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1.
Org Lett ; 23(20): 7839-7844, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34581593

RESUMO

A practical and eco-friendly strategy for the radical-mediated decarboxylative [3 + 2] and [4 + 2] annulation of enynals and γ,σ-unsaturated N-(acyloxy)phthalimides through the photoactivation of an electron donor-acceptor (EDA) complex has been developed. A wide range of primary, secondary, and tertiary alkyl N-hydroxyphthalimide (NHP) esters can be used as suitable substrates for the synthesis of fused ketones without any transition-metal catalysts or oxidants. This protocol features a broad substrate scope, excellent selectivity, and clean reaction conditions.

2.
Zhongguo Zhong Yao Za Zhi ; 46(16): 4230-4237, 2021 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-34467737

RESUMO

This study aimed to explore the mechanism of Xiaoyao San(XYS) in the treatment of three diseases of liver depression and spleen deficiency, ie, depression, breast hyperplasia, and functional dyspepsia, and to provide a theoretical basis for the interpretation of the scientific connotation of "treating different diseases with the same method" of traditional Chinese medicines. Traditional Chinese medicine systems pharmacology database and analysis platform(TCMSP) was used to screen the active components of XYS which underwent principal component analysis(PCA) with the available drugs for these three diseases to determine the corresponding biological activities. The targets of XYS on depression, breast hyperplasia, and functional dyspepsia were obtained from GeneCards, TTD, CTD, and DrugBank databases. Cytoscape was used to plot the "individual herbal medicine-active components-potential targets" network. The resulting key targets were subjected to Kyoto encyclopedia of genes and genomes(KEGG) pathway analysis and gene ontology(GO) enrichment analysis. A total of 121 active components of XYS and 38 common targets in the treatment of depression, breast hyperplasia, and functional dyspepsia were collected. The key biological pathways were identified, including advanced glycation and products(AGEs)-receptor for advanced glycation and products(RAGE) signaling pathway in diabetic complications, HIF-1 signaling pathway, and cancer-related pathways. The key targets of XYS in the treatment of depression, breast hyperplasia, and functional dyspepsia included IL6, IL4, and TNF, and the key components were kaempferol, quercetin, aloe-emodin, etc. As revealed by the molecular docking, a strong affinity was observed between the key components and the key targets, which confirmed the results. The therapeutic efficacy of XYS in the treatment of diseases of liver depression and spleen deficiency was presumedly achieved by reducing the inflammatory reactions. The current findings are expected to provide novel research ideas and approaches to classify the scientific connotation of "treating different diseases with the same method" of Chinese medicines, as well as a theoretical basis for understanding the mechanism of XYS and exploring its clinical applications.


Assuntos
Medicamentos de Ervas Chinesas , Dispepsia , Depressão/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Dispepsia/tratamento farmacológico , Humanos , Hiperplasia/tratamento farmacológico , Medicina Tradicional Chinesa , Simulação de Acoplamento Molecular
3.
J Pharm Biomed Anal ; 201: 114123, 2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-33989991

RESUMO

This study aimed to demonstrate the scientific connotations and compatibility effects of Xiaoyaosan (XYS) based on the theory of "Treating Diseases via Regulating the Liver's Function" by hepatic metabolomics. XYS was divided into two efficacy groups, i.e. the Shugan (SG) and the Jianpi (JP) groups, according to the strategy of "Efficacy Compositions". The chronic unpredictable mild stress (CUMS) depression model was constructed. A 1H NMR-based hepatic metabolomics approach coupled with multivariate data (MVD) analysis was performed. Meanwhile, relative distance (RD) and Efficacy Index (EI) were calculated. XYS and its efficacy groups significantly reversed the abnormality of behavior and hepatic metabolomics of depression rats, but to different degrees. The results of ethology and metabolomics showed the same order, i.e. XYS > JP > SG. Two metabolites, i.e. tyrosine and malate, were regulated by all the treatment groups. Four metabolites were significantly regulated only by XYS group. Of note, the results showed the two efficacy groups of XYS exhibited synergistic anti-depression effects, and glutamate, malate and taurine could be the key hepatic metabolites for these synergistic effects. The current study not only complements and consummates the mechanisms of depression and the anti-depression effects of XYS from the perspective of hepatic metabolomics, but also lays a solid foundation for comprehensively and deeply understanding the compatibility effects of XYS against depression, especially from the points of view of compatibility in Traditional Chinese medicine (TCM) theory and synergism in modern medicine theory.


Assuntos
Medicamentos de Ervas Chinesas , Medicina Tradicional Chinesa , Animais , Antidepressivos , Depressão/tratamento farmacológico , Depressão/etiologia , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/farmacologia , Fígado , Metabolômica , Ratos
4.
J Pharm Biomed Anal ; 197: 113949, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33618131

RESUMO

Compatibility investigations are vital but also the most difficult aspect of traditional Chinese medicine (TCM) prescriptions. Previous researches have demonstrated that Xiaoyaosan (XYS) is an effective treatment for depression. However, the compatibility rules of XYS and the underlying mechanisms remain unclear. Herein, we combined network pharmacology and serum metabolomics to investigate the scientific connotations and the compatibility effects of XYS. First, the Traditional Chinese Medicine Systems Pharmacology (TCMSP) and the GeneCards databases were applied to identify the chemical components and the putative targets of XYS, and its efficacy groups. We then analyzed the herb-component-target pathways and constructed PPI networks. Potential pathways were determined by gene ontology (GO) and pathway enrichment analyses. Additionally, a chronic unpredictable mild stress (CUMS) model was applied on rats. A proton nuclear magnetic resonance spectrometry (1H NMR) based serum metabolomics was then used to identify potential metabolites and the corresponding pathways that were involved in depression and the potential anti-depression effects of XYS and its efficacy groups. A total of 121 components of XYS and 111 targets were associated with depression. Additionally, we screened 105 targets of 24 components in Shugan (SG) group and 106 targets of 95 components in Jianpi (JP) group. 13 targets were common to all three groups. Protein-protein interaction network analysis showed that Caspase-3 and Nitric oxide synthase-3 were nodes that overlapped with proteins known to be associated with depression. Pathway enrichment analysis further indicated that the putative targets of XYS and its efficacy groups mostly participated in pathways associated with cancer. Also, XYS and its efficacy groups significantly reversed abnormalities of serum metabolites and metabolic pathways, but to different degrees. Overall, different efficacy groups of XYS exhibit synergistic anti-depression effects and contribute to the whole prescription against depression. This study shows that the combination of network pharmacology and metabolomics is an effective approach to demonstrate scientific connotations and compatibility of TCMs from a holistic perspective.


Assuntos
Antidepressivos , Medicamentos de Ervas Chinesas , Animais , Depressão/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Metabolômica , Ratos
5.
Eur J Med Chem ; 208: 112789, 2020 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-32883640

RESUMO

As our research focuses on anticancer drugs, a series of novel derivatives of flexicaulin A (FA), an ent-kaurene diterpene, condensed with an aromatic ring were synthesized, and their antiproliferative activities against four human cancer cell lines (TE-1, EC109, MCF-7, and MGC-803) were evaluated. The activities of most of the new compounds were better than those of FA. Compound 2y exhibited the best activity with an IC50 value reaching 0.13 µM against oesophageal cancer cells (EC109 cells). The IC50 values for 2y in normal cells (GES-1 cells and HUVECs) were 0.52 µM and 0.49 µM, respectively. Subsequent mechanistic investigations found that compound 2y can inhibit the proliferation of cancer cells and cell cloning. In addition, 2y could reduce the mitochondrial membrane potential, increase the apoptosis rate, and increase the ROS level in EC109 cells. Moreover, 2y can upregulate the expression of ROS/JNK pathway-related proteins (p-ASK1, p-MKK4, p-JNK, and p-Cjun (ser63)) and pro-apoptotic proteins (Bax, Bad, and Bim). In vivo experiments showed that 2y can inhibit tumour growth in nude mice. The mechanism involves an increase in protein expression in the ROS pathway, leading to changes in apoptosis-related proteins. In addition, compound 2y shows low toxicity. These results indicate that compound 2y holds promising potential as an antiproliferative agent.


Assuntos
Antineoplásicos/uso terapêutico , Proliferação de Células/efeitos dos fármacos , Diterpenos/uso terapêutico , Neoplasias/tratamento farmacológico , Acetilcisteína/farmacologia , Animais , Antineoplásicos/síntese química , Antineoplásicos/toxicidade , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Diterpenos/síntese química , Diterpenos/toxicidade , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Mitocôndrias/metabolismo , Estrutura Molecular , Espécies Reativas de Oxigênio/metabolismo , Relação Estrutura-Atividade , Ensaios Antitumorais Modelo de Xenoenxerto
6.
Zhongguo Zhong Yao Za Zhi ; 45(16): 3776-3783, 2020 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-32893570

RESUMO

Depression is a common affective disorder. The application of antidepressants can significantly alleviate the symptoms of depression, which is the most important way to treat depression in clinical practice. Due to the complex etiology, wide variety, as well as diversity and severity of serious concomitant symptoms, rational addition of other drugs into antidepressants can significantly improve the cure rates of depression, reduce adverse reactions, and improve patient compliances. Therefore, the combined applications of differential drugs have been commonly used in clinic. In this paper, more than 600 literatures about depression from 2010 to 2019 were collected based on the key words of antidepressant, depression, combined medication, synergism and increase efficiency. Based on this, by summarizing and classifying the existing combinations of antidepressant drugs, this paper systematically expounds the current combined applications of antidepressant drugs in three categories, i.e. western medicines combined with western medicines, western medicines combined with traditional Chinese medicines, and traditional Chinese medicines combined with traditional Chinese medicines, in the expectation of providing the direction and basis for the selection of rational combinations of antidepressant drugs in clinic.


Assuntos
Antidepressivos , Medicina Tradicional Chinesa , Interações Medicamentosas , Humanos
7.
Chin J Nat Med ; 18(6): 460-471, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32503737

RESUMO

The quality of Astragali Radix (AR) was closely related to the growth period. However, the current commodity grades of AR were only divided by diameter but not directly related to the growth period, which leads to the contradiction between the grade standard and the quality evaluation index. Therefore, solving this problem will be the key for the quality evaluation of AR. The present study established a potential quality evaluation approach for the absolute growth years' wild Astragali Radix (WAR) and transplanted Astragali Radix (TAR) based on the chemical components and anti-heart failure efficacy through adopting a bare-handed sections approach to rapidly identify the growth years of WAR. In this study, the absolute growth years of WAR were obtained by identifying the growth rings of 1-6 growth years root through the methods. The contents of flavonoids and saponins in 2-6 growth years' WAR were determined by HPLC-UV-ELSD. The contents of 12 chemical components and the anti-fatigue failure effects of WAR (4-year-old) and TAR were compared on rat models of heart failure induced by doxorubicin. Meanwhile, NMR-based untargeted metabolomics studies were performed to investigate the regulative effects of WAR and TAR. The result shows that the numbers of growth rings were consistent with the actual growth periods of AR. The HPLC-UV-ELSD determination indicated that the content of total flavonoids in WAR was significantly higher than that in TAR. Pharmacodynamics analysis revealed that the effects of WAR on cardiac function parameters (EF, FS and LVIDs), contents of serum CK and BNP were superior to those of TAR. 13 metabolites of heart were identified that had a higher rate of change in WAR group than TAR. Overall, a rapid identification method for the growth years of WAR was established, and the fact that WAR were significantly better than TAR in the heart failure rats was first proved in the paper. This study provided a scientific basis for establishing a novel commodity specification and grade of AR for clinical rational drug use.


Assuntos
Astrágalo (Planta)/química , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Flavonoides/farmacologia , Insuficiência Cardíaca/tratamento farmacológico , Saponinas/farmacologia , Animais , Modelos Animais de Doenças , Doxorrubicina , Raízes de Plantas/química , Ratos , Ratos Sprague-Dawley
8.
Environ Pollut ; 263(Pt A): 114569, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32311638

RESUMO

The determination of the spatiotemporal patterns and driving factors of PM2.5 is of great interest to the atmospheric and climate science community, who aim to understand and better control the atmospheric linkage indicators. However, most previous studies have been conducted on pollution-sensitive cities, and there is a lack of large-scale and long-term systematic analyses. In this study, we investigated the spatiotemporal evolution of PM2.5 and its influencing factors by using an exploratory spatiotemporal data analysis (ESTDA) technique and spatial econometric model based on remote sensing imagery inversion data of the Yangtze River Economic Belt (YREB), China, between 2000 and 2016. The results showed that 1) the annual value of PM2.5 was in the range of 23.49-37.67 µg/m3 with an inverted U-shaped change trend, and the PM2.5 distribution presented distinct spatial heterogeneity; 2) there was a strong local spatial dependence and dynamic PM2.5 growth process, and the spatial agglomeration of PM2.5 exhibited higher path-dependence and spatial locking characteristics; and 3) the endogenous interaction effect of PM2.5 was significant, where each 1% increase in the neighbouring PM2.5 levels caused the local PM2.5 to increase by at least 0.4%. Natural and anthropogenic factors directly and indirectly influenced the PM2.5 levels. Our results provide spatial decision references for coordinated trans-regional air pollution governance as well as support for further studies which can inform sustainable development strategies in the YREB.


Assuntos
Poluentes Atmosféricos/análise , Poluição do Ar/análise , China , Cidades , Monitoramento Ambiental , Material Particulado/análise , Rios , Fatores Socioeconômicos
9.
Rejuvenation Res ; 23(2): 138-149, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30982406

RESUMO

Guilingji (GLJ), a traditional Chinese medicine, is of wide concern because of its remarkable antiaging effect with a long application history. It mainly consists of traditional Chinese herbs, that is, Ginseng radix et rhizoma rubra. This study focused on the anti-aging effects of GLJ on natural aging rats and its underlying mechanisms. Morris water maze was used to determine the learning and memory ability of rats. The levels of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), malondialdehyde (MDA), acetylcholine (ACh), and acetylcholinesterase (AChE) in serum were determined. Furthermore, a 1H-NMR-based serum metabolomics coupled with multivariate data analysis was used to identify potential biomarkers and corresponding metabolic pathways. The results showed that GLJ significantly improved the learning and memorial dysfunctions of natural aging rats. The mechanisms of the anti-aging and memory ameliorative effects of GLJ related to balancing oxidative stress, improving cholinergic system. Its specific mechanism of action may be through regulating pyruvate metabolism and arginine and proline metabolism.


Assuntos
Envelhecimento/efeitos dos fármacos , Biomarcadores/sangue , Medicamentos de Ervas Chinesas/farmacologia , Aprendizagem em Labirinto/efeitos dos fármacos , Transtornos da Memória/tratamento farmacológico , Metaboloma/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Animais , Masculino , Ratos , Ratos Sprague-Dawley
10.
J Ethnopharmacol ; 238: 111839, 2019 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-30928501

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Guilingji (GLJ), a famous and classical traditional Chinese medicine (TCM) prescription, has been used to extend the lifespan and improve the life qualities of the elderly for hundreds of years in China. AIM OF THE STUDY: We aimed to explore the protective effects of GLJ on the testicular dysfunction of aging rats, as well as the regulating effects of GLJ on the metabolic disturbance and metabolite changes in natural aging rats. MATERIALS AND METHODS: Forty 23-month-old rats were divided randomly into four groups, including the old control group and three groups of GLJ treatment at 37.5, 75, and 150 mg/kg doses, respectively. Additionally, 10 four-month rats were included as the youth control group. Testicular dysfunction was first evaluated by measuring the changes in the wet weights of the testicles, concentration of serum testosterone (T), and morphologic changes of the testis. Subsequently, an 1H NMR-based metabolomics approach coupled with multivariate analysis, including partial least squares discriminant analysis (PLS-DA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) was applied to monitor the metabolite changes. RESULTS: Compared with the old control group, the wet weights of the testicles and T concentration were significantly increased, while the morphologic abnormality of testicular tissues was improved by a 4-week treatment course with GLJ. Furthermore, compared with the old control group, the urinary levels of alanine, pantothenate, phenylalanine, ß-hydroxybutyrate and pyruvate were significantly decreased after a 4-week treatment course with GLJ. Additionally, we found that amino acid metabolism and pyruvate metabolism were significantly involved in the regulatory effect of GLJ. CONCLUSIONS: The current findings provided, for the first time, sound evidence of the protective effects of GLJ on testicular dysfunction from both biochemical and metabolomics perspectives. The mechanisms of GLJ could be related to regulating amino acid metabolism and pyruvate metabolism. The current study lays an important foundation for further research and for the broad clinical application of GLJ.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Substâncias Protetoras/farmacologia , Testículo/efeitos dos fármacos , Envelhecimento , Aminoácidos/metabolismo , Animais , Masculino , Metabolômica , Espectroscopia de Prótons por Ressonância Magnética , Ácido Pirúvico/metabolismo , Ratos , Ratos Sprague-Dawley , Testículo/patologia , Testosterona/sangue
11.
J Phys Condens Matter ; 31(12): 125601, 2019 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-30630143

RESUMO

Using functional renormalization group method, we studied the phase diagram of the one-dimensional extended Hubbard model at different dopings. At half filling, variety of states strongly compete with each other. These states include spin-density wave, charge-density wave, s-wave and p -wave superconductivity, phase separation, and an exotic bond-order wave. By doping, system favours superconductivity more than density waves. At 1/8 doping, a new area of extended s-wave superconductivity emerges between charge density wave and bond-order wave regions. If the system is doped to 1/4-doping, a new area of p -wave superconductivity emerges between charge-density wave and spin-density wave regions.

12.
Sci Rep ; 8(1): 16183, 2018 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-30385788

RESUMO

Comparative studies of subspecies under different ecological environments offer insights into intraspecies evolutionary adaptive mechanisms. Golden snub-nosed monkeys (Rhinopithecus roxellana) include three subspecies in China classified mainly by their morphological variations: R. r. roxellana (Sichuan and Gansu province), R. r. qinlingensis (Shaanxi province) and R. r. hubeiensis (Hubei province). These three subspecies live in three isolated area with different environments. Past works focused on the last two subspecies, but little information of habitat and behaviors of the nominated subspecies (R. r. roxellana) is available to date. We conducted a two-year study on the diet, activity budget, home range and social organization of 4 herds of R. r. roxellana, based on a total of 106 days' observation in Laohegou (LHG) Nature Reserve, Sichuan province. By using scan sampling method, our results suggest that the R. r roxellana feeds predominantly on leaves (77.5%), and spends more time feeding (40.0%) and resting (27.0%) while compared to the other two subspecies. Kernel Density Estimation Method based on GPS technology confirms that R. r roxellana has relatively larger home ranges (49.1 km2). The unit size (8.3 ± 3.5 individuals) of R. r roxellana is also smaller. Therefore, it is possible that differences in food availability in relation to habitats have important impacts on the feeding strategy and social system of the golden snub-nosed monkey. These results provide data to further explore intraspecific adaptations of living primates.


Assuntos
Evolução Biológica , Colobinae/fisiologia , Comportamento Alimentar/fisiologia , Animais , China , Colobinae/classificação , Dieta , Ecologia , Ecossistema
13.
J Air Waste Manag Assoc ; 67(2): 212-218, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27629354

RESUMO

Sludge is an important source of greenhouse gas (GHG) emissions, both in the form of direct process emissions and as a result of indirect carbon-derived energy consumption during processing. In this study, the carbon budgets of two sludge disposal processes at two well-known sludge disposal sites in China (for biodrying and heat-drying pretreatments, both followed by mono-incineration) were quantified and compared. Total GHG emissions from heat drying combined with mono-incineration was 0.1731 tCO2e t-1, while 0.0882 tCO2e t-1 was emitted from biodrying combined with mono-incineration. Based on these findings, a significant reduction (approximately 50%) in total GHG emissions was obtained by biodrying instead of heat drying prior to sludge incineration. IMPLICATIONS: Sludge treatment results in direct and indirect greenhouse gas (GHG) emissions. Moisture reduction followed by incineration is commonly used to dispose of sludge in China; however, few studies have compared the effects of different drying pretreatment options on GHG emissions during such processes. Therefore, in this study, the carbon budgets of sludge incineration were analyzed and compared following different pretreatment drying technologies (biodrying and heat drying). The results indicate that biodrying combined with incineration generated approximately half of the GHG emissions compared to heat drying followed by incineration. Accordingly, biodrying may represent a more environment-friendly sludge pretreatment prior to incineration.


Assuntos
Poluentes Atmosféricos/análise , Poluição do Ar/prevenção & controle , Efeito Estufa , Eliminação de Resíduos/métodos , Esgotos/análise , China , Dessecação , Temperatura Alta , Incineração
14.
J Toxicol Sci ; 41(6): 757-763, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27853104

RESUMO

About forty certified patients aged around 50 years old existed as living witnesses to fetal-type Minamata disease (methylmercury poisoning due to in utero exposure) in Minamata, Japan in 2006. Computerized hand tremor and postural sway tests with spectral analysis were conducted for 24 of them and in matched control subjects to examine the pathophysiological feature of neuromotor function. The tremor intensities of the patients with fetal-type Minamata disease were significantly larger than those of the 67 controls at every frequency band for both hands. In the patients, proportions for intensity at 1-6 Hz of both hands were larger, but those of the intensity at 6-10 Hz were smaller compared with the controls. The center frequency of a tremor was significantly lower in the patients than in the controls. Only eight males of the 24 patients were examined to evaluate postural sway because of extremely low scores in activities of daily living in the remaining. Most of the postural sway parameters obtained with eyes open and closed were significantly larger in the patients than in the male controls. Likewise, Romberg quotients of postural sway in anterior-posterior direction were significantly higher in the patients. In conclusion, the patients with fetal-type Minamata disease of our study showed a larger tremor of low frequency at less than 6 Hz and postural instability. Spectral analyses of computerized hand tremor and postural sway are suggested to be useful for assessing the pathophysiological change, related to a lesion of the cerebellum, resulting from prenatal methylmercury exposure.


Assuntos
Mãos/inervação , Intoxicação do Sistema Nervoso por Mercúrio/complicações , Compostos de Metilmercúrio/efeitos adversos , Equilíbrio Postural , Efeitos Tardios da Exposição Pré-Natal , Transtornos das Sensações/etiologia , Tremor/etiologia , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Intoxicação do Sistema Nervoso por Mercúrio/classificação , Intoxicação do Sistema Nervoso por Mercúrio/diagnóstico , Intoxicação do Sistema Nervoso por Mercúrio/fisiopatologia , Pessoa de Meia-Idade , Exame Neurológico , Gravidez , Transtornos das Sensações/diagnóstico , Transtornos das Sensações/fisiopatologia , Tremor/diagnóstico , Tremor/fisiopatologia
15.
PeerJ ; 4: e2291, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27547584

RESUMO

Considering the industrial interest of biodegradable polymer poly-3-hydroxybutyrate (PHB), the marine bacteria Neptunomonas antarctica was studied for its ability to accumulate PHB. The extracted polymer was confirmed to be PHB by nuclear magnetic resonance analysis. In shake flask cultures using natural seawater as medium components, PHB was produced up to 2.12 g/L with a yield of 0.18 g PHB/g fructose. In the presence of artificial seawater, the PHB titer and yield reached 2.13 g/L and 0.13 g PHB/g fructose, respectively. The accumulated polymer gradually decreased when fructose was exhausted, indicating that intracellular PHB was degraded by N. antarctica. The weight-average and number-average molecular weights of PHB produced within natural seawater were 2.4 × 10(5) g/mol and 1.7 × 10(5) g/mol, respectively. Our results highlight the potential of N. antarctica for PHB production with seawater as a nutrient source.

16.
Nanoscale Res Lett ; 11(1): 325, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27401088

RESUMO

In situ external magnetic field was applied during the synthesis of FePt nanoparticles via a chemical solution method. FePt nanoparticle films were prepared on Si by a drop-coating method with and without a magnetic field. Annealing at 700 °C in reductive atmosphere was explored to obtain ferromagnetic FePt L10 phase. The effect of in situ-applied magnetic field on the structure, morphology, and magnetic properties of FePt nanoparticle films was characterized. It is found that the applied magnetic field during the chemical synthesis of FePt nanoparticles plays a key role in the crystallinity and magnetic property of FePt nanoparticle films. As-synthesized FePt nanoparticles under the magnetic field are monodispersed and can be self-assembled over a larger area by a dropping method. The applied magnetic field during the synthesis of FePt nanoparticles not only significantly improves the nanoparticles' c-axis preferred orientation but also benefits the phase transition of FePt nanoparticles from face-centered cubic to face-centered tetragonal structure during the annealing process. The FePt nanoparticle films derived under magnetic field also show some magnetic anisotropy.

17.
Neurosci Bull ; 32(4): 374-82, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27306655

RESUMO

Alzheimer disease (AD), a progressive neurodegenerative disorder, is characterized by cognitive decline and the accumulation of senile plaques in the brain. Amyloid ß protein (Aß) in the plaques is thought to be responsible for the memory loss in AD patients. [Gly14]-humanin (HNG), a derivative of humanin (HN), has much stronger neuroprotective effects than natural HN in vitro. However, clarification of the Aß active center and the neuroprotective mechanism of HN still need in vivo evidence. The present study first compared the in vivo biological effects of three Aß fragments (1-42, 31-35, and 35-31) on spatial memory in rats, and investigated the neuroprotective effects and molecular mechanisms of HNG. The results showed that intrahippocampal injection of Aß1-42 and Aß31-35 almost equally impaired spatial learning and memory, but the reversed sequence Aß35-31 did not have any effect; a high dose of Aß31-35 (20 nmol) produced a more detrimental response than a low dose (2 nmol); Aß31-35 injection also disrupted gene and protein expression in the hippocampus, with up-regulation of caspase3 and down-regulation of STAT3; pretreatment with HNG not only protected spatial memory but also rescued STAT3 from Aß-induced disruption; and the neuroprotective effects of HNG were effectively counteracted by genistein, a specific tyrosine kinase inhibitor. These results clearly show that sequence 31-35 in Aß is the shortest active center responsible for the neurotoxicity of Aß from molecule to behavior; and HNG protects spatial learning and memory in rats against Aß-induced insults; and probably involves the activation of tyrosine kinases and subsequent beneficial modulation of STAT3 and caspase3.


Assuntos
Peptídeos beta-Amiloides/toxicidade , Peptídeos e Proteínas de Sinalização Intracelular/uso terapêutico , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/tratamento farmacológico , Fármacos Neuroprotetores/uso terapêutico , Aprendizagem Espacial/efeitos dos fármacos , Animais , Caspase 3/metabolismo , Modelos Animais de Doenças , Reação de Fuga/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Genisteína/farmacologia , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Masculino , Aprendizagem em Labirinto , Transtornos da Memória/patologia , Inibidores de Proteínas Quinases/farmacologia , Ratos , Ratos Sprague-Dawley , Tempo de Reação/efeitos dos fármacos , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/metabolismo , Fatores de Tempo
18.
J Biosci Bioeng ; 122(6): 685-688, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27353858

RESUMO

The cofactor NADPH participates in a variety of anabolic reactions and its availability is considered to play a critical role in biotransformation processes. NADH kinase (Pos5) from Saccharomyces cerevisiae catalyzes the phosphorylation of NADH to generate NADPH. To investigate the effect of NADH kinase on poly-3-hydroxybutyrate (PHB) production, pos5 was co-expressed with PHB synthetic operon phbCAB in Escherichia coli. The recombinant strain carrying pos5 and phbCAB co-expression plasmid reached 5.96 g/L cell dry weight with 64.1% PHB accumulation in 72 h shake flask cultivation, while the control strain without pos5 yielded 3.93 g/L cell dry weight with 58.5% PHB content. PHB production titer was enhanced from 2.30 g/L to 3.82 g/L. Intracellular cofactor concentration analysis revealed that the ratio of NADP/NAD in pos5 overexpression strain was two times more compared with that of the control without pos5. The results showed that NADH kinase could be employed as an effective metabolic manipulation target to improve PHB synthesis.


Assuntos
Hidroxibutiratos/metabolismo , Proteínas Mitocondriais/metabolismo , Fosfotransferases (Aceptor do Grupo Álcool)/metabolismo , Poliésteres/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/enzimologia , Escherichia coli/genética , Escherichia coli/metabolismo , Regulação Bacteriana da Expressão Gênica , Proteínas Mitocondriais/genética , NAD/metabolismo , NADP/metabolismo , Organismos Geneticamente Modificados , Fosfotransferases (Aceptor do Grupo Álcool)/genética , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/genética
19.
Horm Behav ; 83: 83-92, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27222435

RESUMO

Alzheimer's disease (AD) is an age-related mental disorder characterized by progressive loss of memory and multiple cognitive impairments. The overproduction and aggregation of Amyloid ß protein (Aß) in the brain, especially in the hippocampus, are closely involved in the memory loss in the patients with AD. Accumulating evidence indicates that the Aß-induced imbalance of dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) in the brain plays an important role in the AD pathogenesis and progression. The level of DHEA is elevated, while DHEAS is dramatically decreased in the AD brain. The present study tried to restore the balance between DHEA and DHEAS by using a non-steroidal sulfatase inhibitor DU-14, which increases endogenous DHEAS through preventing DHEAS converted back into DHEA. We found that: (1) DU-14 effectively attenuated the Aß1-42-induced cognitive deficits in spatial learning and memory of rats in Morris water maze test; (2) DU-14 prevented Aß1-42-induced decrease in the cholinergic theta rhythm of hippocampal local field potential (LFP) in the CA1 region; (3) DU-14 protected hippocampal synaptic plasticity against Aß1-42-induced suppression of long term potentiation (LTP). These results provide evidence for the neuroprotective action of DU-14 against neurotoxic Aß, suggesting that up-regulation of endogenous DHEAS by DU-14 could be beneficial to the alleviation of Aß-induced impairments in spatial memory and synaptic plasticity.


Assuntos
Peptídeos beta-Amiloides/toxicidade , Plasticidade Neuronal/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Memória Espacial/efeitos dos fármacos , Esteril-Sulfatase/antagonistas & inibidores , Tiramina/análogos & derivados , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Animais , Transtornos Cognitivos/metabolismo , Transtornos Cognitivos/prevenção & controle , Hipocampo/efeitos dos fármacos , Potenciação de Longa Duração/efeitos dos fármacos , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Transtornos da Memória/prevenção & controle , Ratos , Ratos Sprague-Dawley , Tiramina/farmacologia , Regulação para Cima/efeitos dos fármacos
20.
ACS Nano ; 9(10): 10113-24, 2015 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-26331631

RESUMO

Despite numerous applications, the cellular-clearance mechanism of multiwalled carbon nanotubes (MWCNTs) has not been clearly established yet. Previous in vitro studies showed the ability of oxidative enzymes to induce nanotube degradation. Interestingly, these enzymes have the common capacity to produce reactive oxygen species (ROS). Here, we combined material and life science approaches for revealing an intracellular way taken by macrophages to degrade carbon nanotubes. We report the in situ monitoring of ROS-mediated MWCNT degradation by liquid-cell transmission electron microscopy. Two degradation mechanisms induced by hydroxyl radicals were extracted from these unseen dynamic nanoscale investigations: a non-site-specific thinning process of the walls and a site-specific transversal drilling process on pre-existing defects of nanotubes. Remarkably, similar ROS-induced structural injuries were observed on MWCNTs after aging into macrophages from 1 to 7 days. Beside unraveling oxidative transformations of MWCNT structure, we elucidated an important, albeit not exclusive, biological pathway for MWCNT degradation in macrophages, involving NOX2 complex activation, superoxide production, and hydroxyl radical attack, which highlights the critical role of oxidative stress in cellular processing of MWCNTs.


Assuntos
Macrófagos/metabolismo , Nanotubos de Carbono/análise , Espécies Reativas de Oxigênio/metabolismo , Animais , Linhagem Celular , Humanos , Macrófagos/efeitos dos fármacos , Masculino , Glicoproteínas de Membrana/metabolismo , NADPH Oxidase 2 , NADPH Oxidases/metabolismo , Nanotubos de Carbono/toxicidade , Nanotubos de Carbono/ultraestrutura , Estresse Oxidativo/efeitos dos fármacos , Ratos Sprague-Dawley
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