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1.
J Colloid Interface Sci ; 608(Pt 1): 435-445, 2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34626987

RESUMO

HYPOTHESIS: Factor Va (FXa) and Xa (FVa) can assemble on the phosphatidylserine (PS) membrane (of platelet) to form prothrombinase complex and contribute to blood clotting. Very recently, we discovered that Ca-zeoliteacts as a type of reinforced activated inorganic platelet to enable assembly of prothrombinase complex and display an unusual zymogen (prothrombin) activation pattern. Inspired but not constrained by nature, it is of great interest to understand how FVa and FXa assembly on the inorganic surface (e.g., zeolites) and perform their biocatalytic function. EXPERIMENTS: Given the important role of FVa C1-C2 domains in the assembly and activity of the prothrombinase complex, in this work, molecular dynamics simulations were performed to investigate the binding details of FVa A3-C1-C2 domains on the PS membranes and Ca2+-LTA-type (CaA) zeolite surface. FINDINGS: We found that different from the natural PS membrane, FVa light chain repeatedly exhibits a strong C2 domain anchoring interaction on the CaA zeolite. It mainly arises from the porous surface structure of CaA zeolite and local highly dense solvation water clusters on the CaA zeolite surface restrict the movement of some lysine residues on the C2 domain. The anchoring interaction can be suppressed by reducing the surface negative charge density, so that FVa light chain can change from single-foot (only C2 domain) to double-foot (both C1-C2 domain) adsorption states on the zeolite surface. This double-foot adsorption state is similar to natural PS membrane systems, which may make FVa have higher cofactor activity.

2.
Int J Biol Macromol ; 188: 369-374, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34371044

RESUMO

Sodium channels selectively conduct Na+ ions across cellular membrane with extraordinary efficiency, which is essential for initiating action potentials. However, how Na+ ions permeate the ionic channels remains obscure and ambiguous. With more than 40 conductance events from microsecond molecular dynamics simulation, the soft knock-on ion permeation mediated by water molecules was observed and confirmed by the free energy profile and electrostatic potential calculation in this study. During the soft knock-on process, the change of average distance between four oxygen atoms in Glu177-Glu177 plays a very important role for the permeation of Na+ ion. Exploration of the ionic conductance mechanism could provide a guideline for designing ion channel targeted drug.

3.
Diagnostics (Basel) ; 11(8)2021 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-34441432

RESUMO

Dark skin-type individuals have a greater tendency to have pigmentary disorders, among which melasma is especially refractory to treat and often recurs. Objective measurement of melanin amount helps evaluate the treatment response of pigmentary disorders. However, naked-eye evaluation is subjective to weariness and bias. We used a cellular resolution full-field optical coherence tomography (FF-OCT) to assess melanin features of melasma lesions and perilesional skin on the cheeks of eight Asian patients. A computer-aided detection (CADe) system is proposed to mark and quantify melanin. This system combines spatial compounding-based denoising convolutional neural networks (SC-DnCNN), and through image processing techniques, various types of melanin features, including area, distribution, intensity, and shape, can be extracted. Through evaluations of the image differences between the lesion and perilesional skin, a distribution-based feature of confetti melanin without layering, two distribution-based features of confetti melanin in stratum spinosum, and a distribution-based feature of grain melanin at the dermal-epidermal junction, statistically significant findings were achieved (p-values = 0.0402, 0.0032, 0.0312, and 0.0426, respectively). FF-OCT enables the real-time observation of melanin features, and the CADe system with SC-DnCNN was a precise and objective tool with which to interpret the area, distribution, intensity, and shape of melanin on FF-OCT images.

4.
Mar Pollut Bull ; 169: 112517, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34049071

RESUMO

We developed a dimethylsulfide (DMS) module coupled to an ecological dynamics model studying the annual DMS cycle of the Yellow and East China seas (YECS). The model results showed that surface DMS concentrations ([DMS]) peaked in August along the coast, and there exhibited several DMS peaks offshore annually. In addition, surface [DMS] were higher in the Yellow Sea than that in the East China Sea. The annual mean surface [DMS] of the YECS reached to 4.55 nmol/L, and oceanic DMS emissions from this sea area was 6.78 µmol/(m2 day). Several sensitivity experiments demonstrated that phytoplankton community and sea water temperature exerted crucial effects on seasonal variations of surface [DMS]; and phytoplankton community or temperature changed the timing of surface DMS peak while photolysis affected the magnitude of [DMS]. Moreover, the effect size of phytoplankton community or water temperature varied spatially.


Assuntos
Fitoplâncton , Água do Mar , China , Oceanos e Mares , Estações do Ano
5.
ACS Omega ; 6(16): 10936-10943, 2021 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-34056246

RESUMO

Graphene quantum dots (GQDs), a new quasi-zero-dimensional nanomaterial, have the advantages of a smaller transverse size, better biocompatibility, and lower toxicity. They have potential applications in biosensors, drug delivery, and biological imaging. Therefore, it is particularly important to understand the transport mechanism of the GQDs on the cell membrane. In particular, the effect of the GQD shapes on the translocation mechanism should be well understood. In this study, the permeation process of the GQDs with different shapes through a 1-palmitoyl-2-oleoylphosphatidylcholine membrane was studied using molecular dynamics. The results show that all small-sized GQDs with different shapes translocated through the lipid membrane at a nanosecond timescale. The GQDs tend to remain on the surface of the cell membrane; then, the corners of the GQDs spontaneously enter the cell membrane; and, finally, the entire GQDs enter the cell membrane and tend to stabilize in the middle of the cell membrane. Moreover, the GQDs do not induce notable damage to the cell membrane, indicating that they are less toxic to cells and can be used as a potential biomedical material.

6.
World J Biol Psychiatry ; 22(7): 526-534, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33143498

RESUMO

OBJECTIVES: Environmental and genetic factors play important roles in the development of schizophrenia (SCZ), bipolar disorder (BPD) or major depressive disorder (MDD). Some risk loci are identified with shared genetic effects on major psychiatric disorders. To investigate whether SNX29 gene played a significant role in these psychiatric disorders in the Han Chinese population. METHODS: We focussed on 11 single-nucleotide polymorphisms (SNPs) harbouring SNX29 gene and carried out case-control studies in patients with SCZ (n = 1248), BPD (n = 1344), or MDD (n = 1056), and 1248 healthy controls (HC) recruited from the Han Chinese population. We constructed weighted gene co-expression network analysis (WGCNA) and extracted significant modules by R package. RESULTS: We found that rs3743592 was significantly associated with MDD and rs6498263 with BPD in both allele and genotype distributions. Before correction, rs3743592 showed allelic and genotypic significance with SCZ, rs6498263 showed allelic significance with SCZ. WGCNA identified top 10 modules of co-expressed genes. Gene Ontology (GO) and pathway analysis were used to examine the functions of SNX29, which revealed that SNX29 was involved in the regulation of a number of biological processes, such as TGF-beta, ErbB, and Wnt signalling pathway, etc. CONCLUSIONS: Our results supported common risk factors in SNX29 might share among these three mental disorders in the Han Chinese population.


Assuntos
Transtorno Bipolar , Transtorno Depressivo Maior , Transtornos Mentais , Nexinas de Classificação/genética , Grupo com Ancestrais do Continente Asiático/genética , Estudos de Casos e Controles , China , Transtorno Depressivo Maior/genética , Predisposição Genética para Doença/genética , Humanos , Polimorfismo de Nucleotídeo Único
7.
Orthop Surg ; 12(6): 1890-1899, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33112045

RESUMO

OBJECTIVE: To report outcomes of geriatric patients undergoing hip fracture surgery or arthroplasty with or without preoperative pneumonia and to evaluate the influence of pneumonia severity on patient prognosis. METHODS: In this single center retrospective study, we included geriatric patients (≥60 years old) who had undergone hip fracture surgery or arthroplasty at Peking University People's Hospital from January 2008 to September 2018. Patients with fractures caused by neoplasms or patients with incomplete clinical data were excluded. Using logistic regression and the CURB-65 (confusion, uremia, respiratory rate, blood pressure, and age ≥65 years) score as a prediction tool of 1-year mortality, the effect of preoperative pneumonia on 1-year mortality was evaluated. Survival of patients with different response to pneumonia-specific therapy and survival of patients with different pneumonia severity (evaluated with CURB-65 score) were analyzed using Cox regression. RESULTS: A total of 1386 patients were included; among them, 109 patients (7.86%) were diagnosed with preoperative pneumonia. Outcomes were evaluated in August 2019 (at least 1 year after surgery for all patients). Compared to patients without preoperative pneumonia, patients with this condition had higher 30-day mortality (11.9% vs 5%, P = 0.002) and 1-year mortality rates (33.9% vs 16.3%, P < 0.001) and higher incidence of acute heart failure (7.3% vs 3.4%, P = 0.034) and acute kidney injury (5.5% vs 1.8%, P = 0.009). In multivariate regression, preoperative pneumonia was identified as an independent predictor of 1-year mortality (odds ratio [OR], 1.45; 95% confidence interval [CI] 1.39-3.52; P = 0.021), with other factors including age (≥84 years, OR, 1.46; 95% CI 1.08-1.60; P = 0.027), body mass index (<18.5 kg/m2 , OR 2.23; 95% CI 1.52-3.17, P < 0.001), anesthesia type (regional, OR 0.87; 95% CI 0.19-0.97, P = 0.042), preoperative pneumonia (OR 1.45; 95% CI 1.39-3.52; P = 0.002), congestive heart failure (OR 2.05, 95% CI 1.57-6.21, P < 0.001), chronic kidney disease (OR 1.73; 95% CI 1.50-2.62; P < 0.001). There was a trend of increased 1-year mortality as the CURB-65 score elevated (P for trend = 0.006). Cox regression reveals a higher risk of mortality in patient with preoperative pneumonia, especially in patients with no radiologic improvements after therapy (log-rank, P = 0.035). Analysis of the impact of pneumonia severity on patient survival using Cox regression reveals that a CURB-65 score ≥3 indicated a lower rate of survival (CURB-65 score of 3: hazard ratio [HR] 3.12, 95% CI 1.39-7.03, P = 0.006; score of 4: HR 3.41, 95% CI 1.69-6.92, P = 0.001; score of 5: HR 6.28, 95% CI 2.95-13.35, P < 0.001). CONCLUSION: In this single center retrospective study, preoperative pneumonia was identified as an independent risk factor of 1-year mortality in geriatric patients undergoing hip fracture surgery or arthroplasty. A CURB-65 score ≥3 indicated a higher risk of mortality.


Assuntos
Artroplastia de Quadril/mortalidade , Artroplastia de Quadril/métodos , Fixação Interna de Fraturas/mortalidade , Fixação Interna de Fraturas/métodos , Fraturas do Quadril/mortalidade , Fraturas do Quadril/cirurgia , Pneumonia/complicações , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/mortalidade , Período Pré-Operatório , Prognóstico , Estudos Retrospectivos
8.
Zootaxa ; 4777(1): zootaxa.4777.1.1, 2020 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-33055599

RESUMO

The species-rich genus Eupines King of New Zealand is revised to include 48 species, with 22 known species redescribed. Twenty-two new species are described: Eupines (Byraxis) brevis sp. n., E. (B.) caesta sp. n., E. (B.) carinata sp. n., E. (B.) coalita sp. n., E. (B.) complector sp. n., E. (B.) dugdalei sp. n., E. (B.) gigas sp. n., E. (B.) graceae sp. n., E. (B.) huizhenae sp. n., E. (B.) hoarei sp. n., E. (B.) insolita sp. n., E. (B.) mayae sp. n., E. (B.) minuta sp. n., E. (B.) obtusa sp. n., E. (B.) ovalis sp. n., E. (B.) pannicula sp. n., E. (B.) petila sp. n., E. (B.) protibialis sp. n., E. (B.) whirinaki sp. n., E. (B.) waikaremoana sp. n., Eupines (Eupines) undecim sp. n. and Eupines novem sp. n. The following 11 synonymies are proposed: E. (B.) dispar (Sharp) (= E. (B.) munroi Broun syn. n.), E. (B.) hectori Broun (= E. (B.) diversides Newton syn. n.), E. (B.) impar (Sharp) (= E. (B.) sanguineua Broun syn. n., E. (B.) foveatissima Broun syn. n.), E. (B.) monstrosa (Reitter) (= E. (B.) rudicornis Broun syn. n., E. (B.) costata Broun syn. n.), E. (B.) mundula (Schaufuss) (= E. (B.) forficulida Broun syn. n.), E. (B.) paganus (Broun) (= E. (B.) allocera Broun syn. n., E. (B.) sylvicola Broun syn. n., E. (B.) rhyssarthra Broun syn. n.) and Eupinolus altulus (Broun) (= E. (E.) nasuta Broun syn. n.). New combinations are proposed for four species previously described in Eupines: Eupinolus calcaratus (Broun) new comb., Eupinolus nasutus (Broun) new comb., Gastrobothrus ignotus (Broun) new comb. and Gastrobothrus platynotus (Broun) new comb. A key and distribution maps for all New Zealand members of Eupines are provided.


Assuntos
Besouros , Animais , Nova Zelândia
10.
Carbohydr Polym ; 248: 116809, 2020 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-32919542

RESUMO

The safe and effective delivery of anticancer drug molecules (e.g., doxorubicin [DOX]) into target sites is of great significance in cancer therapy. Recently, considerable attention has been devoted to non-covalently functionalized graphene as a potential anticancer delivery material. Herein, molecular dynamics simulations were performed to investigate the interaction mechanism between DOX and chitosan-decorated graphene with atomic details at the molecular level. The results demonstrated that the controllable loading and release of DOX by chitosan-decorated graphene may be achieved by adjusting the solution pH (the protonation state of chitosan) and the concentration of both DOX and chitosan molecules. In particular, the bare surface of graphene can be controlled by the aggregation and dispersion of chitosan, which further affects the adsorption and release of DOX molecules.


Assuntos
Quitosana/química , Doxorrubicina/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Grafite/química , Simulação de Dinâmica Molecular , Adsorção , Antibióticos Antineoplásicos/administração & dosagem , Antibióticos Antineoplásicos/química , Antibióticos Antineoplásicos/farmacocinética , Doxorrubicina/química , Doxorrubicina/farmacocinética , Liberação Controlada de Fármacos , Humanos , Concentração de Íons de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas
11.
Nat Neurosci ; 23(7): 869-880, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32483349

RESUMO

Besides generating vision, light modulates various physiological functions, including mood. While light therapy applied in the daytime is known to have anti-depressive properties, excessive light exposure at night has been reportedly associated with depressive symptoms. The neural mechanisms underlying this day-night difference in the effects of light are unknown. Using a light-at-night (LAN) paradigm in mice, we showed that LAN induced depressive-like behaviors without disturbing the circadian rhythm. This effect was mediated by a neural pathway from retinal melanopsin-expressing ganglion cells to the dorsal perihabenular nucleus (dpHb) to the nucleus accumbens (NAc). Importantly, the dpHb was gated by the circadian rhythm, being more excitable at night than during the day. This indicates that the ipRGC→dpHb→NAc pathway preferentially conducts light signals at night, thereby mediating LAN-induced depressive-like behaviors. These findings may be relevant when considering the mental health effects of the prevalent nighttime illumination in the industrial world.


Assuntos
Ritmo Circadiano/fisiologia , Ritmo Circadiano/efeitos da radiação , Depressão/fisiopatologia , Luz/efeitos adversos , Vias Visuais/fisiologia , Animais , Depressão/etiologia , Habenula/fisiologia , Habenula/efeitos da radiação , Camundongos , Núcleo Accumbens/fisiologia , Núcleo Accumbens/efeitos da radiação , Células Ganglionares da Retina/fisiologia , Células Ganglionares da Retina/efeitos da radiação , Vias Visuais/efeitos da radiação
12.
Phys Chem Chem Phys ; 22(14): 7224-7233, 2020 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-32207513

RESUMO

Graphene-based membranes have been extensively explored owing to their excellent separation properties. In this paper, multiple factors regarding desalination performance were investigated by molecular dynamics (MD) simulations. These factors include the interlayer spacing distance (H), the gap width (dG), offset (O), and the number of gaps and layers in a multilayer graphene membrane (MGM). It is found that salt rejection is influenced significantly by the interlayer spacing distance owing to the largest free energy between ions and graphene sheets as well as the relatively larger size of the hydration layer around the ions. The optimal desalting parameter (dG = 1 nm, H = 0.8 nm) was selected; MGM systems based on the optimized parameter exhibited excellent salt rejection for NaCl, MgCl2 and CaCl2 solutions. These results can provide some ideas for the future design of graphene-based membranes.

13.
Int J Pharm ; 580: 119241, 2020 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-32197982

RESUMO

Doxorubicin (DOX) is a broad-spectrum anti-tumor drug, but it has certain limitations in its therapeutic effects due to poor tumor selectivity. Chitosan-based pH-sensitive polymers drug delivery systems could improve DOX's activity and selectivity against tumor cells. Understanding the atomic interaction mechanism between chitosan and DOX at different pH levels is important in the design and application of chitosan-based drug delivery systems. In this study, molecular dynamics simulations were performed to investigate the encapsulation and release of DOX by chitosan at different pH levels. Our results show that the protonation state of amine groups of chitosan and the π-π stacking interaction between the conjugated anthraquinone ring of DOX regulate the interaction behavior between chitosan and DOX. Moreover, DOX could gradually release from chitosan at acidic pH environment in tumor tissue. These results revealed the underlying atomic interaction mechanism between DOX and chitosan at various pH levels and may provide novel ideas for the design and application of chitosan-based drug delivery system.


Assuntos
Antineoplásicos/química , Quitosana/química , Doxorrubicina/química , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Concentração de Íons de Hidrogênio , Simulação de Dinâmica Molecular , Nanopartículas/química , Polímeros/química
14.
Int J Pharm ; 574: 118921, 2020 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-31812796

RESUMO

DNA delivery through cell membrane is a fundamental step for efficiency gene therapy. As a potential DNA carrier, carbon nanotubes (CNTs) have been extensively studied due to its unique properties. However, the mechanism of DNA translocation with CNTs through cell membrane is still not well understood. In this study, the DNA translocation process through POPC (1-palmitoyl-2-oleoylphosphatidylcholine) membrane with the assistance of CNTs was explored by molecular dynamics (MD) simulation. Our simulation results demonstrated that the CNTs could insert steadily into the POPC membrane, and DNA molecules tends to insert into the inner space of CNTs. With the assistance of CNTs, the free energy of nucleotides passing through the POPC membrane decreases. Moreover, the free energy of nucleotides (DA (deoxyadenosine), DT (deoxythymidine), DC (deoxycytidine), and DG (deoxyguanosine)) passing through POPC membrane follows the order: DA (deoxyadenosine) > DG (deoxyguanosine) > DC (deoxycytidine) > DT (deoxythymidine). These results may promote the design and application of CNT-based gene delivery system.


Assuntos
Membrana Celular/metabolismo , DNA/metabolismo , Bicamadas Lipídicas/metabolismo , Lipídeos de Membrana/metabolismo , Nanotubos de Carbono/química , Técnicas de Transferência de Genes , Simulação de Dinâmica Molecular
15.
Zootaxa ; 4614(2): zootaxa.4614.2.2, 2019 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-31716378

RESUMO

A catalogue for the eight Goniaceritae genera that occur in New Zealand is presented, treating a total of 62 species. Seventeen holotypes are confirmed, 38 lectotypes and 99 paralectotypes are designated herein for all valid species but Eupines acceptus Broun, for which type material was not located. One synonymy is proposed: Anabaxis electrica (King, 1863) (= Rybaxis brevis Oke, 1928). Four species of Eupines known only by females are valid species, but without subgeneric assignment. Images of primary type specimens and their original labels are provided.


Assuntos
Besouros , Distribuição Animal , Animais , Feminino , Nova Zelândia
16.
Nanoscale ; 11(10): 4503-4514, 2019 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-30806416

RESUMO

Graphene quantum dots (GQDs) are increasingly being recognized as anti-cancer drug carriers, e.g., doxorubicin delivery, in many experiments. In this work, the structure, thermodynamics and dynamic properties of model drugs (doxorubicin and deoxyadenosine) translocating into a POPC lipid membrane with the assistance of GQDs were investigated via MD simulation and free energy calculation. The simulation results imply that GQD19 can facilitate the permeation of model drugs into the lipid membrane on the nanosecond timescale with less deformation of the cell membrane structure. More importantly, free energy calculations further revealed that the translocation free energy of doxorubicin or deoxyadenosine permeating into the lipid bilayer could be significantly reduced with the assistance of GQD19. Our results suggest that GQDs with appropriate size may assist in the drug delivery process by reducing the translocation free energy permeating into the biomembrane. These results may promote the molecular design and application of GQD-based drug delivery systems.


Assuntos
Doxorrubicina , Portadores de Fármacos , Grafite , Membranas Artificiais , Fosfatidilcolinas/química , Pontos Quânticos/química , Doxorrubicina/química , Doxorrubicina/farmacocinética , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Grafite/química , Grafite/farmacocinética
17.
Mol Pharm ; 16(3): 987-994, 2019 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-30624945

RESUMO

A combination of different chemotherapy approaches can obtain the best response for many cancers. However, the greatest challenge is the development of a nanoparticle formulation that can encapsulate different chemotherapeutic agents to achieve the proper synergetic chemotherapy for the tumor. Here, amphiphilic ferrocenium-tetradecyl (Fe-C14) was constructed to form cationic micelles in an aqueous solution via self-assembly. Then, it was coated by hyaluronic acid (HA) through electrostatic interactions to generate HA-Fe-C14 micelles. The HA-Fe-C14 micelles were used to deliver doxorubicin (DOX), and it showed that the DOX could be released rapidly under a high-GSH tumor environment. The HA-Fe-C14/DOX micelles were able to accumulate efficiently in tumor and showed significant anticancer effect both in vitro and in vivo. These results suggest that HA-Fe-C14/DOX micelles are a useful drug delivery system that enhances synergic antitumor treatment effects.


Assuntos
Doxorrubicina/química , Doxorrubicina/uso terapêutico , Sistemas de Liberação de Medicamentos , Compostos Ferrosos/química , Glutationa/química , Ácido Hialurônico/química , Metalocenos/química , Micelas , Neoplasias/terapia , Alcanos/química , Animais , Sobrevivência Celular/efeitos dos fármacos , Terapia Combinada , Liberação Controlada de Fármacos , Compostos Ferrosos/síntese química , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Neoplasias/patologia , Células PC-3 , Solubilidade , Resultado do Tratamento , Carga Tumoral
18.
Nat Prod Res ; 33(4): 477-485, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29086600

RESUMO

Michael reaction acceptors (MRAs) are a class of active compounds. There is a great prospect to screen STAT3 inhibitors from Eupatorium lindleyanum, furthermore, to discover lead compounds for anti-triple-negative breast cancer (TNBC). In this study, glutathione (GSH) was employed, and a UPLC-MS screening method was developed to discover MRAs. We screened MRAs which can inhibit STAT3 using a STAT3-dependent reporter system. Six sesquiterpene lactones, including a new compound Eupalinolide O (1), together with five known compounds, Eupalinolide I (2), Eupalinolide K (3), Eupalinolide H (4), Eupalinolide J (5) and Eupalinolide G (6) were isolated. Eupalinolide J was identified as MRA that decreased luciferase activity of STAT3. Preliminary activity assessment showed that Eupalinolide J could inhibit the viability of TNBC cell lines. We demonstrated that Eupalinolide J, which is a natural typical MRA, has a notable inhibition of STAT3 activity and a potential cytotoxic activity against TNBC cell lines.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Eupatorium/química , Fator de Transcrição STAT3/antagonistas & inibidores , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Antineoplásicos Fitogênicos/química , Linhagem Celular Tumoral , Cromatografia Líquida/métodos , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Glutationa/metabolismo , Humanos , Extratos Vegetais/farmacologia , Sesquiterpenos/química , Sesquiterpenos/farmacologia , Espectrometria de Massas em Tandem/métodos , Neoplasias de Mama Triplo Negativas/patologia
19.
Colloids Surf B Biointerfaces ; 174: 575-581, 2019 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-30502669

RESUMO

Due to the unique structural and mechanical properties, graphene quantum dots (GQDs) are considered as potential candidates in the field of biosensors, bioimaging, and drug delivery etc. In this work, the adsorption of protein villin headpiece (HP35) on GQDs with different sizes was investigated by molecular dynamics simulations. The simulation results identified the key role of the π-π stacking interactions between the aromatic residues of HP35 and GQDs as the binding site. More importantly, with the increase of GQD size, the amount and binding strength of adsorbed residues increase, and sequentially enhance the structure change of adsorbed protein, verified by various analysis of protein structures etc. These findings may improve the understanding of the cytotoxicity and biosafety of GQDs, and hence promote the design and application of GQDs-based biomedical devices.


Assuntos
Técnicas Biossensoriais , Grafite/química , Proteínas de Neurofilamentos/metabolismo , Fragmentos de Peptídeos/metabolismo , Pontos Quânticos , Humanos , Proteínas de Neurofilamentos/química , Fragmentos de Peptídeos/química
20.
Phys Chem Chem Phys ; 20(45): 28886-28893, 2018 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-30420980

RESUMO

Nanopore-based DNA sequencing is considered to be a low-cost, high resolution and superfast method. Solid state nanopores, especially MoS2 nanopores, have been considered to be a promising choice for DNA sequencing. However, researchers still have a very limited understanding of the effects of multiple factors on MoS2-based DNA sequencing. In this study, the effects of the applied voltage and the diameter of the MoS2 nanopore on the resolution of DNA sequencing were investigated. Our results demonstrate that the translocation time of DNA can increase with a decrease in the applied voltage. DNA can be stretched significantly to translocate a 2 nm nanopore under a high applied voltage (>400 mV nm-1). To achieve a 1 base per µs translocation speed (1 GHz bandwidth), we suggest that three methods could be applied, including a decrease in the applied voltage, a decrease in the diameter of the MoS2 nanopore or modification of the MoS2 nanopore. In addition, the size of the nanopore can severely affect the possibility of DNA entering the nanopore, and the translocation time of DNA could be significantly increased with a smaller MoS2 nanopore. These findings may help to design MoS2 nanopores with higher resolution for use in DNA sequencing.


Assuntos
DNA/química , Dissulfetos/química , Molibdênio/química , Nanoporos , Sequência de Bases , Técnicas Eletroquímicas/métodos , Simulação de Dinâmica Molecular , Análise de Sequência de DNA/métodos
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