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1.
Dalton Trans ; 52(3): 659-667, 2023 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-36537538

RESUMO

Building metal-organic frameworks (MOFs) covalently modified by onium halides is a promising approach to develop efficient MOF-based heterogeneous catalysts for the cycloaddition of CO2 to epoxides (CCE) into cyclic carbonates. Herein, we report a novel zirconium-based MOF covalently modified by methyl pyridinium bromide, Zr6O4(OH)4(MPTDC)2.2(N-CH3-MPTDC)3.8Br3.8 ((Br-)CH3-Pyridinium-MOF-1), where MPTDC denotes 3-methyl-4-pyridin-4-yl-thieno[2,3-b] thiophene-2,5-dicarboxylate. The structure and composition of this complex were fully characterized with PXRD, NMR, XPS, TEM and so on. CO2 adsorption experiments show that (Br-)CH3-Pyridinium-MOF-1 has a higher affinity for CO2 than its electrically neutral precursor, which should be attributed to the fact that charging frameworks containing pyridinium salt have stronger polarization to CO2. (Br-)CH3-Pyridinium-MOF-1 integrated reactive Lewis acid sites and Br- nucleophilic anions and exhibited efficient catalytic activity for CCE under ambient pressure in the absence of co-catalysts and solvents. Furthermore, (Br-)CH3-Pyridinium-MOF-1 was recycled after five successive cycles without substantial loss in catalytic activity. The corresponding reaction mechanism also was speculated.

2.
Chin J Nat Med ; 20(2): 155-160, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35279243

RESUMO

Three new ursane-type triterpenoids, 3-oxours-12-en-20, 28-olide (1), 3ß-hydroxyurs-12-en-20, 28-olide (2) and 3ß-hydroxyurs-11, 13(18)-dien-20, 28-olide (3), were isolated from a potent anti-inflammatory and antibacterial fraction of the ethanolic extract of Rosmarinus officinalis. Their structures were elucidated by a combination of extensive 1D- and 2D-NMR experiments, MS data and comparisons with literature reports. Compounds 1-3 exhibited significantly inhibitory effects on nitric oxide production in lipopolysaccharide-activated mouse RAW264.7 macrophages, but no antibacterial activity was found at a concentration of 128 µg·mL-1.


Assuntos
Medicamentos de Ervas Chinesas , Rosmarinus , Triterpenos , Animais , Medicamentos de Ervas Chinesas/química , Camundongos , Estrutura Molecular , Triterpenos/química
3.
Adv Rheumatol ; 61(1): 17, 2021 03 10.
Artigo em Inglês | MEDLINE | ID: mdl-33691801

RESUMO

BACKGROUND: Hyperhomocysteinemia is associated with autoimmune diseases such as ankylosing spondylitis (AS), systemic lupus erythematosus (SLE), and rheumatoid arthritis (RA). Current findings regarding plasma/serum homocysteine (HCY) levels in AS patients are inconsistent. This study aims to systematically evaluate the association between circulating HCY levels and AS. METHODS: Online electronic databases (PubMed, Web of Science, Embase, ScienceDirect, China National Knowledge Infrastructure (CNKI), and Wanfang data) were used to retrieve all relevant articles published up to May 7, 2020. The pooled standardized mean difference (SMD) with 95% confidence interval (CI) was calculated using the random-effect model, Stata16 software. RESULTS: Nine articles containing 778 AS patients and 522 controls were included in this meta-analysis. No significant differences in HCY levels were found between AS and control groups (pooled SMD = 0.46, 95% CI = - 0.30 to 1.23, P = 0.23). However, subgroup analysis suggested that HCY levels were significantly higher (P < 0.05) in the AS group treated with methotrexate (MTX) compared with the control group. In contrast, HCY levels were significantly (P < 0.05) lower in the AS group receiving anti-TNF-α treatment compared with the control group. No significant differences were detected between HCY levels and disease activity scores (Bath AS disease activity index, BASDAI), and methylenetetrahydrofolate reductase (MTHFR) C677T genotype. CONCLUSION: This meta-analysis indicates that HCY levels are similar between AS and controls, and do not correlate with disease activity. However, different medical treatments cause fluctuations of circulating HCY levels in AS patients. Further and larger-scale studies are needed to confirm these findings. TRIAL REGISTRATION: This study was registered at international prospective register of systematic reviews (PROSPERO), registration number: CRD42020184426 .


Assuntos
Homocisteína , Espondilite Anquilosante , Homocisteína/sangue , Humanos , Espondilite Anquilosante/sangue , Espondilite Anquilosante/epidemiologia
4.
Int J Biol Macromol ; 167: 1020-1029, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33186645

RESUMO

Sr3.8Fe25.7O70.4-chitosan magnetic microparticles (Sr3.8Fe25.7O70.4-CMNs) with a core-shell structure were synthesized, characterized and applied for the removal of two model cationic dyes. The results showed that these magnetic microparticles possess fast adsorption rate and high adsorption efficiency for both crystal violet (CV) and basic red 9 (BR9) at a temperature ranging 30 °C to 40 °C and suitable pH range (pH ≥ 7). The maximum removal efficiency for CV and BR9 attained to 94.5% and 97.5% in 30 min, which was significantly faster and higher than that of chitosan (<50% in 60 min) (P<0.01). And its maximum adsorption capacity for CV and BR9 reached 29.46 mg/g and 32.16 mg/g, respectively. The adsorption process of Sr3.8Fe25.7O70.4-CMNs follows the Langmuir isotherm with a high correlation coefficient (R2 > 0.97) and the pseudo-second-order model. Additionally, the synthesized Sr3.8Fe25.7O70.4-CMNs were easy to regeneration and reuse, and the removal rate remained above 90% after 5 recycle times. This study would provide a new more environmental friendly material and method for the treatment of wastewater containing toxic dyes.


Assuntos
Cátions/química , Quitosana/química , Corantes/química , Fenômenos Magnéticos , Microesferas , Algoritmos , Violeta Genciana/química , Concentração de Íons de Hidrogênio , Cinética , Modelos Teóricos , Estrutura Molecular , Análise Espectral , Águas Residuárias , Poluentes Químicos da Água/química , Purificação da Água/métodos
5.
Adv Rheumatol ; 61: 17, 2021. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1152736

RESUMO

Abstract Background: Hyperhomocysteinemia is associated with autoimmune diseases such as ankylosing spondylitis (AS), systemic lupus erythematosus (SLE), and rheumatoid arthritis (RA). Current findings regarding plasma/serum homocysteine (HCY) levels in AS patients are inconsistent. This study aims to systematically evaluate the association between circulating HCY levels and AS. Methods: Online electronic databases (PubMed, Web of Science, Embase, ScienceDirect, China National Knowledge Infrastructure (CNKI), and Wanfang data) were used to retrieve all relevant articles published up to May 7, 2020. The pooled standardized mean difference (SMD) with 95% confidence interval (CI) was calculated using the random-effect model, Stata16 software. Results: Nine articles containing 778 AS patients and 522 controls were included in this meta-analysis. No significant differences in HCY levels were found between AS and control groups (pooled SMD = 0.46, 95% CI = − 0.30 to 1.23, P = 0.23). However, subgroup analysis suggested that HCY levels were significantly higher (P < 0.05) in the AS group treated with methotrexate (MTX) compared with the control group. In contrast, HCY levels were significantly (P < 0.05) lower in the AS group receiving anti-TNF-α treatment compared with the control group. No significant differences were detected between HCY levels and disease activity scores (Bath AS disease activity index, BASDAI), and methylenetetrahydrofolate reductase (MTHFR) C677T genotype. Conclusion: This meta-analysis indicates that HCY levels are similar between AS and controls, and do not correlate with disease activity. However, different medical treatments cause fluctuations of circulating HCY levels in AS patients. Further and larger-scale studies are needed to confirm these findings. Trial registration: This study was registered at international prospective register of systematic reviews (PROSPERO), registration number: CRD42020184426.(AU)


Assuntos
Humanos , Espondilite Anquilosante/etiologia , Homocisteína/análise , Estudos de Casos e Controles , Metotrexato/uso terapêutico , Fator de Necrose Tumoral alfa/uso terapêutico
6.
J Am Med Dir Assoc ; 21(9): 1346-1348, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32723534

RESUMO

In recent years, subacute care units (SCUs) have emerged as alternatives to acute hospitalization for selected emergency department (ED) patients who might benefit from a short period of inpatient stay within a less acute setting. We developed a new protocol to directly admit selected older patients from our acute hospital's (AH) ED to the SCU of a partner community hospital, making use of our ED's short-stay ward as a transit area to overcome administrative, financial, and clinical barriers. The new protocol has removed the need for intervening stays of longer than 24 hours at our AH, reduced overall length of stay across both institutions, decreased hospital admissions, and reduced the number of patient hand-offs.


Assuntos
Serviço Hospitalar de Emergência , Cuidados Semi-Intensivos , Hospitalização , Hospitais Comunitários , Humanos , Tempo de Internação , Admissão do Paciente
7.
Molecules ; 25(4)2020 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-32085417

RESUMO

Gymnadenia conopsea R. Br. is a traditional Tibetan medicinal plant that grows at altitudes above 3000 m, which is used to treat neurasthenia, asthma, coughs, and chronic hepatitis. However, a comprehensive configuration of the chemical profile of this plant has not been reported because of the complexity of its chemical constituents. In this study, a rapid and precise method based on ultra-high performance liquid chromatography (UPLC) combined with an Orbitrap mass spectrometer (UPLC-Orbitrap-MS/MS) was established in both positive- and negative-ion modes to rapidly identify various chemical components in the tubers of G. conopsea for the first time. Finally, a total of 91 compounds, including 17 succinic acid ester glycosides, 9 stilbenes, 6 phenanthrenes, 19 alkaloids, 11 terpenoids and steroids, 20 phenolic acid derivatives, and 9 others, were identified in the tubers of G. conopsea based on the accurate mass within 3 ppm error. Furthermore, many alkaloids, phenolic acid derivates, and terpenes were reported from G. conopsea for the first time. This rapid method provides an important scientific basis for further study on the cultivation, clinical application, and functional food of G. conopsea.


Assuntos
Orchidaceae/química , Tubérculos/química , Espectrometria de Massas em Tandem/métodos , Cromatografia Líquida de Alta Pressão , Ésteres/química , Glicosídeos/química , Compostos Fitoquímicos/análise , Extratos Vegetais/química , Ácido Succínico/química
8.
Genes (Basel) ; 9(8)2018 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-30071697

RESUMO

Nowadays, various machine learning-based approaches using sequence information alone have been proposed for identifying DNA-binding proteins, which are crucial to many cellular processes, such as DNA replication, DNA repair and DNA modification. Among these methods, building a meaningful feature representation of the sequences and choosing an appropriate classifier are the most trivial tasks. Disclosing the significances and contributions of different feature spaces and classifiers to the final prediction is of the utmost importance, not only for the prediction performances, but also the practical clues of biological experiment designs. In this study, we propose a model stacking framework by orchestrating multi-view features and classifiers (MSFBinder) to investigate how to integrate and evaluate loosely-coupled models for predicting DNA-binding proteins. The framework integrates multi-view features including Local_DPP, 188D, Position-Specific Scoring Matrix (PSSM)_DWT and autocross-covariance of secondary structures(AC_Struc), which were extracted based on evolutionary information, sequence composition, physiochemical properties and predicted structural information, respectively. These features are fed into various loosely-coupled classifiers such as SVM and random forest. Then, a logistic regression model was applied to evaluate the contributions of these individual classifiers and to make the final prediction. When performing on the training dataset PDB1075, the proposed method achieves an accuracy of 83.53%. On the independent dataset PDB186, the method achieves an accuracy of 81.72%, which outperforms many existing methods. These results suggest that the framework is able to orchestrate various predicted models flexibly with good performances.

9.
Cell Rep ; 22(13): 3598-3611, 2018 03 27.
Artigo em Inglês | MEDLINE | ID: mdl-29590626

RESUMO

Newborn neurons undergo inside-out migration to their final destinations during neocortical development. Reelin-induced tyrosine phosphorylation of disabled 1 (Dab1) is a critical mechanism controlling cortical neuron migration. However, the roles of Reelin-independent phosphorylation of Dab1 remain unclear. Here, we report that deleted in colorectal carcinoma (DCC) interacts with Dab1 via its P3 domain. Netrin 1, a DCC ligand, induces Dab1 phosphorylation at Y220 and Y232. Interestingly, knockdown of DCC or truncation of its P3 domain dramatically delays neuronal migration and impairs the multipolar-to-bipolar transition of migrating neurons. Notably, the migration delay and morphological transition defects are rescued by the expression of a phospho-mimetic Dab1 or a constitutively active form of Fyn proto-oncogene (Fyn), a member of the Src-family tyrosine kinases that effectively induces Dab1 phosphorylation. Collectively, these findings illustrate a DCC-Dab1 interaction that ensures proper neuronal migration during neocortical development.


Assuntos
Receptor DCC/metabolismo , Neocórtex/crescimento & desenvolvimento , Proteínas do Tecido Nervoso/metabolismo , Neurônios/citologia , Neurônios/metabolismo , Animais , Animais Recém-Nascidos , Movimento Celular/fisiologia , Feminino , Células HEK293 , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Neocórtex/citologia , Neocórtex/metabolismo , Netrina-1/metabolismo , Fosforilação , Domínios Proteicos , Proto-Oncogene Mas , Proteína Reelina
10.
PLoS One ; 12(12): e0188129, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29287069

RESUMO

DNA-binding proteins play pivotal roles in alternative splicing, RNA editing, methylating and many other biological functions for both eukaryotic and prokaryotic proteomes. Predicting the functions of these proteins from primary amino acids sequences is becoming one of the major challenges in functional annotations of genomes. Traditional prediction methods often devote themselves to extracting physiochemical features from sequences but ignoring motif information and location information between motifs. Meanwhile, the small scale of data volumes and large noises in training data result in lower accuracy and reliability of predictions. In this paper, we propose a deep learning based method to identify DNA-binding proteins from primary sequences alone. It utilizes two stages of convolutional neutral network to detect the function domains of protein sequences, and the long short-term memory neural network to identify their long term dependencies, an binary cross entropy to evaluate the quality of the neural networks. When the proposed method is tested with a realistic DNA binding protein dataset, it achieves a prediction accuracy of 94.2% at the Matthew's correlation coefficient of 0.961. Compared with the LibSVM on the arabidopsis and yeast datasets via independent tests, the accuracy raises by 9% and 4% respectively. Comparative experiments using different feature extraction methods show that our model performs similar accuracy with the best of others, but its values of sensitivity, specificity and AUC increase by 27.83%, 1.31% and 16.21% respectively. Those results suggest that our method is a promising tool for identifying DNA-binding proteins.


Assuntos
Proteínas de Ligação a DNA/metabolismo , Sequência de Aminoácidos , Arabidopsis/genética , Proteínas de Ligação a DNA/química , Modelos Teóricos , Reprodutibilidade dos Testes , Leveduras/genética
11.
Oncotarget ; 8(56): 96089-96102, 2017 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-29221189

RESUMO

Drug resistance is becoming an obstacle in anti-cancer therapies. For target-based therapy of lung cancer, gefitinib, as the first generation of tyrosine kinase inhibitors (TKIs), demonstrated good initial response to the non-small cell lung cancer (NSCLC) patients whom harbors epidermal growth factor receptor (EGFR) mutation. However, within one year, additional EGFR mutation occurred, leading to eventual gefitinib-resistance. Therefore, it is urgently to discover novel effective small molecule inhibitors for those patients. Abnormal energy metabolism is accepted as new cancer hallmark. Recently, a metabolism rate-limiting enzyme 5'-adenosine menophosphate-activated protein kinase (AMPK) has become a promising anti-cancer target. In this study, we have identified a novel direct AMPK agonist, D561-0775 from a compound library by using molecular docking screening technique. We demonstrated that D561-0775 exhibited significant inhibitory effect on gefitinib-resistant NSCLC cell lines but less cytotoxicity on normal cells. Furthermore, D561-0775 demonstrated a remarkable in vitro AMPK enzyme activation effect. Taken together, D561-0775 showed potential anti-cancer activity via inducing apoptosis, cell cycle arrest, suppressing glycolysis and cholesterol synthesis after activation of AMPK in gefitinib-resistant H1975 cells. D561-0775 has provided a new chemical structure that could be developed as cancer drug for gefitinib-resistant NSCLC patients through inhibition lipid metabolism by directly targeting at AMPK directly.

12.
Biochem Biophys Res Commun ; 493(4): 1457-1463, 2017 12 02.
Artigo em Inglês | MEDLINE | ID: mdl-28780350

RESUMO

ELOVL3 is involved in elongating saturated and monounsaturated fatty acids, and is a critical enzyme for lipid accumulation in brown adipocytes during the early phase of tissue recruitment. In addition, ELOVL3 is related to increased fatty acid oxidation in brown adipocytes. However, the potential functions of ELOVL3 in bovine cells remain unclear. Herein, we aimed to elucidate the effect of the ELOVL3 on the differentiation of bovine skeletal muscle-derived satellite cells (MDSCs). Western blot and immunofluorescence analyses were used for elucidating ELOVL3 expression pattern in bovine MDSCs during differentiation in vitro. We activated or inhibited ELOVL3 to study the effect of alterations in its expression on in vitro differentiation of bovine MDSCs. ELOVL3 expression increased gradually during bovine MDSC differentiation, and its levels were higher in the more highly differentiated myotubes. Activation of ELOVL3 promoted MDSC differentiation, while inhibition of ELOVL3 hindered differentiation of these cells. Here, for the first time, we demonstrate the importance of ELOVL3 during bovine MDSC differentiation, which may assist in increasing beef cattle muscularity.


Assuntos
Acetiltransferases/metabolismo , Células Satélites de Músculo Esquelético/citologia , Células Satélites de Músculo Esquelético/metabolismo , Acetiltransferases/antagonistas & inibidores , Acetiltransferases/genética , Animais , Sistemas CRISPR-Cas , Bovinos , Diferenciação Celular/genética , Diferenciação Celular/fisiologia , Células Cultivadas , Ativação Enzimática , Inibidores Enzimáticos/farmacologia , Elongases de Ácidos Graxos , Regulação da Expressão Gênica no Desenvolvimento , Desenvolvimento Muscular/genética , Desenvolvimento Muscular/fisiologia , Interferência de RNA , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/genética
13.
J Antibiot (Tokyo) ; 70(6): 733-736, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28293035

RESUMO

Two novel γ-butyrolactones ghanamycins A (1) and B (2) were isolated from the fermentation broth of marine-derived Streptomyces ghanaensis TXC6-16. Their structures were elucidated by spectroscopic analysis. These two novel compounds exhibited antimicrobial activities against some phytopathogens. The minimum IC (MIC) of 2 against Pseudomonas syringae and Erwinia sp. were 50 µg ml-1.


Assuntos
4-Butirolactona/análogos & derivados , 4-Butirolactona/isolamento & purificação , Anti-Infecciosos/isolamento & purificação , Streptomyces/metabolismo , 4-Butirolactona/química , 4-Butirolactona/farmacologia , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Erwinia/efeitos dos fármacos , Fermentação , Testes de Sensibilidade Microbiana , Pseudomonas syringae/efeitos dos fármacos , Análise Espectral
14.
Ying Yong Sheng Tai Xue Bao ; 28(10): 3111-3118, 2017 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-29692127

RESUMO

Soil black carbon (BC) is considered to be the main component of passive C pool because of its inherent biochemical recalcitrance. In this paper, soil BC in the middle part of Great Xing'an Mountains was quantified, the distribution of BC in different particle size fractions was analyzed, and BC stabilization mechanism and its important role in soil C pool were discussed. The results showed that BC expressed obvious accumulation in surface soil, accounting for about 68.7% in the whole horizon (64 cm), and then decreased with the increasing soil depth, however, BC/OC showed an opposite pattern. Climate conditions redistributed BC in study area, and the soil under cooler and moister conditions would sequester more BC. BC proportion in different particle size fractions was in the order of clay>silt>fine sand>coarse sand. Although BC content in clay was the highest and was enhanced with increasing soil depth, BC/OC in clay did not show a marked change. Thus, the rise of BC/OC was attributed to the preservation of BC particles in the fine sand and silt fractions. Biochemical recalcitrance was the main stabilization mechanism for surface BC, and with the increasing soil depth, the chemical protection from clay mineral gradually played a predominant role. BC not only was the essential component of soil stable carbon pool, but also took up a sizable proportion in particulate organic carbon pool. Therefore, the storage of soil stable carbon and the potential of soil carbon sequestration would be enhanced owing to the existence of BC.


Assuntos
Solo , Carbono , China , Florestas , Tamanho da Partícula
15.
Medchemcomm ; 8(10): 1914-1918, 2017 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-30108712

RESUMO

ALK-fusion proteins play a fundamental role in the development of about 5% of non-small cell lung cancers. Herein, we identified the compound 5067-0952 as a potent ALK inhibitor, which inhibited cell growth, induced apoptosis, and suppressed the phosphorylation of ALK, subsequently blocking its downstream signaling pathway.

16.
Biotechnol Biofuels ; 9: 103, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27175216

RESUMO

BACKGROUND: Water-forming NADH oxidase can oxidize cytosolic NADH to NAD(+), thus relieving cytosolic NADH accumulation in Saccharomyces cerevisiae. Previous studies of the enzyme were conducted under aerobic conditions, as O2 is the recognized electron acceptor of the enzyme. In order to extend its use in industrial production and to study its effect on anaerobes, the effects of overexpression of this oxidase in S. cerevisiae BY4741 and Clostridium acetobutylicum 428 (Cac-428) under anaerobic conditions were evaluated. RESULTS: Glucose was exhausted in the NADH oxidase-overexpressing S. cerevisiae strain (Sce-NOX) culture after 26 h, while 43.51 ± 2.18 g/L residual glucose was left in the control strain (Sce-CON) culture at this time point. After 30 h of fermentation, the concentration of ethanol produced by Sce-NOX reached 36.28 ± 1.81 g/L, an increase of 56.38 % as compared to Sce-CON (23.20 ± 1.16 g/L), while the byproduct glycerol was remarkably decreased in the culture of Sce-NOX. In the case of the C. acetobutylicum strain (Cac-NOX) overexpressing NADH oxidase, glucose consumption, cell growth rate, and the production of acetone-butanol-ethanol (ABE) all decreased, while the concentrations of acetic acid and butyric acid increased as compared to the control strain (Cac-CON). During fermentation of Cac-CON and Cac-NOX in 100-mL screw-capped bottles, the concentrations of ABE increased with increasing headspace. Additionally, several alternative electron acceptors in C. acetobutylicum fermentation were tested. Nitroblue tetrazolium and 2,6-dichloroindophenol were lethiferous to both Cac-CON and Cac-NOX. Methylene blue could relieve the effect caused by the overexpression of the NADH oxidase on the metabolic network of C. acetobutylicum strains, while cytochrome c aggravated the effect. CONCLUSIONS: The water-forming NADH oxidase could regulate the metabolism of both the S. cerevisiae and the C. acetobutylicum strains in anaerobic conditions. Thus, the recombinant S. cerevisiae strain might be useful in industrial production. Besides the recognized electron acceptor O2, methylene blue and/or the structural analogs may be the alternative elector acceptor of the NADH oxidase in anaerobic conditions.

17.
Molecules ; 21(3): 374, 2016 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-26999101

RESUMO

Non-small-cell lung cancer (NSCLC) dominates over 85% of all lung cancer cases. Epidermal growth factor receptor (EGFR) activating mutation is a common situation in NSCLC. In the clinic, molecular-targeting with Gefitinib as a tyrosine kinase inhibitor (TKI) for EGFR downstream signaling is initially effective. However, drug resistance frequently happens due to additional mutation on EGFR, such as substitution from threonine to methionine at amino acid position 790 (T790M). In this study, we screened a traditional Chinese medicine (TCM) compound library consisting of 800 single compounds in TKI-resistance NSCLC H1975 cells, which contains substitutions from leucine to arginine at amino acid 858 (L858R) and T790M mutation on EGFR. Attractively, among these compounds there are 24 compounds CC50 of which was less than 2.5 µM were identified. We have further investigated the mechanism of the most effective one, Digitoxin. It showed a significantly cytotoxic effect in H1975 cells by causing G2 phase arrest, also remarkably activated 5' adenosine monophosphate-activated protein kinase (AMPK). Moreover, we first proved that Digitoxin suppressed microtubule formation through decreasing α-tubulin. Therefore, it confirmed that Digitoxin effectively depressed the growth of TKI-resistance NSCLC H1975 cells by inhibiting microtubule polymerization and inducing cell cycle arrest.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Glicosídeos Cardíacos/administração & dosagem , Digitoxina/administração & dosagem , Resistencia a Medicamentos Antineoplásicos/genética , Microtúbulos/efeitos dos fármacos , Proteínas Quinases Ativadas por AMP/biossíntese , Apoptose/efeitos dos fármacos , Carcinoma Pulmonar de Células não Pequenas/genética , Glicosídeos Cardíacos/química , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Digitoxina/química , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Receptores ErbB/biossíntese , Receptores ErbB/genética , Gefitinibe , Regulação Neoplásica da Expressão Gênica , Humanos , Medicina Tradicional Chinesa , Microtúbulos/patologia , Mutação , Quinazolinas/uso terapêutico , Tubulina (Proteína)/biossíntese , Tubulina (Proteína)/genética
18.
Cancer Cell Int ; 16: 13, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26900348

RESUMO

OBJECTIVES: Paclitaxel (PTX) is frequently used in the clinical treatment of solid tumors. But the PTX-resistance is a great obstacle in cancer treatment. Exploration of the mechanisms of drug resistance suggests that tumor suppressor genes (TSGs) play a key role in the response of chemotherapeutic drugs. TSGs, a set of genes that are often inactivated in cancers, can regulate various biological processes. In this study, an overview of the contribution of TSGs to PTX resistance and their underlying relationship in cancers are reported by using GeneMANIA, a web-based tool for gene/protein function prediction. METHODS: Using PubMed online database and Google web site, the terms "paclitaxel resistance" or "taxol resistance" or "drug resistance" or "chemotherapy resistance", and "cancer" or "carcinoma", and "tumor suppressor genes" or "TSGs" or "negative regulated protein" or "antioncogenes" were searched and analyzed. GeneMANIA data base was used to predict gene/protein interactions and functions. RESULTS: We identified 22 TSGs involved in PTX resistance, including BRCA1, TP53, PTEN, APC, CDKN1A, CDKN2A, HIN-1, RASSF1, YAP, ING4, PLK2, FBW7, BLU, LZTS1, REST, FADD, PDCD4, TGFBI, ING1, Bax, PinX1 and hEx. The TSGs were found to have direct and indirect relationships with each other, and thus they could contribute to PTX resistance as a group. The varied expression status and regulation function of the TSGs on cell cycle in different cancers might play an important role in PTX resistance. CONCLUSION: A further understanding of the roles of tumor suppressor genes in drug resistance is an important step to overcome chemotherapy tolerance. Tumor suppressor gene therapy targets the altered genes and signaling pathways and can be a new strategy to reverse chemotherapy resistance.

19.
Transl Pediatr ; 1(1): 15-22, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26835259

RESUMO

OBJECTIVE: To carry out a nationwide epidemiologic survey on the neonates in urban hospitals with an attempt to understand the disease spectrum and treatment outcomes of hospitalized neonates in China. METHODS: The clinical data of 43,289 hospitalized neonates from 86 hospitals in 47 Chinese cities (22 provinces) between January 1, 2005 and December 31, 2005 were retrospectively analyzed. RESULTS: The male:female ratio was 1.73:1. Premature infants accounted for 26.2% of the hospitalized neonates, which was higher than that reported in 2002 (19.7%). The top three diseases during the neonatal period were jaundice, pneumonia, and hypoxic-ischemic encephalopathy. The incidences of pneumonia, meconium aspiration syndrome, and bilirubin encephalopathy in term infants were higher than those in premature infants, while the incidences of asphyxia, respiratory distress syndrome, and pulmonary hemorrhage in term infants were lower than those in premature infants. The incidences of asphyxia, small for gestational age infant, and wet lung were higher in neonates whose mother had pregnancy induced hypertension. The outcomes of these hospitalized neonates included: recovered, 63.9%; improved, 27.3%; discharged due to the family's own decisions, 7.6%, and died, 1.2%. Nearly half (46.4%) of the neonatal death occurred within 24 hrs after admission. CONCLUSION: The incidence of premature birth shows an increasing trend among hospitalized neonates. Since the neonatal deaths mainly occur within 24 hrs after admission, monitoring during this period should be enhanced.

20.
Acta Crystallogr Sect E Struct Rep Online ; 65(Pt 4): m375, 2009 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-21582328

RESUMO

In the title compound, [Co(C(12)H(15)O(4))(2)(H(2)O)(2)](n), adjacent Co(II) atoms ( symmetry) are bridged by 3-carboxy-adamantane-1-carboxyl-ate anions, forming a chain running along [001]. Inter-chain O-H⋯O hydrogen bonds link the chains into layers parallel to (100); the layers are further connected via inter-layer hydrogen bonds inter-actions, forming a three-dimensional framework.

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