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1.
Eur J Pharmacol ; 876: 173065, 2020 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-32171792

RESUMO

Inhibition of Aß aggregation and neurotoxicity has been developed as an attractive therapeutic strategy to combat Alzheimer's disease (AD). Bis(propyl)-cognitin (B3C) is a multifunctional dimer derived from tacrine. Herein, the anti-aggregation and disassembly effects of B3C on Aß, together with the neuroprotective effects and underlying mechanisms of B3C against Aß-induced neurotoxicity were investigated in silico, in vitro and in vivo. Data from Thioflavin-T fluorescence and atomic force microscopy assays indicated that B3C (1-10 µM), but not its monomer tacrine, greatly inhibited the formation of Aß fibrils and disaggregated pre-formed mature Aß fibrils. Comparative molecular dynamics simulation results revealed a possible binding mode that prevented Aß fibrils formation, showing that B3C favorably bound to Aß via hydrophobic interactions. Additionally, B3C was able to block the neurotoxicity caused by Aß fibrils in cultured PC12 cells. Very encouragingly, B3C (0.3 and 0.45 mg/kg) markedly alleviated the cognitive impairments in rats insulted by intra-hippocampal injection of Aß1-42 fibrils, more potently than tacrine (1 and 2 mg/kg). Furthermore, mechanistic studies demonstrated that B3C reversed the inhibition of phospho-GSK3ß at Ser9 site in vitro and in vivo caused by Aß, suggesting the neuroprotection of B3C was achieved through the inhibition of GSK3ß pathway. These findings indicate that B3C could serve as an effective inhibitor of Aß aggregation and neurotoxicity, and provide novel molecular insights into the potential application of B3C in AD prevention and treatment.

3.
Oxid Med Cell Longev ; 2020: 6579696, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32148654

RESUMO

Mitophagy is involved in sepsis-induced acute lung injury (ALI). Bcl-2 family proteins play an important role in mitochondrial homeostasis. However, whether targeting Bcl-2 proteins (Bcl-2 and Bad) could influence mitophagy in ALI remains unclear. In this study, lipopolysaccharide (LPS) was used to induce injury in A549 cells and ALI in mice. LPS treatment resulted in elevated cell apoptosis, enhanced mitophagy, decreased Bcl-2 expression, increased Bad expression, and activation of PINK1/Parkin signaling in cells and lung tissues. Both Bcl-2 overexpression and Bad knockdown attenuated LPS-induced injury, inhibited cell apoptosis and mitophagy, and improved survival. Atg5 knockout (KO) inhibited LPS-induced cell apoptosis. Furthermore, Bcl-2 proteins regulated mitophagy by modulating the recruitment of Parkin from the cytoplasm to mitochondria via direct protein-protein interactions. These results were further confirmed in Park2 KO cells and Park2-/- mice. This is the first study to demonstrate that Bcl-2 proteins regulated mitophagy in LPS-induced ALI via modulating the PINK1/Parkin signaling pathway, promoting new insights into the mechanisms and investigation of therapeutic strategies for a septic patient with ALI.

4.
BMC Psychiatry ; 20(1): 97, 2020 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-32131778

RESUMO

BACKGROUND: Many studies have related biochemical characteristics to violence and have reported schizophrenia could elevated the risk of violent behaviour. However, the metabolic characteristics of schizophrenia patients with violence (V.SC) are unclear. METHODS: To explore the metabolic characteristics of schizophrenia with violence and to identify potential biomarkers, untargeted metabolomics was performed by using gas chromatography time-of-flight mass spectrometry to analyse the plasma metabolites of fifty-three V.SC and twenty-four schizophrenia patients without violence (NV.SC). Multivariate and univariate analyses were performed to identify differential metabolites and biomarkers. Violence was assessed by the MacArthur Violence Assessment Study method. Psychiatric symptoms were assessed by the Positive and Negative Syndrome Scale. RESULTS: Multivariate analysis was unable to distinguish V.SC from NV.SC. Glycerolipid metabolism and phenylalanine, tyrosine and tryptophan biosynthesis were the differential metabolic pathways between V.SC and NV.SC. We confirmed ten metabolites and five metabolites as metabolic biomarkers of V.SC by random forest and support vector machine analysis, respectively. The biomarker panel, including the ratio of L-asparagine to L-aspartic acid, vanillylmandelic acid and glutaric acid, yielded an area under the receiver operating characteristic curve of 0.808. CONCLUSIONS: This study gives a holistic view of the metabolic phenotype of schizophrenia with violence which is characterized by the dysregulation of lipids and amino acids. These results might provide information for the aetiological understanding and management of violence in schizophrenia; however, this is a preliminary metabolomics study about schizophrenia with violence, which needs to be repeated in future studies.

5.
ACS Nano ; 2020 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-32191030

RESUMO

Mesoporous metal sulfide hybrid (meso-MoS2/CoMo2S4) materials via a soft-templating approach using diblock copolymer polystyrene-block-poly (acrylic acid) (PS-b-PAA) micelles are reported. The formation of the meso-MoS2/CoMo2S4 heterostructures is based on the sophisticated co-assembly of dithiooxamide (DTO) and metal precursors (i.e., Co2+, PMo12), that are subsequently annealed in nitrogen atmosphere to generate the mesoporous material. Decomposing the polymer leaves behind mesopores throughout the spherical MoS2/CoMo2S4 hybrid particles, generating numerous electrochemical active sites in a network of pores that enable faster charge transfer and mass/gas diffusion that enhance the electrocatalytic performance of MoS2/CoMo2S4. Doping the spherical meso-MoS2/CoMo2S4 heterostructures with iron improves the electronic properties of the hybrid meso-Fe-MoS2/CoMo2S4 material and consequently results in its superior electrochemical activities for both hydrogen evolution reaction (HER) and oxygen evolution reaction (OER).

7.
Protein Cell ; 2020 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-32125673

RESUMO

In the original publication the bands in Fig. 1J and Fig. 2B were not visible. The correct versions of Fig. 1J and Fig. 2B are provided in this correction.

8.
Brief Bioinform ; 2020 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-32055842

RESUMO

Drug development involves a deep understanding of the mechanisms of action and possible side effects of each drug, and sometimes results in the identification of new and unexpected uses for drugs, termed as drug repurposing. Both in case of serendipitous observations and systematic mechanistic explorations, confirmation of new indications for a drug requires hypothesis building around relevant drug-related data, such as molecular targets involved, and patient and cellular responses. These datasets are available in public repositories, but apart from sifting through the sheer amount of data imposing computational bottleneck, a major challenge is the difficulty in selecting which databases to use from an increasingly large number of available databases. The database selection is made harder by the lack of an overview of the types of data offered in each database. In order to alleviate these problems and to guide the end user through the drug repurposing efforts, we provide here a survey of 102 of the most promising and drug-relevant databases reported to date. We summarize the target coverage and types of data available in each database and provide several examples of how multi-database exploration can facilitate drug repurposing.

9.
Environ Pollut ; 259: 113955, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32023800

RESUMO

Biogenic volatile organic compounds (BVOCs) play essential roles in tropospheric chemistry, on both regional and global scales. The emissions of large quantities of species-specific BVOC depend not only on environmental (temperature, T; photosynthetically active radiation, PAR), but also physiological parameters (i.e. net photosynthetic rate, Pn; transpiration rate, Tr; stomatal conductance, gs and intercellular CO2 concentration, Ci). Here, isoprene, monoterpene and sesquiterpene emissions were determined from five dominant mature woody tree species in northern China, which are two evergreen conifers (Pinus tabuliformis and Platycladus orientalis) and three broad-leaved deciduous trees (Quercus variabilis, Populus tomentosa and Robinia pseudoacacia). A dynamic enclosure technique combined with GC-MS was used to sample BVOCs and analyse their fractional composition at daily and annual scales. The diurnal data showed that both isoprene and monoterpene emissions increased with increasing temperature, and reached their maximum emission rates in the peak of growing season for both coniferous and broad-leaved species. The emissions of individual compound within the monoterpenes and sesquiterpenes were statistically correlated with each other for all species. Furthermore, some oxygenated monoterpene emissions were highly correlated to sesquiterpenes in all tree species. Linking BVOC emissions to environmental and leaf physiological parameters exhibited that monoterpene emissions were linearly and positively correlated to the variation of T, PAR, Pn and Tr, while their relationship to gs and Ci is more complex. Collectively, these findings provided important information for improving current model estimations in terms of the linkage between BVOC emissions and plant physiological traits. The data presented in this study can be used to update emission capacity used in models, as this is the first time of reporting BVOC emissions from five dominant species in this region. The whole-year measurement of leaf-level BVOCs can also advance our understanding of seasonal variation in BVOC emissions.

10.
Biosens Bioelectron ; 154: 112078, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32056972

RESUMO

Metal nanoclusters (NCs), typically consisting of a few to tens of metal atoms, bridge the gap between organometallic compounds and crystalline metal nanoparticles. As their size approaches the Fermi wavelength of electrons, metal NCs exhibit discrete energy levels, which in turn result in the emergence of intriguing physical and chemical (or physicochemical) properties, especially strong fluorescence. Compared with noble metals, copper is a relatively earth-abundant and cost-effective metal. Theoretical and experimental studies have shown that copper NCs (CuNCs) possess unique photoluminescent properties. To highlight these achievements, this review begins by providing an overview of a multitude of factors that play central roles in the fluorescence of CuNCs. Additionally, a critical perspective of how the aggregation of CuNCs can efficiently improve the florescent stability, tunability and intensity is also discussed. Following, we present representative applications of CuNCs in detection and in-vivo/in-vitro imaging and point out that in-situ generation of CuNCs for sensing and bioimaging may be an entry point for the in-depth studies of CuNCs as an intriguing probe. Finally, we outline current challenges and our perspective on the development of CuNCs.

11.
J Mol Biol ; 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-32044343

RESUMO

Comparative biological studies typically require plenty of samples to ensure full representation of the given problem. A frequently-encountered question is how many samples are sufficient for a particular study. This question is traditionally assessed using the statistical power, but it alone may not guarantee the full and reproducible discovery of features truly discriminating biological groups. Two new types of statistical criteria have thus been introduced to assess sample sufficiency from different perspectives by considering diagnostic accuracy and robustness. Due to the complementary nature of these criteria, a comprehensive evaluation based on all criteria is necessary for achieving a more accurate assessment. However, no such tool is available yet. Herein, an online tool SSizer (https://idrblab.org/ssizer/) was developed and validated to enable the assessment of the sample sufficiency for a user-input biological dataset, and three statistical criteria were adopted to achieve comprehensive and collective assessment. A sample simulation based on a user-input dataset was performed to expand the data and then determine the sample size required by the particular study. In sum, SSizer is unique for its ability to comprehensively evaluate whether the sample size is sufficient and determine the required number of samples for the user-input dataset, which, therefore, facilitates the comparative and OMIC-based biological studies.

12.
Sensors (Basel) ; 20(4)2020 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-32079124

RESUMO

Real-time sensing and modeling of the human body, especially the hands, is an important research endeavor for various applicative purposes such as in natural human computer interactions. Hand pose estimation is a big academic and technical challenge due to the complex structure and dexterous movement of human hands. Boosted by advancements from both hardware and artificial intelligence, various prototypes of data gloves and computer-vision-based methods have been proposed for accurate and rapid hand pose estimation in recent years. However, existing reviews either focused on data gloves or on vision methods or were even based on a particular type of camera, such as the depth camera. The purpose of this survey is to conduct a comprehensive and timely review of recent research advances in sensor-based hand pose estimation, including wearable and vision-based solutions. Hand kinematic models are firstly discussed. An in-depth review is conducted on data gloves and vision-based sensor systems with corresponding modeling methods. Particularly, this review also discusses deep-learning-based methods, which are very promising in hand pose estimation. Moreover, the advantages and drawbacks of the current hand gesture estimation methods, the applicative scope, and related challenges are also discussed.

13.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(1): 275-282, 2020 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-32027289

RESUMO

OBJECTIVE: To investigate the effect of prostaglandin E2 recoptor 4 antagonist (EP4A) on the self-renewal ability of human CD34+ cells and its mechamism. METHODS: The peripheral blood hematopoietic stem cell of 20 healthy donors received the G-CSF-mobilization were collected, then the human CD34+ cells were sorted out by MACS microbead kit. The human CD34+ cells were treated with DMSO (control group), EP4A (EP4A group) and EP4A+EP4A antagonist (EP4A+EP4A group) for 72 hours. The differential genes and pathways related with CD34+ cell stemness were detected by Thermogram and Pathway enrichment analysis. and then the expression levels of protein and gene (ß-catenin, Nanog, Oct4, Sox2, Stat3, AKT, P38) were detected by qRT-PCR and Western blot respectively. RESULTS: EP4A could elevate the mRNA and protein expression of ß-catenin, Nanog, Oct4, Sox2, in comparison with control group, however, mRNA and protein expression of STAT3, AKT, P38 were not changed. When human CD34+ cell were cultured with EP4A+XAV939 it was found that the mRNA and protein expression of ß-catenin was downregulated, moreover the mRNA and protein expression of Nanog, Oct4, Sox2 were reduced. CONCLUSION: EP4A can upregulate stemness factors-ß-catenin, Nanog, Oct4 and Sox2 in human CD34+ cell in vitro, but not STAT3, AKT and P38.


Assuntos
Receptores de Prostaglandina E Subtipo EP4/metabolismo , Antígenos CD34 , Movimento Celular , Fator Estimulador de Colônias de Granulócitos , Humanos , Proteína Homeobox Nanog , Fator 3 de Transcrição de Octâmero , Prostaglandinas , RNA Mensageiro , Linfócitos T
14.
Nat Prod Res ; : 1-5, 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-31960722

RESUMO

In clinical trials, the healing of wounds remains a substantial physiological and financial incumbrance on patients. Therefore, the development of new drugs that can accelerate wound healing is vital. Based on genomic methods, we identified a new peptide (RL-RL10) with the amino acid sequence 'RLFKCWKKDS' from the skin of an amphibian frog species (Rana limnocharis). RL-RL10 promoted wound healing of human keratinocytes (HaCaT) in a concentration-dependent manner. RL-RL10 also had an effect on the migration and proliferation of HaCaT cells and promoted healing of a full-thickness wound in mice in a dose-dependent manner. In conclusion, we discovered RL-RL10 that promoted healing activity of cellular and animal wounds, thus providing a new peptide template for the development of novel wound-repairing drugs.

16.
Virology ; 542: 8-19, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31957664

RESUMO

The H3 subtype avian influenza virus (AIV) poses a threat to both animal and human health. In this study, phylogenetic analysis showed that the H3 AIVs had various genomic constellations and extensive reassortments, increasing genetic diversity and the emergence of new pathogenic viruses that might infect human beings. Molecular analysis demonstrated that the major molecular markers linked to drug resistance were identified in M genes of three studied viruses, and there might be wide range of resistant virus infections in poultry in the future. Although all the H3 viruses preferentially bound to the avian-type receptor, the growth kinetics experiments showed that the selected H3 viruses were capable of efficient replication in mammalian cells, suggesting a potential cross-species transmission of H3 viruses. Overall, our results emphasize the need for continued surveillance of H3 outbreaks and may also help us improve knowledge on H3 AIVs prevention and control.

17.
Cancer Biomark ; 27(3): 343-356, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31903983

RESUMO

BACKGROUND: Uveal melanoma (UM) is the most common primary intraocular tumor in adults, which has a high mortality rate and worse prognosis. Therefore, early potential molecular detection and prognostic evaluation seem more important for early diagnosis and treatment. METHODS: Gene expression data were obtained from The Cancer Genome Atlas-Uveal melanomas database. Survival genes were identified by univariate analysis and were regarded to be associated with the overall survival of UM patients. Then, pathway enrichment analysis of these survival genes was performed. Robust likelihood-based survival model and multivariate survival analysis were conducted to identify more reliable genes and the prognostic signature for UM survival prediction. Two internal datasets and another two UM datasets from Gene Expression Omnibus (GEO) were used for the validation of prognostic signature. RESULTS: Firstly, 2,010 survival genes were screened by univariate survival analysis. GO and KEGG analysis revealed that these genes were mainly involved in pathways such as mRNA processing, RNA splicing, spliceosome and ubiquitin mediated proteolysis. Secondly, a six-gene signature was identified by Robust likelihood-based survival model approach. The gene expression of the six genes can successfully divide UM samples into high- and low-risk groups and have strong survival prediction ability. What's more, the expression of six genes was compared in 80 healthy adipose tissue samples obtained from GTEx (Genotype-Tissue Expression) database and further validated in internal datasets and GEO datasets, which also can predict UM patient survival. CONCLUSIONS: The six genes (SH2D3A, TMEM201, LZTS1, CREG1, NIPA1 and HIST1H4E) model might play a vital role in prognosis of UM, which should be helpful for further insight into the treatment of uveal melanoma.

18.
Artigo em Inglês | MEDLINE | ID: mdl-31910357

RESUMO

Background: Oral tongue squamous cell carcinoma (OTSCC) is a common type of oral tumor. LncRNAs (long noncoding RNAs) and miRNAs (microRNAs) were identified as regulators in many human cancers. This study aims to explore the molecular basis of HOXA transcript at the distal tip (HOTTIP) in regulating OTSCC progression. Materials and Methods: The expression of HOTTIP, miR-124-3p, and high-mobility group AT-hook 2 (HMGA2) was detected by quantitative real-time polymerase chain reaction. Next, the proliferation was evaluated by 3-(4,5-dimethylthiazole-2-y1)-2,5-biphenyl tetrazolium bromide (MTT) assay. The migration and invasion were assessed by transwell assay. Furthermore, dual-luciferase reporter assay was performed to confirm the combination between HOTTIP and miR-124-3p, miR-124-3p, and HMGA2. Protein levels of HMGA2, ß-catenin, c-Myc, and E-cadherin were examined by western blot. The nude mice model was employed to test the tumor growth in vivo. Results: HOTTIP was upregulated in OTSCC tissues and cells, and was highly expressed in positive lymph node metastasis and late-stage OTSCC patients. Silencing HOTTIP impeded proliferation, migration, and invasion of OTSCC cells. Moreover, HOTTIP knockdown inhibited proliferation, migration, and invasion of OTSCC cells by targeting miR-124-3p. Besides, miR-124-3p targeted HMGA2 to block proliferation, migration, and invasion. HMGA2 could rescue the inhibitory effects of HOTTIP interference on proliferation, migration, and invasion. In addition, HMGA2 overexpression reversed the downregulation of ß-catenin and c-Myc protein levels and upregulation of E-cadherin level affected by HOTTIP silencing. Finally, HOTTIP silencing repressed tumor growth and resulted in a great rise on miR-124-3p and E-cadherin expression and a distinct fall on HMGA2, ß-catenin, and c-Myc protein levels. Conclusions: HOTTIP knockdown restrained proliferation, migration, and invasion of OTSCC cells by miR-124-3p/HMGA2 axis through Wnt/ß-catenin pathway.

19.
Phys Med ; 69: 233-240, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31918375

RESUMO

PURPOSE: It is vital to appropriately power clinical trials towards discovery of novel disease-modifying therapies for Parkinson's disease (PD). Thus, it is critical to improve prediction of outcome in PD patients. METHODS: We systematically probed a range of robust predictor algorithms, aiming to find best combinations of features for significantly improved prediction of motor outcome (MDS-UPDRS-III) in PD. We analyzed 204 PD patients with 18 features (clinical measures; dopamine-transporter (DAT) SPECT imaging measures), performing different randomized arrangements and utilizing data from 64%/6%/30% of patients in each arrangement for training/training validation/final testing. We pursued 3 approaches: i) 10 predictor algorithms (accompanied with automated machine learning hyperparameter tuning) were first applied on 32 experimentally created combinations of 18 features, ii) we utilized Feature Subset Selector Algorithms (FSSAs) for more systematic initial feature selection, and iii) considered all possible combinations between 18 features (262,143 states) to assess contributions of individual features. RESULTS: A specific set (set 18) applied to the LOLIMOT (Local Linear Model Trees) predictor machine resulted in the lowest absolute error 4.32 ± 0.19, when we firstly experimentally created 32 combinations of 18 features. Subsequently, 2 FSSAs (Genetic Algorithm (GA) and Ant Colony Optimization (ACO)) selecting 5 features, combined with LOLIMOT, reached an error of 4.15 ± 0.46. Our final analysis indicated that longitudinal motor measures (MDS-UPDRS-III years 0 and 1) were highly significant predictors of motor outcome. CONCLUSIONS: We demonstrate excellent prediction of motor outcome in PD patients by employing automated hyperparameter tuning and optimal utilization of FSSAs and predictor algorithms.

20.
Int Ophthalmol ; 40(1): 43-49, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31735992

RESUMO

PURPOSE: To report a novel technique to treat superficial limbal dermoid by using the corneal intrastromal lenticules obtained from SMILE and to evaluate the initial clinical outcomes of lenticule patch graft for treatment of limbal dermoid. METHODS: In this single-center case series, lenticules were obtained from patients undergoing SMILE for the correction of myopia and the lenticule patch graft was performed in three patients with limbal dermoid. Patients were postoperatively followed at first, second weeks and first, third months after surgery. The main measured outcome parameters were included the best-corrected visual acuity, transparency of graft, tectonic integrity and restoration of optical transparency. RESULTS: All surgeries were successful, and all patients recovered well. Obviously, improving tendency in visual acuity and astigmatism was seen at the final follow-up in all eyes. No statistically significant difference has found in the thickness of the cornea between the surgical field and the corresponding normal field. Globe integrity was achieved in all cases, and no immune rejection or perforation was detected until the last follow-up visit in all eyes treated. CONCLUSIONS: Lenticule keratoplasty may be a safe, feasible and inexpensive surgical option for the treatment of corneal dermoid. It retains globe integrity and decreases the risk of complications such as postoperative limbal ectasia and visible corneal scarring and should be widely promoted in the areas with shortage of donor corneas.

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