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1.
Plant J ; 116(3): 635-649, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37675639

RESUMO

Peyote (Lophophora williamsii) is an entheogenic and medicinal cactus native to the Chihuahuan desert. The psychoactive and hallucinogenic properties of peyote are principally attributed to the phenethylamine derivative mescaline. Despite the isolation of mescaline from peyote over 120 years ago, the biosynthetic pathway in the plant has remained undiscovered. Here, we use a transcriptomics and homology-guided gene discovery strategy to elucidate a near-complete biosynthetic pathway from l-tyrosine to mescaline. We identified a cytochrome P450 that catalyzes the 3-hydroxylation of l-tyrosine to l-DOPA, a tyrosine/DOPA decarboxylase yielding dopamine, and four substrate-specific and regiospecific substituted phenethylamine O-methyltransferases. Biochemical assays with recombinant enzymes or functional analyses performed by feeding putative precursors to engineered yeast (Saccharomyces cerevisiae) strains expressing candidate peyote biosynthetic genes were used to determine substrate specificity, which served as the basis for pathway elucidation. Additionally, an N-methyltransferase displaying broad substrate specificity and leading to the production of N-methylated phenethylamine derivatives was identified, which could also function as an early step in the biosynthesis of tetrahydroisoquinoline alkaloids in peyote.


Assuntos
Cactaceae , Mescalina , Mescalina/análise , Mescalina/química , Vias Biossintéticas , Fenetilaminas , Tirosina/metabolismo , Metiltransferases/metabolismo , Cactaceae/química , Cactaceae/metabolismo
2.
Opt Express ; 32(2): 2839-2845, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38297802

RESUMO

Neuro-transfer functions (neuro-TF) modeling method has been developed as one of the popular methods for parametric modeling of electromagnetic (EM) filter responses. The discontinuity issue of zero and pole data caused by extraction using vector fitting w.r.t. geometrical parameters change affects the neuro-TF training process and limits its modeling accuracy. This issue is addressed by this paper which proposes a novel systematic pole-zero sorting method for neuro-TF parametric modeling. The proposed method can obtain continuous pole-zero data which change much more smooth w.r.t. geometrical parameters change than the existing neuro-TF method, especially solves the difficulty of disorder of positive and negative values due to small values. The proposed systematic sorting method can substantially improve the modeling accuracy during the establishment and training of neuro-TF model over the existing neuro-TF method without systematic sorting.

3.
Appl Microbiol Biotechnol ; 108(1): 296, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38607413

RESUMO

Sophorolipids (SLs) are promising glycolipid biosurfactants as they are easily produced and functional. SLs from microorganisms are comprised of mixtures of multiple derivatives that have different structures and properties, including well-known acidic and lactonic SL (ASLs and LSLs, respectively). In this study, we established a method for analyzing all SL derivatives in the products of Starmerella bombicola, a typical SL-producing yeast. Detailed component analyses of S. bombicola products were carried out using reversed-phase high-performance liquid chromatography and mass spectrometry. Methanol was used as the eluent as it is a good solvent for all SL derivatives. With this approach, it was possible to not only quantify the ratio of the main components of ASL, LSL, and SL glycerides but also confirm trace components such as SL mono-glyceride and bola-form SL (sophorose at both ends); notably, this is the first time these components have been isolated and identified successfully in naturally occurring SLs. In addition, our results revealed a novel SL derivative in which a fatty acid is bonded in series to the ASL, which had not been reported previously. Using the present analysis method, it was possible to easily track compositional changes in the SL components during culture. Our results showed that LSL and ASL are produced initially and that SL glycerides accumulate from the middle stage during the fermentation process. KEY POINTS: • An easy and detailed component analysis method for sophorolipids (SLs) is introduced. • Multiple SL derivatives were identified different from known SLs. • A novel hydrophobic acidic SL was isolated and characterized.


Assuntos
Ácidos Oleicos , Saccharomycetales , Ácidos Graxos , Glicerídeos
4.
Angew Chem Int Ed Engl ; 63(8): e202318533, 2024 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-38196066

RESUMO

Photochemical regulation provides precise control over enzyme activities with high spatiotemporal resolution. A promising approach involves anchoring "photoswitches" at enzyme active sites to modulate substrate recognition. However, current methods often require genetic mutations and irreversible enzyme modifications for the site-specific anchoring of "photoswitches", potentially compromising the enzyme activities. Herein, we present a pioneering reversible nano-inhibitor based on molecular imprinting technique for bidirectional regulation of intracellular enzyme activity. The nano-inhibitor employs a molecularly imprinted polymer nanoparticle as its body and azobenzene-modified inhibitors ("photoswitches") as the arms. By using a target enzyme as the molecular template, the nano-inhibitor acquires oriented binding sites on its surface, resulting in a high affinity for the target enzyme and non-covalently firm anchoring of the azobenzene-modified inhibitor to the enzyme active site. Harnessing the reversible isomerization of azobenzene units upon exposure to ultraviolet and visible light, the nano-inhibitor achieves bidirectional enzyme activity regulation by precisely docking and undocking inhibitor at the active site. Notably, this innovative approach enables the facile in situ regulation of intracellular endogenous enzymes, such as carbonic anhydrase. Our results represent a practical and versatile tool for precise enzyme activity regulation in complex intracellular environments.


Assuntos
Luz , Impressão Molecular , Compostos Azo/farmacologia , Compostos Azo/química , Impressão Molecular/métodos , Sítios de Ligação
5.
Artigo em Inglês | MEDLINE | ID: mdl-36920984

RESUMO

A Gram-negative, aerobic bacterial strain, designated LX-88T, was isolated from seleniferous soil in Enshi, Hubei Province, PR China. Strain LX-88Toxidized elemental selenium to selenite, and produced carotenoids but not bacteriochlorophyll. The isolate grew optimally at 28 °C, pH 8.0 and with 0.5 % (w/v) NaCl. Phylogenetic analysies of the organism's 16S rRNA and bacterial core gene set sequences indicated that LX-88T belongs to the genus Croceibacterium, and has the highest degree of 16S rRNA gene sequence similarity to Croceibacterium soli MN-1T (97.4 %). The LX-88T genome was 3.4 Mbp and had a G+C content of 63.6 mol%. The average nucleotide identity and digital DNA-DNA hybridization values showed low relatedness (below 95 and 70 %, respectively) between strain LX-88T and other strains in the genus Croceibacterium. Ubiquinone-10 was the predominant quinone. The polar lipid profile was dominated by diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, sphingoglycolipid, an unidentified aminolipid, an unidentified phospholipid and an unidentified lipid. The major fatty acid was summed feature 8 (C18 : 1 ω7c and/or C18 : 1 ω6c). These physiological and biochemical tests facilitated the differentiation of strain LX-88T from other members of the genus Croceibacterium. The results of this multifaceted taxonomic study indicate that strain LX-88T represents a novel species in the genus Croceibacterium, for which the name Croceibacterium selenioxidans sp. nov. is proposed. The type strain is LX-88T (=MCCC 1K08007T=LMG 32570T).


Assuntos
Ácidos Graxos , Fosfolipídeos , Ácidos Graxos/química , Filogenia , RNA Ribossômico 16S/genética , Composição de Bases , Técnicas de Tipagem Bacteriana , DNA Bacteriano/genética , Análise de Sequência de DNA , Fosfolipídeos/química , Ubiquinona/química
6.
Analyst ; 148(7): 1399-1421, 2023 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-36752059

RESUMO

The concept of digital microfluidics (DMF) enables highly flexible and precise droplet manipulation at a picoliter scale, making DMF a promising approach to realize integrated, miniaturized "lab-on-a-chip" (LOC) systems for research and clinical purposes. Owing to its simplicity and effectiveness, electrowetting-on-dielectric (EWOD) is one of the most commonly studied and applied effects to implement DMF. However, complex biomedical assays usually require more sophisticated sample handling and detection capabilities than basic EWOD manipulation. Alternatively, combined systems integrating EWOD actuators and other fluidic handling techniques are essential for bringing DMF into practical use. In this paper, we briefly review the main approaches for the integration/combination of EWOD with other microfluidic manipulation methods or additional external fields for specified biomedical applications. The form of integration ranges from independently operating sub-systems to fully coupled hybrid actuators. The corresponding biomedical applications of these works are also summarized to illustrate the significance of these innovative combination attempts.


Assuntos
Técnicas Analíticas Microfluídicas , Microfluídica , Microfluídica/métodos , Eletroumectação/métodos , Técnicas Analíticas Microfluídicas/métodos , Dispositivos Lab-On-A-Chip
7.
Macromol Rapid Commun ; 44(23): e2300378, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37534564

RESUMO

Cerebral soluble ß-amyloid aggregates (sAßs) accumulation is one of the most important causes in Alzheimer's disease (AD) progression. In order to mitigate the neurotoxicity induced by sAßs and achieve enhanced AD therapeutic outcomes, robust sAßs clearance become an emerging task. Herein, a self-destructive nanoscavenger (SDNS) is reported based on multifunctional peptide-polymer complexes that can capture extracellular sAßs via hydrogen-bonding interactions and deliver them into microglial lysosomes. The internalized SDNS then occurs self-destruction within lysosomes and upregulates autophagy, thereby promoting the degradation of neurotoxic sAßs. Importantly, the enhanced autophagy also significantly suppresses the secretion of inflammatory factors by microglia, which is induced by internalized sAßs. Given that cerebral persistent inflammatory environment disturbs microglia-mediated phagocytosis and degradation, it is believed that this synergistic approach has valuable potential as a therapeutic strategy for AD.


Assuntos
Doença de Alzheimer , Peptídeos beta-Amiloides , Humanos , Peptídeos beta-Amiloides/metabolismo , Doença de Alzheimer/metabolismo , Fagocitose/fisiologia , Microglia/metabolismo , Lisossomos/metabolismo
8.
Molecules ; 28(3)2023 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-36770907

RESUMO

Cancer is a severe threat to human life. Recently, various therapeutic strategies, such as chemotherapy, photodynamic therapy, and combination therapy have been extensively applied in cancer treatment. However, the clinical benefits of these therapeutics still need improvement. In recent years, supramolecular chemistry based on host-guest interactions has attracted increasing attention in biomedical applications to address these issues. In this review, we present the properties of the major macrocyclic molecules and the stimulus-response strategies used for the controlled release of therapeutic agents. Finally, the applications of supramolecular-macrocycle-based nanomaterials in cancer therapy are reviewed, and the existing challenges and prospects are discussed.


Assuntos
Nanoestruturas , Neoplasias , Fotoquimioterapia , Humanos , Sistemas de Liberação de Medicamentos , Nanoestruturas/uso terapêutico , Nanoestruturas/química , Neoplasias/tratamento farmacológico
9.
Stat Med ; 41(21): 4112-4129, 2022 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-35728799

RESUMO

Transfer learning has drawn growing attention with the target of improving statistical efficiency of one study (dataset) by digging up information from similar and related auxiliary studies (datasets). In this article, we consider transfer learning problem in estimating undirected semiparametric graphical model. We propose an algorithm called Trans-Copula-CLIME for estimating an undirected graphical model while uncovering information from similar auxiliary studies, characterizing the similarity between the target graph and each auxiliary graph by the sparsity of a divergence matrix. The proposed method relaxes the restrictive Gaussian distribution assumption, which deviates from reality for the fMRI dataset related to attention deficit hyperactivity disorder (ADHD) considered here. Nonparametric rank-based correlation coefficient estimators are utilized in the Trans-Copula-CLIME procedure to achieve robustness against normality. We establish the convergence rate of the Trans-Copula-CLIME estimator under some mild conditions, which demonstrates that if the similarity between the auxiliary studies and the target study is sufficiently high and the number of informative auxiliary samples is sufficiently large, the Trans-Copula-CLIME estimator shows great advantage over the existing non-transfer-learning ones. Simulation studies also show that Trans-Copula-CLIME estimator has better performance especially when data are not from Gaussian distribution. Finally, the proposed method is applied to infer functional brain connectivity pattern for ADHD patients in the target Beijing site by leveraging the fMRI datasets from some other sites.


Assuntos
Algoritmos , Encéfalo , Encéfalo/diagnóstico por imagem , Simulação por Computador , Humanos , Aprendizado de Máquina , Distribuição Normal
10.
J Appl Toxicol ; 42(11): 1777-1786, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35665945

RESUMO

Alzheimer's disease (AD) is a neurodegenerative disease in elderly population. Pterostilbene (PTS) is a resveratrol analog with neuroprotective activity. However, the biological mechanisms of PTS in AD progression are largely uncertain. An animal model of AD was established using streptozotocin (STZ)-treated C57BL/6J mice. Monoamine oxidase B (MAOB) expression was analyzed by bioinformatics analysis and detected by western blotting assay. The memory impairment was investigated by Morris water maze test. The levels of Tau hyperphosphorylation and death-related proteins were detected by western blotting analysis. The levels of amyloid ß (Aß)1-42 accumulation, oxidative stress-related markers (ROS, MDA, SOD, and GSH), and inflammation-relative markers (TNF-α, IL-1ß, IL-6, and p-NF-κB) were measured by ELISA. MAOB expression was increased in hippocampus of AD mice, and it was decreased by PTS. PTS attenuated STZ-induced body weight loss and memory impairment by regulating MAOB. PTS mitigated Aß1-42 accumulation and Tau hyperphosphorylation by regulating MAOB in STZ-treated mice. PTS attenuated neuronal death by decreasing cleaved caspase-3 and Bax levels and increasing Bcl2 expression in hippocampus by regulating MAOB in STZ-treated mice. PTS weakened STZ-induced oxidative stress in hippocampus by decreasing ROS and MDA levels and increasing SOD and GSH levels by regulating MAOB. PTS protected against STZ-induced neuroinflammation in hippocampus by inhibiting TNF-α, IL-1ß, IL-6, and p-NF-κB levels through regulating MAOB. In conclusion, PTS alleviates STZ-induced memory impairment, Aß1-42 accumulation, Tau hyperphosphorylation, neuronal death, oxidative stress, and inflammation by decreasing MAOB in AD mice, proving anti-AD potential of PTS.


Assuntos
Doença de Alzheimer , Doenças Neurodegenerativas , Idoso , Doença de Alzheimer/induzido quimicamente , Doença de Alzheimer/tratamento farmacológico , Peptídeos beta-Amiloides/metabolismo , Peptídeos beta-Amiloides/farmacologia , Animais , Caspase 3 , Modelos Animais de Doenças , Humanos , Inflamação , Interleucina-6 , Camundongos , Camundongos Endogâmicos C57BL , Monoaminoxidase , NF-kappa B/metabolismo , Espécies Reativas de Oxigênio , Resveratrol , Estilbenos , Estreptozocina/toxicidade , Superóxido Dismutase , Fator de Necrose Tumoral alfa/metabolismo , Proteína X Associada a bcl-2
11.
Molecules ; 27(6)2022 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-35335160

RESUMO

Colchicine (COL) is a well-known plant alkaloid long used for medical purposes due to the selective anti-inflammatory effect on acute gouty arthritis. It is also a kind of mitosis toxin with strong inhibitory effects of cell division and is therefore being applied to the treatment of various cancers. However, this product shows a variety of adverse effects that are significantly correlated with the dosage and have attracted much attention. For the first time, the present work obtained a new insight into the gastrointestinal toxicity of colchicine analogues by molecular docking analysis, which was based on the 3D structure of intestinal tight junction protein ZO-1 and the ligand library containing dozens of small-molecule compounds with the basic skeleton of COL and its metabolites. The binding energy and mode of protein-ligand interaction were investigated to better understand the structure-toxicity relationships of COL analogues and the mechanism of action as well. Cluster analysis clearly demonstrated the strong correlation between the binding energy and toxicity of ligand molecules. The interaction mode further revealed that the hydrogen bonding (via the C-7 amide or C-9 carbonyl group) and hydrophobic effect (at ring A or C) were both responsible for ZO-1-related gastrointestinal toxicity of COL analogues, while metabolic transformation via phase I and/or phase II reaction would significantly attenuate the gastrointestinal toxicity of colchicine, indicating an effective detoxication pathway through metabolism.


Assuntos
Colchicina , Intestinos , Colchicina/química , Ligantes , Simulação de Acoplamento Molecular , Proteína da Zônula de Oclusão-1
12.
Angew Chem Int Ed Engl ; 61(30): e202116073, 2022 07 25.
Artigo em Inglês | MEDLINE | ID: mdl-35415965

RESUMO

Photochemical regulation provides a promising approach for controlling enzyme activity on demand owing to its high spatiotemporal resolution. However, reversible regulation of the enzyme activity by light usually requires genetic mutations and covalent modifications of the target enzymes, which may lead to irreversible changes in the enzyme structure and subsequent loss of the enzymatic activity. Herein, we have developed a novel strategy based on a polymeric inhibitor-encapsulated enzyme, which noncovalently anchors the azobenzene-modified inhibitors to the enzyme active site, thereby achieving reversible control of the activity of native enzymes using light. As neither genetic mutation nor chemical modification of enzymes is required for this method, negligible loss of the enzymatic activity was observed for the encapsulated enzymes compared to their native counterparts. Thus, this approach has demonstrated a promising strategy for achieving reversible regulation of the activity of native enzymes.

13.
J Exp Biol ; 223(Pt 14)2020 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-32457065

RESUMO

Maximum whole-body force production can influence behavioral outcomes for volant taxa, and may also be relevant to aerodynamic optimization in microair vehicles. Here, we describe a new method for measuring maximum force production in free-flying animals, and present associated data for the wandering glider dragonfly. Flight trajectories were repeatedly acquired from pull-up responses by insects dropped in mid-air with submaximal loads attached beneath the center of body mass. Forces were estimated from calculations of the maximum time-averaged acceleration through time, and multiple estimates were obtained per individual so as to statistically facilitate approximation of maximum capacity through use of the Weibull distribution. On a group level, wandering glider dragonflies were here estimated to be capable of producing total aerodynamic force equal to ∼4.3 times their own body weight, a value which significantly exceeds earlier estimates made for load-lifting dragonflies, and also for other volant taxa in sustained vertical load-lifting experiments. Maximum force production varied isometrically with body mass. Falling and recovery flight with submaximal load represents a new context for evaluating limits to force production by flying animals.


Assuntos
Voo Animal , Odonatos , Animais , Fenômenos Biomecânicos , Insetos , Asas de Animais
14.
Acta Pharmacol Sin ; 41(1): 93-100, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31285534

RESUMO

PARK2, which encodes Parkin, is a disease-causing gene for both neurodegenerative disorders and cancer. Parkin can function as a neuroprotector that plays a crucial role in the regulation of mitophagy, and germline mutations in PARK2 are associated with Parkinson's disease (PD). Intriguingly, recent studies suggest that Parkin can also function as a tumor suppressor and that somatic and germline mutations in PARK2 are associated with various human cancers, including lung cancer. However, it is presently unknown how the tumor suppressor activity of Parkin is affected by these mutations and whether it is associated with mitophagy. Herein, we show that wild-type (WT) Parkin can rapidly translocate onto mitochondria following mitochondrial damage and that Parkin promotes mitophagic clearance of mitochondria in lung cancer cells. However, lung cancer-linked mutations inhibit the mitochondrial translocation and ubiquitin-associated activity of Parkin. Among all lung cancer-linked mutants that we tested, A46T Parkin failed to translocate onto mitochondria and could not recruit downstream mitophagic regulators, including optineurin (OPTN) and TFEB, whereas N254S and R275W Parkin displayed slower mitochondrial translocation than WT Parkin. Moreover, we found that deferiprone (DFP), an iron chelator that can induce mitophagy, greatly increased the death of A46T Parkin-expressing lung cancer cells. Taken together, our results reveal a novel mitophagic mechanism in lung cancer, suggesting that lung cancer-linked mutations in PARK2 are associated with impaired mitophagy and identifying DFP as a novel therapeutic agent for PARK2-linked lung cancer and possibly other types of cancers driven by mitophagic dysregulation.


Assuntos
Genes Supressores de Tumor , Mutação em Linhagem Germinativa/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Mitofagia/genética , Proteínas Quinases/metabolismo , Ubiquitina-Proteína Ligases/genética , Células A549 , Morte Celular/efeitos dos fármacos , Deferiprona/farmacologia , Humanos , Quelantes de Ferro/farmacologia , Neoplasias Pulmonares/metabolismo , Mitofagia/efeitos dos fármacos , Células Tumorais Cultivadas , Ubiquitina-Proteína Ligases/metabolismo
15.
J Cell Biochem ; 120(5): 7015-7023, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30368886

RESUMO

Bupivacain, a common local anesthetic, can cause neurotoxicity and permanent neurological disorders. Paeoniflorin has been widely reported as a potential neuroprotective agent in neural injury models. However, the roles and molecular basis of paeoniflorin in bupivacaine-induced neurotoxicity are still undefined. In the current study, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was performed to detect cell viability. Apoptotic rate was measured through double-staining of Annexin V-FITC and propidium iodide on a flow cytometer. Western blot assay was carried out to examine the protein levels of p38 mitogen-activated protein kinase (p38 MAPK), phosphorylated-p38 MAPK (p-p38 MAPK), Bcl-2, and Bax. caspase-3 activity was determined using a caspase-3 activity assay kit. We found that paeoniflorin dose-dependently attenuated bupivacaine-induced viability inhibition and apoptosis in SH-SY5Y cells. Moreover, paeoniflorin inhibited bupivacaine-induced activation of p38 MAPK pathway in SH-SY5Y cells. Paeoniflorin alone showed no significant effect on cell viability, apoptosis and p38 MAPK signaling in SH-SY5Y cells. Inhibition of p38 MAPK signaling by SB203580 or small interfering RNA targeting p38 (si-p38) abated bupivacaine-induced viability inhibition and apoptosis in SH-SY5Y cells. In conclusion, paeoniflorin alleviated bupivacaine-induced neurotoxicity in SH-SY5Y cells via suppression of the p38 MAPK pathway, highlighting the potential values of paeoniflorin in relieving bupivacaine-induced neurotoxicity.

16.
Lasers Med Sci ; 34(3): 607-614, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30218348

RESUMO

Photobiomodulation therapy (PBMT) has been demonstrated as regulating osteoblast proliferation. MicroRNAs (miRNAs) are involved in various pathophysiologic processes in osteoblast, but the role of miRNAs in the PBMT-based promotion of osteoblast proliferation remains unclear. This study aimed to investigate the effects of PBMT treatment (3.75 J/cm2) on mouse pre-osteoblast cell line MC3T3-E1 proliferation and apoptosis via the miR-503/Wnt3a pathway; meanwhile, detect the expressions of miR-503 and Wnt3a after PBMT treatment and the role of miR-503 in regulating Wnt signaling molecules Wnt3a, ß-catenin, Runx2, apoptotic proteins caspase-3, and Bcl-2 in vitro. The PBMT parameters were as follows: 808 nm continuous wavelength, 0.401 W output power, 0.042 W/cm2 power density, 9.6 cm2 spot size, 36 J energy, 3.75 J/cm2 energy density, 90 s irradiation for three times per 12 h, 14.5 cm distance of the laser source and the angle of divergence of the laser beam was 7°. In our present study, the target relationship was predicted and verified by bioinformatics analysis and luciferase reporter assays. Gene mRNA and protein expressions were examined by qPCR and western blot analysis. The MTT method was used to evaluate the effect of miR-503 on MC3T3-E1 cells proliferation. And cell apoptosis was examined by flow cytometry. The results showed that PBMT treatment reduced the expression of miR-503 and increased the level of Wnt3a (p < 0.01). Bioinformatics analysis and luciferase reporter assays revealed that Wnt3a was a target of miR-503, and Wnt3a was regulated by miR-503. Furthermore, miR-503 was found to functionally inhibit proliferation and promote apoptosis (p < 0.01). And during this process, Wnt3a, ß-catenin, Runx2, and Bcl-2 expressions were significantly inhibited (p < 0.01); however, caspase-3 level was upregulated (p < 0.01). These results suggest that miR-503 plays a role in osteoblast proliferation and apoptosis in response to PBMT, which is potentially amenable to therapeutic manipulation for clinical application.


Assuntos
Apoptose/efeitos da radiação , Terapia com Luz de Baixa Intensidade , MicroRNAs/metabolismo , Osteoblastos/citologia , Osteoblastos/efeitos da radiação , Transdução de Sinais , Proteína Wnt3/metabolismo , Animais , Apoptose/genética , Sequência de Bases , Linhagem Celular , Proliferação de Células/genética , Proliferação de Células/efeitos da radiação , Regulação para Baixo/genética , Regulação para Baixo/efeitos da radiação , Camundongos , MicroRNAs/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Regulação para Cima/genética , Regulação para Cima/efeitos da radiação , Proteína Wnt3/genética
17.
Sensors (Basel) ; 19(11)2019 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-31174379

RESUMO

Fused filament fabrication (FFF) is one of the most widely used additive manufacturing (AM) technologies and it has great potential in fabricating prototypes with complex geometry. For high quality manufacturing, monitoring the products in real time is as important as maintaining the FFF machine in the normal state. This paper introduces an approach that is based on the vibration sensors and data-driven methods for in-situ monitoring and diagnosing the FFF process. The least squares support vector machine (LS-SVM) algorithm has been applied for identifying the normal and filament jam states of the FFF machine, besides fault diagnosis in real time. The identification accuracy for the case studies explored here using LS-SVM is greater than 90%. Furthermore, to ensure the product quality during the FFF process, the back-propagation neural network (BPNN) algorithm has been used to monitor and diagnose the quality defects, as well as the warpage and material stack caused by abnormal leakage for the products in-situ. The diagnosis accuracy for the case studies explored here using BPNN is greater than 95%. Results from the experiments show that the proposed approach can accurately recognize the machine failures and quality defects during the FFF process, thus effectively assuring the product quality.

18.
Zhongguo Zhong Yao Za Zhi ; 44(20): 4309-4316, 2019 Oct.
Artigo em Zh | MEDLINE | ID: mdl-31872614

RESUMO

At present,China manages cannabis into industrial and medical types. Industrial cannabis( THC<0. 3%) is grown for fiber and seed,while medical cannabis( THC>0. 3%) is prohibited from being planted and used. In recent years,breakthroughs have been made in the applications for a variety of fields of CBD,a non-psychoactive cannabinoid of Cannabis. However,China made a minimal contribution to this international research hotspot,mainly due to the outdated way of classification on cannabis. Here we reviewed the medicinal use history of cannabis,achievements in the study of Cannabis germplasm,and first proposed the three-level classification of management: psychoactive medicinal cannabis( THC>0. 3%),non-psychoactive medicinal cannabis( THC<0. 3%,high CBD)and industrial cannabis( THC<0. 3%,for fiber and seed,low CBD). Based on summarizing the research progress of the non-psychoactive medicinal cannabis,four key research strategies of breeding,sex control,plant factory,and synthetic biology are proposed.


Assuntos
Cannabis , Maconha Medicinal , Analgésicos , China , Dronabinol , Projetos de Pesquisa
19.
J Cell Biochem ; 119(8): 7053-7062, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29737568

RESUMO

Neuroinflammation has been known as an important pathogenetic contributor of Alzheimer's disease (AD). Pterostilbene is a natural compound which has neuroprotective activity. However, the effect of pterostilbene on amyloid-ß (Aß)-induced neuroinflammation has not been clarified. The aim of the present study was to investigate the effect of pterostilbene on Aß-induced neuroinflammation in microglia. The results indicated that pterostilbene attenuated Aß1-42 -induced cytotoxicity of BV-2 cells. Aß1-42 induced NO production and iNOS mRNA and protein expression, while pterostilbene inhibited the induction. The expression and secretion levels of IL-6, IL-1ß, and TNF-α were enhanced by Aß1-42 treatment, whereas pterostilbene decreased them. Aß1-42 activated NLRP3/caspase-1 inflammasome, which was inactivated by pterostilbene. In addition, the inhibitor of caspase-1 Z-YVAD-FMK attenuated the Aß1-42 -induced neuroinflammation in BV-2 cells. In conclusion, pterostilbene attenuated the neuroinflammatory response induced by Aß1-42 in microglia through inhibiting the NLRP3/caspase-1 inflammasome pathway, indicating that pterostilbene might be an effective therapy for AD.


Assuntos
Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Caspase 1/metabolismo , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Fragmentos de Peptídeos/metabolismo , Estilbenos/farmacologia , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/genética , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/genética , Animais , Caspase 1/genética , Inibidores de Caspase/farmacologia , Linhagem Celular Transformada , Inflamassomos/genética , Inflamação/genética , Inflamação/metabolismo , Inflamação/patologia , Camundongos , Microglia , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Fragmentos de Peptídeos/genética , Tosilfenilalanil Clorometil Cetona/análogos & derivados , Tosilfenilalanil Clorometil Cetona/farmacologia
20.
Med Sci Monit ; 24: 7595-7602, 2018 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-30356032

RESUMO

BACKGROUND The purpose of this study was to analyze tear inflammatory cytokines of different subclasses of dry eye disease (DED) patients using Luminex technology. MATERIAL AND METHODS Forty-five DED patients including 20 Sjogren syndrome aqueous tear deficiency (SS-ATD) patients, 20 non-Sjogren syndrome aqueous tear deficiency (NSS-ATD) patients, 15 meibomian gland dysfunction (MGD) patients, and 15 normal participants were enrolled in this study. Concentrations of 11 inflammatory cytokines in tear samples of study participants were measured by Luminex assay; ELISA assay was further applied for validation. RESULTS The levels of cytokines were mostly increased (TNF-α, IL-1α, IL-1ß, IL-6, IL-8, IL-12 P70, IL-13, IFN-γ, and MIP-1α) in DED patients compared with normal participants. And the levels of TNF-α, IL-6, IL-8, and IL-12P70 were significantly elevated in tears of the patient groups compared to tears of participants in the normal group (P<0.05). Statistical differences were also observed among the patient groups (SS-ATD, NSS-ATD, and MGD) for the level of IL-8 and TNF-α. The results of ELISA assay demonstrated the consistence with Luminex assay, confirming the practicality of Luminex technology for the analysis of multiple cytokines in DED patient tears. CONCLUSIONS The levels of inflammatory cytokines were mostly elevated in DED patients, and statistical differences of some cytokines were also found between SS-ATD, NSS-ATD, and MGD groups, suggesting that inflammatory cytokines could be potential supplements for the diagnosis of DED subclasses and therapeutic targets for DED patients.


Assuntos
Síndromes do Olho Seco/metabolismo , Lágrimas/química , Adulto , Biomarcadores/metabolismo , Citocinas/análise , Citocinas/metabolismo , Feminino , Humanos , Interferon gama/metabolismo , Interleucinas/metabolismo , Aparelho Lacrimal/fisiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Lágrimas/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
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