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1.
J Comput Aided Mol Des ; 37(7): 325-338, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37269435

RESUMEN

FGFR3 kinase mutations are associated with a variety of malignancies, but FGFR3 mutant inhibitors have rarely been studied. Furthermore, the mechanism of pan-FGFR inhibitors resistance caused by kinase domain mutations is still unclear. In this study, we try to explain the mechanism of drug resistance to FGFR3 mutation through global analysis and local analysis based on molecular dynamics simulation, binding free energy analysis, umbrella sampling and community network analysis. The results showed that FGFR3 mutations caused a decrease in the affinity between drugs and FGFR3 kinase, which was consistent with the reported experimental results. Possible mechanisms are that mutations affect drug-protein affinity by altering the environment of residues near the hinge region where the protein binds to the drug, or by affecting the A-loop and interfering with the allosteric communication networks. In conclusion, we systematically elucidated the underlying mechanism of pan-FGFR inhibitor resistance caused by FGFR3 mutation based on molecular dynamics simulation strategy, which provided theoretical guidance for the development of FGFR3 mutant kinase inhibitors.


Asunto(s)
Resistencia a Antineoplásicos , Neoplasias , Mutación Puntual , Receptor Tipo 3 de Factor de Crecimiento de Fibroblastos , Humanos , Redes Comunitarias , Simulación de Dinámica Molecular , Mutación , Inhibidores de Proteínas Quinasas/farmacología , Receptor Tipo 3 de Factor de Crecimiento de Fibroblastos/genética , Resistencia a Antineoplásicos/genética
2.
Nanotechnology ; 35(3)2023 Oct 30.
Artículo en Inglés | MEDLINE | ID: mdl-37905427

RESUMEN

Aim. The potential of olfactory ensheathing cells (OECs) as a cell therapy for spinal cord reconstruction and regeneration after injury has drawn significant attention in recent years. This study attempted to investigate the influences of nano-fibrous scaffolds on the growth status and functional properties of OECs.Methods.The ultra-morphology of the scaffolds was visualized using scanning electron microscopy (SEM). To culture OECs, donated cells were subcultured and identified with p75. Cell proliferation, apoptosis, and survival rates were measured through MTT assay, Annexin-V/PI staining, and p75 cell counting, respectively. The adhesion of cells cultured on scaffolds was observed using SEM. Additionally, the functions of OECs cultured on scaffolds were assessed by testing gene expression levels through real time polymerase chain reaction.Results.The electrospun type I collagen-based nano-fibers exhibited a smooth surface and uniform distribution. It was indicated that the proliferation and survival rates of OECs cultured on both randomly oriented and aligned type I collagen-based nano-fibrous scaffolds were higher than those observed in the collagen-coated control. Conversely, apoptosis rates were lower in cells cultured on scaffolds. Furthermore, OEC adhesion was better on the scaffolds than on the control. The expression levels of target genes were significantly elevated in cells cultured on scaffolds versus the controls.Conclusion.As a whole, the utilization of aligned collagen nanofibers has demonstrated significant advantages in promoting cell growth and improving cell function. These findings have important implications for the field of regenerative medicine and suggest that the approach may hold promise for the future therapeutic applications.


Asunto(s)
Nanofibras , Andamios del Tejido , Colágeno Tipo I/genética , Células Cultivadas , Colágeno
3.
Bioorg Chem ; 136: 106543, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37119784

RESUMEN

Curcumin is identified that it has the potential to treat Parkinson's disease (PD), but its instability limits its further application in clinic. The mono-carbonyl analogs of curcumin (MACs) with diketene structure can effectively improve its stability, but it is highly toxic. In the present study, a less cytotoxic and more stable monoketene MACs skeleton S2 was obtained, and a series of monoketene MACs were synthesized by combining 4-hydroxy-3­methoxy groups of curcumin. In the 6-OHDA-induced PD's model in-vitro, some compounds exhibited significant neurotherapeutic effect. The quantitative structure-activity relationship (QSAR) model established by the random forest algorithm (RF) for the cell viability rate of above compounds showed that the statistical results are good (R2 = 0.883507), with strong reliability. Among all compounds, the most active compound A4 played an important role in neuroprotection in the PD models both in vitro and in vivo by activating AKT pathway, and then inhibiting the apoptosis of cells caused by endoplasmic reticulum (ER) stress. In the PD model in-vivo, compound A4 significantly improved survival of dopaminergic neurons and the contents of neurotransmitters. It also enhanced the retention of nigrostriatal function which was better than the effect in the mice treated by Madopar, a classical clinical drug for PD. In summary, we screened out the compound A4 with high stability, less cytotoxic monoketene compounds. And these founding provide evidence that the compound A4 can protect dopaminergic neurons via activating AKT and subsequently suppressing ER stress in PD.


Asunto(s)
Curcumina , Fármacos Neuroprotectores , Enfermedad de Parkinson , Animales , Ratones , Apoptosis , Curcumina/farmacología , Curcumina/uso terapéutico , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Enfermedad de Parkinson/tratamiento farmacológico , Enfermedad de Parkinson/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Reproducibilidad de los Resultados
4.
J Enzyme Inhib Med Chem ; 37(1): 2357-2369, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36039017

RESUMEN

Curcumin is a natural medicine with a wide range of anti-tumour activities. However, due to ß-diketone moiety, curcumin exhibits poor stability and pharmacokinetics which significantly limits its clinical applications. In this article, two types of dicarbonyl curcumin analogues with improved stability were designed through the calculation of molecular stability by density functional theory. Twenty compounds were synthesised, and their anti-tumour activity was screened. A plurality of analogues had significantly stronger activity than curcumin. In particular, compound B2 ((2E,2'E)-3,3'-(1,4-phenylene)bis(1-(2-chlorophenyl)prop-2-en-1-one)) exhibited excellent anti-lung cancer activity in vivo and in vitro. In addition, B2 could upregulate the level of reactive oxygen species in lung cancer cells, which in turn activated the endoplasmic reticulum stress and led to cell apoptosis and pyroptosis. Taken together, curcumin analogue B2 is expected to be a novel candidate for lung cancer treatment with improved chemical and biological characteristics.


Asunto(s)
Antineoplásicos , Curcumina , Neoplasias Pulmonares , Antineoplásicos/química , Apoptosis , Línea Celular Tumoral , Proliferación Celular , Diarilheptanoides/farmacología , Humanos , Neoplasias Pulmonares/patología , Piroptosis , Especies Reactivas de Oxígeno/metabolismo
5.
J Sci Food Agric ; 102(11): 4759-4769, 2022 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-35218222

RESUMEN

BACKGROUND: Phytosterols are considered to be one of the most promising gelators for obtaining oleogel because of their additional health benefits and natural coexist with vegetable oils. Previous studies have confirmed that individual phytosterols are not capable of structuring vegetable oils unless they act synergistically with other components. However, based on the self-assembly properties of stigmasterol (ST) in organic solvents, we speculate that it can also structure vegetable oils as a gelator alone. RESULTS: For the first time, the present study confirmed the feasibility of using ST alone as a gelator for structuring of vegetable oils, including rapeseed oil (RSO), olive oil (OLO) and flaxseed oil (FSO). RSO had the lowest ST gelation concentration (4%, w/w), and the oil-binding capacity and firmness value of the oleogels were the highest. The rheological results showed that all the samples were gelatinous (G' > G″). The results of differential scanning calorimeter and X-ray diffraction further confirmed that the properties of RSO-based oleogels are superior to those prepared by OLO and FSO. The microscopic results also confirmed that the crystal structure of RSO oleogels was more uniform, smaller and more densely distributed. CONCLUSION: The structural properties of the oleogels were positively correlated with the ST concentration, and various analysis indicators showed that the performance of the oleogel based on RSO was better than that of OLO and FSO. In summary, the present study used ST as a gelator to successfully prepare oleogels with excellent properties, which provides a feasible reference for researchers in related fields. © 2022 Society of Chemical Industry.


Asunto(s)
Fitosteroles , Estigmasterol , Compuestos Orgánicos/química , Aceites de Plantas/química
6.
Microb Pathog ; 152: 104650, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33232766

RESUMEN

To provide detail data for Campylobacter jejuni (C.jejuni) vaccine research, this study performed epitope prediction analysis technology to screen the B cell immunodominant epitopes of C. jejuni adhesion protein PEB1 and evaluated the immunoprotective effect. The overlapping peptides were synthesized and B-cell immunodominant epitopes of PEB1 were identified by ELISA. BALB/c mice were immunized with the immunodominant epitopes of PEB1 conjugated with KLH plus CFA/IFA. The titers for immunodominant peptide antiserum against PEB1 were detected by ELISA. The bacterial colonization and the relative expression level of TNF-α were analyzed after the mice challenged with C. jejuni 11,168. The function of antibody induced by immunodominant PEB1 epitopes were performed by opsonophagocytic killing. The results showed that PEB155-72aa, PEB197-114aa, PEB1211-228aa were the immunodominant peptides and could induce strong B cell mediated humoral immunity response. Antiserum from the immunodominant peptides group significantly enhanced opsonize phagocytosis than CFA/IFA group (P<0.01). Both the bacterial burdens and the TNF-α expression level in the immunodominant peptides groups were significantly lower than those in the control group (P<0.01). Moreover, the immune protective effect of the three immunodominant peptides depended on the B cell immunity response in vivo study. In conclusion, three specific B cell immunodominant epitopes with good immunogenicity and immunoprotection efficacy were successfully identified, indicating that could be used in the anti- C. jejuni vaccine research and development.


Asunto(s)
Campylobacter jejuni , Animales , Linfocitos B , Epítopos de Linfocito B , Epítopos Inmunodominantes , Ratones , Ratones Endogámicos BALB C
7.
Clin Sci (Lond) ; 135(22): 2541-2558, 2021 11 26.
Artículo en Inglés | MEDLINE | ID: mdl-34730176

RESUMEN

OBJECTIVE: Regulated in development and DNA damage responses-1 (REDD1) is a conserved and ubiquitous protein, which is induced in response to multiple stimuli. However, the regulation, function and clinical relevance of REDD1 in Helicobacter pylori-associated gastritis are presently unknown. APPROACH: Immunohistochemistry, real-time PCR and Western blot analyses were performed to examine the levels of REDD1 in gastric samples from H. pylori-infected patients and mice. Gastric tissues from Redd1-/- and wildtype (WT, control) mice were examined for inflammation. Gastric epithelial cells (GECs), monocytes and T cells were isolated, stimulated and/or cultured for REDD1 regulation and functional assays. RESULTS: REDD1 was increased in gastric mucosa of H. pylori-infected patients and mice. H. pylori induced GECs to express REDD1 via the phosphorylated cytotoxin associated gene A (cagA) that activated MAPKp38 pathway to mediate NF-κB directly binding to REDD1 promoter. Human gastric REDD1 increased with the severity of gastritis, and mouse REDD1 from non-marrow chimera-derived cells promoted gastric inflammation that was characterized by the influx of MHCII+ monocytes. Importantly, gastric inflammation, MHCII+ monocyte infiltration, IL-23 and IL-17A were attenuated in Redd1-/- mice. Mechanistically, REDD1 in GECs regulated CXCL1 production, which attracted MHCII+ monocytes migration by CXCL1-CXCR2 axis. Then H. pylori induced MHCII+ monocytes to secrete IL-23, which favored IL-17A-producing CD4+ cell (Th17 cell) polarization, thereby contributing to the development of H. pylori-associated gastritis. CONCLUSIONS: The present study identifies a novel regulatory network involving REDD1, which collectively exert a pro-inflammatory effect within gastric microenvironment. Efforts to inhibit this REDD1-dependent pathway may prove valuable strategies in treating of H. pylori-associated gastritis.


Asunto(s)
Citocinas/metabolismo , Mucosa Gástrica/microbiología , Gastritis/microbiología , Infecciones por Helicobacter/microbiología , Helicobacter pylori/patogenicidad , Células Th17/microbiología , Factores de Transcripción/metabolismo , Animales , Antígenos Bacterianos/metabolismo , Proteínas Bacterianas/metabolismo , Estudios de Casos y Controles , Células Cultivadas , Técnicas de Cocultivo , Modelos Animales de Enfermedad , Mucosa Gástrica/inmunología , Mucosa Gástrica/metabolismo , Gastritis/inmunología , Gastritis/metabolismo , Infecciones por Helicobacter/complicaciones , Helicobacter pylori/inmunología , Helicobacter pylori/metabolismo , Interacciones Huésped-Patógeno , Humanos , Ratones Endogámicos C57BL , Ratones Noqueados , FN-kappa B/metabolismo , Fenotipo , Fosforilación , Células Th17/inmunología , Células Th17/metabolismo , Factores de Transcripción/genética , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo
8.
FASEB J ; 34(1): 1169-1181, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31914631

RESUMEN

BHLHE40, a member of the basic helix-loop-helix transcription factor family, has been reported to play an important role in inflammatory diseases. However, the regulation and function of BHLHE40 in Helicobacter pylori (H pylori)-associated gastritis is unknown. We observed that gastric BHLHE40 was significantly elevated in patients and mice with H pylori infection. Then, we demonstrate that H pylori-infected GECs express BHLHE40 via cagA-ERK pathway. BHLHE40 translocates to cell nucleus, and then binds to cagA protein-activated p-STAT3 (Tyr705). The complex increases chemotactic factor CXCL12 expression (production). Release of CXCL12 from GECs fosters CD4+ T cell infiltration in the gastric mucosa. Our results identify the cagA-BHLHE40-CXCL12 axis that contributes to inflammatory response in gastric mucosa during H pylori infection.


Asunto(s)
Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Quimiocina CXCL12/metabolismo , Células Epiteliales/metabolismo , Gastritis/microbiología , Infecciones por Helicobacter/metabolismo , Proteínas de Homeodominio/metabolismo , Factor de Transcripción STAT3/metabolismo , Animales , Linfocitos T CD4-Positivos/citología , Núcleo Celular/metabolismo , Femenino , Mucosa Gástrica/metabolismo , Mucosa Gástrica/microbiología , Gastritis/metabolismo , Regulación de la Expresión Génica , Helicobacter pylori , Humanos , Inflamación , Ratones , Ratones Endogámicos C57BL , Estómago/microbiología , Regulación hacia Arriba
9.
Bioorg Chem ; 114: 105080, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-34225164

RESUMEN

Antioxidants with high efficacy and low toxicity have the potential to treat cerebral ischemia reperfusion injury (CIRI). Dienone monocarbonyl curcumin analogs (DMCA) capable of overcoming the instability and pharmacokinetic defects of curcumin possess notable antioxidant activity but are found to be significantly toxic. In this study, a novel skeleton of the monoenone monocarbonyl curcumin analogue sAc possessing reduced toxicity and improved stability was designed on the basis of the DMCA skeleton. Moreover, 32 sAc analogs were obtained by applying a green, simple, and economical synthetic method. Multiple sAc analogs with an antioxidant protective effect in PC12 cells were screened using an H2O2-induced oxidative stress damage model, and quantitative evaluation of structure-activity relationship (QSAR) model with regression coefficient of R2 = 0.918921 was built through random forest algorithm (RF). Among these compounds, the optimally active compound sAc15 elicited a potent protective effect on cell growth of PC12 cells by effectively eliminating ROS generation in response to oxidative stress injury by activating the Nrf2/HO-1 antioxidant signaling pathway. In addition, sAc15 exhibited good protection against CIRI in the mice middle cerebral artery occlusion (MCAO) model. In this paper, we provide a novel class of antioxidants and a potential compound for stroke treatment.


Asunto(s)
Antioxidantes/farmacología , Curcumina/farmacología , Tecnología Química Verde , Infarto de la Arteria Cerebral Media/tratamiento farmacológico , Sustancias Protectoras/farmacología , Daño por Reperfusión/tratamiento farmacológico , Animales , Antioxidantes/síntesis química , Antioxidantes/química , Células Cultivadas , Curcumina/análogos & derivados , Curcumina/química , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Diseño de Fármacos , Evaluación Preclínica de Medicamentos , Infarto de la Arteria Cerebral Media/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Estructura Molecular , Estrés Oxidativo/efectos de los fármacos , Células PC12 , Sustancias Protectoras/síntesis química , Sustancias Protectoras/química , Ratas , Daño por Reperfusión/patología , Relación Estructura-Actividad
10.
J Am Chem Soc ; 142(6): 3165-3173, 2020 02 12.
Artículo en Inglés | MEDLINE | ID: mdl-31944691

RESUMEN

The rational design of wholly synthetic receptors that bind active substrates with ultrahigh affinities is a challenging goal, especially in water. Here, we report the synthesis of a tricyclic octacationic cyclophane, which exhibits complementary stereoelectronic binding toward a widely used fluorescent dye, perylene diimide, with picomolar affinity in water. The ultrahigh binding affinity is sustained by a large and rigid hydrophobic binding surface, which provides a highly favorable enthalpy and a slightly positive entropy of complexation. The receptor-substrate complex shows significant improvement in optical properties, including red-shifted absorption and emission, turn-on fluorescence, and efficient energy transfer. An unusual single-excitation, dual-emission, imaging study of living cells was performed by taking advantage of a large pseudo-Stokes shift, produced by the efficient energy transfer.


Asunto(s)
Colorantes Fluorescentes/química , Imidas/química , Perileno/análogos & derivados , Cationes , Entropía , Transferencia Resonante de Energía de Fluorescencia , Perileno/química , Especificidad por Sustrato , Agua/química
11.
J Pharmacol Sci ; 143(1): 45-51, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-32169433

RESUMEN

The leaves of Lindera aggregate (Sims) Kosterm. are traditionally used as healthy tea for the prevention and treatment of hyperlipidemia in Chinese. The aim of this study was to evaluate the antihyperlipidemic effects and potential mechanisms of the aqueous extracts from L. aggregate leaves (AqLA-L) on normal and hypercholesterolemic (HCL) mice. HCL mice were induced by high fat diet (HFD) and orally administrated with or without AqLA-L for ten days. The results showed that AqLA-L (0.3, 0.6, 1.2 g/kg) significantly reduced serum TG, ALT, but elevated fecal TG in normal mice. AqLA-L (0.3, 0.6, 1.2 g/kg) also remarkably lowered serum TC, TG, LDL, N-HDL, ALT, GLU, APOB, hepatic GLU and increased serum HDL, APOA-I, fecal TG levels in HCL mice. These results revealed that AqLA-L treatment regulated the disorders of the serum lipid and liver function, reduced hepatic GLU contents both in normal and HCL mice. The potential mechanisms for cholesterol-lowering effects of AqLA-L might be up-regulation of cholesterol 7-alpha-hydroxylase (CYP7A1) and ATP-binding cassette transporter A1 (ABCA1), as well as down-regulation of 3-hydroxy-3-methylglutaryl CoA reductase (HMGCR). The data indicated that AqLA-L has potential therapeutic value in treatment of hyperlipidemia with great application security.


Asunto(s)
Hipercolesterolemia/sangre , Hipercolesterolemia/metabolismo , Lindera/química , Metabolismo de los Lípidos/efectos de los fármacos , Lípidos/sangre , Extractos Vegetales/farmacología , Hojas de la Planta/química , Transportador 1 de Casete de Unión a ATP/metabolismo , Administración Oral , Animales , Colesterol 7-alfa-Hidroxilasa/metabolismo , Hidroximetilglutaril-CoA Reductasas/metabolismo , Hipercolesterolemia/tratamiento farmacológico , Hipercolesterolemia/fisiopatología , Hígado/fisiopatología , Masculino , Ratones Endogámicos ICR , Fitoterapia , Extractos Vegetales/administración & dosificación , Regulación hacia Arriba/efectos de los fármacos , Agua
12.
J Cell Physiol ; 234(3): 2491-2499, 2019 03.
Artículo en Inglés | MEDLINE | ID: mdl-30317552

RESUMEN

Human mesenchymal stem cells (hMSCs) are fibroblastoid multipotent adult stem cells with capacities of differentiation into osteoblasts and chondrocytes and show great potential in new bone formation and bone repair-related clinical settings, such as osteoporosis. Long noncoding RNAs (lncRNAs) have been demonstrated to play important roles in various biological processes. Here, we report an antisense lncRNA SEMA3B-AS1 regulating hMSCs osteogenesis. SEMA3B-AS1 is proximal to a member of the semaphorin family Sema3b. Overexpression of SEMA3B-AS1 using the lentivirus system markedly inhibits the proliferation of hMSCs and meanwhile reduces osteogenic differentiation. Using a comprehensive proteomic technique named isobaric tag for relative and absolute quantitation, we found that SEMA3B-AS1 significantly alters the process of osteogenesis through downregulating the expression of proteins involved in actin cytoskeleton, focal adhesion, and extracellular matrix-receptor interaction, while increasing the expression of proteins in the spliceosome. Collectively, we find that SEMA3B-AS1 is a target for controlling osteogenesis of hMSCs.


Asunto(s)
Glicoproteínas de Membrana/genética , Células Madre Mesenquimatosas/metabolismo , Osteogénesis/genética , ARN Largo no Codificante/genética , Semaforinas/genética , Diferenciación Celular/genética , Condrocitos/citología , Condrocitos/metabolismo , Humanos , Glicoproteínas de Membrana/antagonistas & inhibidores , Proteómica , Semaforinas/antagonistas & inhibidores , Transducción de Señal/genética
13.
J Cell Physiol ; 234(9): 15698-15707, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-30710368

RESUMEN

Heat shock proteins (HSPs) are crucial proteins in maintaining the homeostasis of human gastric epithelial cells. Tumor necrosis factor receptor-associated protein 1 (TRAP1), a member of the HSP90 family, has been shown to be involved in various crucial physiological processes, particularly against apoptosis. However, the regulation and function of TRAP1 in Helicobacter pylori infection is still unknown. Here, we found that TRAP1 expression was downregulated on human gastric epithelial cells during H. pylori infection by real-time polymerase chain reaction (PCR) and western blot analysis. Through virulence factors mutant H. pylori strains infection and inhibitors screening, we found that H. pylori vacuolating cytotoxin A ( vacA), but not cytotoxin-associated gene A ( cagA) protein, induced human gastric epithelial cells to downregulate TRAP1 via P38MAPK pathway by real-time PCR and western blot analysis. Furthermore, downregulation of TRAP1 with lentivirus carrying TRAP1 short hairpin RNA constructs impairs mitochondrial function, and increases apoptosis of gastric epithelial cells. The results indicate that H. pylori vacA downregulated TRAP1 is involved in the regulation of gastric epithelial cell apoptosis.

14.
Adv Funct Mater ; 29(42)2019 Oct 17.
Artículo en Inglés | MEDLINE | ID: mdl-34335131

RESUMEN

The principle cause of cardiovascular disease (CVD) is atherosclerosis, a chronic inflammatory condition characterized by immunologically complex fatty lesions within the intima of arterial vessel walls. Dendritic cells (DCs) are key regulators of atherosclerotic inflammation, with mature DCs generating pro-inflammatory signals within vascular lesions and tolerogenic DCs eliciting atheroprotective cytokine profiles and regulatory T cell (Treg) activation. Here, we engineered the surface chemistry and morphology of synthetic nanocarriers composed of poly(ethylene glycol)-b-poly(propylene sulfide) copolymers to selectively target and modulate DCs by transporting the anti-inflammatory agent 1, 25-Dihydroxyvitamin D3 (aVD) and ApoB-100 derived antigenic peptide P210. Polymersomes decorated with an optimized surface display and density for a lipid construct of the P-D2 peptide, which binds CD11c on the DC surface, significantly enhanced the cytosolic delivery and resulting immunomodulatory capacity of aVD in vitro. Intravenous administration of the optimized polymersomes achieved selective targeting of DCs in atheroma and spleen compared to all other cell populations, including both immune and CD45- cells, and locally increased the presence of tolerogenic DCs and cytokines. aVD-loaded polymersomes significantly inhibited atherosclerotic lesion development in high fat diet-fed ApoE-/- mice following 8 weeks of administration. Incorporation of the P210 peptide generated the largest reductions in vascular lesion area (~33%, p<0.001), macrophage content (~55%, p<0.001), and vascular stiffness (4.8-fold). These results correlated with an ~6.5-fold increase in levels of Foxp3+ regulatory T cells within atherosclerotic lesions. Our results validate the key role of DC immunomodulation during aVD-dependent inhibition of atherosclerosis and demonstrate the therapeutic enhancement and dosage lowering capability of cell-targeted nanotherapy in the treatment of CVD.

15.
J Bone Miner Metab ; 35(3): 289-297, 2017 May.
Artículo en Inglés | MEDLINE | ID: mdl-27023332

RESUMEN

The relationship between hip fracture risk and opioid use remains controversial. Thus, we performed a meta-analysis to assess the risk of hip fracture among opioid users. PubMed and EMBASE were searched for studies published from the inception of the databases until June 2015. The information was extracted independently by two teams of authors. When the heterogeneity was significant, the random-effects model was used to calculate the overall pooled risk estimates. Ten studies with 697,011 patients were included in the final meta-analysis. The overall combined relative risk for the use of opioids and hip fracture was 1.54 [95 % confidence interval (CI) 1.34-1.77]. Subgroup analyses revealed sources of heterogeneity, and sensitivity analysis indicated stable results, and no publication bias was observed. This meta-analysis demonstrates that opioids significantly increase the risk of hip fracture.


Asunto(s)
Analgésicos Opioides/efectos adversos , Fracturas de Cadera/inducido químicamente , Fracturas de Cadera/epidemiología , Trastornos Relacionados con Opioides/epidemiología , Anciano , Estudios de Cohortes , Humanos , Persona de Mediana Edad , Sesgo de Publicación , Factores de Riesgo
16.
Sensors (Basel) ; 17(3)2017 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-28257073

RESUMEN

The vigilance of the driver is important for railway safety, despite not being included in the safety management system (SMS) for high-speed train safety. In this paper, a novel fatigue detection system for high-speed train safety based on monitoring train driver vigilance using a wireless wearable electroencephalograph (EEG) is presented. This system is designed to detect whether the driver is drowsiness. The proposed system consists of three main parts: (1) a wireless wearable EEG collection; (2) train driver vigilance detection; and (3) early warning device for train driver. In the first part, an 8-channel wireless wearable brain-computer interface (BCI) device acquires the locomotive driver's brain EEG signal comfortably under high-speed train-driving conditions. The recorded data are transmitted to a personal computer (PC) via Bluetooth. In the second step, a support vector machine (SVM) classification algorithm is implemented to determine the vigilance level using the Fast Fourier transform (FFT) to extract the EEG power spectrum density (PSD). In addition, an early warning device begins to work if fatigue is detected. The simulation and test results demonstrate the feasibility of the proposed fatigue detection system for high-speed train safety.

17.
Sensors (Basel) ; 17(6)2017 Jun 06.
Artículo en Inglés | MEDLINE | ID: mdl-28587275

RESUMEN

Bus Rapid Transit (BRT) has become an increasing source of concern for public transportation of modern cities. Traditional contact sensing techniques during the process of health monitoring of BRT viaducts cannot overcome the deficiency that the normal free-flow of traffic would be blocked. Advances in computer vision technology provide a new line of thought for solving this problem. In this study, a high-speed target-free vision-based sensor is proposed to measure the vibration of structures without interrupting traffic. An improved keypoints matching algorithm based on consensus-based matching and tracking (CMT) object tracking algorithm is adopted and further developed together with oriented brief (ORB) keypoints detection algorithm for practicable and effective tracking of objects. Moreover, by synthesizing the existing scaling factor calculation methods, more rational approaches to reducing errors are implemented. The performance of the vision-based sensor is evaluated through a series of laboratory tests. Experimental tests with different target types, frequencies, amplitudes and motion patterns are conducted. The performance of the method is satisfactory, which indicates that the vision sensor can extract accurate structure vibration signals by tracking either artificial or natural targets. Field tests further demonstrate that the vision sensor is both practicable and reliable.

18.
Neurochem Res ; 41(10): 2728-2751, 2016 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-27394418

RESUMEN

Fucoxanthin is rich in seaweed and considered as effective anti-cancer drug because of powerful antioxidant properties. The objective of this study was to investigate the role of fucoxanthin on apoptosis, invasion and migration of glioma cells. Firstly, fucoxanthin showed obvious cytotoxicity against human glioma cancer cell line U87 and U251, however, there was no inhibitory effect on normal neuron. And then, fucoxanthin induced apoptotic cell death showed by the condensation of chromatin material stained with Hoechest 33342, and reduced mitochondrial membrane potential via DIOC6(3) staining, and enhanced apoptosis by annexin V-FITC/SYTOX Green double staining on U87 and U251 cell lines. Transmission electron microscopy and western blotting were used to determine ultrastructure of U87 cell and expression of proteins related to apoptosis. A scratch wound healing assay and the expression of matrix metalloproteinases (MMPs), and a tans-well assay were used to investigate cell migration and invasion, respectively. Additionally, we uncovered upstream signaling Akt/mTOR and p38 pathways induced by incubation U87 and U251 cell lines with fucoxanthin that mediated cell apoptosis, migration and invasion by using PI3K and p38 inhibitors. Moreover, incubation of fucoxanthin obviously reduced the weight and volume of glioma mass of U87 cells in nude mice. Furthermore, we also examined the glioma mass of U87 cells by hematoxylin-eosin staining, TUNEL assay and western blot, and these outcomes in vivo consistently confirmed that above results in vitro. Taken together, these findings suggest that fucoxanthin augments apoptosis, and reduces cell proliferation, migration and invasion, and reveals a potential mechanism of fucoxanthin-mediated Akt/mTOR and p38 susspression in human glioblastoma cell line.


Asunto(s)
Apoptosis/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Glioblastoma/metabolismo , Glioblastoma/patología , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Xantófilas/farmacología , Animales , Antineoplásicos/farmacología , Glioblastoma/tratamiento farmacológico , Glioma/tratamiento farmacológico , Masculino , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Ratones Endogámicos BALB C , Ratones Desnudos , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal/efectos de los fármacos , Serina-Treonina Quinasas TOR/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo
19.
Med Sci Monit ; 22: 1571-81, 2016 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-27160807

RESUMEN

BACKGROUND Spinal cord injury (SCI) is the most critical complication of spinal injury. We aimed to identify differentially expressed genes (DEGs) and to find associated pathways that may function as targets for SCI prognosis and therapy. MATERIAL AND METHODS Seven gene microarray expression profiles, downloaded from the GEO database (ID: GSE33886), were used to screen the DEGs of leg tissue and to compare these between SCI patients and corresponding normal specimens. Then, GO enrichment analysis was performed on these selected DEGs. Afterwards, interactions among these DEGs were analyzed by String database and then a PPI network was constructed to obtain topology character and modules in the PPI network. Finally, roles of the critical proteins in the pathway were explained by comparing the enrichment results of the genes in sub-modules and all the DEGs. RESULTS A total of 113 DEGs were determined. We found that 21 up-regulated genes were enriched in 7 biological processes, while 9 down-regulated genes were significantly enriched in 4 KEGG pathways. The PPI network was constructed, including 40 interacting genes and 73 interactions. Three obvious function modules were identified by exploring the PPI network, and ACTC1 was identified as the critical protein in the 3 enriched signal pathways. However, no obvious difference was found in the signal pathway in which both the 11 genes in module 1 and all 113 DEGs participated. CONCLUSIONS Core proteins in the signal pathway associated with spinal cord injury may serve as potential prognostic and predictive markers for the diagnosis and treatment of spinal cord injury in clinical applications.


Asunto(s)
Traumatismos de la Médula Espinal/genética , Regulación hacia Abajo , Redes Reguladoras de Genes , Humanos , Análisis de Secuencia por Matrices de Oligonucleótidos/métodos , Análisis de Secuencia de ADN/métodos , Transcriptoma , Regulación hacia Arriba
20.
Sensors (Basel) ; 16(6)2016 Jun 09.
Artículo en Inglés | MEDLINE | ID: mdl-27294931

RESUMEN

Environmental perception and information processing are two key steps of active safety for vehicle reversing. Single-sensor environmental perception cannot meet the need for vehicle reversing safety due to its low reliability. In this paper, we present a novel multi-sensor environmental perception method using low-rank representation and a particle filter for vehicle reversing safety. The proposed system consists of four main steps, namely multi-sensor environmental perception, information fusion, target recognition and tracking using low-rank representation and a particle filter, and vehicle reversing speed control modules. First of all, the multi-sensor environmental perception module, based on a binocular-camera system and ultrasonic range finders, obtains the distance data for obstacles behind the vehicle when the vehicle is reversing. Secondly, the information fusion algorithm using an adaptive Kalman filter is used to process the data obtained with the multi-sensor environmental perception module, which greatly improves the robustness of the sensors. Then the framework of a particle filter and low-rank representation is used to track the main obstacles. The low-rank representation is used to optimize an objective particle template that has the smallest L-1 norm. Finally, the electronic throttle opening and automatic braking is under control of the proposed vehicle reversing control strategy prior to any potential collisions, making the reversing control safer and more reliable. The final system simulation and practical testing results demonstrate the validity of the proposed multi-sensor environmental perception method using low-rank representation and a particle filter for vehicle reversing safety.

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