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1.
Artigo em Inglês | MEDLINE | ID: mdl-32133300

RESUMO

In this original study, we retrospectively reviewed the cases of nocardiosis diagnosed through culture and next-generation sequencing (NGS) methods between 2014 and 2018 in Huashan Hospital and found out that the latter way can not only improve the detection rate of Nocardia spp. but also greatly reduce the turnaround time. In addition, by comparing nocardiosis and non-nocardiosis patients both of whose samples had Nocardia spp. detected by NGS, we found that Nocardia's specific reads ranking among top two might be a satisfactory cutoff value for clinical diagnosis of the disease. Our study introduced the promising value of the NGS method in the rapid diagnosis of nocardiosis.

2.
Am J Chin Med ; 48(1): 143-160, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31903780

RESUMO

Baicalin is a flavonoid extracted from Scutellariae Radix and shows a variety of biological activities as reducing lipids, diminishing inflammation, and inhibiting bacterial infection. However, there is no report of baicalin against CVB3 infection. In this study, we found that baicalin can reduce viral titer in a dose-dependent manner in vitro at a dose with no direct virucidal effect. Moreover, we revealed that baicalin can also improve survival rate, reduce heart weight/body weight ratio, prevent virus replication, and relieve myocardial inflammation in the acute viral myocarditis mouse model induced by CVB3. Then, in order to explore the mechanism of baicalin inhibiting CVB3 replication, we respectively examined the expression of autophagosome marker LC3-II by Western blot, tested the concentration of free fatty acid (FFA) and cholesterol (CHO) by commercial kits, detected the mRNA levels of fatty acid synthase (Fasn) and acetyl coenzyme a carboxylase (ACC) by RT-PCR, and observed the lipid content of cells by fluorescence staining. The results showed that CVB3 infection increased autophagosome formation and lipid content in HeLa cells, but these changes were significantly blocked by baicalin. Finally, in order to confirm that baicalin inhibits viral replication and reduces autophagosome formation by reducing cellular lipids, we added exogenous palmitate to cell culture supernatants to promote intracellular lipid synthesis and found that palmitate did not alter LC3-II and CVB3/VP1 expression in HeLa cells with or without CVB3 infection. Interestingly, palmitate can reverse the inhibitory effect of baicalin on autophagosome formation and viral replication. In conclusion, our results indicated that lipids play an important role in CVB3 replication, and the effect of baicalin against CVB3 was associated with its ability to reduce cellular lipid synthesis to limit autophagosome formation.

3.
Chin Med J (Engl) ; 133(1): 17-24, 2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31923100

RESUMO

BACKGROUND: Blood glucose control is closely related to type 2 diabetes mellitus (T2DM) prognosis. This multicenter study aimed to investigate blood glucose control among patients with insulin-treated T2DM in North China and explore the application value of combining an elastic network (EN) with a machine-learning algorithm to predict glycemic control. METHODS: Basic information, biochemical indices, and diabetes-related data were collected via questionnaire from 2787 consecutive participants recruited from 27 centers in six cities between January 2016 and December 2017. An EN regression was used to address variable collinearity. Then, three common machine learning algorithms (random forest [RF], support vector machine [SVM], and back propagation artificial neural network [BP-ANN]) were used to simulate and predict blood glucose status. Additionally, a stepwise logistic regression was performed to compare the machine learning models. RESULTS: The well-controlled blood glucose rate was 45.82% in North China. The multivariable analysis found that hypertension history, atherosclerotic cardiovascular disease history, exercise, and total cholesterol were protective factors in glycosylated hemoglobin (HbA1c) control, while central adiposity, family history, T2DM duration, complications, insulin dose, blood pressure, and hypertension were risk factors for elevated HbA1c. Before the dimensional reduction in the EN, the areas under the curve of RF, SVM, and BP were 0.73, 0.61, and 0.70, respectively, while these figures increased to 0.75, 0.72, and 0.72, respectively, after dimensional reduction. Moreover, the EN and machine learning models had higher sensitivity and accuracy than the logistic regression models (the sensitivity and accuracy of logistic were 0.52 and 0.56; RF: 0.79, 0.70; SVM: 0.84, 0.73; BP-ANN: 0.78, 0.73, respectively). CONCLUSIONS: More than half of T2DM patients in North China had poor glycemic control and were at a higher risk of developing diabetic complications. The EN and machine learning algorithms are alternative choices, in addition to the traditional logistic model, for building predictive models of blood glucose control in patients with T2DM.

4.
Acad Radiol ; 27(3): e35-e44, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31151899

RESUMO

OBJECTIVE: The aim of the present study was to use pharmacokinetic quantitative parameters with histogram and texture features on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to differentiate between the luminal A and luminal B molecular subtypes of breast cancer. METHODS: We retrospectively reviewed the data of 94 patients with histopathologically proven breast cancer. The pharmacokinetic quantitative parameters (Ktrans, Kep, and Ve) with their corresponding histogram and texture features based on preoperative DCE-MRI were obtained. The parameters were compared using the Mann-Whitney U-test between the luminal A and luminal B groups, the human epidermal growth factor receptor-2 (HER2)-positive luminal B and HER2-negative luminal B groups, and the lymph node metastasis (LNM)-positive and LNM-negative groups. Receiver operating characteristic curves were generated for parameters that presented significant between-group differences. RESULTS: The maximum values of Ktrans, Kep, and Ve, and the mean and 90th percentile values of Ve were significantly higher in the luminal B group than in the luminal A group. Among the texture features, only skewness of Ktrans significantly differed between the luminal A and B groups. All histogram features of Ktrans were higher in the HER2-positive luminal B group than in the HER2-negative luminal B group. However, no parameter differed between the LNM-positive and LNM-negative groups. CONCLUSION: Pharmacokinetic quantitative parameters with histogram and texture features obtained from DCE-MRI are associated with the molecular subtypes of breast cancer, and may serve as potential imaging biomarkers to differentiate between the luminal A and luminal B molecular subtypes.

5.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(6): 1973-1978, 2019 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-31839069

RESUMO

OBJECTIVE: To explore the efficacy and safety of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of relapsed or refractory peripheral T-cell lymphoma(PTCL). METHODS: The clinical data of 6 patients with relapsed or refractory PTCL undergoing allo-HSCT from Sep. 2014 to Sep. 2018 in the department of hematology, aerospace center hospital were retrospectively analyzed. Complications and disease-free survival after HSCT were observed. RESULTS: All the patients could well tolerate the conditioning regimen and acquired hematopoietic recon-struction. Following up till December 2018, with a median time of 11.5 months (1-51); acute GVHD developed in 2 cases and chronic GVHD developed in 5 cases, Among 6 cases one case died of viral pheumonia and the other 5 patients remained disease-free survival. The longest disease-free survival time has reached 51 months. CONCLUSION: allo-HSCT is a safe and effective method for relapsed or refractory peripheral T-cell lymphoma, which can be chosen as salvage treatment method for patients with primary resistance. Optimization of the conditioning regimen may result in better efficacy of allo-HSCT.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Linfoma de Células T Periférico , Humanos , Linfoma de Células T Periférico/terapia , Estudos Retrospectivos , Condicionamento Pré-Transplante , Transplante Homólogo
6.
J Appl Toxicol ; 2019 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-31869448

RESUMO

Due to excellent metal-insulator transition property, vanadium dioxide nanoparticles (VO2 NPs)-based nanomaterials are extensively studied and applied in various fields, and thus draw safety concerns of VO2 NPs exposure through various routes. Herein, the cytotoxicity of VO2 NPs (N-VO2 ) and titanium dioxide-coated VO2 NPs (T-VO2 ) to typical human lung cell lines (A549 and BEAS-2B) was studied by using a series of biological assays. It was found that both VO2 NPs induced a dose-dependent cytotoxicity, and the two cell lines displayed similar sensitivity to VO2 NPs. Under the same conditions, T-VO2 NPs showed slightly lower cytotoxicity than N-VO2 in both cells, indicating the surface coating of titanium dioxide mitigated the toxicity of VO2 NPs. Titanium dioxide coating changed the surface property of VO2 NPs and reduced the vanadium release of particles, and thus helped lowing the toxicity of VO2 NPs. The induced cell viability loss was attributed to apoptosis and proliferation inhibition, which were supported by the assays of apoptosis, mitochondrial membrane damage, caspase-3 level, and cell cycle arrest. The oxidative stress, i.e., enhanced reactive oxygen species generation and suppressed reduced glutathione , in A549 and BEAS-2B cells was one of the major mechanisms of the cytotoxicity of VO2 NPs. These findings provide safety guidance for the practical applications of vanadium dioxide-based materials.

7.
Chin Med J (Engl) ; 2019 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-31880745

RESUMO

BACKGROUND: Blood glucose control is closely related to type 2 diabetes mellitus (T2DM) prognosis. This multicenter study aimed to investigate blood glucose control among patients with insulin-treated T2DM in North China and explore the application value of combining an elastic network (EN) with a machine-learning algorithm to predict glycemic control. METHODS: Basic information, biochemical indices, and diabetes-related data were collected via questionnaire from 2787 consecutive participants recruited from 27 centers in six cities between January 2016 and December 2017. An EN regression was used to address variable collinearity. Then, three common machine learning algorithms (random forest [RF], support vector machine [SVM], and back propagation artificial neural network [BP-ANN]) were used to simulate and predict blood glucose status. Additionally, a stepwise logistic regression was performed to compare the machine learning models. RESULTS: The well-controlled blood glucose rate was 45.82% in North China. The multivariable analysis found that hypertension history, atherosclerotic cardiovascular disease history, exercise, and total cholesterol were protective factors in glycosylated hemoglobin (HbA1c) control, while central adiposity, family history, T2DM duration, complications, insulin dose, blood pressure, and hypertension were risk factors for elevated HbA1c. Before the dimensional reduction in the EN, the areas under the curve of RF, SVM, and BP were 0.73, 0.61, and 0.70, respectively, while these figures increased to 0.75, 0.72, and 0.72, respectively, after dimensional reduction. Moreover, the EN and machine learning models had higher sensitivity and accuracy than the logistic regression models (the sensitivity and accuracy of logistic were 0.52 and 0.56; RF: 0.79, 0.70; SVM: 0.84, 0.73; BP-ANN: 0.78, 0.73, respectively). CONCLUSIONS: More than half of T2DM patients in North China had poor glycemic control and were at a higher risk of developing diabetic complications. The EN and machine learning algorithms are alternative choices, in addition to the traditional logistic model, for building predictive models of blood glucose control in patients with T2DM.

8.
Braz J Microbiol ; 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31667800

RESUMO

NADPH oxidases are enzymes that have been reported to generate reactive oxygen species (ROS) in animals, plants and many multicellular fungi in response to environmental stresses. Six genes of the NADPH oxidase complex components, including vvnoxa, vvnoxb, vvnoxr, vvbema, vvrac1 and vvcdc24, were identified based on the complete genomic sequence of the edible fungus Volvariella volvacea. The number of vvnoxa, vvrac1, vvbema and vvcdc24 transcripts fluctuated with ageing, and the gene expression patterns of vvnoxa, vvrac1 and vvbema were significantly positively correlated. However, the expression of vvnoxb and vvnoxr showed no significant difference during ageing. In hyphae subjected to mechanical injury stress, both O2- and H2O2 concentrations were increased. The expression of vvnoxa, vvrac1, vvbema and vvcdc24 was substantially upregulated, but vvnoxb and vvnoxr showed no response to mechanical injury stress at the transcriptional level. Additionally, the transcription of vvnoxa, vvrac1, vvbema and vvcdc24 could be repressed when the intracellular ROS were eliminated by diphenyleneiodonium (DPI) chloride and reduced glutathione (GSH) treatments. These results indicated a positive feedback loop involving NADPH oxidase and intracellular ROS, which might be the reason for the oxidative burst during injury stress.

9.
Int J Mol Sci ; 20(23)2019 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-31775357

RESUMO

Carbon dioxide is commonly used as one of the significant environmental factors to control pileus expansion during mushroom cultivation. However, the pileus expansion mechanism related to CO2 is still unknown. In this study, the young fruiting bodies of a popular commercial mushroom Flammulina filiformis were cultivated under different CO2 concentrations. In comparison to the low CO2 concentration (0.05%), the pileus expansion rates were significantly lower under a high CO2 concentration (5%). Transcriptome data showed that the up-regulated genes enriched in high CO2 concentration treatments mainly associated with metabolism processes indicated that the cell metabolism processes were active under high CO2 conditions. However, the gene ontology (GO) categories and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways associated with cell division processes contained down-regulated genes at both 12 h and 36 h under a high concentration of CO2. Transcriptome and qRT-PCR analyses demonstrated that a high CO2 concentration had an adverse effect on gene expression of the ubiquitin-proteasome system and cell cycle-yeast pathway, which may decrease the cell division ability and exhibit an inhibitory effect on early pileus expansion. Our research reveals the molecular mechanism of inhibition effects on early pileus expansion by elevated CO2, which could provide a theoretical basis for a CO2 management strategy in mushroom cultivation.

11.
Sci Rep ; 9(1): 15040, 2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31636294

RESUMO

The XRF, XRD, polarizing microscopy and SEM-EDS were used to study the alteration mechanism of copper-bearing biotite and the leachable property of copper-bearing minerals in Mulyashy Copper Mine, Zambia. It was found that biotite can be divided into copper-bearing biotite and copper-free biotite. Some copper-bearing biotite existed in the form of monomer, and others aggregated with copper-bearing chlorite, malachite or copper-bearing limonite. The main reason for the occurrence of biotite aggregations was that copper-bearing biotite underwent two kinds of alteration mechanisms as follows: altering into copper-bearing chlorite and malachite, and altering into copper-bearing chlorite and copper-bearing limonite. The order of factors effecting the copper leaching rate of the ores in acid leaching experiments was temperature > sample size > H2SO4 concentration > leaching time > stirring speed. In addition, the copper leaching rate of copper-bearing minerals at different temperatures was in the following order: malachite, chrysocolla and pseudomalachite > copper-bearing chlorite > copper-bearing muscovite > copper-bearing biotite > copper-bearing limonite. The leachable property of biotite is closely related to its special structure.

12.
Chin Med J (Engl) ; 132(19): 2315-2324, 2019 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-31567376

RESUMO

BACKGROUND: Nucleos(t)ide analog (NA) in combination with peginterferon (PegIFN) therapy in patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) shows better effectiveness than NA monotherapy in hepatitis B surface antigen loss, termed "functional cure," based on previous published studies. However, it is not known which strategy is more cost-effective on functional cure. The aim of this study was to analyze the cost-effectiveness of first-line monotherapies and combination strategies in HBeAg-positive CHB patients in China from a social perspective. METHODS: A Markov model was developed with functional cure and other five states including CHB, compensated cirrhosis, decompensated cirrhosis, hepatocellular carcinoma, and death to assess the cost-effectiveness of seven representative treatment strategies. Entecavir (ETV) monotherapy and tenofovir disoproxil fumarate (TDF) monotherapy served as comparators, respectively. RESULTS: In the two base-case analysis, compared with ETV, ETV generated the highest costs with $44,210 and the highest quality-adjusted life-years (QALYs) with 16.78 years. Compared with TDF, treating CHB patients with ETV and NA - PegIFN strategies increased costs by $7639 and $6129, respectively, gaining incremental QALYs by 2.20 years and 1.66 years, respectively. The incremental cost-effectiveness ratios were $3472/QALY and $3692/QALY, respectively, which were less than one-time gross domestic product per capita. One-way sensitivity analysis and probabilistic sensitivity analyses showed the robustness of the results. CONCLUSION: Among seven treatment strategies, first-line NA monotherapy may be more cost-effective than combination strategies in HBeAg-positive CHB patients in China.

13.
Front Pharmacol ; 10: 959, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31555137

RESUMO

Herpes simplex virus type 1 (HSV-1), an enveloped DNA virus, plays a key role in varieties of diseases including recurrent cold sores, keratoconjunctivitis, genital herpes and encephalitis in humans. Great efforts have been made in developing more effective and less side-effects anti-herpes simplex virus agents, including traditional Chinese herbal medicines. In the present study, we evaluated the antiviral efficacy of Rheum tanguticum nanoparticles against HSV-1 in vitro and in vivo. R. tanguticum nanoparticles could inactivate the HSV-1 virions and block the viral attachment and entry into cells. Time-of-addition assay indicated that R. tanguticum nanoparticles could interfere with the entire phase of viral replication. Besides, R. tanguticum nanoparticles showed the ability to inhibit the mRNA expression of HSV-1 immediate early gene ICP4 and early gene ICP8 as well as the expression of viral protein ICP4 and ICP8. Moreover, R. tanguticum nanoparticles have been proved to protect mice against HSV-1 induced lethality by decreasing the viral load and alleviated pathological changes in brain tissues. In conclusion, we demonstrated that R. tanguticum nanoparticles could inhibit HSV-1 infection through multiple mechanisms. These results suggest that R. tanguticum nanoparticles may have novel roles in the treatment of HSV-1 infection.

14.
Carbohydr Res ; 485: 107820, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31546144

RESUMO

As part of our ongoing investigation of the bioactive constituents from the roots of Glycyrrhiza uralensis Fisch., seven new flavonoid glycosides (1-7) were obtained along with 19 known compounds (8-26). All of the isolates possessed one or more sugar moieties. Their structures, as well as the absolute configurations, were elucidated on the basis of spectroscopic data (UV, IR, HRESIMS, 1D and 2D NMR, and CD). In the in vitro assay, compounds 3 and 7 showed moderate antioxidant activities at a concentration of 0.1 µM; compound 2 showed hepatoprotective activity at a concentration of 10 µM.


Assuntos
Antioxidantes/química , Antioxidantes/farmacologia , Flavonoides/química , Glicosídeos/química , Glicosídeos/farmacologia , Glycyrrhiza uralensis/química , Raízes de Plantas/química , Relação Dose-Resposta a Droga , Fígado/efeitos dos fármacos , Fígado/metabolismo
16.
Ultrason Sonochem ; 59: 104734, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31479886

RESUMO

Currently near-infrared (NIR) luminescence of lanthanide ions has received great attention because of their unique emissions in the near-infrared region (800-1700 nm). These NIR luminescent materials behave excellent applications in many fields such as sensors and probes in optical amplification, laser systems, biological systems and organic light-emitting diodes. In this work, two new near-infrared (NIR) emission three-dimensional (3D) YbIII and NdIII cluster-based coordination materials, namely {[Yb2(L)2(DMF)(H2O)4]·(DMF)2 (H2O)}n (NIR-MOF 1) and [Nd(L)(DMF)2]n (NIR-MOF 2) (H3L = terphenyl-3,4″,5-tricarboxylic acid) have been synthesized through the facile sono-chemical preparation methods. Both the near-infrared materials 1 and 2 have been characterized by single crystal X-ray diffraction, powder X-ray diffraction (PXRD) and scanning electron microscopy (SEM). Further the mixed-lanthanide near-infrared emission material Nd0.35Yb0.65L (NIR-MOF 3) can also be prepared under the sono-chemical conditions. NIR-MOF 3 can be successfully applied as the ratiometric NIR-MOF-based thermometer, which should origin from the emission intensity ratio between Yb3+ (976 nm) and Nd3+ (1056 nm) in the temperature range of 308-348 K. Besides these, the micro-morphologies of NIR-MOF 1 can be deliberately tuned through different sono-chemical reaction factors (reaction time, reaction temperature and sono-chemical powers). These tuned nano-sized materials NIR-MOF 1 (100 W, 80 min) can be utilized as the fluorescent sensing material to distinguish furazolidone and sulfasalazine from other antibiotics. At the same time, NIR-MOF 2 can be applied as the first example of MOFs-based sensors for discriminating l-arginine from other amino acids through the "turn-on" mode in the near-infrared emission region.


Assuntos
Antibacterianos/análise , Arginina/análise , Técnicas de Química Analítica/instrumentação , Raios Infravermelhos , Neodímio/química , Ondas Ultrassônicas , Itérbio/química , Antibacterianos/química , Arginina/química , Furazolidona/análise , Furazolidona/química , Cinética , Limite de Detecção , Modelos Moleculares , Conformação Molecular , Compostos Organometálicos/química , Solventes/química , Sulfassalazina/análise , Sulfassalazina/química , Temperatura Ambiente
17.
Eur J Pharm Sci ; 140: 105058, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31472255

RESUMO

The biofilm formation of Pseudomonas aeruginosa (P. aeruginosa) is regulated by a phenomenon of quorum sensing (QS). With 5-hydroxyl-3,4-halogenated-5H-furan-2-ones as beginning, analogs bearing alkyl chains, vinyl bromide, or aromatic rings were designed and synthesized. The minimum inhibitory concentration (MIC) of the compounds against P. aeruginosa was assayed and the biofilm inhibition ratio was determined at different concentrations lower than the MIC. C-5 aromatic substituted furanones showed remarkable biofilm formation as well as inhibition of virulence factor production in P. aeruginosa. Fluorescence report analysis identified the QS regulatory mechanism of the most active compound 29. This study provides us a novel candidate for combating drug resistant bacteria strains by merely inhibiting biofilm formation. Without suppressing the regular life cycle of the bacteria, bacterial resistance mechanisms may not be activated.


Assuntos
Furanos/química , Furanos/farmacologia , Pseudomonas aeruginosa/efeitos dos fármacos , Percepção de Quorum/efeitos dos fármacos , Animais , Biofilmes/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Halogenação , Camundongos , Testes de Sensibilidade Microbiana , Células RAW 264.7 , Fatores de Virulência/metabolismo
18.
Yi Chuan ; 41(6): 524-533, 2019 Jun 20.
Artigo em Chinês | MEDLINE | ID: mdl-31257200

RESUMO

Normal development of the cerebral cortex is a basis for the formation and function of mammalian brains. During this process, the radial migration of cortical neurons, as well as the axon projection into specific layers, are the most important steps regulated by some transcription factors, but the underlying molecular mechanisms are still obscure. BMAL1 (brain and muscle Arnt-like protein 1) is a newly identified transcription factor that plays important roles in the circadian rhythms. It was recently found to regulate the proliferation of hippocampal neuronal progenitor/precursor cells (NPCs), implicating Bmal1 in the brain development. Here we employed both RT-RCR and real-time PCR to explore the expression pattern of the Bmal1 gene in the developing brain. We found BMAl1 is enriched in the brain cortex during the perinatal stages and peaked in P3 mouse brains. Combined with in utero electroporation and interference with RNAi, we found that reducing the expression level of Bmal1 in neurons, the radial migration of embryonic cortical neurons was largely delayed, in a gene dose-effect pattern. Moreover, reducing the level of Bmal1 expression in mouse brains, the axonal projection in the corpus callosum was also disrupted from ipsilateral to the lateral cerebral hemisphere. These findings indicate that BMAL1 is essential for the radial migration of neurons in the cerebral cortex and the axonal projection of the corpus callosum, providing insights into the molecular mechanisms of cerebral cortex development.


Assuntos
Fatores de Transcrição ARNTL/fisiologia , Axônios , Movimento Celular , Córtex Cerebral/embriologia , Neurogênese , Animais , Feminino , Camundongos , Gravidez
20.
Psychopharmacology (Berl) ; 236(11): 3169-3182, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31172225

RESUMO

RATIONALE: Levo-tetrahydropalmatine (l-THP), an active ingredient of Corydalis yanhusuo, has been reported to be a partial agonist for dopamine D1 receptors (D1R) and an antagonist for D2R. Although it has been safely used clinically in China for decades as an analgesic with sedative/hypnotic properties, there are few studies that address the mechanisms by which l-THP exerts its beneficial effects in chronic pain-induced sleep disturbance. OBJECTIVES: To investigate the effects and mechanisms of l-THP on sleep disturbance in a neuropathic pain-like condition. METHODS: A mouse model of chronic neuropathic pain induced by partial sciatic nerve ligation (PSNL) was employed. The antinociceptive and hypnotic effects of l-THP were evaluated by measurement of mechanical allodynia, thermal hyperalgesia, and electroencephalogram (EEG) recordings in PSNL mice. Pharmacological approaches and c-Fos expression were used to clarify the mechanisms of l-THP. RESULTS: Intraperitoneal injection of l-THP at 5 and 10 mg/kg not only significantly increased the mechanical threshold by 134.4% and 174.8%, and prolonged the thermal latency by 49.4% and 69.2%, but also increased non-rapid eye movement sleep by 17.5% and 29.6%, and decreased sleep fragmentation in PSNL mice, compared with the vehicle control. Moreover, the antinociceptive effect of l-THP was prevented by D1R antagonist SCH23390 or D2R agonist quinpirole; meanwhile, the hypnotic effect of l-THP was blocked by quinpirole rather than by SCH23390. Immunohistochemistry demonstrated that l-THP inhibited c-Fos overexpression induced by PSNL in the cingulate cortex and the periaqueductal gray. CONCLUSIONS: These findings indicated that l-THP exerted analgesic effects by agonism D1R and antagonism D2R, and the antagonism of D2R mediated the hypnotic effect of l-THP in PSNL mice.


Assuntos
Analgésicos não Entorpecentes/uso terapêutico , Alcaloides de Berberina/uso terapêutico , Hipnóticos e Sedativos/uso terapêutico , Neuralgia/tratamento farmacológico , Receptores de Dopamina D1/fisiologia , Receptores de Dopamina D2/fisiologia , Analgésicos não Entorpecentes/farmacologia , Animais , Alcaloides de Berberina/farmacologia , Modelos Animais de Doenças , Antagonistas dos Receptores de Dopamina D2/farmacologia , Antagonistas dos Receptores de Dopamina D2/uso terapêutico , Eletroencefalografia/efeitos dos fármacos , Hipnóticos e Sedativos/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neuralgia/fisiopatologia , Receptores de Dopamina D1/agonistas
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