover, the expression of integrin α5, ß3 and matrix metalloproteinase 9 (MMP-9), which is known to regulate cell adhesion, migration and invasion, were suppressed. In conclusion, our data indicate that 4.1B is an important regulator during EMT progression in melanoma cells, which may present a potential target for the prevention and treatment of melanoma.


Assuntos
Neoplasias Pulmonares/genética , Melanoma Experimental/genética , Proteínas dos Microfilamentos/genética , Proteínas de Neoplasias/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Citoesqueleto/genética , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/secundário , Metaloproteinase 9 da Matriz/genética , Melanoma Experimental/patologia , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Metástase Neoplásica
11.
BMC Cancer ; 18(1): 793, 2018 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-30081850

RESUMO

BACKGROUND: CRC is one of the most common malignancies worldwide, and its molecular mechanisms remain unclear. Elevated levels of BAG3 have been reported in various tumors. The present study aimed to explore the expression and function of BAG3 in CRC. METHODS: BAG3 protein expression was evaluated in 90 CRC specimens using immunohistochemistry in tissue microarrays, and the correlation between BAG3 expression and the clinicopathological features were assessed. In HCT116 cells BAG3 overexpression cell models were constructed, and CRISPR/Cas9 was used for BAG3 knockout. Western blotting and quantitative real-time PCR were used to determine BAG3 expression in HCT-116 Cells. Cell proliferation, migration and invasion were analyzed by cell counting, colony formation assay, EdU cell proliferation assay, RTCA growth curve assays, wound-healing migration assay and transwell invasion assay. The influence of BAG3 expression level on chemoresistance in HCT-116 cells was examined. Gene expression microarray and IPA analyses were employed to explore signaling pathways associated with the control of BAG3. RESULTS: Using immunohistochemistry, this study found that BAG3 was markedly upregulated in colorectal cancer tissues and that BAG3 levels were significantly associated with tumor size and gender. BAG3 overexpression promoted HCT-116 cell growth, migration and invasion in vitro. In contrast, BAG3 knockout inhibited HCT-116 cell growth, migration and invasion. HCT-116 cells with high expression of BAG3 had higher cell viability and lower apoptosis rate than control cells after treatment with 5-FU, while the BAG3 knockout group demonstrated the opposite effects. So BAG3 expression level was associated with chemoresistance to 5-FU in HCT-116 cells. Gene expression microarrays and bioinformatics analyses of HCT-116 cells with BAG3 knockout demonstrated the involvement of BAG3 in signaling pathways associated with the control of cell proliferation, migration, invasion and chemoresistance in CRC. CONCLUSIONS: In conclusion, this study provided evidence that BAG3 has a relevant role in CRC biology, and defined potential molecular pathways and networks. So BAG3 may be considered as a potential therapeutic target for anti-tumor therapy in colorectal cancer.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas Reguladoras de Apoptose/metabolismo , Movimento Celular , Proliferação de Células , Neoplasias Colorretais/metabolismo , Resistencia a Medicamentos Antineoplásicos , Proteínas Adaptadoras de Transdução de Sinal/genética , Idoso , Antimetabólitos Antineoplásicos/farmacologia , Proteínas Reguladoras de Apoptose/genética , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Fluoruracila/farmacologia , Regulação Neoplásica da Expressão Gênica , Células HCT116 , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Transdução de Sinais , Regulação para Cima
12.
Biomed Chromatogr ; 30(9): 1378-85, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26848536

RESUMO

A rapid and sensitive LC-MS/MS method with good accuracy and precision was developed and validated for the pharmacokinetic study of quercetin-3-O-ß-d-glucopyranosyl-7-O-ß-d-gentiobioside (QGG) in Sprague-Dawley rats. Plasma samples were simply precipitated by methanol and then analyzed by LC-MS/MS. A Venusil® ASB C18 column (2.1 × 50 mm, i.d. 5 µm) was used for separation, with methanol-water (50:50, v/v) as the mobile phase at a flow rate of 300 µL/min. The optimized mass transition ion-pairs (m/z) for quantitation were 787.3/301.3 for QGG, and 725.3/293.3 for internal standard. The linear range was 7.32-1830 ng/mL with an average correlation coefficient of 0.9992, and the limit of quantification was 7.32 ng/mL. The intra- and inter-day precision and accuracy were less than ±15%. At low, medium and high quality control concentrations, the recovery and matrix effect of the analyte and IS were in the range of 89.06-92.43 and 88.58-97.62%, respectively. The method was applied for the pharmacokinetic study of QGG in Sprague-Dawley rats. Copyright © 2016 John Wiley & Sons, Ltd.


Assuntos
Cromatografia Líquida/métodos , Glucosídeos/farmacocinética , Quercetina/análogos & derivados , Espectrometria de Massas em Tandem/métodos , Animais , Glucosídeos/sangue , Limite de Detecção , Masculino , Quercetina/sangue , Quercetina/farmacocinética , Ratos , Ratos Sprague-Dawley
13.
Acta Cardiol ; 70(1): 67-72, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26137805

RESUMO

The angiotensin II type 1 receptor (AT1R) antagonist protects the heart against acute ischaemia-reperfusion injury. The underlying mechanism is unclear. To determine the effects of angiotensin II type 1 receptor blockade, valsartan on AT1 and AT2 receptor during ischaemia reperfusion in isolated rat, the hearts of 24 SD rats were isolated, linked to Langendorff perfusion apparatus, and exposed to ischaemia for 30 min.The left ventricular systolic pressure, maximal uprising velocity of left ventricular pressure (+dp/dt(max)), maximal decreasing velocity of left ventricular pressure (-dp/dt(max)) and coronary flow were measured after stabilization of the perfusion.The isoenzyme of creatine kinase in the effluent liquid from the heart, AT1 and AT2 receptor mRNA and protein expression were measured after stabilization of the perfusion. The results showed that ischaemia-reperfusion induced a marked decrease in left ventricular systolic pressure, +dp/dt(max) and -dp/dt(max) indicating severe cardiac dysfunction and decreased coronary effluence. Concurrently, myocardial AT1 and AT2 receptor mRNA and protein expression were increased with valsartan. However, AT2 receptor mRNA and protein expression decreased during ischaemia-reperfusion. The creatine kinase levels at different time points of the valsartan group were significantly lower. The results suggested that valsartan improved left ventricular function and increased coronary effluence because the angiotensin receptor blocker valsartan induced cardioprotection associated with upregulating AT2 receptor protein and mRNA expression after ischaemia-reperfusion in isolated rats.


Assuntos
Regulação da Expressão Gênica , Traumatismo por Reperfusão Miocárdica/genética , RNA Mensageiro/genética , Receptor Tipo 2 de Angiotensina/genética , Tetrazóis/farmacologia , Regulação para Cima/efeitos dos fármacos , Valina/análogos & derivados , Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Animais , Western Blotting , Circulação Coronária/efeitos dos fármacos , Modelos Animais de Doenças , Masculino , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Traumatismo por Reperfusão Miocárdica/metabolismo , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase em Tempo Real , Receptor Tipo 2 de Angiotensina/biossíntese , Valina/farmacologia , Valsartana
14.
Ocul Immunol Inflamm ; 32(8): 1564-1579, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38427350

RESUMO

PURPOSE: Numerous uveitis articles were published in this century, underneath which hides valuable intelligence. We aimed to characterize the evolution and patterns in this field. METHODS: We divided the 15,994 uveitis papers into four consecutive time periods for bibliometric analysis, and applied latent Dirichlet allocation topic modeling and machine learning techniques to the latest period. . RESULTS: The yearly publication pattern fitted the curve: 1.21335x2 - 4,848.95282x + 4,844,935.58876 (R2 = 0.98311). The USA, the most productive country/region, focused on topics like ankylosing spondylitis and biologic therapy, whereas China (mainland) focused on topics like OCT and Behcet disease. The logistic regression showed the highest accuracy (71.6%) in the test set. CONCLUSION: In this century, a growing number of countries/regions/authors/journals are involved in the uveitis study, promoting the scientific output and thematic evolution. Our pioneering study uncovers the evolving academic trends and frontier patterns in this field using bibliometric analysis and AI algorithms.


Assuntos
Bibliometria , Aprendizado de Máquina , Processamento de Linguagem Natural , Uveíte , Humanos , Uveíte/tratamento farmacológico , Uveíte/diagnóstico , Pesquisa Biomédica/tendências , Publicações Periódicas como Assunto , Algoritmos
15.
Artigo em Inglês | MEDLINE | ID: mdl-38878162

RESUMO

Activation of fatty acids as acyl-adenylates by fatty acid-AMP ligase (FAAL) is a well-established process contributing to the formation of various functional natural products. Enzymatic characterization of FAALs is pivotal for unraveling both the catalytic mechanism and its role in specific biosynthetic pathways. In this study, we recombinantly expressed and characterized a novel FAAL derived from marine Pseudoalteromonas citrea (PcFAAL). PcFAAL was a cold-adapted neutral enzyme, demonstrating optimal activity at 30 °C and pH 7.5. Notably, its specific activity relied on the presence of Mg2+; however, higher concentrations exceeding 10 mM resulted in inhibition of enzyme activity. Various organic solvents, especially water-immiscible organic solvents, demonstrated an activating effect on the activity of PcFAAL on various fatty acids. The specific activity exhibited a remarkable 50-fold increase under 4% (v/v) n-hexane compared to the aqueous system. PcFAAL displayed a broad spectrum of fatty acid substrate selectivity, with the highest specific activity for octanoic acid (C8:0), and the catalytic efficiency (kcat/Km) for octanoic acid was determined to be 1.8 nM-1·min-1. Furthermore, the enzyme demonstrated biocatalytic promiscuity in producing a class of N-acyl amino acid natural products, as verified by LC-ESI MS. Results indicated that the PcFAAL exhibits promiscuity towards 10 different kinds of amino acids and further demonstrated their potential value in the biosynthesis of corresponding functional N-acyl amino acids.

16.
ACS Appl Mater Interfaces ; 16(21): 27301-27310, 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38757947

RESUMO

The in-plane heterojunctions with atomic-level thickness and chemical-bond-connected tight interfaces possess high carrier separation efficiency and fully exposed surface active sites, thus exhibiting exceptional photocatalytic performance. However, the construction of in-plane heterojunctions remains a significant challenge. Herein, we prepared an in-plane ZnIn2S4/In(OH)3 heterojunction (ZISOH) by partial conversion of ZnIn2S4 to In(OH)3 through the addition of H2O2. This in situ oxidation etching-hydrolysis approach enables the ZISOH heterojunction to not only preserve the original nanosheet morphology of ZnIn2S4 but also form an intimate interface. Moreover, generated In(OH)3 serves as an electron-accepting platform and also promotes the adsorption of CO2. As a result, the heterojunction exhibits a remarkably enhanced performance for photocatalytic CO2 reduction. The production rate and selectivity of CO reach 1760 µmol g-1 h-1 and 78%, respectively, significantly higher than those of ZnIn2S4 (842 µmol g-1 h-1 and 65%). This work puts forward a feasible and facile approach to construct in-plane heterojunctions to enhance the photocatalytic performance of two-dimensional metal sulfides.

18.
Eur J Med Chem ; 276: 116635, 2024 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-38964258

RESUMO

Fifteen betulonic/betulinic acid conjugated with nucleoside derivatives were synthesized to enhance antitumor potency and water solubility. Among these, the methylated betulonic acid-azidothymidine compound (8c) exhibited a broad-spectrum of antitumor activity against three tested tumor cell lines, including SMMC-7721 (IC50 = 5.02 µM), KYSE-150 (IC50 = 5.68 µM), and SW620 (IC50 = 4.61 µM) and along with lower toxicity (TC50 > 100 µM) estimated by zebrafish embryos assay. Compared to betulinic acid (<0.05 µg/mL), compound 8c showed approximately 40-fold higher water solubility (1.98 µg/mL). In SMMC-7721 cells, compound 8c induced autophagy and apoptosis as its concentration increased. Transcriptomic sequencing analysis was used to understand the potential impacts of the underlying mechanism of 8c on SMMC-7721 cells. Transcriptomic studies indicated that compound 8c could activate autophagy by inhibiting the PI3K/AKT pathway in SMMC-7721 cells. Furthermore, in the xenograft mice study, compound 8c significantly slowed down the tumor growth, as potent as paclitaxel treated group. In conclusion, methylated betulonic acid-azidothymidine compound (8c) not only increases water solubility, but also enhances the potency against hepatocellular carcinoma cells by inducing autophagy and apoptosis, and suppressing the PI3K/Akt/mTOR signaling pathway.


Assuntos
Antineoplásicos , Carcinoma Hepatocelular , Proliferação de Células , Neoplasias Hepáticas , Nucleosídeos , Triterpenos , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Triterpenos/farmacologia , Triterpenos/química , Triterpenos/síntese química , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Animais , Camundongos , Relação Estrutura-Atividade , Proliferação de Células/efeitos dos fármacos , Nucleosídeos/farmacologia , Nucleosídeos/química , Nucleosídeos/síntese química , Peixe-Zebra , Ensaios de Seleção de Medicamentos Antitumorais , Estrutura Molecular , Apoptose/efeitos dos fármacos , Relação Dose-Resposta a Droga , Transcriptoma/efeitos dos fármacos , Linhagem Celular Tumoral , Camundongos Nus
19.
Biochem Biophys Res Commun ; 439(2): 235-40, 2013 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-23973488

RESUMO

Apelin-13 plays an important role in the migration and proliferation of vascular smooth muscle cells (VSMCs); however, the underlying mechanisms are still unclear. Egr-1 is a nuclear transcription factor, which is considered to be the critical initiating factor of the processes of VSMC proliferation and migration. Egr-1 is known to regulate the expression of osteopontin (OPN), which is a marker of the phenotypic modulation that is a necessary condition of VSMC proliferation and migration. We hypothesized that the role of Apelin-13 is mediated via upregulation of Egr-1. To test this hypothesis, we analyzed the effects of Apelin-13 treatment on Egr-1 mRNA and protein expression in A10 rat aortic VSMCs by RT-PCR and Western blotting, respectively. Results showed that, Apelin-13 upregulated the expression of Egr-1. Furthermore, treatment with the extracellular-regulated protein kinase (ERK) inhibitor, PD98059, inhibited the upregulation of Egr-1 by Apelin-13. In addition, this upregulation was inhibited by treatment of VSMCs with the Egr-1 specific deoxyribozyme ED5 (DNAenzyme/10-23 DRz). Furthermore, ED5 treatment was found to significantly inhibit Apelin-13-induced migration and proliferation of VSMCs using transwell and MTT assays, respectively. The evaluation of OPN mRNA and protein expression levels by RT-PCR and Western blot analyses revealed that ED5 treatment also inhibited Apelin-13-induced OPN upregulation. The results of this study indicated that Apelin-13 upregulates Egr-1 via ERK. Furthermore, Apelin-13 induced the proliferation and migration of VSMCs as well as the upregulation of OPN via the upregulation of Egr-1. These results will provide an important theoretical and experimental basis for the control of inappropriate remodeling of vessel walls, and will hopefully lead to the prevention and treatment of vascular remodeling diseases.


Assuntos
Proteína 1 de Resposta de Crescimento Precoce/genética , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Miócitos de Músculo Liso/citologia , Miócitos de Músculo Liso/metabolismo , Regulação para Cima , Animais , Linhagem Celular , Movimento Celular , Proliferação de Células , Proteína 1 de Resposta de Crescimento Precoce/metabolismo , Sistema de Sinalização das MAP Quinases , Osteopontina/genética , Ratos
20.
Chemistry ; 19(20): 6329-33, 2013 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-23526489

RESUMO

A facile and reversible phase-transfer protocol for luminescent ZnO quantum dots (QDs) between methanol and hexane is presented. Oleylamine together with acetic acid trigger this reversible phase-transfer process, during which the structure and optical properties of the ZnO QDs are well-protected. ZnO QDs with a diameter of approximately 5 nm emit yellow light at 525 nm, while those with a diameter of approximately 4 nm emit green light at 510 nm. The positions of the emission peaks remain unchanged during the presented phase-transfer process. The Pearson's hard and soft (Lewis) acid and base principle, together with the principle that similar substances are more likely to be dissolved by each other, describes the current reversible phase-transfer process. Herein, we circumvent the time-consuming work required to synthesize ZnO QDs in different environments, making it possible to combine the advantages of ZnO QDs dispersed in polar and nonpolar solvents.

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