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1.
Small ; : e2309867, 2023 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-38048539

RESUMO

Due to its high information density, DNA is very attractive as a data storage system. However, a major obstacle is the high cost and long turnaround time for retrieving DNA data with next-generation sequencing. Herein, the use of a microfluidic very large-scale integration (mVLSI) platform is described to perform highly parallel and rapid readout of data stored in DNA. Additionally, it is demonstrated that multi-state data encoded in DNA can be deciphered with on-chip melt-curve analysis, thereby further increasing the data content that can be analyzed. The pairing of mVLSI network architecture with exquisitely specific DNA recognition gives rise to a scalable platform for rapid DNA data reading.

2.
Small ; 19(37): e2205636, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37209020

RESUMO

Pooled nucleic acid amplification test is a promising strategy to reduce cost and resources for screening large populations for infectious disease. However, the benefit of pooled testing is reversed when disease prevalence is high, because of the need to retest each sample to identify infected individual when a pool is positive. Split, Amplify, and Melt analysis of Pooled Assay (SAMPA) is presented, a multicolor digital melting PCR assay in nanoliter chambers that simultaneously identify infected individuals and quantify their viral loads in a single round of pooled testing. This is achieved by early sample tagging with unique barcodes and pooling, followed by single molecule barcode identification in a digital PCR platform using a highly multiplexed melt curve analysis strategy. The feasibility is demonstrated of SAMPA for quantitative unmixing and variant identification from pools of eight synthetic DNA and RNA samples corresponding to the N1 gene, as well as from heat-inactivated SARS-CoV-2 virus. Single round pooled testing of barcoded samples with SAMPA can be a valuable tool for rapid and scalable population testing of infectious disease.


Assuntos
COVID-19 , Doenças Transmissíveis , Humanos , SARS-CoV-2/genética , COVID-19/diagnóstico , Doenças Transmissíveis/diagnóstico , Reação em Cadeia da Polimerase , Técnicas de Amplificação de Ácido Nucleico , Sensibilidade e Especificidade , RNA Viral/genética , Teste para COVID-19
3.
Zhongguo Zhong Yao Za Zhi ; 45(24): 6043-6052, 2020 Dec.
Artigo em Zh | MEDLINE | ID: mdl-33496146

RESUMO

To systematically evaluate the efficacy of traditional Chinese medicine(TCM) compounds combined with levodopa medicine in the treatment of Parkinson's disease(PD), and screen basic herbs to provide certain evidence-based medical proof and program for better guidance on clinical drug use. Six databases were searched to screen out the randomized controlled trial on the TCM compounds combined with levodopa medicine in the treatment of PD. Literature quality of the included studies was evaluated by improved Jadad rating scale, and the Meta-analysis was performed by RevMan 5.3 software. After the data of the basic TCM compounds involved were sorted out, the strong association rules were found by using Apriori algorithm of SPSS Modeler 18.0 software, and then the basic herbs for the treatment of PD could be picked out. A total of 20 studies were eventually included, involving 1 784 patients. Ten studies were of high-quality literature, Jadad score≥4 points. Meta-analysis showed that efficacy of TCM combined with levodopa medicine was better than levodopa medicine alone in lowering Unified Parkinson's Disease Rating Scale(UPDRS) score: UPDRS Ⅰ(MD=-0.43, 95%CI[-0.62,-0.24], P<0.000 1), UPDRS Ⅱ(MD=-2.72, 95%CI[-3.24,-2.21], P<0.000 01), UPDRS Ⅲ(MD =-1.97, 95%CI[-2.69,-1.25], P<0.000 01), UPDRS Ⅳ(MD=-0.28, 95%CI[-0.46,-0.11], P=0.002). And the improvement in UPDRS score reduction rate of TCM combined with levodopa medicine was better than that in levodopa medicine alone: effective rate(OR=4.81, 95%CI[3.50, 6.62], P<0.000 01). Data mining results showed that the basic prescription for treating PD consisted of Paeoniae Radix Alba-Rehmanniae Radix Praeparata-Gastrodiae Rhizoma in general. According to each part of UPDRS, the basic prescription for treating mentation, behavior and mood(UPDRS Ⅰ) consists of Paeoniae Radix Alba-Rehmanniae Radix Praeparata-Glycyrrhizae Radix et Rhizoma Praeparata Cum Melle, Among which Glycyrrhizae Radix et Rhizoma Praeparata Cum Melle might have unique efficacy. The basic prescriptions for treating UPDRS Ⅱ and UPDRS Ⅲ consisted of Paeoniae Radix Alba-Rehmanniae Radix Praeparata, or Chuanxiong Rhizoma-Angelicae Sinensis Radix(two drug combinations). However, in the treatment of UPDRS Ⅳ, the drugs were scattered. But due to the limitations in the quantity and quality of clinical studies, the results obtained still need further research and clinical confirmation of its efficacy.


Assuntos
Medicamentos de Ervas Chinesas , Medicina , Doença de Parkinson , China , Glycyrrhiza , Humanos , Levodopa , Medicina Tradicional Chinesa
4.
Biomed Eng Online ; 18(1): 85, 2019 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-31362738

RESUMO

BACKGROUND: Ratcheting strain is produced due to the repeated accumulation of compressive strain in cartilage and may be a precursor to osteoarthritis. The aim of this study was to investigate the ratcheting behaviors of young and adult articular cartilages under cyclic compression by experiments and theoretical predictions. METHODS: A series of uniaxial cyclic compression tests were conducted for young and adult cartilage, and the effects of different loading conditions on their ratcheting behaviors were probed. A theoretical ratcheting model was constructed and applied to predict the ratcheting strains of young and adult cartilages with different loading conditions. RESULTS: Ratcheting strains of young and adult cartilages rapidly increased at the initial stage, followed by a slower increase in subsequent stages. The strain accumulation value and its rate for young cartilage were greater than them for adult cartilage. The ratcheting strains of the two groups of cartilage samples decreased with increasing stress rate, while they increased with increasing stress amplitude. As the stress amplitude increased, the gap between the ratcheting strains of young and adult cartilages increased gradually. The ratcheting strains of young and adult cartilages decreased along the cartilage depth from the surface to the deep layer. The ratcheting strains of different layers increased with the compressive cycle, and the difference among the three layers was noticeable. Additionally, the theoretical predictions agreed with the experimental data. CONCLUSIONS: Overall, the ratcheting behavior of articular cartilage is affected by the degree of articular cartilage maturation.


Assuntos
Cartilagem Articular , Teste de Materiais , Estresse Mecânico , Envelhecimento/fisiologia , Animais , Fenômenos Biomecânicos , Cartilagem Articular/fisiologia , Força Compressiva , Suínos
5.
Int J Clin Oncol ; 24(11): 1479-1489, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31278532

RESUMO

BACKGROUND: We investigated the microarray data GSE42352 to identify genes that can be used as prognosis factors in osteosarcoma. METHODS: Gene Ontology (GO) biological process analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of Cytoscape ClueGo were used in verifying the function of different genes. Realtime-PCR were used to confirm the microarray results. 83 patient samples were collected and underwent Kaplan-Meier survival analysis and multivariate analysis to predict the prospect of genes using as prognosis factors. RESULTS: After analyzing the microarray data GSE42352, mitosis metaphase to anaphase-related genes CDC20, securin, cyclin A2 and cyclin B2 were found to be overexpressed in osteosarcoma cell lines. Kaplan-Meier survival analysis showed that overexpression of these genes can predict poor prognosis outcomes in osteosarcoma patients. Furthermore, any combination of the four genes seems to be more effective in predicting osteosarcoma outcomes than any of these genes alone. CONCLUSIONS: CDC20 and its downstream substracts securin, cyclin A2 and cyclin B2 are good factors that can predict prognosis outcomes in osteosarcoma. Any two combination of these four genes are more effective to be used as osteosarcoma prognosis factors.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias Ósseas/genética , Proteínas Cdc20/genética , Osteossarcoma/genética , Adolescente , Adulto , Idoso , Neoplasias Ósseas/mortalidade , Linhagem Celular Tumoral , Criança , Ciclina A2/genética , Ciclina B2/genética , Bases de Dados Genéticas , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos , Osteossarcoma/mortalidade , Prognóstico , Securina/genética , Adulto Jovem
6.
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
7.
J Org Chem ; 83(13): 6893-6906, 2018 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-29508610

RESUMO

The stereoselective construction of the CDEFGH ring system of lancifodilactone G is described. The key steps in this synthesis are (i) ring-closing metathesis for formation of the oxa-bridged eight-membered ring; (ii) an intramolecular Pauson-Khand reaction for construction of the sterically congested F ring; and (iii) sequential cross-metathesis, hydrogenation, and lactonization reactions for installation of the anomerically stabilized bis-spiro ketal fragment of lancifodilactone G.

8.
J Org Chem ; 83(13): 6907-6923, 2018 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-29508620

RESUMO

The asymmetric total synthesis of lancifodilactone G acetate was accomplished in 28 steps. The key steps in this synthesis include (i) an asymmetric Diels-Alder reaction for formation of the scaffold of the BC ring; (ii) an intramolecular ring-closing metathesis reaction for the formation of the trisubstituted cyclooctene using a Hoveyda-Grubbs II catalyst; (iii) an intramolecular Pauson-Khand reaction for construction of the sterically congested F ring; (iv) sequential cross-metathesis, hydrogenation, and lactonization reactions for installation of the anomerically stabilized bis-spiro ketal fragment of lancifodilactone G; and (v) a Dieckmann-type condensation reaction for installation of the A ring. The strategy and chemistry developed for the total synthesis will be useful in the synthesis of other natural products and complex molecules.

9.
Cereb Cortex ; 27(7): 3842-3855, 2017 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-28475719

RESUMO

Neuritin is a neurotrophic factor involved in neural development and synaptic plasticity. However, its role in modulating synaptic transmission remains unclear. Here, we investigated the effects of neuritin on miniature excitatory postsynaptic currents (mEPSCs) and glutamate release in the medial prefrontal cortex (mPFC) in mice. Incubation of mPFC slices with neuritin for 45 min significantly increased mEPSC frequency and glutamate release as measured by high-performance liquid chromatography, which was mimicked by insulin and abrogated by an insulin receptor (IR) inhibitor. Neuritin-induced upregulation of synaptic transmission was correlated with activation of ERK, and inhibition of mitogen-activated protein kinases/extracellular signal-regulated kinases (MEK/ERK) activity attenuated the neuritin-induced increase in mEPSC frequency and glutamate release. T-type calcium channel inhibitors but not the L-type inhibitor abolished the inward calcium current and the effects of neuritin on mEPSC frequency and glutamate release. Western blotting of membrane proteins showed that neuritin promoted surface expression of CaV3.3 α-subunit, which was also eliminated by inhibition of IR or MEK/ERK activity. The effects of neuritin on mEPSC frequency, glutamate release, and CaV3.3 α-subunit expression were inhibited by an intracellular protein-transport inhibitor. These results confirm involvement of the IR and ERK signaling pathway, and provide novel insights into the mechanisms of neuritin function in synaptic transmission.


Assuntos
Canais de Cálcio Tipo T/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Neuropeptídeos/farmacologia , Córtex Pré-Frontal/citologia , Transmissão Sináptica/efeitos dos fármacos , Potenciais de Ação/efeitos dos fármacos , Animais , Bloqueadores dos Canais de Cálcio/farmacologia , Relação Dose-Resposta a Droga , Estimulação Elétrica , Inibidores Enzimáticos/farmacologia , Feminino , Proteínas Ligadas por GPI/metabolismo , Proteínas Ligadas por GPI/farmacologia , Ácido Glutâmico/metabolismo , Técnicas In Vitro , Camundongos , Camundongos Endogâmicos C57BL , Plasticidade Neuronal , Neuropeptídeos/metabolismo , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Coloração pela Prata , Transmissão Sináptica/fisiologia , Fatores de Tempo , Transdução Genética
10.
J Biol Chem ; 291(33): 17369-81, 2016 08 12.
Artigo em Inglês | MEDLINE | ID: mdl-27307045

RESUMO

Neuritin is an important neurotrophin that regulates neural development, synaptic plasticity, and neuronal survival. Elucidating the downstream molecular signaling is important for potential therapeutic applications of neuritin in neuronal dysfunctions. We previously showed that neuritin up-regulates transient potassium outward current (IA) subunit Kv4.2 expression and increases IA densities, in part by activating the insulin receptor signaling pathway. Molecular mechanisms of neuritin-induced Kv4.2 expression remain elusive. Here, we report that the Ca(2+)/calcineurin (CaN)/nuclear factor of activated T-cells (NFAT) c4 axis is required for neuritin-induced Kv4.2 transcriptional expression and potentiation of IA densities in cerebellum granule neurons. We found that neuritin elevates intracellular Ca(2+) and increases Kv4.2 expression and IA densities; this effect was sensitive to CaN inhibition and was eliminated in Nfatc4(-/-) mice but not in Nfatc2(-/-) mice. Stimulation with neuritin significantly increased nuclear accumulation of NFATc4 in cerebellum granule cells and HeLa cells, which expressed IR. Furthermore, NFATc4 was recruited to the Kv4.2 gene promoter loci detected by luciferase reporter and chromatin immunoprecipitation assays. More importantly, data obtained from cortical neurons following adeno-associated virus-mediated overexpression of neuritin indicated that reduced neuronal excitability and increased formation of dendritic spines were abrogated in the Nfatc4(-/-) mice. Together, these data demonstrate an indispensable role for the CaN/NFATc4 signaling pathway in neuritin-regulated neuronal functions.


Assuntos
Calcineurina/metabolismo , Sinalização do Cálcio/fisiologia , Cálcio/metabolismo , Espinhas Dendríticas/metabolismo , Regulação da Expressão Gênica/fisiologia , Fatores de Transcrição NFATC/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Neuropeptídeos/metabolismo , Canais de Potássio Shal/biossíntese , Animais , Calcineurina/genética , Cerebelo/metabolismo , Espinhas Dendríticas/genética , Proteínas Ligadas por GPI/genética , Proteínas Ligadas por GPI/metabolismo , Células HeLa , Humanos , Camundongos , Camundongos Knockout , Fatores de Transcrição NFATC/genética , Proteínas do Tecido Nervoso/genética , Neuropeptídeos/genética , Canais de Potássio Shal/genética
11.
J Am Chem Soc ; 139(16): 5732-5735, 2017 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-28391693

RESUMO

Asymmetric total synthesis of structurally intriguing and highly oxygenated lancifodilactone G acetate (7) has been achieved for the first time in 28 steps from a cheap commodity chemical, 2-(triisopropylsiloxy)-1,3-butadiene.


Assuntos
Acetatos/síntese química , Triterpenos/síntese química , Acetatos/química , Cristalografia por Raios X , Modelos Moleculares , Conformação Molecular , Triterpenos/química
12.
Sheng Li Xue Bao ; 69(1): 109-121, 2017 Feb 25.
Artigo em Zh | MEDLINE | ID: mdl-28217814

RESUMO

Growth differentiation factor-15 (GDF-15) is a member of the transforming growth factor beta superfamily. GDF-15 expression is dramatically upregulated during acute brain injury, cancer, cardiovascular disease, and inflammation, suggesting its potential value as a disease biomarker. It has been suggested that GDF-15 has neurotropic effects in the nervous system. Our studies showed that GDF-15 modulated the expression of neuronal K+ and Ca2+ ion channels and increased the release of excitatory transmitter in the medial prefrontal cortex of mice. GDF-15 is also involved in the complex modulation of cancer and cardiovascular disease. Here, we reviewed studies involving the modulation of GDF-15 expression and its mechanisms, the primary pathological and physiological functions of GDF-15 in neurological and cardiovascular systems, and its role in cancer progression. The biological effects and the values of GDF-15 in basic research and clinical applications were also addressed.


Assuntos
Doenças Cardiovasculares/fisiopatologia , Fator 15 de Diferenciação de Crescimento/metabolismo , Neoplasias/fisiopatologia , Sistema Nervoso/metabolismo , Animais , Lesões Encefálicas/fisiopatologia , Canais de Cálcio/metabolismo , Progressão da Doença , Humanos , Inflamação , Camundongos , Canais de Potássio/metabolismo , Córtex Pré-Frontal/metabolismo , Fator de Crescimento Transformador beta , Regulação para Cima
13.
Sensors (Basel) ; 16(11)2016 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-27809272

RESUMO

The TanSat carbon satellite is to be launched at the end of 2016. In order to verify the performance of its instruments, a flight test of TanSat instruments was conducted in Jilin Province in September, 2015. The flight test area covered a total area of about 11,000 km² and the underlying surface cover included several lakes, forest land, grassland, wetland, farmland, a thermal power plant and numerous cities and villages. We modeled the column-average dry-air mole fraction of atmospheric carbon dioxide (XCO2) surface based on flight test data which measured the near- and short-wave infrared (NIR) reflected solar radiation in the absorption bands at around 760 and 1610 nm. However, it is difficult to directly analyze the spatial distribution of XCO2 in the flight area using the limited flight test data and the approximate surface of XCO2, which was obtained by regression modeling, which is not very accurate either. We therefore used the high accuracy surface modeling (HASM) platform to fill the gaps where there is no information on XCO2 in the flight test area, which takes the approximate surface of XCO2 as its driving field and the XCO2 observations retrieved from the flight test as its optimum control constraints. High accuracy surfaces of XCO2 were constructed with HASM based on the flight's observations. The results showed that the mean XCO2 in the flight test area is about 400 ppm and that XCO2 over urban areas is much higher than in other places. Compared with OCO-2's XCO2, the mean difference is 0.7 ppm and the standard deviation is 0.95 ppm. Therefore, the modelling of the XCO2 surface based on the flight test of the TanSat instruments fell within an expected and acceptable range.

14.
Anesthesiology ; 122(6): 1235-52, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25751232

RESUMO

BACKGROUND: One-lung ventilation (OLV) can result in local and systemic inflammation. This prospective, randomized trial was to evaluate the effect of therapeutic hypercapnia on lung injury after OLV. METHOD: Fifty patients aged 20 to 60 yr undergoing lobectomy were randomly provided with air or carbon dioxide (partial pressure of carbon dioxide: 35 to 45 mmHg or 60 to 70 mmHg). Peak pressure, plateau pressure, and lung compliance were recorded. Bronchoalveolar lavage fluid (BALF) and blood samples were collected. Adverse events were monitored. The primary outcome was the concentration of BALF tumor necrosis factor, and the secondary outcomes were serum cytokine concentrations. RESULTS: The BALF tumor necrosis factor was lower in the carbon dioxide group than in the air group (median [range], 51.1 [42.8 to 76.6] vs. 71.2 [44.8 to 92.7]; P = 0.034). Patients in the carbon dioxide group had lower concentrations of serum and BALF interleukin (IL)-1, IL-6, and IL-8, but higher serum concentrations of IL-10, accompanied by reduced numbers of cells and neutrophils as well as lower concentrations of protein in the BALF. Also, patients in the carbon dioxide group had lower peak (mean ± SD, 22.2 ± 2.9 vs. 29.8 ± 4.6) and plateau pressures (20.5 ± 2.4 vs. 27.1 ± 2.9), but higher dynamic compliance (46.6 ± 5.8 vs. 38.9 ± 6.5). Furthermore, patients in the carbon dioxide group had higher postoperation oxygenation index values. Ten patients experienced slightly increased blood pressure and heart rate during OLV in the carbon dioxide group. CONCLUSION: Under intravenous anesthesia, therapeutic hypercapnia inhibits local and systematic inflammation and improves respiratory function after OLV in lobectomy patients without severe complications.


Assuntos
Dióxido de Carbono/uso terapêutico , Hipercapnia/fisiopatologia , Ventilação Monopulmonar/métodos , Procedimentos Cirúrgicos Pulmonares/métodos , Adulto , Idoso , Anestesia Geral/métodos , Líquido da Lavagem Broncoalveolar/química , Dióxido de Carbono/sangue , Feminino , Humanos , Hipercapnia/sangue , Inflamação/sangue , Pulmão/cirurgia , Complacência Pulmonar , Masculino , Pessoa de Meia-Idade , Oxigênio/sangue , Estudos Prospectivos , Testes de Função Respiratória , Fator de Necrose Tumoral alfa/análise , Fator de Necrose Tumoral alfa/metabolismo
15.
Eur J Clin Pharmacol ; 71(6): 681-686, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25948472

RESUMO

OBJECTIVE: Tramadol is a synthetic opioid which has analgesic efficacy in the postoperative pain. It is metabolized by polymorphic enzyme cytochrome P450 (CYP2D6). Patients with different CYP2D6 genotypes would have different responses to tramadol in pain relief. The CYP2D6*10 allele is the most common allele in a Chinese population. The aim of this study was to evaluate whether the different CYP2D6*10 genotypes have an effect on the postoperative tramadol analgesia in the Chinese population after elective nephrectomy. METHODS: One hundred and twenty patients after performed elective nephrectomy were enrolled in this study after being approved by the local Ethics Committee. The patients were given patient-controlled analgesia (PCA) which included 10 mg/ml tramadol after receiving a loading dose of 100 mg tramadol and 1 mg granisetron intravenously. Blood samples were collected after induction of anesthesia. The CYP2D6*10 polymorphism was analyzed by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). According to the results, the patients were divided into three groups (CYP2D6*1/*1, n = 33; CYP2D6*1/*10, n = 28; CYP2D6*10/*10, n = 50). The total consumption of tramadol, visual analogue scale (VAS) score, and PCA control times among the three genotype groups for 2, 4, 24, 48, and 72 h after operation were compared. RESULTS: Nine out of 120 patients were dropped out of the study; 111 patients completed the study. The frequency of CYP2D6*10 allele was 57.7%. The demographic data among the three groups were comparable. The consumption of tramadol, patient self-control times of pump, and VAS score in CYP2D6*10/*10 group were significantly higher than that in CYP2D6*1/*1 or CYP2D6*1/*10 group at 2 and 4 h (P < 0.05), while it did not differ between CYP2D6*1/*1 and CYP2D6*1/*10 group (P > 0.05). There was no difference in the incidence of nausea and vomiting among the three groups (P > 0.05). No sever apnea was recorded in these groups. CONCLUSIONS: Different CYP2D6*10 genotypes have an influence on the analgesic effect of tramadol in Han nationality patients after elective nephrectomy.


Assuntos
Analgésicos Opioides/uso terapêutico , Povo Asiático/genética , Citocromo P-450 CYP2D6/genética , Dor Pós-Operatória/tratamento farmacológico , Polimorfismo Genético/genética , Tramadol/uso terapêutico , Alelos , Analgesia Controlada pelo Paciente/métodos , Etnicidade/genética , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Nefrectomia/métodos , Dor Pós-Operatória/genética
16.
J Cell Mol Med ; 18(6): 1060-70, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24548607

RESUMO

Although melatonin (MT) has been reported to protect cells against oxidative damage induced by electromagnetic radiation, few reports have addressed whether there are other protective mechanisms. Here, we investigated the effects of MT on extremely low-frequency electromagnetic field (ELF-EMF)-induced Nav activity in rat cerebellar granule cells (GCs). Exposing cerebellar GCs to ELF-EMF for 60 min. significantly increased the Nav current (INa ) densities by 62.5%. MT (5 µM) inhibited the ELF-EMF-induced INa increase. This inhibitory effect of MT is mimicked by an MT2 receptor agonist and was eliminated by an MT2 receptor antagonist. The Nav channel steady-state activation curve was significantly shifted towards hyperpolarization by ELF-EMF stimulation but remained unchanged by MT in cerebellar GC that were either exposed or not exposed to ELF-EMF. ELF-EMF exposure significantly increased the intracellular levels of phosphorylated PKA in cerebellar GCs, and both MT and IIK-7 did not reduce the ELF-EMF-induced increase in phosphorylated PKA. The inhibitory effects of MT on ELF-EMF-induced Nav activity was greatly reduced by the calmodulin inhibitor KN93. Calcium imaging showed that MT did not increase the basal intracellular Ca(2+) level, but it significantly elevated the intracellular Ca(2+) level evoked by the high K(+) stimulation in cerebellar GC that were either exposed or not exposed to ELF-EMF. In the presence of ruthenium red, a ryanodine-sensitive receptor blocker, the MT-induced increase in intracellular calcium levels was reduced. Our data show for the first time that MT protects against neuronal INa that result from ELF-EMF exposure through Ca(2+) influx-induced Ca(2+) release.


Assuntos
Cálcio/metabolismo , Cerebelo/citologia , Grânulos Citoplasmáticos/metabolismo , Campos Eletromagnéticos/efeitos adversos , Melatonina/farmacologia , Substâncias Protetoras/farmacologia , Canais de Sódio Disparados por Voltagem/metabolismo , Animais , Antioxidantes/farmacologia , Células Cultivadas , Cerebelo/efeitos dos fármacos , Cerebelo/metabolismo , Cerebelo/efeitos da radiação , Grânulos Citoplasmáticos/efeitos dos fármacos , Grânulos Citoplasmáticos/efeitos da radiação , Masculino , Camundongos , Oxirredução , Técnicas de Patch-Clamp , Fosforilação/efeitos dos fármacos , Fosforilação/efeitos da radiação , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/efeitos da radiação
17.
J Neurochem ; 128(3): 350-62, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24118019

RESUMO

In addition to their neurotoxic role in Alzheimer's disease (AD), ß-amyloid peptides (Aßs) are also known to play physiological roles. Here, we show that recombinant Aß40 significantly increased the outward current of the GABA(A) receptor containing (GABA(A)α6) in rat cerebellar granule neurons (CGNs). The Aß40-mediated increase in GABA(A)α6 current was mediated by an increase in GABA(A)α6 protein expression at the translational rather than the transcriptional level. The exposure of CGNs to Aß40 markedly induced the phosphorylation of ERK (pERK) and mammalian target of rapamycin (pmTOR). The increase in GABA(A)α6 current and expression was attenuated by specific inhibitors of ERK or mTOR, suggesting that the ERK and mTOR signaling pathways are required for the effect of Aß40 on GABA(A)α6 current and expression in CGNs. A pharmacological blockade of the p75 neurotrophin receptor (p75(NTR)), but not the insulin or α7-nAChR receptors, abrogated the effect of Aß40 on GABA(A)α6 protein expression and current. Furthermore, the expression of GABA(A)α6 was lower in CGNs from APP(-/-) mice than in CGNs from wild-type mice. Moreover, the internal granule layer (IGL) in APP(-/-) mice was thinner than the IGL in wild-type mice. The injection of Aß40 into the cerebellum reversed this effect, and the application of p75(NTR) blocking antibody abolished the effects of Aß40 on cerebellum morphology in APP(-/-) mice. Our results suggest that low concentrations of Aß40 play a role in regulating CGN maturation through p75(NTR).


Assuntos
Peptídeos beta-Amiloides/farmacologia , Cerebelo/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Neurônios/metabolismo , Fragmentos de Peptídeos/farmacologia , Receptores de GABA-A/biossíntese , Serina-Treonina Quinases TOR/efeitos dos fármacos , Precursor de Proteína beta-Amiloide/genética , Animais , Biotinilação , Western Blotting , Cerebelo/citologia , Cerebelo/efeitos dos fármacos , Feminino , Imunoprecipitação , Camundongos , Camundongos Endogâmicos C57BL , Neurônios/efeitos dos fármacos , Técnicas de Patch-Clamp , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase em Tempo Real , Receptor de Fator de Crescimento Neural/metabolismo , Transdução de Sinais/efeitos dos fármacos , Ácido gama-Aminobutírico/fisiologia
18.
Ying Yong Sheng Tai Xue Bao ; 34(11): 2919-2928, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37997402

RESUMO

Vegetation plays a critical role in the water and carbon cycling and energy flow, serving as an indicator for regulating land carbon balance and reflecting climate change and human activities. We analyzed the spatiotemporal variations of normalized difference vegetation index (NDVI) during the growing season in southern Jiangxi from 2000 to 2020, using statistical methods, including the Mann-Kendall test, Theil-Sen Median analysis, Hurst index, and coefficient of variation. We employed the geodetector model to comprehensively assess the impacts of climate, topography, soil and human factors on spatial differentiation of vegetation NDVI. The results showed NDVI exhibited an upward fluctuating trend with a rate of 0.003 per year from 2000 to 2020. The proportion of high-grade and medium-high-grade NDVI areas were 55.8% and 41.9%, respectively, while the areas with low and relatively low fluctuations accounted for 92.3%. The proportions of areas showing extremely significant improvement and significant improvement were 40.4% and 19.4%, respectively. In contrast, the combined proportion of areas displaying extremely significant degradation and significant degradation was only 2.2%. The proportions of areas demonstrating continuous improvement and future improvement were 28.0% and 60.2%, respectively. Elevation, precipitation, relative humidity, temperature, landform type, land use type, population density, and nighttime light were identified as the major factors for the vairations of NDVI in the study area, followed by slope, soil type, and GDP, while slope aspect and vegetation type had indirect influence. Throughout the study period, NDVI in southern Jiangxi was overall stable, with future changes primarily indicating improvement. Notably, human factors such as land use type, population density, and nighttime light index exhibited an upward trend in their impacts on NDVI.


Assuntos
Mudança Climática , Solo , Humanos , China , Temperatura , Carbono , Ecossistema
19.
Adv Sci (Weinh) ; 10(27): e2301630, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37485651

RESUMO

Digital PCR (dPCR) is an important tool for precise nucleic acid quantification in clinical setting, but the limited multiplexing capability restricts its applications for quantitative gene panel profiling. Here, this work describes melt-encoded-tags for expanded optical readout in digital PCR (METEOR-dPCR), a simple two-step assay that enables simultaneous quantification of a large panel of arbitrary genes in a dPCR platform. Target genes are quantitatively converted into DNA tags with unique melting temperatures through a ligation approach. These tags are then counted and distinguished by their melt-curve profiles on a dPCR platform. A multiplexing capacity of M^N, where M is the number of resolvable melting temperature and N is the number of fluorescence channel, can be achieved. This work validates METEOR-dPCR with simultaneous DNA copy number profiling of 60 targets using dPCR in cancer cells, and demonstrates its sensitivity for estimating tumor fraction in mixed tumor and normal DNA samples. The rapid, quantitative, and highly multiplexed METEOR-dPCR assay will have wide appeal for many clinical applications.


Assuntos
DNA , Reação em Cadeia da Polimerase , DNA/genética
20.
J Cardiovasc Transl Res ; 15(6): 1327-1339, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-35426038

RESUMO

Vascular calcification (VC) is a significant risk factor for cardiovascular mortality and morbidity in patients with atherosclerosis (AS), chronic kidney disease, and diabetes. Dickkopf1 (Dkk1) is a multifunctional secreted glycoprotein that has been explored as a novel potential antitumor target. Recently, Dkk1 was shown to be closely associated with AS development. However, the role of Dkk1 in VC remains elusive. In this study, we explored the role and molecular mechanisms of Dkk1 in VC based on a smooth muscle-specific Dkk1-knockout (Dkk1SMKO) mouse model. Our data indicated that Dkk1 expression was decreased under calcifying conditions and that Dkk1 overexpression alleviated high phosphate-induced vascular calcification. In vivo, smooth muscle Dkk1-specific knockout aggravated vascular calcification in mice. However, phospholipase D1 (PLD1) overexpression partially weakened the protective effect of Dkk1 against vascular calcification. Mechanistically, Dkk1 slowed vascular calcification by promoting the degradation of PLD1 via the regulating autophagosome formation and maturation. In conclusion, we found that Dkk1 could alleviate vascular calcification by regulating the degradation of PLD1.


Assuntos
Peptídeos e Proteínas de Sinalização Intercelular , Fosfolipase D , Insuficiência Renal Crônica , Calcificação Vascular , Animais , Camundongos , Miócitos de Músculo Liso/patologia , Fosfolipase D/metabolismo , Calcificação Vascular/genética , Calcificação Vascular/prevenção & controle , Camundongos Knockout , Peptídeos e Proteínas de Sinalização Intercelular/genética
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