Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 114
Filtrar
Mais filtros

Base de dados
País/Região como assunto
Tipo de documento
Intervalo de ano de publicação
1.
Environ Res ; 252(Pt 1): 118820, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38555093

RESUMO

As a typical energetic compound widely used in military activities, 2,4,6-trinitrotoluene (TNT) has attracted great attention in recent years due to its heavy pollution and wide distribution in and around the training facilities, firing ranges, and demolition sites. However, the subcellular targets and the underlying toxic mechanism of TNT remain largely unknown. In this study, we explored the toxic effects of TNT biological reduction on the mitochondrial function and homeostasis in Caenorhabditis elegans (C. elegans). With short-term exposure of L4 larvae, 10-1000 ng/mL TNT reduced mitochondrial membrane potential and adenosine triphosphate (ATP) content, which was associated with decreased expression of specific mitochondrial complex involving gas-1 and mev-1 genes. Using fluorescence-labeled transgenic nematodes, we found that fluorescence expression of sod-3 (muls84) and gst-4 (dvls19) was increased, suggesting that TNT disrupted the mitochondrial antioxidant defense system. Furthermore, 10 ng/mL TNT exposure increased the expression of the autophagy-related gene pink-1 and activated mitochondrial unfolded protein response (mt UPR), which was indicated by the increased expression of mitochondrial stress activated transcription factor atfs-1, ubiquitin-like protein ubl-5, and homeobox protein dve-1. Our findings demonstrated that TNT biological reduction caused mitochondrial dysfunction and the development of mt UPR protective stress responses, and provided a basis for determining the potential risks of energetic compounds to living organisms.


Assuntos
Proteínas de Caenorhabditis elegans , Caenorhabditis elegans , Mitocôndrias , Trinitrotolueno , Animais , Caenorhabditis elegans/efeitos dos fármacos , Caenorhabditis elegans/genética , Trinitrotolueno/toxicidade , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Transporte de Elétrons/efeitos dos fármacos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Trifosfato de Adenosina/metabolismo
2.
BMC Ophthalmol ; 24(1): 195, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38664615

RESUMO

BACKGROUND: Analyzing the glaucoma burden in "Belt and Road" (B&R) countries based on age, gender, and risk factors from 1990 to 2019 in order to provide evidence for future prevention strategies. METHODS: We applied global burden of disease(GBD) 2019 to compare glaucoma prevalence and Years lived with disabilities (YLDs) from 1990 to 2019 in the B&R countries. Trends of disease burden between 1990 and 2019 were evaluated using the average annual percent change and the 95% uncertainty interval (UI) were reported. RESULTS: From 1990 to 2019, most B&R countries showed a downward trend in age-standardized prevalence and YLDs (all P < 0.05). Additionally, only the age-standardized YLDs in males of Pakistan has a 0.35% increase (95%CI:0.19,0.50,P < 0.001), and most B&R countries has a decline(all P < 0.05) in age-standardized YLDs in every 5 years age group after 45 years old except for Pakistan(45-79 years and > 85 years), Malaysia(75-84 years), Brunei Darussalam(45-49 years), Afghanistan(70-79 years). Finally, in all Central Asian countries, the age-standardized YLDs due to glaucoma caused by fasting hyperglycemia demonstrated have an increase between 1990 and 2019 (all P < 0.05), but Armenia and Mongolia have a decrease between 2010 and 2019 (all P < 0.05). CONCLUSION: The prevalence of glaucoma continues to pose a significant burden across regions, ages, and genders in countries along the "B&R". It is imperative for the "B&R" nations to enhance health cooperation in order to collaboratively tackle the challenges associated with glaucoma.


Assuntos
Glaucoma , Humanos , Glaucoma/epidemiologia , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Prevalência , Idoso de 80 Anos ou mais , Adulto , Fatores de Risco , Distribuição por Idade , Carga Global da Doença/tendências , Distribuição por Sexo , Adulto Jovem , Adolescente , Efeitos Psicossociais da Doença , Anos de Vida Ajustados por Deficiência/tendências
3.
Eur Heart J ; 44(29): 2730-2742, 2023 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-37377160

RESUMO

AIMS: Excess dietary sodium intake and retention lead to hypertension. Impaired dermal lymphangiogenesis and lymphatic dysfunction-mediated sodium and fluid imbalance are pathological mechanisms. The adenosine A2A receptor (A2AR) is expressed in lymphatic endothelial cells (LECs), while the roles and mechanisms of LEC-A2AR in skin lymphangiogenesis during salt-induced hypertension are not clear. METHODS AND RESULTS: The expression of LEC-A2AR correlated with lymphatic vessel density in both high-salt diet (HSD)-induced hypertensive mice and hypertensive patients. Lymphatic endothelial cell-specific A2AR knockout mice fed HSD exhibited 17 ± 2% increase in blood pressure and 17 ± 3% increase in Na+ content associated with decreased lymphatic density (-19 ± 2%) compared with HSD-WT mice. A2AR activation by agonist CGS21680 increased lymphatic capillary density and decreased blood pressure in HSD-WT mice. Furthermore, this A2AR agonist activated MSK1 directly to promote VEGFR2 activation and endocytosis independently of VEGF as assessed by phosphoprotein profiling and immunoprecipitation assays in LECs. VEGFR2 kinase activity inhibitor fruquintinib or VEGFR2 knockout in LECs but not VEGF-neutralizing antibody bevacizumab suppressed A2AR activation-mediated decrease in blood pressure. Immunostaining revealed phosphorylated VEGFR2 and MSK1 expression in the LECs were positively correlated with skin lymphatic vessel density and A2AR level in hypertensive patients. CONCLUSION: The study highlights a novel A2AR-mediated VEGF-independent activation of VEGFR2 signaling in dermal lymphangiogenesis and sodium balance, which might be a potential therapeutic target in salt-sensitive hypertension.


Assuntos
Hipertensão , Linfangiogênese , Camundongos , Animais , Receptor A2A de Adenosina/metabolismo , Células Endoteliais/metabolismo , Inibidores de Proteínas Quinases , Sódio/metabolismo
4.
Ecotoxicol Environ Saf ; 260: 115074, 2023 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-37257349

RESUMO

As one of the most frequently used explosives, hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) can cause persistent pollution in the environment, leading to the potential ecological threat crossing the generations. In this study, we employed Caenorhabditis elegans to explore the toxic effects of RDX on the parental and offspring worms and the involved signaling pathways. Exposure up to 1000 ng/mL of RDX produced a significant increase in reactive oxygen species (ROS) production, germ cell apoptosis, and decrease in eggs laid. Various mutants were used to demonstrate the RDX-induced apoptosis signaling pathway, and the metabolism of RDX in the nematodes was found related to cytochrome P450 and GST through RNA sequencing. Exposure of parental worms to RDX produced significant reproductive toxicity in F1 and F2, but was recovered in F3 and F4. The transgenerational effects were associated with the decreased expression of met-2, spr-5, and set-2. Our findings revealed the signaling pathways related to the reproductive toxicity caused by RDX in C. elegans and their future generations, which provided the basis for further exploration of the ecological risks of energetic compounds in the environment.


Assuntos
Caenorhabditis elegans , Triazinas , Animais , Triazinas/toxicidade , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais
5.
Int Ophthalmol ; 43(1): 113-120, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35794406

RESUMO

BACKGROUND: To investigate whether the sclera of guinea pig contains stem cells with multiple differentiation potentials. METHODS: Scleral tissue from guinea pig was separated from the retina and choroid and digested to release single cells. The cells cultured was identified as stem cells by flow cytometric analysis, semiquantitative RT-PCR. Abilities for multipotent differentiation were analyzed by histochemical staining technique (oil-red-O staining, alcian blue staining and alizarin red staining). Scleral fibroblast cell was treated as control group. RESULTS: The cultured scleral stem cells were positive for CD44 and CD105 (mesenchymal stem cell surface markers) by flow cytometry. The cells cultured expressed stem cell markers ABCG2, Notch1, Six2, and Pax6, and the most important component of sclera type I collagen. The positive staining informed that the cells cultured were able to differentiate to adipogenic, chondrogenic, and osteogenic lineages. Scleral fibroblast cell was stained negative by oil-red-O staining and alizarin red staining. Expression of Sox9 in the cells cultured after chondrogenic differentiation significantly increased compared with scleral fibroblast cell. CONCLUSION: The guinea pig sclera contained stem cells with multiple differentiation potentials. The cells were also related to scleral collagen and cartilage related proteins. The finding may provide a new tool to help clarify mechanisms of sclera related disease in further studies.


Assuntos
Células-Tronco Multipotentes , Esclera , Animais , Cobaias , Antraquinonas/metabolismo , Diferenciação Celular
6.
Yi Chuan ; 44(10): 958-966, 2022 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-36384731

RESUMO

Cleavage under target and tagment (CUT&Tag) is a technology that utilizes the fusion protein of Tn5 transposase and protein A/G which can guide Tn5 enzyme to the antibody bound to target protein and cleave the chromatin regions adjacent to target protein. Chromatin libraries are then tagged and sequenced by the high-throughput sequencing to obtain chromatin information at specific sites or protein binding locations. CUT&Tag technology plays an important role in the research of DNA and protein interactions. It can be used to understand the modifications of histone and the bindings of transcription factors. Compared with the traditional chromatin immunoprecipitation-sequencing (ChIP-seq) technology, the CUT&Tag has the strengths of high signal-to-noise ratio, good repeatability, short experimental period, and low cell input. It shows great advantages in early embryonic development, stem cells, cancer, epigenetics and other research fields. In this article, we described the protocol of CUT&Tag for metabolic tissue cells (mouse primary islet cells), to provide an epigenetic method for studying metabolic cells.


Assuntos
Cromatina , Histonas , Camundongos , Animais , Imunoprecipitação da Cromatina/métodos , Análise de Sequência de DNA/métodos , Histonas/metabolismo , Sequenciamento de Nucleotídeos em Larga Escala
7.
BMC Cancer ; 21(1): 845, 2021 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-34294055

RESUMO

BACKGROUND: The understanding of molecular changes in mCRC during treatment could be used to personalise therapeutic strategies. The aim of our study was to explore the association of circulating tumour DNA (ctDNA) with clinical outcome in metastatic colorectal cancer (mCRC). METHODS: Sequential patients with mCRC receiving standard first-line chemotherapy were included prospectively. Both plasma ctDNA and serum CEA were assessed in samples obtained before treatment and after 4 cycles of chemotherapy (C4). Computed tomography (CT) scans were carried out at baseline and post-C4 (8-10 weeks) and were assessed using Response Evaluation Criteria In Solid Tumours version 1.1 (RECIST v1.1). Target-capture deep sequencing with a panel covering 1021 genes was performed to detected somatic mutations in ctDNA. RESULTS: A total of 20 patients were prospectively included and treated with either leucovorin, fluorouracil, and oxaliplatin (FOLFOX) (15/20) or leucovorin, fluorouracil, and irinotecan (FOLFIRI) (5/20). Median follow-up was 6.9 months (range 1.6-26.6). Somatic mutations for baseline ctDNA analysis were identified in 85% (17/20) of the patients. Mutation variations of ctDNA after chemotherapy were tested in 16/20 (80.0%) of the patients. In multivariate analyses, a high baseline molecular tumour burden index (mTBI) in ctDNA was associated with a higher risk of disease progression, as well as emergence of new mutations in ctDNA during chemotherapy. Patients with newly detected mutations had shorter progression-free survival (PFS) compared to those without (median 3.0 versus 7.3 months; hazard ratio (HR), 5.97; 95% confidence interval (CI), 0.70-50.69; P = 0.0003). Fold changes in mTBI from baseline to post-C4 were obtained in 80.0% (16/20) of the patients, which were also related to PFS. Patients with fold reduction in mTBI above 0.8-fold had longer PFS compared to those below (median 9.3 versus 4.1 months; HR, 4.51; 95% CI, 1.29-15.70; P = 0.0008). CONCLUSIONS: Newly detected mutations in ctDNA during treatment might potentially be associated with clinical outcome in mCRC and may provide important clinical information.


Assuntos
Biomarcadores Tumorais , DNA Tumoral Circulante , Neoplasias Colorretais/genética , Neoplasias Colorretais/mortalidade , Mutação , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/tratamento farmacológico , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Tomografia Computadorizada por Raios X
8.
J Environ Manage ; 291: 112729, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-33965705

RESUMO

Plasma technology is increasingly being used for the degradation of residual antibiotics in aquatic environments. However, the electrodes in conventional plasma generators are subject to erosion, which can pollute the reaction system and shorten its lifetime. To overcome these drawbacks, we developed an electrodeless high-flow atmospheric microwave plasma jet (MPJ) for fast and efficient degradation of residual norfloxacin (NOR), a typical fluoroquinolone antibiotic that is frequently detected in the aquatic environment owing to its widespread use in the treatment of various infectious diseases. Stable plasma was generated through a low-cost magnetron with the assistance of injection-locking technology. The degradation efficiency of NOR (20 mg/L) reached 98.27 ± 1.03% at 6 min and the mineralisation efficiency reached 68.67 ± 3.21% at 15 min. The fast degradation process of the NOR solution contributes to the large cross-section (approximately 153 mm2) of the plasma in direct contact with the solution. Hydroxyl radical (•OH) scavengers were used to identify the generated oxidising species, which indicated that their non-selective oxidation plays a major role in NOR degradation. Three main possible degradation pathways and mechanisms were proposed, namely the attack of •OH on the piperazine ring, quinolone ring, and benzene ring. The NOR solution was not toxic to Escherichia coli after 20 min of degradation. Thus, the high-flow atmospheric MPJ is an effective technology for the degradation of antibiotics in aqueous solutions.


Assuntos
Poluentes Químicos da Água , Purificação da Água , Antibacterianos , Micro-Ondas , Norfloxacino , Poluentes Químicos da Água/análise
9.
Artigo em Inglês | MEDLINE | ID: mdl-32087969

RESUMO

Hypertensive cardiac remodeling is a constellation of abnormalities that includes cardiomyocyte hypertrophy and death and tissue fibrosis. Adenosine is a long-known vasodilator, through interacting with its four cell surface receptor subtypes in cardiovascular system. However, it is unclear that whether adenosine A2A receptor (A2AR) activation is involved in the cardiac remodeling in hypertension. WT mice were utilized to induce DOCA-salt sensitive hypertension and received A2AR agonist CGS21680 or antagonist KW6002 treatment. Cardiac functional phenotyping measurement by echocardiography showed that CGS21680 improved cardiac dysfunction in DOCA-salt mice. Moreover, CGS21680 reduced cardiomyocyte hypertrophy, cardiac inflammation and fibrosis. However, iBAT depletion surgery induces dramatic cardiac remodeling in DOCA-salt mice, and the protective function of CGS21680 was blocked without intact iBAT. Mechanistically, A2AR agonist CGS21680 increased iBAT-derived fibroblast growth factor 21 (FGF21). Our data suggest that activation of A2AR could be a potential therapeutic strategy in preventing heart damage in hypertension.

10.
Small ; 16(7): e1906669, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31994345

RESUMO

High-temperature sodium ion batteries (SIBs) have drawn significant heed recently for large-scale energy storage. Yet, conventional SIBs are in the depths of inferior charge/discharge efficiency and cyclability at elevated temperatures. Rational structure design is highly desirable. Hence, a 3D hierarchical flower architecture self-assembled by carbon-coated Na3 V2 (PO4 )3 (NVP) nanosheets (NVP@C-NS-FL) is fabricated via a microwave-assisted glycerol-mediated hydrothermal reaction combined with a post heat-treatment. The growth mechanism of NVP@C-NS-FL is systematically investigated, by forming a microspherical glycerol/polyglycerol-NVP complex initially and then converting into flower-like architecture during the subsequent annealing at a low temperature ramping rate. Benefiting from the integrated structure, fast Na+ transportation, and highly effective heat transfer, the as-obtained NVP@C-NS-FL exhibits an excellent high-temperature SIB performance, e.g., 65 mAh g-1 (100 C) after 1000 cycles under 60 °C. When coupled with NaTi2 (PO4 )3 anode, the full cell can still display superior power capability of 1.4 kW kg-1 and long-term cyclability (2000 cycles) under 60 °C.

11.
Opt Express ; 28(13): 18633-18648, 2020 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-32672160

RESUMO

For an on-orbit lasercom receiver, the space thermal environment, microgravity environment and the adjustment error will deform the optical antenna, distorting the received wavefront and deteriorating the system performance. The axial non-confocal antenna is a deformed antenna caused by the despace of the secondary or primary mirror. Based on the simplified combination method of ray tracing and diffraction theory (simplified CMRD, or SCMRD), the calculation model of the normalized intensity distribution (NID) and the normalized received power (NRP) is established for an axial non-confocal antenna. The numerical results show that, the axial non-confocal antenna will flatten the received light spot, causing interruption of the communication link and deterioration of the bit error rate (BER) performance. The quantitative relations of the NID versus the axial non-confocal distance and the NRP versus the axial non-confocal distance would provide a reference for optical design, structural design, thermal design, assembly and adjustment accuracy design and detector selection. Besides, the numerical results are compared to those calculated by the wavefront fitting method and CMRD. The pros and cons of all methods are discussed. This work would advance the development of extending the SCMRD to analyze other deformed antennas' impact on an on-orbit lasercom receiver.

12.
Retina ; 39(6): 1100-1109, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29443795

RESUMO

PURPOSE: To observe the vitreous in highly myopic eyes with posterior precortical vitreous pockets (PPVPs) using enhanced vitreous imaging of spectral domain optical coherence tomography. METHODS: Fifty-two highly myopic eyes with PPVPs of 36 patients were included in this study. All subjects underwent enhanced vitreous imaging optical coherence tomography. The size of PPVPs was measured, and the frequency of imaging features was recorded. RESULTS: Nine imaging features of the vitreous in highly myopic eyes with PPVPs were found. The average age of subjects was 38.1 ± 10.8 years. The mean height of PPVPs was 1,177 ± 704 µm, and the mean width was 7,440 ± 755 µm. Hyperreflective line and the interlayer were observed in 30 (57.7%) eyes. Hyperreflective dots were found in 37 (71.2%) eyes. More central vitreous space was more frequently detected in younger patients. Prevascular vitreous fissure was detected in 7 (13.5%) eyes. W-shaped cavity, identified as an empty space with a smooth W-shaped edge, was demonstrated to be the fusion of Cloquet's canal and the extension of PPVPs. Perpendicular hyperreflective parallel strands were detected in 3 (5.8%) eyes. Hyperreflective network was observed in 10 (19.2%) eyes. Hyperreflective parapapillary tubercle was found in 7 (13.5%) eyes. CONCLUSION: Nine imaging features of the vitreous in highly myopic eyes with PPVPs were visualized by enhanced vitreous imaging optical coherence tomography.


Assuntos
Miopia/diagnóstico , Tomografia de Coerência Óptica/métodos , Corpo Vítreo/patologia , Adulto , Estudos Transversais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Índice de Gravidade de Doença
13.
Retina ; 39(9): 1732-1741, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29912094

RESUMO

PURPOSE: To observe features of the posterior vitreous and vitreoretinal interface in highly myopic eyes with retinoschisis using enhanced vitreous imaging optical coherence tomography. METHODS: Comprehensive ophthalmologic examination and enhanced vitreous imaging optical coherence tomography were performed in 77 eyes of 63 patients with highly myopic retinoschisis. Two different modes of spectral domain optical coherence tomography were employed to estimate retinoschisis and the posterior vitreous features in optical coherence tomography images, respectively. The types and distribution of vitreoretinal interface abnormalities were also analyzed. RESULTS: Complete posterior vitreous detachment (PVD) was identified in 55 eyes (71.4%) with a Weiss ring. Residual cortex was found in 39 eyes (70.9%) with complete PVD. Vitreoretinal interface changes, including vitreoretinal adhesion and epiretinal membrane (ERM), most frequently appeared in the macular area (47.3%), followed by the inferior arched vessels region (34.5%). In partial PVD eyes, vitreoretinal traction, vitreoretinal adhesion, and epiretinal membrane tended to be observed in the inferior and superior arched vessels regions (54.5 and 40.9%, respectively). Among all types of vitreoretinal interface abnormalities, epiretinal membrane comprised the largest proportion (46.8%) despite the status of PVD. The presence of inner layers of retinoschisis connoted a relatively high possibility of vitreoretinal interface abnormalities occurring. CONCLUSION: Enhanced vitreous imaging optical coherence tomography reveals a high prevalence of vitreoretinal interface abnormalities in highly myopic eyes with retinoschisis. Vitreous cortex tends to remain on the macular area in eyes with complete PVD. Our findings may lead to better guidance for the surgical treatment of highly myopic retinoschisis.


Assuntos
Miopia Degenerativa/diagnóstico por imagem , Retinosquise/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Membrana Epirretiniana/diagnóstico por imagem , Membrana Epirretiniana/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Miopia Degenerativa/complicações , Miopia Degenerativa/patologia , Erros de Refração/diagnóstico por imagem , Erros de Refração/patologia , Retinosquise/complicações , Retinosquise/patologia , Tomografia de Coerência Óptica/métodos , Corpo Vítreo/diagnóstico por imagem
14.
Chem Biodivers ; 16(11): e1900400, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31482617

RESUMO

The Keap1-Nrf2/ARE signaling pathway is an important defense system against exogenous and endogenous oxidative stress injury. The dysregulation of the signaling pathway is associated with many diseases, such as cancer, diabetes, and respiratory diseases. Over the years, a wide range of natural products has provided sufficient resources for the discovery of potential therapeutic drugs. Among them, polyphenols possess Nrf2 activation, not only inhibit the production of ROS, inhibit Keap1-Nrf2 protein-protein interaction, but also degrade Keap1 and regulate the Nrf2 related pathway. In fact, with the continuous improvement of natural polyphenols separation and purification technology and further studies on the Keap1-Nrf2 molecular mechanism, more and more natural polyphenols monomer components of Nrf2 activators have been gradually discovered. In this view, we summarize the research status of natural polyphenols that have been found with apparent Nrf2 activation and their action modes. On the whole, this review may guide the design of novel Keap1-Nrf2 activator.


Assuntos
Produtos Biológicos/farmacologia , Proteína 1 Associada a ECH Semelhante a Kelch/antagonistas & inibidores , Fator 2 Relacionado a NF-E2/antagonistas & inibidores , Polifenóis/farmacologia , Transdução de Sinais/efeitos dos fármacos , Produtos Biológicos/química , Humanos , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Estrutura Molecular , Fator 2 Relacionado a NF-E2/metabolismo , Polifenóis/química
15.
Chem Biodivers ; 16(9): e1900304, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31338947

RESUMO

Glycogen synthase kinase-3 (GSK-3) plays an important regulatory role in various signaling pathways; such as PI3 K/AKT, which is closely related to the occurrence and development of tumors. At present, the most reported active GSK-3 inhibitors have the same structure: lactam ring or amide structure. To find out the GSK-3ß small molecule inhibitor with novel, safe, efficient and more uncomplicated synthesis method, we analyzed in-depth reported crystal-binding patterns of GSK-3ß small molecule inhibitor with GSK-3ß protein, and designed and synthesized 17 non-reported 3,5-diamino-N-substituted benzamide compounds. Their structures were confirmed by 1 H-NMR, 13 C-NMR, and HR-MS. The preliminary screening of tumor cytotoxicity of compounds in vitro was detected by MTT, and their structure-activity relationships were illustrated. The results have shown that 3,5-diamino-N-[3-(trifluoromethyl)phenyl]benzamide (4d) exhibited significant tumor cytotoxicity against human colon cancer cells (HCT-116) with IC50 of 8.3 µm and showed commendable selectivity to GSK-3ß. In addition, Compound 4d induced apoptosis to some extent and possessed modest PK properties.


Assuntos
Antineoplásicos/farmacologia , Benzamidas/farmacologia , Desenho de Fármacos , Glicogênio Sintase Quinase 3 beta/antagonistas & inibidores , Inibidores de Proteínas Quinases/farmacologia , Bibliotecas de Moléculas Pequenas/farmacologia , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Benzamidas/síntese química , Benzamidas/química , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Glicogênio Sintase Quinase 3 beta/metabolismo , Humanos , Masculino , Estrutura Molecular , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/química , Ratos , Ratos Sprague-Dawley , Bibliotecas de Moléculas Pequenas/síntese química , Bibliotecas de Moléculas Pequenas/química , Relação Estrutura-Atividade
16.
Water Environ Res ; 91(5): 369-376, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30714277

RESUMO

In this study, algal growth potential tests were performed in water samples collected from six sampling sites in Meiliang Bay, Lake Taihu. The potential release of soluble reactive phosphorus (SRP) by enzymatic hydrolysis of enzymatically hydrolyzable phosphorus (EHP) was simultaneously evaluated. Results show that all studied regions were in highly eutrophic states, with additional nitrogen (N) or phosphorus (P) inputs, inducing negligible further increase in algal growth. EHP in water could be rapidly transformed into SRP, further supporting the proliferation of algal blooms. The shortest EHP mineralization time was calculated as 69 minutes; therefore, limiting specific nutrient inputs alone in extremely eutrophic lakes can have a limited effect on suppressing the proliferation of algal blooms. Methods to establish a suitable environmental fate for excessive nitrogen and phosphorus nutrients may be more effective and provide more significant results. PRACTITIONER POINTS: N and P were no longer serving as the limiting factors in Meiliang Bay. Enzymatically hydrolysable phosphorus could be hydrolyzed into soluble reactive phosphorus in a very short period during algal blooms. Both enzymatically hydrolysable phosphorus and soluble reactive phosphorus are required to be curbed in practical eutrophication control.


Assuntos
Fosfatase Alcalina/metabolismo , Baías , Monitoramento Ambiental , Eutrofização/efeitos dos fármacos , Lagos/química , Nutrientes/metabolismo , Fósforo/metabolismo , Sedimentos Geológicos/química , Hidrólise , Nitrogênio/metabolismo , Nitrogênio/farmacologia , Nutrientes/farmacologia , Fósforo/farmacologia
17.
Nanotechnology ; 29(22): 225703, 2018 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-29451131

RESUMO

Radiation effects on semiconductor nanowires (NWs) have attracted the attention of the research community due to their potential applications in space and atomic fields. The effective implementation of NW devices in a radiation environment is a matter of concern. Here, the photoluminescence (PL) and time-resolved PL (TRPL) measurements were performed on both GaAs and InP NWs at room temperature before and after 1 MeV H+ irradiation with fluences ranging from 1 × 1011 to 5 × 1013 p cm-2. It is found that the degradation of lifetime is size-dependent, and typically the minority carrier lifetime damage coefficient is closely correlated with the material and NW diameter. Compared to GaAs and InP bulk material counterparts, the lifetime damage coefficient of NWs decreases by a factor of about one order of magnitude. After irradiation, GaAs NWs with a smaller diameter show a much lower lifetime damage coefficient while InP NWs show an increase in carrier radiative lifetime. The increased size-dependent radiation hardness is mainly attributed to the defect sink effect and/or the improvement of a room temperature dynamic annealing mechanism of the NWs. The InP NWs also showed higher radiation tolerance than GaAs NWs.

18.
Int J Mol Sci ; 19(3)2018 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-29558421

RESUMO

A superkine variant of interleukin-2 with six site mutations away from the binding interface developed from the yeast display technique has been previously characterized as undergoing a distal structure alteration which is responsible for its super-potency and provides an elegant case study with which to get insight about how to utilize allosteric effect to achieve desirable protein functions. By examining the dynamic network and the allosteric pathways related to those mutated residues using various computational approaches, we found that nanosecond time scale all-atom molecular dynamics simulations can identify the dynamic network as efficient as an ensemble algorithm. The differentiated pathways for the six core residues form a dynamic network that outlines the area of structure alteration. The results offer potentials of using affordable computing power to predict allosteric structure of mutants in knowledge-based mutagenesis.


Assuntos
Interleucina-2/química , Simulação de Dinâmica Molecular , Mutação , Regulação Alostérica , Animais , Sítios de Ligação , Humanos , Interações Hidrofóbicas e Hidrofílicas , Interleucina-2/genética , Interleucina-2/metabolismo , Transdução de Sinais
19.
Molecules ; 23(2)2018 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-29473864

RESUMO

Five previously undescribed triterpenoid saponins (1-5), along with eight known ones (6-13), were isolated from the whole plants of Anemone rivularis var. flore-minore. Their structures were clarified by extensive spectroscopic data and chemical evidence. For the first time, the lupane-type saponins (3 and 12) were reported from the Anemone genus. The anti-proliferative activity of all isolated saponins was evaluated on hepatic stellate cells (HSC-T6). Saponins 12 and 13, which possess more monosaccharides than the others, displayed potent anti-proliferative activity, with IC50 values of 18.21 and 15.56 µM, respectively.


Assuntos
Anemone/química , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Saponinas/química , Saponinas/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Humanos , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Relação Estrutura-Atividade
20.
Angew Chem Int Ed Engl ; 57(50): 16436-16441, 2018 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-30334306

RESUMO

Two-dimensional (2D) carbon hybrids have promise in various areas such as energy storage and catalysis. Simple methods for controllable fabrication of 2D graphitic carbon hybrids in a scalable manner remains challenging. Now, a microwave-assisted strategy for mass production of 2D carbon hybrids based on self-boosting catalytic carbonization of a metal-agarose framework is demonstrated. Hybrids including hollow Fe3 C nanoparticles, Ni/Co nanoparticles, and hollow FeOx nanoparticles uniformly embedded in 2D graphitic carbon nanosheets (GCNs) are obtained, demonstrating the generality of the approach. Metal-polymer coordination and microwave-enabled fast catalytic decomposition of precursors play vital roles in facilitating the formation of the nanosheet structure. The resulting FeOx -GCNs hybrid exhibits superior lithium-storage performance (1118 mAh g-1 at 500 mA g-1 and 818 mAh g-1 at 2000 mA g-1 after 1200 cycles).

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA