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1.
J Transl Med ; 17(1): 382, 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31747915

RESUMO

BACKGROUND: In the process of drug development, computational drug repositioning is effective and resource-saving with regards to its important functions on identifying new drug-disease associations. Recent years have witnessed a great progression in the field of data mining with the advent of deep learning. An increasing number of deep learning-based techniques have been proposed to develop computational tools in bioinformatics. METHODS: Along this promising direction, we here propose a drug repositioning computational method combining the techniques of Sigmoid Kernel and Convolutional Neural Network (SKCNN) which is able to learn new features effectively representing drug-disease associations via its hidden layers. Specifically, we first construct similarity metric of drugs using drug sigmoid similarity and drug structural similarity, and that of disease using disease sigmoid similarity and disease semantic similarity. Based on the combined similarities of drugs and diseases, we then use SKCNN to learn hidden representations for each drug-disease pair whose labels are finally predicted by a classifier based on random forest. RESULTS: A series of experiments were implemented for performance evaluation and their results show that the proposed SKCNN improves the prediction accuracy compared with other state-of-the-art approaches. Case studies of two selected disease are also conducted through which we prove the superior performance of our method in terms of the actual discovery of potential drug indications. CONCLUSION: The aim of this study was to establish an effective predictive model for finding new drug-disease associations. These experimental results show that SKCNN can effectively predict the association between drugs and diseases.

2.
iScience ; 21: 549-561, 2019 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-31715498

RESUMO

Multi-targeted kinase inhibitors, such as sorafenib, have been used in various malignancies, but their efficacy in clinical applications varies among individuals and lacks pretherapeutic prediction measures. We applied the concept of "click chemistry" to pathological staining and established a drug-loaded probe staining assay. We stained the cells and different types of pathological sections and demonstrated that the assay was reliable. We further verified in cells, cell-derived xenograft model, and clinical level that the staining intensity of the probe could reflect drug sensitivity. The stained samples from 300 patients who suffered from hepatocellular carcinoma and used the sorafenib probe also indicated that staining intensity was closely related to clinical information and could be used as an independent marker without undergoing sorafenib therapy for prognosis. This assay provided new ideas for multi-target drug clinical trials, pre-medication prediction, and pathological research.

3.
Autophagy ; : 1-15, 2019 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-31711362

RESUMO

BAG2 (BCL2 associated athanogene 2) is associated with cell fate determination in response to various pathological conditions. However, the effects of BAG2 on M. tuberculosis-induced endoplasmic reticulum (ER) stress remain elusive. Herein, we report that M. tuberculosis infection of macrophages triggered ER stress and downregulated BAG2 expression. Overexpression of BAG2 enhanced autophagic flux and activated macroautophagy/autophagy targeted to the ER (reticulophagy). In addition, through increasingly localizing SQSTM1 to the ER in BAG2-overexpressing macrophages, we found that the autophagy receptor protein SQSTM1/p62 (sequestosome 1) is associated with the BAG2-induced reticulophagy. Our data also confirmed that BAG2 could render cells resistant to M. tuberculosis-induced cellular damage, and the anti-apoptotic effects of BAG2 in M. tuberculosis-treated macrophages were partially abolished by the autophagic flux inhibitor bafilomycin A1. Furthermore, the dissociation of BECN1 and BCL2 mediated by activation of mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) was responsible for BAG2-activated autophagy. In addition, XBP1 downstream of the ERN1/IRE1 signaling pathway was bound to the Bag2 promoter region and transcriptionally inhibited BAG2 expression. Collectively, these results indicated that BAG2 has anti-apoptotic effects on M. tuberculosis-induced ER stress, which is dependent on the promotion of autophagic flux and the induction of selective autophagy. We revealed a potential host defense mechanism that links BAG2 to ER stress and autophagy during M. tuberculosis infection.Abbreviations: ATF6: activating transcription factor 6; BECN1: beclin 1; Baf A1: bafilomycin A1; CASP3: caspase 3; DDIT3/CHOP/GADD153: DNA damage inducible transcript 3; DAPI: 4',6-diamidino-2-phenylindole; EIF2AK3/PERK: eukaryotic translation initiation factor 2 alpha kinase 3; ER: endoplasmic reticulum; ERN1/IRE1: endoplasmic reticulum to nucleus signaling 1; HSPA5/GRP78/BiP: heat shock protein 5; MAP1LC3B/LC3B: microtubule associated protein 1 light chain 3 beta; MAPK/ERK: mitogen-activated protein kinase; SQSTM1/p62: sequestosome 1; UPR: unfolded protein response; XBP1: x-box binding protein 1.

4.
Neuroscience ; 2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31711814

RESUMO

Excessive dietary fat intake is considered a great risk factor for metabolic disorders as well as cognitive dysfunction. However, the potential mechanisms underlying the effects of a high-fat diet (HFD) on the brain remain rather obscure. The purpose of this study was to address how early exposure to HFD induces biochemical changes in different brain regions and affects short- and long-term memory. Mice were fed HFD or normal chow for 4 or 7 weeks beginning in adulthood. Our results showed that oxidative stress and biochemical alterations first appeared in the hippocampus after 4 weeks of exposure and were aggravated by a longer exposure time. Additionally, the HFD-fed mice displayed long-term memory impairments, but the performance of the mice in both the HF-4W and HF-7W groups on behavioral tests relying on short-term memory was not affected. The effect of HFD on the brain was also assessed by electrophysiology, which detected a gradual decrease in long-term potentiation in the CA1 region of the hippocampus. The abnormal expression of proteins associated with synaptic function, e.g. synaptophysin, CaMKII, CaMKIV, calcineurin A, ERK and c-fos, was observed in the hippocampus in response to HFD. These results indicate that HFD elicits rapid biochemical and neurological abnormalities in the hippocampus that contribute to cognitive defects and are potentially connected to the HFD-induced suppression of brain activity.

5.
Artigo em Inglês | MEDLINE | ID: mdl-31725029

RESUMO

OBJECTIVE: The characteristics of right heart intracardiac mass in hepatitis B virus infection patients are not well known. Our aim is to describe their ultrasonographic features and nature of such masses. METHODS: We retrospectively reviewed imaging reports of hepatitis B virus infection patients from January 2014 to December 2018. Patients with a confirmed finding of right heart intracardiac mass were included, whose pathology reports and contrast-enhanced images were analyzed. Various masses were compared to a general control group from a published study. RESULTS: Thirty-eight cases were finally included. Different types of masses presented with a variety of echocardiographic manifestations. Thirty-six cases had masses located in the right atrium, including five thrombus and 31 metastatic carcinoma. The later included one metastatic non-Hodgkin lymphoma and 30 metastatic hepatic carcinoma cases (27 of which had inferior vena cava tumor thrombus). Two cases presented with masses in the right ventricle that included one multiple myxoma and one tricuspid valve leaflet vegetation. Compared with the general population, no primary malignant tumor was found in our study (65% vs. 100%, P = 0.001), and hepatic metastasis was the most common type of malignant tumors (P < 0.001). CONCLUSION: The nature and ultrasonographic features of right heart intracardiac masses in hepatitis B virus infection patients are diverse, and the incidence of malignant tumors was similar to that seen in the general population. Hepatic metastasis, possibly extending via the inferior vena cava into the right atrium, was the most common type. Our study may improve understanding of the right heart intracardiac mass in hepatitis B virus infection patients.

6.
Artigo em Inglês | MEDLINE | ID: mdl-31742381

RESUMO

The applications of metal organic frameworks (MOFs) as sulfur hosts focus on the pristine MOFs and their carbonization products for establishing high performance lithium sulfur batteries (LSBs). However, the mecha-nism that modulate the specific nanostructures and the compositions at different treatment temperatures still needs further exploration. In this work, we modulate the pyrolysis products of UiO-66-NH2@rGO (U@rGO) at the predeter-mined specific temperature by TG analysis and systematically investigate their microstructure and chemical character-istic evolution. The composite processed at 300 °C (U@rGO-P300) results in rearrangement of octahedral nano phase into an amorphous material while retaining a large number of functional groups of -NH2 and COO-, which leading to additional nano-structure interface and the high BET surface area of 298.4 m2 g-1. Moreover, the new created abundant sub oxidative Zr3+ atom sites serves as the polysulfide anchor and transfer mediator active sites. The assembled LSBs could deliver the capacity 906.1 and retain 801.7 mA h g-1 after 300 cycles at 1 C with a low value around 0.05% per cycle and the improved rate performance 619.1 mAh g-1 at 4C. The Li+ diffusion coefficients are significantly increased by 10-60 times. The work provides a simple route to activate the metal sites in MOF category with sub-oxidative state, lead-ing to the intriguing and unanticipated property.

7.
Artigo em Inglês | MEDLINE | ID: mdl-31668370

RESUMO

Anti-angiogenic drugs are an effective therapeutic method for the treatment of melanomas. Apatinib is a small-molecule tyrosine kinase inhibitor, which has potent inhibitory activity on tumor angiogenesis. Due to the low water solubility and stability of Apatinib, we aimed to design and develop poly (lactic-co-glycolic acid) (PLGA) and Poloxamer 407 nanoparticles to encapsulate Apatinib (Apa/p NPs) to improve the efficacy of application in melanoma treatment. The size and morphology of the nanoparticles were characterized by dynamic light scattering (DLS) and transmission electron microscopy (TEM). In vitro proliferation assays were used to assess the capacity of Apa/p NPs to suppress the growth of B16 cells. Furthermore, we constructed melanoma models using C57BL/6 mice, and preliminary evaluation of the effect and mechanism of Apa/p NPs on tumor inhibition was performed in vivo. The results showed that the size of Apa/p NPs averaged 136 ±â€¯0.27 nm and the nanoparticles were evenly dispersed. Moreover, Apa/p NPs significantly inhibited the growth of B16 cells and melanoma tumors, compared with the naked drug treatment and control groups. The protein levels of VEGFR-2, phosphorylated (p)-VEGFR-2 and p-ERK1/2 in tumor tissues were inhibited by Apa/p NP treatment, as detected by Western blot. The results of this study suggested that Apa/p NPs could inhibit the growth of melanoma tumors by inhibiting the phosphorylation and expression of VEGFR-2 and downstream ERK1/2, providing a theoretical basis for the clinical application of Apatinib in the treatment of melanoma.

8.
Zhongguo Zhen Jiu ; 39(11): 1149-53, 2019 Nov 12.
Artigo em Chinês | MEDLINE | ID: mdl-31724347

RESUMO

OBJECTIVE: To explore the clinical therapeutic effect and mechanism of acupuncture on headache in the recovery phase of ischemic stroke. METHODS: A total of 97 patients with headache in the recovery phase of ischemic stroke were randomized into an acupuncture group (57 cases) and a western medication group (40 cases). In the western medication group, flunarizine hydrochloride capsule was taken orally 5 mg each time, once a day. In the acupuncture group, acupuncture was applied at Qiuxu (GB 40), Zulinqi (GB 41), Xuanli (GB 6), Shuaigu (GB 8), Fengchi (GB 20) and Baihui (GV 20) for migraine; Chongyang (ST 42), Neiting (ST 44), Jiexi (ST 41), Zusanli (ST 36), Hegu (LI 4), Cuanzhu (BL 2) and Baihui (GV 20) for forehead pain; Jinggu (BL 64), Kunlun (BL 60), Tianzhu (BL 10), Fengchi (GB 20), Baihui (GV 20) and Sishencong (EX-HN 1) for occipital headache; Taichong (LR 3), Yongquan (KI 1), Sanyinjiao (SP 6), Fengchi (GB 20), Baihui (GV 20) and Sishencong (EX-HN 1) for parietal headache. The needles were retained for 30 min each time, once a day and 5 times a week. Both of the two groups were given consecutive treatment for 14 days. The visual analogue scale (VAS) and the headache scores before and after treatment and the recurrence rate 1 month after treatment were observed to evaluate the therapeutic effect, before and after treatment, the contents of substance P (SP), dopamine (DA), serotonin (5-HT), alpha-endorphin (α-EP) and beta-endorphin (ß-EP) in plasma were determined by ELISA in the two groups. RESULTS: Compared before treatment, the VAS scores, the headache scores and the contents of SP, DA and 5-HT in plasma were reduced and the contents ofα-EP andß-EP in plasma were increased in the two groups (all P<0.01). After treatment, the changes of the VAS score, the headache score and the contents of pain-related factors and endogenous opioid peptides in plasma in the acupuncture group were larger than the western medication group (all P<0.05). The total effective rate in the acupuncture group was 84.2% (48/57), which was superior to 62.5% (25/40) in the western medication group, and the recurrence rate in the acupuncture group was lower than the western medication group (both P<0.01). CONCLUSION: The therapeutic effect of acupuncture on headache in the recovery phase of ischemic stroke is superior to flunarizine hydrochloride capsule, and the mechanism may relate to down-regulate the pain-related factors and up-regulate endogenous opioid peptides in plasma.


Assuntos
Terapia por Acupuntura , Cefaleia/terapia , Acidente Vascular Cerebral , Pontos de Acupuntura , Terapia por Acupuntura/métodos , Isquemia Encefálica , Flunarizina/uso terapêutico , Humanos , Acidente Vascular Cerebral/complicações , Resultado do Tratamento , Vasodilatadores/uso terapêutico
9.
Cell Death Differ ; 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31685978

RESUMO

Cancer cells reprogram their energy metabolic system from the mitochondrial oxidative phosphorylation (OXPHOS) pathway to a glucose-dependent aerobic glycolysis pathway. This metabolic reprogramming phenomenon is known as the Warburg effect, a significant hallmark of cancer. However, the detailed mechanisms underlying this event or triggering this reprogramming remain largely unclear. Here, we found that histone H2B monoubiquitination (H2Bub1) negatively regulates the Warburg effect and tumorigenesis in human lung cancer cells (H1299 and A549 cell lines) likely through controlling the expression of multiple mitochondrial respiratory genes, which are essential for OXPHOS. Moreover, our work also suggested that pyruvate kinase M2 (PKM2), the rate-limiting enzyme of glycolysis, can directly interact with H2B in vivo and in vitro and negatively regulate the level of H2Bub1. The inhibition of cell proliferation and nude mice xenograft of human lung cancer cells induced by PKM2 knockdown can be partially rescued through lowering H2Bub1 levels, which indicates that the oncogenic function of PKM2 is achieved, at least partially, through the control of H2Bub1. Furthermore, PKM2 and H2Bub1 levels are negatively correlated in cancer specimens. Therefore, these findings not only provide a novel mechanism triggering the Warburg effect that is mediated through an epigenetic pathway (H2Bub1) but also reveal a novel metabolic regulator (PKM2) for the epigenetic mark H2Bub1. Thus, the PKM2-H2Bub1 axis may become a promising cancer therapeutic target.

10.
Opt Express ; 27(21): 30909-30918, 2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-31684332

RESUMO

Aluminum (Al) plasmonic nanostructures have recently demonstrated remarkable optical nonlinear phenomena, such as enhanced second harmonic (SH) generation. However, the relatively weak field enhancement resulted from large optical losses associated with aluminum nanostructures in combination with the difficulties in controlling the emission polarization pose as a challenge for SH enhancement and tuning. In this paper, we show that the SH emission of aluminum nanostructures can be efficiently enhanced with the polarization properties simultaneously tunable by using metal-insulator-metal (MIM) nanostructures, constituting of Al cross nanoantenna arrays on top of Al mirrors with a SiO2 spacing layer. Specifically, femtosecond laser beam with a linear polarization parallel to one arm illuminates on the structure while the orthogonal arms were physically modified by the laser-induced photothermal reshaping technique to control the SH radiation by the plasmonic resonances. Under the resonance at the SH wavelength, we observed one order of magnitude larger emission enhancement compared to that at the off-resonant condition. Interestingly, the polarization states can be well manipulated simultaneously by controlling the resonances of the orthogonal arms. The enhanced SH conversion and tunable polarization states pave the way for the development of nonlinear optical sources and advanced functional metasurfaces.

11.
J Adhes Dent ; 21(5): 401-411, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31624805

RESUMO

PURPOSE: To investigate the effects of grit blasting, acidic or alkaline/heat treatments, and metal primer application on the shear bond strength (SBS) of resin cement to machined commercially pure titanium (CP-Ti). MATERIALS AND METHODS: Titanium plates were machined and received one of the following treatments: grit-blasting (GB), or grit-blasting followed by either acidic treatment (GB/AC) or alkaline/heat treatment (GB/AH). The specimens were randomly divided into 4 groups and treated with Rely X Ceramic Primer (RCP), Z Prime Plus (ZPP), and Alloy Primer (ALP), or without primer as the control. The pairs of titanium plates were cemented together with the Rely X Unicem cement. SBS was measured before and after thermocycling between 5°C and 55°C for 5000 cycles. RESULTS: SEM observation showed that honeycomb-shaped pores formed on the surface of machined CP-Ti after GB/AC treatment, whereas a uniform net-like pattern formed after GB/AH treatment. In descending order, the surface roughness was GB, GB/AC, and GB/AH. The GB/AH group showed the highest SBS among all the treatments. As for primers, ALP group showed the highest SBS, while the RCP group showed the lowest. GB followed by ALP presented the highest SBS. CONCLUSION: A fine, uniform network structure was formed on the surface of CP-Ti following GB/AH treatment, providing an effective micromechanical interlocking mechanism for resin bonding. At the same time, after AH treatment, the -OH formed on the surface of the machined CP-Ti triggered a chemical reaction with the acid monomers in the resin adhesives, creating a chemical bond. As a result, GB/AH treatment significantly improved the bond strength relative to GB/AC treatment. In addition, ALP treatment facilitated the formation of hydrogen bonds, which further improved the chemical bond strength. Finally, the combination of the effects mentioned above resulted in the most robust bond between machined CP-Ti and the resin adhesives.


Assuntos
Colagem Dentária , Cimentos de Resina , Cimentos Dentários , Corrosão Dentária , Análise do Estresse Dentário , Teste de Materiais , Resistência ao Cisalhamento , Propriedades de Superfície , Titânio
12.
Commun Biol ; 2: 373, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31633064

RESUMO

Aggressive behavior in our modern, civilized society is often counterproductive and destructive. Identifying specific proteins involved in the disease can serve as therapeutic targets for treating aggression. Here, we found that overexpression of RGS2 in explicitly serotonergic neurons augments male aggression in control mice and rescues male aggression in Rgs2 -/- mice, while anxiety is not affected. The aggressive behavior is directly correlated to the immediate early gene c-fos induction in the dorsal raphe nuclei and ventrolateral part of the ventromedial nucleus hypothalamus, to an increase in spontaneous firing in serotonergic neurons and to a reduction in the modulatory action of Gi/o and Gq/11 coupled 5HT and adrenergic receptors in serotonergic neurons of Rgs2-expressing mice. Collectively, these findings specifically identify that RGS2 expression in serotonergic neurons is sufficient to drive male aggression in mice and as a potential therapeutic target for treating aggression.

13.
Biomed Pharmacother ; 120: 109470, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31590124

RESUMO

Fufang Xueshuantong (FXST), a Chinese patent medicine, is composed of Panax notoginseng, Salviae miltiorrhizae, Astragali Radix and Radix Scrophulariae and has been found to prevent diabetic retinopathy. Yes-associated protein (YAP) participates in the pathophysiology of retinal disease and promotes endothelial cell proliferation and angiogenesis. Although it is known that YAP activity is altered by FXST, the role of YAP in mediating the effect of FXST remains unclear. In high glucose-treated retinal vascular endothelial cells (RVECs), FXST significantly reduced cell viability, the number of migrating cells and tube length in the present study. Moreover, FXST decreased the levels of YAP mRNA and protein and inhibited the expression of vascular endothelial growth factor (VEGF). Transfection of sh-YAP into the cells decreased the ability of FXST to modulate cell migration and tube formation. The effect of FXST on VEGF expression was also decreased. Similar results were obtained when the cells were stimulated with a YAP inhibitor in combination with FXST. Thus, FXST is shown to protect high glucose-injured RVECs via YAP-mediated effects.

14.
Biosens Bioelectron ; 148: 111795, 2019 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-31665673

RESUMO

In this work, a high-efficiency electrochemiluminescence (ECL) ternary system was constructed for ultrasensitive assay of insulin based on hollow porous graphitic carbon nitride (HP-C3N4) as novel luminophore, S2O82- as coreactant and tri-metallic AuPtAg as coreaction accelerator. Specifically, in comparison with C3N4-based bulk nanomaterials, the as-prepared HP-C3N4 exhibits high luminous efficiency though decreased inner filter effect and minimized inactive ECL emitter. Noteworthy, tri-metallic AuPtAg, possessing the superiority of Au, Pt and Ag, was first used as coreaction accelerator to significantly enhance ECL intensity of HP-C3N4 and S2O82-. As a consequence, with the resultant ECL ternary (HP-C3N4/S2O82-/AuPtAg) system as aptasensing platform, a high-intense initial ECL signal was achieved. Subsequently, ferrocene-labeled quenching probe (Fc-HP2) as ECL quencher was used to quench the initial signal and achieve the low-background noise. Eventually, in the presence of insulin, the target-induced triple-helix molecular switch and Nb.BbvCI-assisted DNA walker amplification were executed to recover a strong ECL signal by releasing Fc-HP2 from the electrode surface. As expected, the constructed aptasensor presents an excellent sensitivity and selectivity for detecting insulin range from 0.05 pg mL-1 to 100 ng mL-1 with a detection limit of 17 fg mL-1. This work provides a new avenue for developing highly efficient HP-C3N4 based ECL ternary system as well as ultrasensitive ECL aptasensors for bioanalysis.

15.
Mol Med Rep ; 20(6): 5064-5074, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31638226

RESUMO

Diffuse large B cell lymphoma (DLBCL) represents the most common subtype of non­Hodgkin lymphoma in China. 1,25­Dihydroxyvitamin D3 [1,25(OH)2D3] has been shown to possess significant antitumor potential and is degraded by 25­hydroxyvitamin D­24­hydroxylase (CYP24A1). In the present study, the role of CYP24A1 and autophagy, and their underlying mechanisms in the anticancer effects of 1,25(OH)2D3 in DLBCL cells, were investigated. It was found that the levels of CYP24A1 in DLBCL lymph node tissues were higher than in hyperplasia lymphadenitis tissue. Moreover, the expression of CYP24A1 was positively associated with the Ann Arbor stage and the International Prognostic Index in patients with DLBCL, and negatively associated with the clinical response to treatment. Patients >60 years of age were found to have a higher level of CYP24A1. 1,25(OH)2D3 inhibited the proliferation of the Pfeiffer DLBCL cell line and increased the G1 phase population of Pfeiffer cells. Rapamycin (RAPA) in combination with 1,25(OH)2D3 increased the G1 phase distribution of Pfeiffer cells. Furthermore, RAPA blocked the increase of CYP24A1 and vitamin D receptor (VDR) expression induced by 1,25(OH)2D3. 1,25(OH)2D3 induced the formation of autophagosomes, increased the expression of autophagy related protein light chain (LC)3II/LC3I and reduced the expression of the ubiquitin binding protein P62. In addition, 1,25(OH)2D3 decreased the phosphorylation of AKT and mammalian target of RAPA (mTOR), and downstream targets eukaryotic translation imitation factor 4E­binding protein 1 and ribosomal protein S6 kinase ß­1 in Pfeiffer cells. The results from the present study suggested that CYP24A1 may be a novel prognostic indicator for DLBCL. 1,25(OH)2D3 inhibited proliferation and induced autophagy of Pfeiffer cells. In addition, 1,25(OH)2D3 increased the G1 phase population of Pfeiffer cells. These effects may be mediated by inhibition of the AKT/mTOR/PI3K signaling pathway. RAPA increased the cell cycle arrest induced by 1,25(OH)2D3 by blocking the upregulated expression of CYP24A1 and VDR.

16.
Analyst ; 144(22): 6641-6646, 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31595888

RESUMO

The detection of the HPV L1 protein provides information about the infection status of the virus, reflects the replication status of the HPV virus in cervical cells, and helps understand the regression and progress of cervical lesions. Herein, we report a novel laser desorption ionization mass spectrometry (LDI MS) method for the sensitive detection of the HPV 16 L1 protein, based on non-covalent competitive adsorption between the HPV 16 L1 aptamer and melamine on gold nanoparticles (AuNPs). The intensity of the MS signal corresponding to the mass tag shows a linear relationship with the HPV 16 L1 concentration in the range 2-80 ng mL-1, with a limit of detection (LOD) of 58.8 pg mL-1. Using this method, the HPV 16 L1 protein is quantitatively analyzed in both clinical and vaccine samples. The described method is simple and has high sensitivity and good reliability.

17.
Artigo em Inglês | MEDLINE | ID: mdl-31581074

RESUMO

Natural human-computer interaction and audio-visual human behaviour sensing systems, which would achieve robust performance in-the-wild are more needed than ever as digital devices are becoming indispensable part of our life more and more. Accurately annotated real-world data are the crux in devising such systems. However, existing databases usually consider controlled settings, low demographic variability, and a single task. In this paper, we introduce the SEWA database of more than 2000 minutes of audio-visual data of 398 people coming from six cultures, 50% female, and uniformly spanning the age range of 18 to 65 years old. Subjects were recorded in two different contexts: while watching adverts and while discussing adverts in a video chat. The database includes rich annotations of the recordings in terms of facial landmarks, facial action units (FAU), various vocalisations, mirroring, and continuously valued valence, arousal, liking, agreement, and prototypic examples of (dis)liking. This database aims to be an extremely valuable resource for researchers in affective computing and automatic human sensing and is expected to push forward the research in human behaviour analysis, including cultural studies. Along with the database, we provide extensive baseline experiments for automatic FAU detection and automatic valence, arousal and (dis)liking intensity estimation.

18.
Chem Commun (Camb) ; 55(86): 12904-12907, 2019 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-31584577

RESUMO

A novel type of hydrogen peroxide (H2O2)-activated diazeniumdiolate based on an α-ketoamide moietey was developed as a nitric oxide (NO) donor. KA-NO-4 inhibited lung cancer cells with submicromolar activity. The H2O2-responsive behaviour of KA-NO-4 was thoroughly investigated. The NO-centered mechanism of action of KA-NO-4 was intracellularly studied.


Assuntos
Amidas/química , Antineoplásicos/química , Compostos Azo/química , Peróxido de Hidrogênio/química , Doadores de Óxido Nítrico/química , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Compostos Azo/farmacologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Óxido Nítrico/metabolismo , Doadores de Óxido Nítrico/farmacologia
19.
Food Funct ; 10(11): 7131-7141, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31595923

RESUMO

Dihydromyricetin (DMY) is a natural flavonoid compound derived from Lysionotus pauciflorus Maxim and has been found to possess numerous biological activities. However, there have been few reports regarding its anti-food allergic activity. In this study, we demonstrated that DMY could upregulate the rectal temperature, suppress the development of diarrhea, decrease the levels of serum specific immunoglobulin (Ig)E, histamine, and mouse mast cell protease-1, and promote the production of interleukin-10 in ovalbumin-allergic mice. Moreover, DMY downregulated the population of B cells and mast cells and upregulated the population of regulatory T cells in the spleens of ovalbumin-allergic mice. Furthermore, DMY blocked the high affinity IgE receptor (FcεRI)-IgE interaction, inhibited the release of ß-hexosaminidase and histamine in rat basophilic leukemia-2H3 cells, and alleviated passive cutaneous anaphylaxis reactions. These findings indicated that L. pauciflorus derived DMY might have the potential to alleviate food hypersensitivity or allergic diseases.

20.
J Cardiovasc Transl Res ; 12(6): 600-607, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31664615

RESUMO

It is well-known that curcumin, as a plant substance, has vascular protective effects. TRPV4 (transient receptor potential vanilloid 4) is a highly Ca2+-selective channel in vascular endothelium. In our study, fluorescent Ca2+ imaging in mesenteric arterial endothelial cells (MAECs) and overexpressed TRPV4 human embryonic kidney (HEK293) cells showed that curcumin dose-dependently stimulated Ca2+ influx. Whole-cell patch clamp proved that curcumin stimulated the TRPV4-mediated currents in TRPV4-HEK293 cells. The TRPV4-specific blocker HC067047 markedly decreased the whole-cell current. Molecular modeling and docking showed that the binding site of curcumin and TRPV4 was mainly in the amino acid sequence LYS340-LEU349 of TRPV4 protein. Furthermore, curcumin dose-dependently induced the endothelium-dependent vessel dilatation in small mesenteric arteries. Therefore, our results demonstrated that curcumin stimulates Ca2+ entry in endothelial cells and improves endothelium-dependent vessel relaxation by activating TRPV4 channels. Moreover, we identified the specific binding sites of curcumin and TRPV4, thereby highlighting its potential therapeutic target of cardiovascular diseases.

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