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1.
Chem Res Toxicol ; 34(11): 2366-2374, 2021 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-34672520

RESUMO

Emerging evidence has revealed that oxidative damages of DNA correlate with the pathogenesis of some diseases, and numerous investigations have also suggested that supplementation of antioxidants is beneficial for keeping health by rectifying in vivo redox status. Here, we construct antioxidative dipeptides with the Ugi four-component reaction (comprising p-aminobenzyl alcohol, benzaldehyde, or vanillin, a series of antioxidative carboxylic acids and isocyanides as reagents) and then attempt to attach the dipeptides to [60]fullerene by the Bingel reaction. However, this endeavor does not lead to the amelioration of the radical-scavenging property because abilities of fullerenyl dipeptides to trap 2,2'-diphenyl-1-picrylhydrazyl and galvinoxyl radicals are still dependent upon the phenolic hydroxyl group in the dipeptide scaffold rather than upon the fullerenyl group. Alternatively, when the obtained fullerenyl dipeptides are evaluated in a peroxyl radical-induced oxidation of DNA, it is found that introducing a fullerene moiety into dipeptide enables antioxidative effect to be enhanced 20-30% because the fullerene moiety facilitates the corresponding dipeptide to intercalate with DNA strands, and thus, to increase the antioxidative efficacy. Our results suggest that connecting an antioxidative skeleton with the hydrophobic fullerene moiety might lead to a series of novel antioxidant hybrids applied for the inhibition of DNA oxidation.


Assuntos
Antioxidantes/farmacologia , DNA/antagonistas & inibidores , Dipeptídeos/farmacologia , Fulerenos/farmacologia , Antioxidantes/química , Compostos de Bifenilo/antagonistas & inibidores , DNA/metabolismo , Dipeptídeos/síntese química , Dipeptídeos/química , Fulerenos/química , Estrutura Molecular , Oxirredução , Picratos/antagonistas & inibidores
2.
Org Biomol Chem ; 19(7): 1610-1615, 2021 02 25.
Artigo em Inglês | MEDLINE | ID: mdl-33528484

RESUMO

Highly enantiopure and bioactive δ-valerolactones and pyrazolones, bearing α-all-carbon quaternary stereocentres, were successfully and sequentially prepared via a one-pot procedure starting from readily available, inexpensive materials, catalysed by a new chiral squaramide under mild reaction conditions. An organocatalytic Michael reaction afforded the valerolactones, while a one-pot Michael-hydrazinolysis-imidization cascade yielded the pyrazolones. This procedure is economically efficient and environmentally benign.

3.
Acta Pharmacol Sin ; 42(11): 1913-1920, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34561552

RESUMO

Sepsis is a dysregulated immune response to infection and potentially leads to life-threatening organ dysfunction, which is often seen in serious Covid-19 patients. Disulfiram (DSF), an old drug that has been used to treat alcohol addiction for decades, has recently been identified as a potent inhibitor of the gasdermin D (GSDMD)-induced pore formation that causes pyroptosis and inflammatory cytokine release. Therefore, DSF represents a promising therapeutic for the treatment of inflammatory disorders. Lactoferrin (LF) is a multifunctional glycoprotein with potent antibacterial and anti-inflammatory activities that acts by neutralizing circulating endotoxins and activating cellular responses. In addition, LF has been well exploited as a drug nanocarrier and targeting ligands. In this study, we developed a DSF-LF nanoparticulate system (DSF-LF NP) for combining the immunosuppressive activities of both DSF and LF. DSF-LF NPs could effectively block pyroptosis and inflammatory cytokine release from macrophages. Treatment with DSF-LF NPs showed remarkable therapeutic effects on lipopolysaccharide (LPS)-induced sepsis. In addition, this therapeutic strategy was also applied to treat ulcerative colitis (UC), and substantial treatment efficacy was achieved in a murine colitis model. The underlying mode of action of these DSF-LF-NPs may contribute to efficiently suppressing macrophage-mediated inflammatory responses and ameliorating the complications caused by sepsis and UC. As macrophage pyroptosis plays a pivotal role in inflammation, this safe and effective biomimetic nanomedicine may offer a versatile therapeutic strategy for treating various inflammatory diseases by repurposing DSF.


Assuntos
Tratamento Farmacológico da COVID-19 , COVID-19 , Colite Ulcerativa , Dissulfiram/farmacocinética , Lactoferrina , Síndrome de Resposta Inflamatória Sistêmica , Inibidores de Acetaldeído Desidrogenases/farmacologia , Animais , Anti-Inflamatórios/farmacologia , Materiais Biomiméticos/farmacologia , COVID-19/imunologia , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/imunologia , Modelos Animais de Doenças , Dissulfiram/farmacologia , Portadores de Fármacos/farmacologia , Humanos , Imunossupressores/farmacologia , Lactoferrina/metabolismo , Lactoferrina/farmacologia , Lipopolissacarídeos/imunologia , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Nanopartículas/uso terapêutico , Piroptose/efeitos dos fármacos , SARS-CoV-2 , Síndrome de Resposta Inflamatória Sistêmica/tratamento farmacológico , Síndrome de Resposta Inflamatória Sistêmica/imunologia , Síndrome de Resposta Inflamatória Sistêmica/metabolismo , Resultado do Tratamento
4.
Appetite ; 159: 105055, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33248191

RESUMO

Abnormal activities in reward-related regions are associated with overeating or obesity. Preliminary studies have shown that changes in neural activity in obesity include not only regional reward regions abnormalities but also impairments in the communication between reward-related regions and multiple functional areas. A recent study has shown that the transitions between different neural networks are nonrandom and hierarchical, and that activation of particular brain networks is more likely to occur after other brain networks. The aims of this study were to investigate the key nodes of reward-related regions in obese males and explore the hierarchical integrated processing of key nodes. Twenty-four obese males and 24 normal-weight male controls of similar ages were recruited. The fMRI data were acquired using 3.0 T MRI. The fMRI data preprocessing was performed in DPABI and SPM 12. Degree centrality analyses were conducted using GRETNA toolkit, and Granger causality analyses were calculated using DynamicBC toolbox. Decreased degree centrality was observed in left ventral medial prefrontal cortex (vmPFC) and right parahippocampal/hippocampal gyrus in group with obesity. The group with obesity demonstrated increased effective connectivity between left vmPFC and several regions (left inferior temporal gyrus, left supplementary motor area, right insular cortex, right postcentral gyrus, right paracentral lobule and bilateral fusiform gyrus). Increased effective connectivity was observed between right parahippocampal/hippocampal gyrus and left precentral/postcentral gyrus. Decreased effective connectivity was found between right parahippocampal/hippocampal gyrus and left inferior parietal lobule. This study identified the features of hierarchical interactions between the key reward nodes and multiple function networks. These findings may provide more evidence for the existing view of hierarchical organization in reward processing.


Assuntos
Mapeamento Encefálico , Recompensa , Encéfalo/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Masculino , Obesidade
5.
Lasers Med Sci ; 36(3): 619-629, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33590365

RESUMO

The aim of this study was comparing different lasers with conventional non-surgical treatment (CNT) for the management of peri-implantitis, regarding probing depth (PD), plaque index (PLI), clinical attachment level (CAL), and sulcus bleeding index (SBI). Randomized controlled trials (RCTs) on different lasers and CNT for peri-implantitis were searched. Pairwise and network meta-analyses were performed to analyze the PD, PLI, CAL, and SBI outcomes. The risk of bias, evidence quality, statistical heterogeneity, and ranking probability were also evaluated. Eleven studies were included in this study, involving three types of lasers. Diode + CNT had significantly superior efficacy to CNT alone, regarding PD reduction, while Er:YAG + CNT had significantly superior efficacy than CNT in terms of the PLI, CAL, and SBI. The highest probability of being most effective for PD was diode + CNT (49%), while Er:YAG + CNT had the highest probability of improving the PLI, CAL, and SBI (66%, 53%, and 79%, respectively). Diode + CNT was significantly superior for PD management in peri-implantitis compared with CNT alone, while Er:YAG + CNT significantly improved the PLI, CAL, and SBI. Therefore, Er:YAG + CNT might be recommended methods considered for management of peri-implantitis.


Assuntos
Lasers , Peri-Implantite/cirurgia , Adulto , Índice de Placa Dentária , Hemorragia/etiologia , Humanos , Metanálise em Rede , Probabilidade , Viés de Publicação , Ensaios Clínicos Controlados Aleatórios como Assunto , Risco , Resultado do Tratamento
6.
J Comput Assist Tomogr ; 44(4): 533-539, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32697523

RESUMO

PURPOSE: The purpose of this study was to investigate the differences of gray matter volume (GMV) alteration patterns between hemodialysis with restless legs syndrome (HD-RLS) and hemodialysis without restless legs syndrome (HD-nRLS) patients using voxel-based morphometry. METHODS: Twenty-three HD-RLS patients, 27 HD-nRLS patients, and 27 age-, sex-, and education-matched healthy controls were included in this study. One-way analysis of covariance and post hoc analyses were used to assess differences in GMV, demographics, and clinical data among the 3 groups. Pearson correlation analysis was conducted between altered GMV in the HD-RLS group and clinical data. RESULTS: Compared with HD-nRLS patients, HD-RLS patients showed decreased GMV in the left primary motor cortex (false discovery rate corrected, P < 0.05). Compared with the healthy controls, both HD subgroups (ie, those with and without RLS) exhibited consistent GMV changes, including decreased GMV in the bilateral anterior cingulate and paracingulate gyrus and left middle temporal gyrus (false discovery rate corrected, P < 0.05). The GMV values in the left precentral gyrus were negatively correlated with the RLS rating scores (r = 0.2138, P = 0.0263). CONCLUSIONS: This abnormal decreased GMV in the sensorimotor cortex provides evidence for a sensory processing disorder in RLS that may be involved in the pathogenesis of RLS in HD patients.


Assuntos
Substância Cinzenta/diagnóstico por imagem , Substância Cinzenta/patologia , Diálise Renal/efeitos adversos , Síndrome das Pernas Inquietas/diagnóstico por imagem , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Córtex Motor/diagnóstico por imagem , Córtex Motor/patologia , Tamanho do Órgão , Síndrome das Pernas Inquietas/complicações
7.
J Magn Reson Imaging ; 50(3): 746-755, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-30648327

RESUMO

BACKGROUND: The Liver Imaging Reporting and Data System (LI-RADS) is widely adopted for noninvasive diagnosis of hepatocellular carcinoma (HCC). It's updated to version 2018 recently, with some major changes compared with v2017. However, the diagnostic performance of LI-RADS v2018 and its difference with v2017 are yet to be validated. PURPOSE: To compare the diagnostic performances of LI-RADS on MR for diagnosing HCC between v2017 and v2018. STUDY TYPE: Retrospective. SUBJECTS: In all, 181 patients with 217 hepatic observations (146 HCCs, 16 non-HCC malignancies and 55 benign lesions) with liver MRI and pathological or follow-up imaging diagnoses. FIELD STRENGTH/SEQUENCE: 1.5 T or 3 T MRI. Dual-echo T1 WI, T2 WI, diffusion-weighted imaging, and a liver acquisition with volume acceleration. Assessment Images were independently interpreted by three radiologists, and then in consensus for observations with different LR categories, according to LI-RADS v2017 and v2018, separately. STATISTICAL TESTS: Sensitivity, specificity, accuracy, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (+LR), and Youden index. RESULTS: When adopting LR-5 as a predictor of HCC, the sensitivity (80.8% vs. 71.2%), NPV (69.6% vs. 60.7%), and accuracy (83.9% vs. 77.9%) were all increased for LI-RADS v2018 compared with v2017, with a greater Youden index (0.709 vs. 0.627). However, the diagnostic performances of MRI for diagnosing HCC were not changed while adopting LR-4/5 as a predictor. The threshold growths of 76% (19/25) observations in v2017 were revised to subthreshold growth in v2018, and 16 LR-4 observations in v2017 were changed to LR-5 based on v2018. DATA CONCLUSION: The diagnostic performance of LI-RADS v2018 for diagnosing HCC is superior to v2017, with a greater sensitivity, NPV, and accuracy. The revisions in v2018 mainly affect the categorization when adopting LR-5 as a predictor of HCC. LEVEL OF EVIDENCE: 4 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2019;50:746-755.


Assuntos
Carcinoma Hepatocelular/diagnóstico por imagem , Neoplasias Hepáticas/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Imageamento por Ressonância Magnética/normas , Sistemas de Informação em Radiologia/normas , Idoso , Feminino , Humanos , Fígado/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade
8.
J Magn Reson Imaging ; 50(2): 541-551, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30653786

RESUMO

BACKGROUND: The reward-related regions have been considered a crucial component in the regulation of eating behavior. Furthermore, appetite-related regions associated with reward can influence eating behaviors through altered functional activity related to food in brain areas associated with emotion, memory, sensory processing, motor function, and cognitive control. PURPOSE: To investigate the key nodes in obese females of reward-related regions and, based on key nodes, to evaluate the directionality of functional connectivity between key nodes and appetite-related regions. STUDY TYPE: Prospective. POPULATION: Twenty-eight obese and 28 normal-weight female controls of similar age. FIELD STRENGTH/SEQUENCE: 3.0 T MRI and echo planar imaging (EPI) sequence, 3D BRAVO sequence. ASSESSMENT: The fMRI data preprocessing was based on the Data Processing & Analysis of Brain Imaging and Statistical Parametric Mapping 12. Degree centrality calculation was based on the GRETNA toolkit and granger causality analysis were based on the DynamicBC toolbox. Statistical Tests: Independent two-sample t-tests were used to assess the differences in demographic and clinical data between two groups. Two-sample t-tests were conducted to test the difference in degree centrality and effective connectivity of key nodes between two groups. RESULTS: Compared with normal-weight controls, obese females showed an increased degree centrality in the left ventral striatum/caudate (t = 2.96808, P < 0.05) and decreased degree centrality in right orbitofrontal cortex (OFC) (t = -3.3558, P < 0.05). The obese females showed directional effective connectivity between left ventral striatum/caudate and several regions (left inferior temporal gyrus, fusiform gyrus, postcentral gyrus, and right precentral gyrus) (P < 0.05). Directional effective connectivity was also observed between the right OFC and several regions (left middle temporal gyrus, cuneus, OFC, superior temporal gyrus, middle frontal gyrus, and right inferior parietal lobule) (P < 0.05). DATA CONCLUSION: The left ventral striatum/caudate and right OFC are key nodes in reward-related regions. The key nodes with reward processing mainly enhance visual processing of information and further participate in cognitive, attention, and sensorimotor processing. LEVEL OF EVIDENCE: 1. Technical Efficacy: Stage 4. J. Magn. Reson. Imaging 2019;50:541-551.


Assuntos
Apetite/fisiologia , Encéfalo/fisiopatologia , Imageamento por Ressonância Magnética/métodos , Obesidade/fisiopatologia , Obesidade/psicologia , Recompensa , Adolescente , Adulto , Mapeamento Encefálico/métodos , Imagem Ecoplanar , Feminino , Humanos , Imageamento Tridimensional , Pessoa de Meia-Idade , Estudos Prospectivos , Transdução de Sinais/fisiologia , Adulto Jovem
9.
J Org Chem ; 84(24): 15854-15864, 2019 12 20.
Artigo em Inglês | MEDLINE | ID: mdl-31804824

RESUMO

We herein attach ferulic and caffeic acids to -OH and -NH2 in cytidine, uridine, adenosine, or guanosine for achieving antioxidative hybrids with three-dimensional (3D) configuration. In the case of molecular docking computation, the nucleoside antioxidants with 3D configuration facilitate to bind with the groove of DNA and to cover the surface of a DNA helix. Experimentally, the antioxidative effects of nucleoside hybrids are measured in the inhibition of DNA oxidation caused by 2,2'-azobis(2-amidinopropane dihydrochloride) (AAPH), and the stoichiometric factor (n, the number of free radical propagations terminated by one molecule of antioxidant) can be selected as a quantitative index for expressing antioxidative effects. It is found that the effect of cytidine tetraferulate against AAPH-induced DNA oxidation is seven times better than that of ferulic acid, even though four ferulic acid moieties are involved and cytidine itself does not exhibit activity. Moreover, the antioxidative effect of cytidine tetracaffeate is almost 20 times higher than that of caffeic acid. The n values of nucleoside antioxidants against AAPH-induced DNA oxidation are found to correlate proportionally with the rate constants for quenching 2,2'-diphenyl-1-picrylhydrazyl and galvinoxyl radicals. Therefore, nucleoside linking with antioxidative carboxylic acid might be a promising way for constructing antioxidants against peroxyl radical-induced oxidation of DNA.


Assuntos
Antioxidantes/farmacologia , DNA/efeitos dos fármacos , Nucleosídeos/farmacologia , Antioxidantes/química , Simulação de Acoplamento Molecular , Estrutura Molecular , Nucleosídeos/química , Oxirredução
10.
J Cell Biochem ; 119(3): 2501-2511, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-28941255

RESUMO

This network meta-analysis was conducted to compare effects of different placebo-controlled insulin-sensitizing drugs, including metformin, pioglitazone, rosiglitazone, and troglitazone on hormonal parameters in polycystic ovary syndrome (PCOS) patients. We searched PubMed, EMBASE, and Cochrane Library databases from their inception to July 2017. Randomized controlled trials (RCTs) met our inclusion criteria were included. We combined direct and indirect evidences to evaluate weighted mean difference (WMD) value and draw surface under the cumulative ranking curve (SUCRA). Totally 28 eligible RCTs were enrolled. The network meta-analysis results indicated that: Compared with placebo, patients treated with pioglitazone had relatively higher sex-hormone-binding globulin (SHBG) (nmol/L) level (WMD = 6.65, 95%CI = 0.57-12.98), patients treated with metformin had comparatively lower total testosterone (TT) (ng/mL) level (WMD = -0.20, 95%CI = -0.39 to -0.02); Compared with rosiglitazone, patients treated with metformin had relatively higher estradiol (E2 ) (pg/mL) level (WMD = 47.91, 95%CI = 11.44-85.55). However, there were no statistical significance among the placebo-controlled insulin-sensitizing drugs in follicle stimulating hormone (FSH) (IU/L), luteinizing hormone (LH) (IU/L), dehydroepiandrostrone-sulphate (DHEAS) (µg/dL), free testosterone (FT) (pg/mL) and androstenedione (ng/mL). The results of cluster analysis showed that rosiglitazone may be the best drug for PCOS patients regarding to DHEAS, TT, FSH, and LH, metformin may be the best drug for PCOS patients as for E2 , FT, and androstenedione. Rosiglitazone had the best effect on PCOS patients in terms of DHEAS, TT, FSH, and LH, metformin had the best effect on PCOS patients for E2 , FT, and androstenedione.


Assuntos
Hormônios Gonadais/sangue , Hipoglicemiantes/uso terapêutico , Síndrome do Ovário Policístico/tratamento farmacológico , Feminino , Humanos , Resistência à Insulina , Metanálise em Rede , Síndrome do Ovário Policístico/sangue , Ensaios Clínicos Controlados Aleatórios como Assunto
11.
Biochem Biophys Res Commun ; 503(3): 1911-1918, 2018 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-30064908

RESUMO

Lysophosphatidylcholine (LPC) is a bioactive lipid constituent of oxidized low density lipoprotein (ox-LDL). It regulates various cellular functions, including migration of circulating monocytes, expression of endothelial adhesion molecules, proliferation and migration of vascular smooth muscle cells (VSMCs). LPC can also be hydrolyzed into lysophosphatidic acid (LPA) by autotaxin (ATX) which possesses lysophospholipase D (lyso-PLD) activity. The aim of this study was to explore the effects of LPC on proliferation and migration of human artery smooth muscle cells (HASMCs) and the involvement of LPC-ATX-LPA pathway in these processes. In vitro, we found that LPC and LPA stimulated HASMCs proliferation and migration. Knockdown of LPA1 by siRNA and inhibit Gi protein with pertussis toxin (PTX) showed the contrary results. Silencing of LPC receptor genes did not significantly affect the LPC induced proliferation and migration. We detected the higher expressed mRNA and protein of ATX in HASMCs, and measured lyso-PLD activity. In atherosclerotic rabbit model, we observed high LPC level and high lyso-D activity in blood, and high expression of LPA1 in aorta walls. We also found that neointima appeared to be thickened and mRNA expressions of LPA1 appeared to be increased. These results revealed that LPC was converted into LPA by ATX to induce the proliferation and migration in HASMCs through LPA1/Gi/o/MAP Kinase signaling pathway. Our research suggested that LPC-ATX-LPA system contributed to the atherogenic action induced by ox-LDL. LPA1 antagonist may be considered as a potential therapeutic and preventative drug for cardiovascular disease.


Assuntos
Aterosclerose/metabolismo , Lisofosfatidilcolinas/metabolismo , Músculo Liso Vascular/metabolismo , Receptores de Ácidos Lisofosfatídicos/metabolismo , Animais , Aterosclerose/genética , Movimento Celular , Proliferação de Células , Células Cultivadas , Cromatografia em Camada Fina , Humanos , Músculo Liso Vascular/citologia , Coelhos
12.
Apoptosis ; 22(10): 1296-1309, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28766061

RESUMO

Human umbilical cord mesenchymal stem cells (hUC-MSCs) are potential stromal cells which are regarded as the most feasible stem cell group in cell therapy. The maintenance of cell survival without differentiation is important in cell transplantation and stem cell therapy. However, negative factors exist in cell transplantation. Lysophosphatidic acid (LPA) is a non-antigenic small molecule phospholipid which induced several fundamental cellular responses, such as cell proliferation, apoptosis and migration. In this study we aimed to explore the effects of LPA on the survival and differentiation of MSCs and its availability in cell therapy. We found that LPA stimulated hUC-MSC proliferation and protected hUC-MSCs from lipopolysaccharide (LPS) induced apoptosis. We also observed that CD29, CD44, CD73, CD90 and CD105 were expressed, whereas CD34 and CD45 were not expressed in hUC-MSCs, and these makers have no change in LPA containing medium, which indicated that LPA accelerated the survival of hUC-MSCs in an undifferentiating status. We also demonstrated that higher expressed LPAR1 involved in LPA stimulated cell survival action. LPA stimulated cell proliferation was associated with LPAR1 mediated Gi/o-proteins/ERK1/2 pathway. On the other hand, LPA protected hUC-MSCs from LPS-induced apoptosis through suppressing caspase-3 activation by LPAR1 coupled with a G protein, but not Gi/o or Gq/11 in hUC-MSC. Collectively, this study demonstrated that LPA increased the proliferation and survival of hUC-MSCs without differentiation through LPAR1 mediated manner. Our findings provide that LPA as a anti-apoptotic agent having potential application prospect in cell transplantation and stem cell therapy.


Assuntos
Diferenciação Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Lisofosfolipídeos/fisiologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Receptores de Ácidos Lisofosfatídicos/metabolismo , Cordão Umbilical/citologia , Antígenos de Diferenciação/genética , Apoptose/efeitos dos fármacos , Apoptose/fisiologia , Caspase 3/metabolismo , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/fisiologia , Células Cultivadas , Subunidades alfa de Proteínas de Ligação ao GTP/antagonistas & inibidores , Subunidades alfa de Proteínas de Ligação ao GTP/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Técnicas de Silenciamento de Genes , Humanos , Lisofosfolipídeos/farmacologia , Sistema de Sinalização das MAP Quinases/fisiologia , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Receptores de Ácidos Lisofosfatídicos/antagonistas & inibidores , Receptores de Ácidos Lisofosfatídicos/genética
13.
Acta Pharmacol Sin ; 37(8): 1110-20, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27292613

RESUMO

AIM: Drug efflux-associated multidrug resistance (MDR) is a main obstacle to effective cancer chemotherapy. Large molecule drugs are not the substrates of P-glycoprotein, and can circumvent drug efflux and be retained inside cells. In this article we report a polymer-drug conjugate nanoparticulate system that can overcome MDR based on size-related exclusion effect. METHODS: Doxorubicin was coupled with the triblock polymeric material cell-penetrating TAT-PEG-poly(aspartic acid). The amphiphilic macromolecules (termed TAT-PEG-Asp8-Dox) could self-assemble into nanoparticles (NPs) in water. The antitumor activity was evaluated in drug-resistant human colon cancer HCT8/ADR cells in vitro and in nude mice bearing HCT8/ADR tumor. RESULTS: The self-assembling TAT-PEG-Asp8-Dox NPs were approximately 150 nm with a narrow particle size distribution, which not only increased the cellular uptake efficiency, but also bypassed P-glycoprotein-mediated drug efflux and improved the intracellular drug retention, thus yielding an enhanced efficacy for killing drug-resistant HCT8/ADR colon cancer cells in vitro. Importantly, the TAT-PEG-Asp8-Dox NPs enhanced the intranuclear disposition of drugs for grater inhibition of DNA/RNA biosynthesis. In nude mice bearing xenografted HCT8/ADR colon cancers, intravenous or peritumoral injection of TAT-PEG-Asp8-Dox NPs for 22 d effectively inhibited tumor growth. CONCLUSION: TAT-PEG-Asp8-Dox NPs can increase cellular drug uptake and intranuclear drug delivery and retain effective drug accumulation inside the cells, thus exhibiting enhanced anticancer activity toward the drug-resistant human colon cancer HCT8/ADR cells.


Assuntos
Antineoplásicos/administração & dosagem , Doxorrubicina/farmacologia , Doxorrubicina/farmacocinética , Portadores de Fármacos/administração & dosagem , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Nanopartículas/administração & dosagem , Animais , Antineoplásicos/farmacocinética , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Peptídeos Penetradores de Células/química , DNA/biossíntese , Doxorrubicina/administração & dosagem , Portadores de Fármacos/farmacocinética , Humanos , Camundongos , Camundongos Nus , Nanopartículas/química , Tamanho da Partícula , Peptídeos/química , Polietilenoglicóis/química , Ensaios Antitumorais Modelo de Xenoenxerto
14.
Sensors (Basel) ; 16(12)2016 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-27999404

RESUMO

Moisture content is an important factor in corn breeding and cultivation. A corn breed with low moisture at harvest is beneficial for mechanical operations, reduces drying and storage costs after harvesting and, thus, reduces energy consumption. Nondestructive measurement of kernel moisture in an intact corn ear allows us to select corn varieties with seeds that have high dehydration speeds in the mature period. We designed a sensor using a ring electrode pair for nondestructive measurement of the kernel moisture in a corn ear based on a high-frequency detection circuit. Through experiments using the effective scope of the electrodes' electric field, we confirmed that the moisture in the corn cob has little effect on corn kernel moisture measurement. Before the sensor was applied in practice, we investigated temperature and conductivity effects on the output impedance. Results showed that the temperature was linearly related to the output impedance (both real and imaginary parts) of the measurement electrodes and the detection circuit's output voltage. However, the conductivity has a non-monotonic dependence on the output impedance (both real and imaginary parts) of the measurement electrodes and the output voltage of the high-frequency detection circuit. Therefore, we reduced the effect of conductivity on the measurement results through measurement frequency selection. Corn moisture measurement results showed a quadric regression between corn ear moisture and the imaginary part of the output impedance, and there is also a quadric regression between corn kernel moisture and the high-frequency detection circuit output voltage at 100 MHz. In this study, two corn breeds were measured using our sensor and gave R² values for the quadric regression equation of 0.7853 and 0.8496.


Assuntos
Eletroquímica/métodos , Umidade , Sementes/química , Zea mays/química , Simulação por Computador , Condutividade Elétrica , Eletrodos , Temperatura
15.
Neuron ; 112(7): 1165-1181.e8, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38301648

RESUMO

Physical exercise is known to reduce anxiety, but the underlying brain mechanisms remain unclear. Here, we explore a hypothalamo-cerebello-amygdalar circuit that may mediate motor-dependent alleviation of anxiety. This three-neuron loop, in which the cerebellar dentate nucleus takes center stage, bridges the motor system with the emotional system. Subjecting animals to a constant rotarod engages glutamatergic cerebellar dentate neurons that drive PKCδ+ amygdalar neurons to elicit an anxiolytic effect. Moreover, challenging animals on an accelerated rather than a constant rotarod engages hypothalamic neurons that provide a superimposed anxiolytic effect via an orexinergic projection to the dentate neurons that activate the amygdala. Our findings reveal a cerebello-limbic pathway that may contribute to motor-triggered alleviation of anxiety and that may be optimally exploited during challenging physical exercise.


Assuntos
Ansiolíticos , Animais , Ansiedade/metabolismo , Hipotálamo , Cerebelo , Transtornos de Ansiedade
16.
Zhonghua Yi Xue Za Zhi ; 93(33): 2622-6, 2013 Sep 03.
Artigo em Zh | MEDLINE | ID: mdl-24360040

RESUMO

OBJECTIVE: To evaluate the sensitivity and specificity of computed tomographic angiography ( CTA) for dural arteriovenous fistulas ( DAVFs) in patients presenting with pulsatile tinnitus( PT). METHODS: The clinical and imaging data were collected for all patients undergoing CTA for PT from 2008 to 2012. Nine PT patients with DAVFs confirmed by digital subtraction angiography ( DSA) and 9 age and gender-matched control PT patients without DAVFs were selected. The CTA images were blindly analyzed by two experienced neuroradiologists for the following signs: asymmetric venous collaterals in extracranial space , asymmetric attenuation of internal jugular vein ( IJV) , asymmetric external carotid artery( ECA) branches, "shaggy" appearance of dural venous sinus, multiple transcalvarial channels, enlarged foramen spinosum, asymmetric cavernous sinus and enlarged cortical veins. RESULTS: The sensitivities of the following DAVFs signs were quite different: asymmetric attenuation of IJV ( 89% ) , asymmetric venous collaterals ( 89%) , asymmetric ECA branches ( 78%) , shaggy dural venous sinus ( 67%) , multiple transcalvarial channels (67%), enlarged foramen spinosum (56%), stenosis of venous sinus (33%) and asymmetric cavernous sinus ( 2 2 % ) . The presence of asymmetric attenuation of IJV , asymmetric ECA branches, shaggy dural venous sinus, multiple transcalvarial channels and asymmetric cavernous sinus all demonstrated a highly specificity of 100% while the presence of asymmetric venous collaterals and enlarged foramen spinosum had a specificity of 89% . The presence of stenosis of venous sinus revealed a specificity of 78%. Enlarged cortical veins were all absent. CONCLUSION: CTA may be used as a screening examination for DA VFs in PT patients. The presence of asymmetric venous collaterals, asymmetric attenuation of UV,asymmetric ECA branches, shaggy dural venous sinus and multiple transcalvarial channels has a high sensitivity and specificity for diagnosis. Enlarged ECA branches usually serve as DA VFs feeders.Meanwhile, DA VF should be considered in PT patients when multiple transcalvarial channels and enlarged foramen spinosum are detected on high-resolution CT of temporal bone.


Assuntos
Malformações Vasculares do Sistema Nervoso Central/diagnóstico por imagem , Zumbido/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Adulto , Idoso , Angiografia Digital , Malformações Vasculares do Sistema Nervoso Central/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osso Temporal/diagnóstico por imagem , Zumbido/etiologia
17.
Zhonghua Yi Xue Za Zhi ; 93(33): 2613-6, 2013 Sep 03.
Artigo em Zh | MEDLINE | ID: mdl-24360038

RESUMO

OBJECTIVE: To evaluate the value of temporal bone dual phase contrast enhancement computed tomography (DPCT) in diagnosing the causes of pulsatile tinnitus (PT). METHODS: We retrospectively analyzed the DPCT findings of 157 patients with unilateral PT. Temporal bone High-resolution CT (HRCT) was performed in 71 patients, magnetic resonance imaging (MRI) in 80 and digital subtraction angiography (DSA) in 89. RESULTS: In 71 patients with both DPCT and HRCT scan, a total of 68 causes were found. The accuracy of DPCT was 100% it was significant higher than that of HRCT (77.9%). In 80 patients with both DPCT and MRI, 83 causes were known. The accuracy of DPCT (94.0%) was significantly higher than that of MRI (8.4%). In 89 patients with both DPCT and DSA scan, 99 causes were identified. The accuracy of DPCT was 91.9% and it was significantly higher than that of DSA (15.2%). CONCLUSION: DPCT may be an ideal imaging modality for diagnosing the causes of PT.


Assuntos
Osso Temporal/diagnóstico por imagem , Zumbido/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Adolescente , Adulto , Idoso , Angiografia Digital , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Adulto Jovem
18.
Mitochondrial DNA B Resour ; 8(5): 550-556, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37197650

RESUMO

Abies ernestii var. salouenensis (Bordères & Gaussen) W. C. Cheng & L. K. Fu is endemic to southwest China, including the southeastern Tibetan Plateau and the northwestern Yunnan Province. The taxonomic relationships between A. ernestii var. salouenensis and two other closely related fir species (A. chensiensis Tiegh. and A. ernestii Rehd.) still need to be determined. Here, we report for the first time the whole chloroplast genome of A. ernestii var. salouenensis. Its genome is 121,759 bp long and is characterized by a circular structure with 68 peptide-encoding genes, 16 tRNAs, six ORFs, and four rRNAs. We also identified 70 microsatellite repeat sequences and 14 tandem repeat sequences in the chloroplast genome of A. ernestii var. salouenensis. Comparative genome analysis indicated considerable variation in ycf1 and ycf2. Phylogenetic analysis supported the monophyly of A. ernestii var. salouenensis, A. chensiensis Tiegh., and A. ernestii Rehd. The relationships among them should be surveyed using more samples at the species level. This study will facilitate taxonomic studies and the development of suitable chloroplast markers for fir species.

19.
Heliyon ; 9(4): e15195, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37089335

RESUMO

Electrical impedance tomography (EIT) has been used by researchers across several areas because of its low-cost and no-radiation properties. Researchers use complex conductivity in bioimpedance experiments to evaluate changes in various indicators within the image target. The diverse volumes and edges of biological tissues and the large impedance range impose dedicated demands on hardware design. The EIT hardware with a high signal-to-noise ratio (SNR), fast scanning and suitable for the impedance range of the image target is a fundamental foundation that EIT research needs to be equipped with. Understanding the characteristics of this technique and state-of-the-art design will accelerate the development of the robust system and provide a guidance for the superior performance of next-generation EIT. This review explores the hardware strategies for EIT proposed in the literature.

20.
Artigo em Zh | MEDLINE | ID: mdl-22931815

RESUMO

OBJECTIVE: To analyze and evaluate the fatigue of shoulder skeletal muscle caused by different lifting loads with surface electromyography (sEMG). METHODS: According to the loading standard of1 Repetition Maximum (1RM), ten male volunteers performed 3 tasks of upper limb flexion, i.e. 10%, 50% and 90%-1RM. During action process, the signals of Upper Trapezius (UT), Lower Trapezius (LT), Serratus Anterior (SA) and Anterior Deltoid (AD) were recorded by sEMG. The Mean Amplitude (MA) served as an index to evaluate the changes in skeletal muscle fatigue. RESULTS: The scores of Borg were 15.6, 15.9 and 15.2 for 3 loads of 10%-1RM, 50%-1RM and 90%-1RM, respectively (P > 0.05). The mean amplitudes (MAs) of Upper Trapezius, Lower Trapezius, Anterior Deltoid and Serratus Anterior in shoulders increased obviously. Under the load intensity of 10%-1RM, the MAs of Upper Trapezius and Anterior Deltoid increased significantly (P < 0.05), which were 0.898 and 0.736, respectively. After the exhaustion, the contribution of mean amplitude in shoulder muscle did not change significantly (P > 0.05). CONCLUSION: The low-load action for long time can induce easily the fatigue of upper trapezius and anterior deltoid.


Assuntos
Remoção , Fadiga Muscular/fisiologia , Ombro/fisiologia , Adulto , Eletromiografia , Humanos , Masculino , Músculo Esquelético/fisiologia , Carga de Trabalho
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