Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 63
Filtrar
1.
J Ethnopharmacol ; 264: 112915, 2021 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-32360044

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: The genus Stellera Linn. consists of species of perennial herbs and shrubs, and is mainly distributed in the temperate regions of east Asia to west Asia. There are 10∼12 species in the world, two species in China: Stellera chamaejasme Linn. and Stellera formosana Hayata ex Li. As recorded, the roots of Stellera species are used to dissipate phlegm and relieve pain. The roots and the barks can be used for papermaking. AIM OF THIS REVIEW: This review aims to summarize the ethnopharmacological uses, chemical constituents, pharmacological activities, clinical applications and toxicology of the genus Stellera to better understand their therapeutic potential in the future. MATERIALS AND METHODS: The relevant information of the genus Stellera was collected from scientific databases (Pubmed, ACS website, SciFinder Scholar, Elsevier, Google Scholar, Web of Science and CNKI). Information was also gathered from 'Flora Republicae Popularis Sinicae (〈〈〉〉)', folk records, conference papers on ethnopharmacology, Ph.D. and Masters' Dissertation. RESULTS: Stellera plants have been studied as traditional folk medicines all around the world. The chemical constituents of Stellera species mainly comprise terpenoids, flavonoids, coumarins, lignans, and so on. Extracts and compounds of Stellera species exhibit extensive pharmacological activities, such as anti-tumor, anti-viral, anti-convulsive, anti-epileptic, anti-bacterial and anti-insect activities, etc. Clinical applications have suggested that the genus Stellera has the effects in treating several skin diseases and cancers, however, the results should be further verification. The genus Stellera plants are toxic and should be used reasonable. CONCLUSION: This paper reviewed the ethnopharmacological uses, chemical constituents, pharmacology, clinical applications and toxicology of the genus Stellera. The genus Stellera has broad application prospects. However, further in-depth studies are needed to determine the medical uses of the genus and its chemical constituents, pharmacological activities, clinical applications and toxicology.

2.
J Pharm Biomed Anal ; 193: 113725, 2020 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-33181429

RESUMO

The use of peptidomics to find diagnostic markers has attracted increasing clinical attention. Ulcerative colitis (UC) is a type of inflammatory bowel disease, and the traditional auxiliary diagnostic technique is colonoscopy. However, this invasive method is not effective in distinguishing between patients with endoscopic remission and healthy people, which carries the risk of delayed diagnosis of UC. In this study, we used peptidomics to find serum diagnostic markers for different stages of UC. A total of 78 serum samples were collected to form a training set (60 samples) and a testing set (18 samples). Among them, patients with active UC, remitting UC and healthy people accounted for one third each. The nano-liquid chromatography coupled with hybrid linear trap quadrupole orbitrap mass spectrometry was used for detection of low molecular weight peptides in serum. According to the protein database search and de novo sequencing algorithm, forty peptides were simultaneously identified in all samples. Six biomarker peptides were screened in the training set through orthogonal partial least-squares-discriminant analysis and receiver operating characteristic curve analysis. These six peptides were derived from proteins involved in coagulation and complement activation. We evaluated the diagnostic ability of the six peptides in the testing set through hierarchical cluster analysis, and showed that perturbation of these peptides could distinguish patients with active UC, patients with remitting UC and healthy people. This study validated the feasibility of serum peptidomics for the discovery of diagnostic markers, and provided a potential method for diagnosing different stages of UC.

3.
Plant Cell Rep ; 39(12): 1705-1717, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32948902

RESUMO

KEY MESSAGE: We identified FLY as a previously uncharacterized RNA-binding-family protein that controls flowering time by positively regulating the expression of FLC clade members. The ability of flowering plants to adjust the timing of the floral transition based on endogenous and environmental signals contributes to their adaptive success. In Arabidopsis thaliana, the MADS-domain protein FLOWERING LOCUS C (FLC) and the FLC clade members FLOWERING LOCUS M/MADS AFFECTING FLOWERING1 (FLM/MAF1), MAF2, MAF3, MAF4, and MAF5 form nuclear complexes that repress flowering under noninductive conditions. However, how FLM/MAF genes are regulated requires further study. Using a genetic strategy, we showed that the previously uncharacterized K-homology (KH) domain protein FLOWERING LOCUS Y (FLY) modulates flowering time. The fly-1 knockout mutant and FLY artificial microRNA knockdown line flowered earlier than the wild type under long- and short-day conditions. The knockout fly-1 allele, a SALK T-DNA insertion mutant, contains an ~ 110-kb genomic deletion induced by T-DNA integration. FLC clade members were downregulated in the fly-1 mutants and FLY artificial microRNA knockdown line, whereas the level of the FLC antisense transcript COOLAIR was similar to that of the wild type. Our results identify FLY as a regulator that affects flowering time through upregulation of FLC clade members.

4.
Bioresour Technol ; 313: 123680, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32562970

RESUMO

Psychrophilic microbial fuel cell (PMFC) offers an alternative method for low temperature wastewater treatment, but is seldom reported. In this study, the two-chamber PMFC was constructed at 10 °C using acetate as an electron donor. The maximum voltage under external resistance of 1000 Ω was around 550 mV. The columbic efficiency (CE) was 82.4% under external resistance of 100 Ω and the max power density was 582.4 mW/m2. After temperature decreasing to 4 °C, the maximum voltage also reached 530 mV and CE was 38.4%. The direct electron transfer was proposed in PMFC according to cyclic voltammetry curves. The short enriching time (~30 days) of biofilm in the anodic electrode may be due to the high activity of enriched novel exoelectrogens of M. fermentans (46.2%) and E. lemanii (15.4%). The development of PMFC involved biotechnologies in low temperature regions shall benefit for valuable chemicals production and energy generation in the future.


Assuntos
Fontes de Energia Bioelétrica , Microbiota , Eletricidade , Eletrodos , Águas Residuárias
5.
Bioresour Technol ; 308: 123318, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32278998

RESUMO

Caproate production by mixed culture fermentation (MCF) is economically attractive. Xylose is known as the second most abundant sugar in nature, however, producing caproate from xylose is never reported. In this study, caproate production from xylose by mesophilic MCF was firstly investigated. The results showed that as pH decreasing to 5.0, the caproate concentration was 2.06 g/L in a batch reactor and was between 0.45 and 1.07 g/L in a continuously stirred reactor. Microbial analysis illustrated that Caproiciproducens and Clostridium_sensu_stricto_12, as two main identified caproate producers, occupied over 50% and around 10% of mixed culture, respectively. Thus, caproate production from xylose was proposed via the fatty acid biosynthesis pathway, not the well-known reverse ß-oxidation pathway. These unexpected differences from literatures gains more understanding about caproate production from organic substrates via MCF.


Assuntos
Caproatos , Xilose , Clostridium , Fermentação , Glucose
6.
PLoS One ; 15(4): e0231888, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32343708

RESUMO

BACKGROUND AND AIMS: Inadequate bowel preparation (BP) is an unfavorable factor that influence the success of colonoscopy. Although standard education (SE) given to patients are proved useful to avoid inadequate BP. Studies concerning the effects of reinforced education (RE) on the quality of BP were inconsistent. The aim of this updated meta-analysis of randomized controlled trial was to compare the quality of BP between patients receiving RE in addition to SE and those receiving SE alone. METHODS: MEDLINE, EMBASE, Web of Science and the Cochrane Library were systemically searched to identify the relevant studies published through April 2019. The primary outcome was the rate of adequate BP. Subgroup analyses were conducted. Secondary outcomes included BP score, adenoma detection rate (ADR), polyp detection rate (PDR), insertion time, withdrawal time, adverse events, >80% purgative intake and diet compliance. Dichotomous variables were reported as odds ratio (OR) with 95% confidence interval (CI). Continuous data were reported as mean difference (MD) with 95%CI. Pooled estimates of OR or MD were calculated using a random-effects model. Statistical heterogeneity was accessed by calculating the I2 value. A P value less than 0.05 was considered significant. RESULTS: A total of 18 randomized controlled trails (N = 6536) were included in this meta-analysis. Patients who received RE had a better BP quality than those only receiving SE (OR 2.59, 95%CI: 2.09-3.19; P<0.001). A higher ADR (OR 1.35; 95%CI: 1.06-1.72; P = 0.020) and PDR (OR 1.24, 95%CI: 1.02-1.50; P = 0.030), shorter insertion (MD -0.76; 95%CI: -1.48-(-0.04); P = 0.040) and withdrawal time (MD -0.83; 95%CI: -1.83-(-0.28); P = 0.003), less nausea/vomiting (OR 0.78; 95%CI: 0.64-0.97; P = 0.020) and abdominal distension (OR 0.72; 95%CI: 0.68-0.92; P = 0.020) were achieved in the RE group. More patients had >80% purgative intake (OR 2.17; 95%CI, 1.09-4.32; P = 0.030) and were compliant with diet restriction (OR 2.38; 95%CI: 1.79-3.17; P<0.001) in the RE group. CONCLUSION: RE significantly improved BP quality, increased ADR and PDR, decreased insertion and withdrawal time and adverse events.


Assuntos
Colonoscopia , Educação de Pacientes como Assunto , Adenoma/patologia , Humanos , Laxantes/administração & dosagem , Laxantes/efeitos adversos , Náusea/etiologia , Razão de Chances , Polietilenoglicóis/administração & dosagem , Polietilenoglicóis/efeitos adversos , Pólipos/patologia , Ensaios Clínicos Controlados Aleatórios como Assunto
7.
Sci Total Environ ; 723: 138080, 2020 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-32220738

RESUMO

Huge amounts of wastewater that contain aromatic compounds such as benzene and phenols are discharged worldwide. Benzoate is a typical intermediate in the anaerobic transformation of those aromatic compounds. In this study, electrically conductive carbon-based materials of granulated activated carbon (GAC), multiwalled carbon nanotubes (MwCNTs), and graphite were evaluated for the ability to promote the benzoate degradation. The results showed that 82-93% of the electrons were recovered in CH4 production from benzoate. The carbon materials stimulated benzoate degradation in the sequence of GAC (5 g/L) > MwCNTs (1 g/L) ~ Graphite (0.1 g/L) > Control. Acetate was the only detected intermediate in the process of benzoate degradation. Taxonomic analyses revealed that benzoate was degraded by Syntrophus to acetate and H2, which were subsequently converted to methane by Methanosarcina (both acetoclastic methanogens and hydrogenotrophic methanogens) and Methanoculleus (hydrogenotrophic methanogens), and direct interspecies electron transfer (DIET) of Desulfovibrio and Methanosarcina. Thus, these results suggest a method to effectively enhance the removal of aromatic compounds and methane recovery.


Assuntos
Methanosarcina , Nanotubos de Carbono , Anaerobiose , Benzoatos , Transporte de Elétrons , Metano
8.
Sci Total Environ ; 720: 137587, 2020 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-32135291

RESUMO

Oxygen can enter into reductive aquifer through natural and artificial processes. However, the joint response of groundwater chemistry and functional microbial communities to oxygenation is not well understood due to the gap between taxonomic and functional microbial composition. Here, two wells named CZK15 and CZK22 at the second confined aquifer in Central China were in situ aerated, and the chemical parameters of groundwater and microbial communities in bio-trapping sand sediment were analysed during aeration. The microbial metabolic functions related to C, N, S, Fe transformation were predicted by Functional Annotation of Prokaryotic Taxa (FAPROTAX) approach and some key functional genes, such as phe, nah, narG, and soxB were verified by the real-time quantitative Polymerase Chain Reaction (qPCR) method. The biomass was promoted, microbial diversity fluctuated, and microbial composition changed remarkably with aeration mainly constrained by reduction-oxidation (redox) variation and SO42- concentration. Among functional microbes, aerobic chemoheterotrophs including aromatic compound degraders (also especially for relative abundance of phe and some nah gene) and methylotrophs are dramatically enriched interpreting dissolved oxygen (DO) consumption and total organic carbon (TOC) decomposing in sediment. Whilst fermenters and methanogen expectedly decreased during aeration. Denitrifying microbes and narG gene relative abundance increased corresponding to the NO3- increase after aeration, while microbes for N2 fixation, ammonification, and nitrification decreased relating to the source of NH4+. The sulfide oxidation causing increased SO42- was reflected by the blooming of sulfur-oxidizing microbes and soxB gene. Some sulfate reducers persisted in sediment after aeration due to sufficient SO42- as substrate. Fe(II) was mainly chemically oxidized as iron-oxidizing microbes were of low abundance and tended to decrease with aeration. The iron-reducing bacteria Geobacteraceae increased with aeration corresponding to the increased Fe(III) oxides formation. The findings of this study could have important implications in understanding the biogeochemical behaviours with cyclic redox conditions.


Assuntos
Microbiota , China , Compostos Férricos , Água Subterrânea , Oxirredução , Poluentes Químicos da Água
9.
iScience ; 23(3): 100903, 2020 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-32109675

RESUMO

Data-independent acquisition mass spectrometry (DIA-MS) is a powerful technique that enables relatively deep proteomic profiling with superior quantification reproducibility. DIA data mining predominantly relies on a spectral library of sufficient proteome coverage that, in most cases, is built on data-dependent acquisition-based analysis of the same sample. To expand the proteome coverage for a pre-determined protein family, we report herein on the construction of a hybrid spectral library that supplements a DIA experiment-derived library with a protein family-targeted virtual library predicted by deep learning. Leveraging this DIA hybrid library substantially deepens the coverage of three transmembrane protein families (G protein-coupled receptors, ion channels, and transporters) in mouse brain tissues with increases in protein identification of 37%-87% and peptide identification of 58%-161%. Moreover, of the 412 novel GPCR peptides exclusively identified with the DIA hybrid library strategy, 53.6% were validated as present in mouse brain tissues based on orthogonal experimental measurement.

10.
J Biol Chem ; 295(3): 717-728, 2020 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-31819005

RESUMO

Cellular membranes contain many lipids, some of which, such as sphingolipids, have important structural and signaling functions. The common sphingolipid glucosylceramide (GlcCer) is present in plants, fungi, and animals. As a major plant sphingolipid, GlcCer is involved in the formation of lipid microdomains, and the regulation of GlcCer is key for acclimation to stress. Although the GlcCer biosynthetic pathway has been elucidated, little is known about GlcCer catabolism, and a plant GlcCer-degrading enzyme (glucosylceramidase (GCD)) has yet to be identified. Here, we identified AtGCD3, one of four Arabidopsis thaliana homologs of human nonlysosomal glucosylceramidase, as a plant GCD. We found that recombinant AtGCD3 has a low Km for the fluorescent lipid C6-NBD GlcCer and preferentially hydrolyzes long acyl-chain GlcCer purified from Arabidopsis leaves. Testing of inhibitors of mammalian glucosylceramidases revealed that a specific inhibitor of human ß-glucosidase 2, N-butyldeoxynojirimycin, inhibits AtGCD3 more effectively than does a specific inhibitor of human ß-glucosidase 1, conduritol ß-epoxide. We also found that Glu-499 and Asp-647 in AtGCD3 are vital for GCD activity. GFP-AtGCD3 fusion proteins mainly localized to the plasma membrane or the endoplasmic reticulum membrane. No obvious growth defects or changes in sphingolipid contents were observed in gcd3 mutants. Our results indicate that AtGCD3 is a plant glucosylceramidase that participates in GlcCer catabolism by preferentially hydrolyzing long-acyl-chain GlcCers.

11.
Bioresour Technol ; 295: 122266, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31669871

RESUMO

The production of value added chemicals from CO2 is of critical importance for the practical application of microbial electrosynthesis (MES). Here, a binary electron donor (ED) design (using electrode and ethanol) was introduced to provide an efficient caproate production with the bioconversion of both CO2 and ethanol. A maximum caproate production rate of 2.41 ±â€¯0.69 g L-1 d-1, and a final concentration of 7.66 ±â€¯1.38 g L-1 was achieved. Caproate production selectivity based on the substrate increased to 91.47 ±â€¯0.58% (Binary EDs) from 32.22 ±â€¯32.58% (open circuit Electrode ED). An observed amount of 23.43 ±â€¯0.69% of carbon within the final binary ED products originated from the CO2. This work proves for the first time the potential of caproate production from CO2 utilization and ethanol upgrading using solid electrodes to regulate the chain elongation process.


Assuntos
Dióxido de Carbono , Etanol , Caproatos , Eletrodos
12.
Int J Biol Macromol ; 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31759015

RESUMO

Butyrate has been shown to be effective in ulcerative colitis (UC). However, its oral administration is rare due to its rancid odour and unpleasant taste. In this study, the effect of a butyrate-releasing polysaccharide derivative, xylan butyrate ester (XylB), was evaluated in a dextran sodium sulphate (DSS)-induced UC model in C57BL/6 mice. Linear xylan was extracted from corn cobs. The C-2 and C-3 positions of the linear xylan were esterified with butyrate, forming XylB. The protective and therapeutic effects of XylB against UC were determined in a DSS-induced mouse model. The results showed that XylB treatments reversed the imbalance between pro- and anti-inflammatory cytokines. Moreover, XylB rebalanced the gut microbiota that interfered with DSS treatment and significantly decreased the relative abundance of the genera Oscillibacter, Ruminococcaceae UCG-009, Erysipelatoclostridium, and Defluviitaleaceae UCG-01. XylB increased butyrate content in the colon, upregulated G-protein coupled receptor 109A protein expression, inhibited histone deacetylase (HDAC) activity, and exerted anti-inflammatory activity through autophagy pathway activation and nuclear factor-κB (NF-κB) inhibition. XylB reduces inflammatory intestinal damage in mice, suggesting that it would be a potential drug for the treatment of UC and could be used to overcome the limitations of the oral administration of sodium butyrate.

13.
Adv Exp Med Biol ; 1163: 225-251, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31707706

RESUMO

G protein-coupled receptors (GPCRs) influence virtually every aspect of human physiology; about one-third of all marketed drugs target members of this family. GPCR allosteric ligands hold the promise of improved subtype selectivity, spatiotemporal sensitivity, and possible biased property over typical orthosteric ligands. However, only a small number of GPCR allosteric ligands have been approved as drugs or in clinical trials since the discovery process is very challenging. The rapid development of GPCR structural biology leads to the discovery of several allosteric sites and sheds light on understanding the mechanism of GPCR allosteric ligands, which is critical for discovering novel therapeutics. This book chapter summarized different GPCR allosteric modulating mechanisms and discussed validated mechanisms based on allosteric modulator-GPCR complex structures.


Assuntos
Descoberta de Drogas , Receptores Acoplados a Proteínas-G , Regulação Alostérica , Sítio Alostérico , Humanos , Ligantes , Relação Estrutura-Atividade
14.
Bioresour Technol ; 291: 121875, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31362846

RESUMO

Although a large amount of textile wastewater is discharged at high temperatures, azo dye reduction under extreme-thermophilic conditions by mixed cultures has gained little attention. In this study, Acid Orange 7 (AO7) was used as the model azo dye to demonstrate the decolorization ability of an extreme-thermophilic mixed culture. The results showed that a decolorization efficiency of over 90% was achieved for AO7. The neutral red (NR, 0.1 mM) could promote AO7 decolorization, in which the group of Cell + NR offered the highest decolorization rate of 1.568 1/h and t1/2 was only 0.44 h, whereas after CuCl2 addition, the decolorization rate (0.141 1/h) was lower and t1/2 (4.92 h) was much longer. Thus, CuCl2 notably inhibited this process. Caldanaerobacter (64.0%) and Pseudomonas (25.4%) were the main enriched bacteria, which were not reported to have the ability for dye decolorization. Therefore, this study extends the application of extreme-thermophilic biotechnology.


Assuntos
Archaea/metabolismo , Compostos Azo/metabolismo , Bactérias Anaeróbias/metabolismo , Benzenossulfonatos/metabolismo , Corantes/metabolismo
15.
J Med Chem ; 62(21): 9983-9989, 2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31408335

RESUMO

We unveiled an underside binding site on smoothened receptor (SMO) by a colocalization strategy using two structurally complementary photoaffinity probes derived from a known ligand Allo-1. Docking study and structural dissection identified key interactions within the site, including hydrogen bonding, π-π interactions, and hydrophobic interactions between Allo-1 and its contacting residues. Taken together, our results reveal the molecular base of Allo-1 binding and provide a basis for the design of new-generation ligands to overcome drug resistance.

16.
Sci Total Environ ; 694: 133660, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31400689

RESUMO

Groundwater table fluctuation during natural and anthropogenic processes can facilitate the interaction between oxygen (O2) from the unsaturated zone and ferrous iron (Fe2+) from the saturated zone. In light of previous findings that Fe(III)-reducing bacteria can be killed by the reactive oxidants produced from Fe2+ oxidation under static oxic conditions, we hypothesize that Fe(III)-reducing bacteria will be attenuated during groundwater table fluctuations. To test this hypothesis, this study explored the variations of cell numbers of Shewanella oneidensis strain MR-1 (MR-1), a typical strain of Fe(III)-reducing bacteria, together with dissolved oxygen (DO) and Fe2+, at different points during controlled groundwater table fluctuations in a sand column. The results showed that, during the rise of the water table, O2 in the pore air was entrapped by the deoxygenated groundwater, and Fe2+ in the groundwater was oxidized by the entrapped O2. In this process, 1.40-2.42 orders of magnitude of viable MR-1 cells were killed at different points in the column. Further investigation proposed that the death of MR-1 is caused by the production of intracellular reactive oxidants, such as O2•- and OH•, from the oxidation of adsorbed/absorbed Fe2+ instead of by bulk reactive oxidants, such as OH• and Fe(IV), produced from the oxidation of aqueous Fe2+. The findings here provide new insights for Fe biogeochemical cycling in the redox-dynamic zone.


Assuntos
Bactérias/metabolismo , Compostos Ferrosos/metabolismo , Água Subterrânea/microbiologia , Poluentes Químicos da Água/metabolismo , Água Subterrânea/química
17.
Water Res ; 163: 114892, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31351355

RESUMO

Sludge, of which alginate-like biomaterial is a major organic component, is an increasing environmental problem. Thus, efficient anaerobic degradation of alginate provides a new method for sludge utilization. In this study, anaerobic alginate hydrolytic bacteria (AHB) were proposed to enrich with methanogens synergetically to reduce the inhibition of intermediate metabolites. The COD of produced methane reached 80.7 ±â€¯1.9% (n = 4) of initial alginate COD. After considering the microbial growth (8%-18% of COD), a good COD balance indicated that alginate was fully consumed and the main final metabolites were methane and CO2. Methanogenesis could promote alginate conversion by AHB. The enriched bacteria for alginate degradation in this study were different from that of former known AHB. The metabolic pathway of alginate degradation was revealed by metagenomics, in which oligo-alginate lyase was detected in twelve bacteria, and typical carbon metabolic pathways to convert alginate to methane were identified. More studies of bacterial isolation and biofuel production are still needed in the future.


Assuntos
Euryarchaeota , Consórcios Microbianos , Alginatos , Anaerobiose , Bactérias , Reatores Biológicos , Metano , Esgotos
18.
Eur J Pharmacol ; 859: 172525, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31288005

RESUMO

Emodin can effectively inhibit colorectal cancer cells, but the mechanism remains elusive. This study analyzed the changes of VEGFR2 signaling pathways in patients with colorectal cancer and the effects of emodin on HCT116 cells and xenograft tumor model. The expression levels of VEGFR2, PI3K, and p-AKT in colorectal cancer tissue samples were significantly higher than those in adjacent normal ones. Docking simulation confirmed that emodin bound the hydrophobic pocket and partially overlapped with the binding sites of VEGFR2, thus disrupting VEGFR2 dimerization. Western blotting further confirmed that emodin significantly inhibited the expression of VEGFR2, and reduced the expressions of PI3K and p-AKT in HCT116 cells. Furthermore, it suppressed the growth, adhesion and migration of HCT116 cells. In addition, emodin inhibited the tumor growth in xenograft model and the expressions of VEGFR2, PI3K and p-AKT in vivo. In conclusion, emodin suppressed the growth of colorectal cancer cells by inhibiting VEGFR2, as a potential candidate for therapy.


Assuntos
Antineoplásicos/farmacologia , Neoplasias Colorretais/patologia , Emodina/farmacologia , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Animais , Antineoplásicos/metabolismo , Adesão Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Emodina/metabolismo , Células HCT116 , Humanos , Masculino , Camundongos , Simulação de Acoplamento Molecular , Invasividade Neoplásica , Fosfatidilinositol 3-Quinases/metabolismo , Conformação Proteica , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/química , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
19.
Plant Physiol ; 181(1): 319-331, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31243063

RESUMO

Sphingolipids act as structural components of cellular membranes and as signals in a variety of plant developmental processes and defense responses, including programmed cell death. Recent studies have uncovered an interplay between abiotic or biotic stress and programmed cell death. In a previous study, we characterized an Arabidopsis (Arabidopsis thaliana) cell-death mutant, accelerated cell death5 (acd5), which accumulates ceramides and exhibits spontaneous cell death late in development. In this work, we report that salt (NaCl) treatment inhibits cell death in the acd5 mutant and prevents the accumulation of sphingolipids. Exogenous application of abscisic acid (ABA) and the salicylic acid (SA) analog benzothiadiazole demonstrated that the effect of NaCl was partly dependent on the antagonistic interaction between endogenous SA and ABA. However, the use of mutants deficient in the ABA pathway suggested that the intact ABA pathway may not be required for this effect. Furthermore, pretreatment with salt enhanced the resistance response to biotic stress, and this enhanced resistance did not involve the pathogen-associated molecular pattern-triggered immune response. Taken together, our findings indicate that salt inhibits sphingolipid accumulation and cell death in acd5 mutants partly via a mechanism that depends on SA and ABA antagonistic interaction, and enhances disease resistance independent of pattern-triggered immune responses.

20.
J Cell Biochem ; 120(4): 5687-5694, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30548286

RESUMO

In this article, we aim to examine the novel effects of ß-sitosterol on murine experimental colitis. ß-Sitosterol significantly reduces the weight loss, colon length, and alleviated microscopic appearances of colitis induced by dextran sulfate sodium. This compound also decreases the levels of TNF-α, IL-6, and IL-1ß in intestinal tissue of mice with experimental colitis in a concentration-dependent manner. ß-Sitosterol treatment to intestinal epithelial cells significantly increases expression of antimicrobial peptides and reduces survival of intracellular Salmonella typhimurium. These results showed the multiple effects of ß-sitosterol against pathogenic bacteria for a novel approach to the treatment of colonic inflammation.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA