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1.
Acta Pharmacol Sin ; 44(1): 32-43, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35896696

RESUMO

Inflammation is one of the pathogenic processes in Parkinson's disease (PD). Dopamine receptor agonist pramipexole (PPX) is extensively used for PD treatment in clinics. A number of studies show that PPX exerts neuroprotection on dopaminergic (DA) neurons, but the molecular mechanisms underlying the protective effects of PPX on DA neurons are not fully elucidated. In the present study, we investigated whether PPX modulated PD-related neuroinflammation and underlying mechanisms. PD model was established in mice by bilateral striatum injection of lipopolyssaccharide (LPS). The mice were administered PPX (0.5 mg·kg-1·d-1, i.p.) 3 days before LPS injection, and for 3 or 21 days after surgery, respectively, for biochemical and histological analyses. We showed that PPX administration significantly alleviated the loss of DA neurons, and suppressed the astrocyte activation and levels of proinflammatory cytokine IL-1ß in the substantia nigra of LPS-injected mice. Furthermore, PPX administration significantly decreased the expression of NLRP3 inflammasome-associated proteins, i.e., cleaved forms of caspase-1, IL-1ß, and apoptosis-associated speck-like protein containing a caspase recruit domain (ASC) in the striatum. These results were validated in LPS+ATP-stimulated primary mouse astrocytes in vitro. Remarkably, we showed that PPX (100-400 µM) dose-dependently enhanced the autophagy activity in the astrocytes evidenced by the elevations in LC3-II and BECN1 protein expression, as well as the increase of GFP-LC3 puncta formation. The opposite effects of PPX on astrocytic NLRP3 inflammasome and autophagy were eliminated by Drd3 depletion. Moreover, we demonstrated that both pretreatment of astrocytes with autophagy inhibitor chloroquine (40 µM) in vitro and astrocyte-specific Atg5 knockdown in vivo blocked PPX-caused inhibition on NLRP3 inflammasome and protection against DA neuron damage. Altogether, this study demonstrates an anti-neuroinflammatory activity of PPX via a Drd3-dependent enhancement of autophagy activity in astrocytes, and reveals a new mechanism for the beneficial effect of PPX in PD therapy.


Assuntos
Doença de Parkinson , Camundongos , Animais , Pramipexol/uso terapêutico , Pramipexol/metabolismo , Pramipexol/farmacologia , Doença de Parkinson/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Inflamassomos/metabolismo , Astrócitos/metabolismo , Lipopolissacarídeos/farmacologia , Autofagia , Camundongos Endogâmicos C57BL
2.
Molecules ; 27(23)2022 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-36500632

RESUMO

The aims of this article were to investigate Bacillus safensis HL3 spore for its capacity to degrade and detoxify indigo carmine and to provide an effective biological agent for the treatment of isatin dye wastewater. Bacillus safensis HL3 spore was found to decolorize indigo carmine by 97% in the presence of acetosyringone within 2 h. Significantly increased activities of spore laccase, intracellular tyrosinase, and lignin peroxidase upon exposure to indigo carmine were observed. The results of RT-qPCR also showed that the expression of laccase gene was significantly increased. The spore has the ability to degrade indigo carmine through oxidization. Furthermore, the pathway by which indigo carmine is degraded was investigated using liquid chromatography-mass spectrometry analysis to identify the biodegradation products. A detailed pathway of indigo carmine degradation by bacterial spores was proposed for the first time. Toxicity tests indicated that the biodegradation products of indigo carmine are non-toxic to Nicotiana tabacum seeds and are less hazardous to human erythrocytes than the original dye. Indigo carmine is a typical recalcitrant dye and severely jeopardizes human health. The results demonstrate the utility of the spore from Bacillus safensis HL3 for the degradation of indigo carmine and simultaneous reduction of its toxicity.


Assuntos
Bacillus , Índigo Carmim , Humanos , Bacillus/metabolismo , Biodegradação Ambiental , Lacase/metabolismo , Corantes/química
3.
Acta Neurol Scand ; 146(5): 553-561, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36237129

RESUMO

OBJECTIVE: Anti-neurofascin 155 (NF155) antibody has been discovered in chronic demyelinating conditions. However, the positive rate and clinical description were insufficient in acute demyelinating conditions, such as Guillain-Barré syndrome (GBS). This study aimed to explore the positive rate of anti-NF155 antibody in GBS patients and determine whether there were unique clinical characteristics in these patients. MATERIALS & METHODS: Serum anti-NF155 antibody was detected from 94 GBS patients and 50 sex- and age-matched healthy controls using cell-based assay and tissue-based assay with immunostaining of mouse teased sciatic nerve fibers. Clinical characteristics, laboratory data, and electrophysiology examinations were retrospectively collected. RESULTS: Seven of 94 (7.45%) GBS patients were positive for anti-NF155 antibody, and the main IgG subclass was IgG1. Compared with anti-NF155 antibody-negative GBS patients, anti-NF155 antibody-positive GBS patients had a higher GBS disability score at nadirs (p = .010), higher modified Erasmus GBS outcome score (p = .022), higher rate of abnormal compound motor action potential (CMAP) amplitude (p = .002), higher frequency of prolonged F-wave latency (p < .001), lower frequency of abnormal sensory conduction velocity (p < .001) and sensory nerve action potential amplitude (p < .001), more axonal type (p = .040), and poorer therapeutic effect (p = .017). CONCLUSIONS: Anti-NF155 antibody exists in a small portion of GBS patients. Anti-NF155 antibody-positive GBS patients possibly have a more severe clinical course, less sensory nerves involved, higher proportion of axonal type, poorer therapeutic effect, and worse prognosis, but the pathogenicity of the anti-NF155 antibody in GBS needs further study.


Assuntos
Síndrome de Guillain-Barré , Animais , Feminino , Síndrome de Guillain-Barré/diagnóstico , Humanos , Imunoglobulina G , Masculino , Camundongos , Condução Nervosa , Estudos Retrospectivos
4.
J Clin Neurosci ; 105: 31-36, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36063751

RESUMO

OBJECTIVES: This study aimed to investigate the role of peripheral neutrophil to lymphocyte ratio (NLR), monocyte to lymphocyte ratio (MLR), and platelet to lymphocyte ratio (PLR) in the progression and severity of the Guillain-Barré syndrome (GBS). METHODS: 47 GBS patients and 50 age and sex-matched healthy controls (HC) were retrospectively included. Demographic and clinical assessment data were reviewed and abstracted. NLR, MLR, and PLR were calculated based on the peripheral blood tests by reviewing clinical data. The relationship between the Hughes' score and NLR, MLR, PLR levels was investigated. RESULTS: The GBS patients had higher NLR levels (P < 0.001), MLR levels (P = 0.001) and PLR levels (P < 0.001) than those in HC. And patients with severe disability score (Hughes' score ≥ 3) had significantly higher NLR (P = 0.007), MLR (P = 0.04), PLR (P = 0.013). Spearman correlation analysis indicated that NLR was positively associated with the Hughes' score (r = 0.331, P = 0.023). In the patients with acute inflammatory demyelinating polyneuropathy (AIDP), Spearman correlation analysis indicated that NLR, MLR and PLR were positively associated to the Hughes' score (r = 0.825, P = 0.001 for NLR, r = 0.727, P = 0.005 for MLR, and r = 0.723, P = 0.005 for PLR). CONCLUSIONS: NLR, MLR, and PLR may be indicators of disease activity in patients with GBS or AIDP. These parameters may benefit the active treatment of GBS patients with a high degree of disability.


Assuntos
Síndrome de Guillain-Barré , Linfócitos , Biomarcadores , Plaquetas , Síndrome de Guillain-Barré/diagnóstico , Humanos , Neutrófilos , Prognóstico , Estudos Retrospectivos
5.
J Nurs Manag ; 30(7): 2670-2680, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35580873

RESUMO

AIM: The purpose of this study was to explore the effect of authentic leadership on nurses' innovation behaviour and the mediating role of work engagement. BACKGROUND: Encouraging nurses to generate more innovation behaviours has become an important development direction for improving the quality of nursing services. METHOD: We employed a self-report questionnaire to collect data in Jinan City, China. A total of 2018 valid surveys were obtained. Hierarchical multiple regression model analysis was conducted to test the study hypothesis. RESULT: The mean values of authentic leadership were 55.72 and 35.29, respectively. It shows that nurses can perceive the authenticity of managers, and their innovation behaviours need to be improved. Work engagement was found to have partially mediating effect on the relationship between authentic leadership and innovation behaviour. CONCLUSION: Results suggest the importance of developing nurse managers' authentic leadership to foster nurses' work engagement and innovation behaviour. IMPLICATIONS FOR NURSING MANAGEMENT: Hospitals should enhance authentic leadership by designing leadership training programmes and establishing authentic culture. In addition, nursing managers can also foster nursing innovation through improvements in work engagement. The study data were collected via questionnaires, and we sent out questionnaires with informed consent forms to the study subjects. All valid subjects signed the consent forms and agreed to join this study. In addition, the questionnaires were collected anonymously, and all the subjects' information is strictly confidential. More importantly, the data are only used for research and do not involve any commercial interests.


Assuntos
Enfermeiros Administradores , Enfermeiras e Enfermeiros , Humanos , Liderança , Engajamento no Trabalho , Negociação , Criatividade , Inquéritos e Questionários
6.
Brain Res ; 1785: 147879, 2022 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-35278479

RESUMO

BACKGROUND: Parkinson's disease (PD) is a common neurodegenerative disorder that affects 1%-2% of the population over 60 years old. Immune response dysfunction in the brain contributes to the occurrence and development of PD. This study aimed to uncover the potential diagnostic genes for PD and characterize the immune cell infiltrates. METHODS: We downloaded the microarray data of patients with PD samples from the Gene Expression Omnibus (GEO) database. Weighted Gene Co-Expression Network Analysis (WGCNA) was used to identify the modules linked to PD in the GSE20163 dataset. Meanwhile, differentially expressed genes (DEGs) between the healthy control samples and PD samples were also identified. Then the PD-related genes were integrated based on the genes in the key module and DEGs. Functional enrichment analysis was used to explore the molecular mechanisms of these PD-related genes. Protein-protein interaction (PPI) network and least absolute shrinkage and selection operator (LASSO) analysis were used to further screen candidate genes for PD. Gene set enrichment analysis (GSEA) was applied to explore the biological functions of these candidate genes. The infiltration of immune cells was detected by single-sample gene set enrichment analysis (ssGSEA) algorithm in the GSE20163 dataset, and Pearson analysis was used to investigate the correlation of candidate genes with immune cells and immune checkpoint proteins. The expression of candidate genes in clinical samples was verified by qPCR. RESULTS: Altogether, we found a unique gene module related to PD, where 109 DEGs were identified in the GSE20163 dataset. Following these results, we screened 68 genes associated with PD. Gene Expression Omnibus (GEO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses suggested that these genes were markedly enriched in the pathway of synthesis and transport of neurons. Three candidate genes (SLC18A2, CALB1, and SYNGR3) were further identified in PD patients through PPI network and LASSO analysis. The receiver operating characteristic (ROC) curve indicated that the three candidate genes had a good performance in distinguishing the PD samples from healthy control samples. The proportions of the aDC, DC, NK CD56dim cells, and follicular helper T cells (TFH) were obviously different between the healthy control and PD samples. Moreover, CTLA4, LAG3, CEACAM1, and CD27 were highly expressed in the PD group. GSEA analysis for candidate genes revealed that they were all closely related to the neurogenic disease. Additionally, the three candidate genes were all strongly correlated with the above immune cells and immune checkpoint proteins. The qPCR results validated the expression differences of SLC18A2 and SYNGR3 in the clinical PD and control samples. CONCLUSION: The three candidate genes may be a useful tool for diagnosing PD patients. These findings provide a reference for exploring new therapeutic targets and strategies for PD treatment.


Assuntos
Proteína Semelhante a ELAV 2/genética , Doença de Parkinson , Biologia Computacional/métodos , Perfilação da Expressão Gênica/métodos , Redes Reguladoras de Genes/genética , Humanos , Proteínas de Checkpoint Imunológico , Pessoa de Meia-Idade , Doença de Parkinson/genética
7.
Biosens Bioelectron ; 194: 113575, 2021 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-34438339

RESUMO

An intracellular leakage-trigged signal-on solid-state electrochemiluminescent (ECL) assay is developed for the detection of Escherichia coli (E. coli). A self-assembled multilayer ensemble of N, S co-doped carbon dots -poly dimethyl diallylammonium chloride grafted carbon nanospheres is used as ECL luminophores with peroxydisulfate (PS) ions as coreactants. The incorporation of molecularly imprinted electrospun nanofibers with the multilayer ensemble enables a robust, highly selective solid-state ECL probe without using any expensive and fragile biological receptor. Upon the imprinted E. coli exposed to the assay, under bactericidal effects of PS ions by destroying the integrity of E. coli cell membrane, intracellular leakage K+-triggered ECL enhancement is first disclosed via prompting the involved 1O2-mediated ECL process. Benefiting from the ECL enhancement upon increasing the concentration of E. coli, a unique intracellular leakage-trigged signal-on ECL system is created for sensing E. coli. Such a assay is proved to be highly specific and sensitive for sensing E. coli in the concentration range from 5 to 107 cfu mL-1, achieving a detection limit of 1 cfu mL-1 (S/N = 3). This label-free, simple and facile assay provides a promising point-of-care diagnostic tool for pathogen detection.


Assuntos
Técnicas Biossensoriais , Técnicas Eletroquímicas , Bioensaio , Escherichia coli , Limite de Detecção , Medições Luminescentes
8.
Front Pharmacol ; 12: 623533, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33762944

RESUMO

Quality control of Chinese medicine (CM) is mainly based on chemical testing, which sometimes shows weak correlation to pharmacological effects. Thus, there is a great demand to establish bioactivity-based assays to ensure the quality of CM. The aim of the present study was to establish a bioassay-based approach to evaluate the biological activity of Xuesaitong injection (XST) based on an in vivo zebrafish model. Zebrafish larvae with arachidonic acid (AA)-induced thrombus were applied to evaluate anti-thrombosis effects of XST and explore the potential mechanism of XST. Analysis of major components in normal and abnormal XST samples was performed by high performance liquid chromatography (HPLC). The results indicate that XST could significantly restore heart red blood cells (RBCs) intensity of thrombotic zebrafish in a dose-dependent manner, whilst decreasing RBCs accumulation in the caudal vein. The results were confirmed using a green fluorescence protein (GFP)-labeled zebrafish thrombosis model. Moreover, we could show that XST downregulates the expression of the fibrinogen alpha chain (fga) gene to inhibit the coagulation cascade during the process of thrombosis in zebrafish. Notoginsenoside R1, ginsenoside Rg1, ginsenoside Rb1 and ginsenoside Rd, which were considered to be the major components of XST, also showed moderate anti-thrombosis efficacy. Further results showed that the zebrafish thrombosis model could efficiently distinguish five abnormal batches of XST from 24 normal batches. Furthermore, the inhibition rates of different batches were correlated with the content level of major components. Our results suggested that the proposed zebrafish thrombosis model could be successfully used to evaluate the batch-to-batch consistency of XST, which provided an alternative way for the quality control of CM.

9.
Int J Occup Saf Ergon ; 27(1): 86-94, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30221592

RESUMO

In this study, common flame-retardant fabrics were treated with single washing or abrasion and their interactions to simulate wearing away during use. The changes in thickness, mass/m2 and protective performance of the fabrics under both flame and radiation environments were evaluated. Results demonstrated that the protective performance was firstly increased after washing or abrasion, and then decreased with further increasing washing or abrasion cycles. After certain treatment cycles, the combined effect of washing and abrasion was significantly greater than the single effect of washing or abrasion alone. The interaction modes of washing and abrasion also showed significant differences in protective performance under a flame test. Under radiation exposure, the effect of combined washing and abrasion was more obvious. There was a positive correlation between the fabric weight and its protective performance with different treatments. The findings provide useful guidance for the actual use and maintenance of protective clothing.


Assuntos
Retardadores de Chama , Humanos , Roupa de Proteção , Têxteis
10.
Mult Scler Relat Disord ; 47: 102629, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33232908

RESUMO

BACKGROUND: Neuromyelitis optica spectrum disorders (NMOSD) and multiple sclerosis (MS) may be similar to each other in clinical features. The differential diagnosis between them remains challenging in clinical practice. This retrospective study is aimed to describe the difference of cerebrospinal fluid (CSF) lactate level between aquaporin-4 antibody (AQP4-Ab) positive NMOSD and MS, to discuss the possible explanation upon immunopathogenesis and the significance in differential diagnosis. METHOD: We retrospectively analysed cerebral biochemical results from 60 AQP4-Ab positive NMOSD and 55 MS Asian patients. To assess the diagnostic ability of cerebrospinal fluid lactate for distinguishing AQP4-Ab positive NMOSD from MS using receiver operating characteristic (ROC) curve analysis. RESULTS: The cerebrospinal fluid lactate level is significantly higher in AQP4-Ab positive NMOSD than in MS based on multiple linear regression (P<0.0001). The differential diagnostic efficacy of cerebrospinal fluid lactate distinguishing AQP4-Ab positive NMOSD from MS reached an area under ROC curve (AUC) of 0.8842 (95% CI 0.82-0.95, P<0.0001), using 1.50 as the diagnostic critical point of the cerebrospinal fluid lactate level, the sensitivity was 88.3%, the specificity was 78.2%. CONCLUSION: The cerebrospinal fluid lactate level differs between AQP4-Ab positive NMOSD and MS, which also contributes in differential diagnosis. The distinct patterns of cerebral biochemical results may cast a light on the immunopathogenesis of AQP4-Ab positive NMOSD.


Assuntos
Neuromielite Óptica , Aquaporina 4 , Autoanticorpos , Diagnóstico Diferencial , Humanos , Lactatos , Neuromielite Óptica/diagnóstico , Estudos Retrospectivos
11.
Neuropsychiatr Dis Treat ; 16: 2649-2660, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33177828

RESUMO

OBJECTIVE: Infectious encephalitis (IE) and autoimmune encephalitis (AE) are symptomatically similar in clinic, however essentially different in pathogenesis. Therefore, the objective of this study was to identify specific features to distinguish the two types of encephalitis for early effective diagnosis and treatments through a comparative analysis. METHODS: Fifty-nine IE patients and 36 AE patients were enrolled. The patients with IE were divided into viral encephalitis (VE) and bacterial encephalitis (BE) according to the pathogens in cerebrospinal fluid (CSF). Patients with AE were categorized by with or without neural autoantibodies (NAAb). We further divided patients with NAAb into those with neural cell-surface antibodies (NSAbs) or intracellular antibodies (Abs). Clinical features, laboratory data, and imaging findings were compared between AE, IE, and subgroups. RESULTS: Memory deficits, involuntary movement, and seizures were relatively more commonly presenting symptoms in AE patients (p < 0.05). The positive rate of Pandy test was higher in IE patients (p = 0.007). Decreased leukocyte, erythrocyte, and platelet counts in blood were found in IE patients (p < 0.05). Lower serum calcium level was found in VE compared to BE (p = 0.027). Meanwhile, higher serum calcium level was found in patients with NSAbs compared with intracellular Abs (p = 0.034). However, higher levels of LDH in CSF were found in patients with intracellular Abs (p = 0.009). In magnetic resonance imaging, hippocampus lesions were more commonly present in patients with AE (p = 0.042). Compared with AE patients, more IE patients displayed the background electroencephalogram rhythm of slow-frequency delta (p = 0.013). CONCLUSION: Involuntary movement and memory deficits were more specifically present in AE patients. CSF Pandy, blood routine test and hippocampus lesions detections were potential markers for distinguishing AE and IE. Further, CSF LDH, and serum calcium levels were potentially useful to distinguish subgroups of encephalitis.

12.
BMC Neurol ; 20(1): 307, 2020 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-32814555

RESUMO

BACKGROUND: Interleukin 36 (IL-36), as a gradually recognized cytokine, is involved in the occurrence and evolution of autoimmune diseases. Nevertheless, the relationship between myasthenia gravis (MG) and IL-36 is rarely reported. METHODS: We evaluated the serum levels of IL-36 (IL-36α, IL-36ß and IL-36γ) by enzyme-linked immunosorbent assay (ELISA). Further, clinical parameters in 97 MG patients and 49 healthy controls (HCs) were carefully measured. RESULTS: Serum IL-36γ levels were significantly elevated in the MG patients compared with the HCs (p < 0.0001). Compared to those in remission, patients in the acute phase exhibited higher levels of IL-36α and IL-36γ (p = 0.038 and p = 0.011, respectively). Furthermore, patients with generalized MG (GMG) exhibited markedly higher serum IL-36γ levels than those with ocular MG (OMG) (p = 0.003). CONCLUSIONS: The serum levels of IL-36γ in patients with MG were increased and positively correlated with disease severity and may thus have potential as a serological MG marker.


Assuntos
Biomarcadores/sangue , Interleucina-1/sangue , Miastenia Gravis/sangue , Miastenia Gravis/imunologia , Adulto , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Adulto Jovem
13.
Immunobiology ; 225(3): 151959, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32517881

RESUMO

AIMS: Neuromyelitis optica spectrum disorders (NMOSD) are aquaporin-4 antibody-mediated diseases of the central nervous system. Endothelin-1 (ET-1) is an inflammatory cytokine released by vascular endothelial cells and activated astrocytes. Previous studies have reported the aberrant expressions of cytokines/chemokines in patients diagnosed with NMOSD. However, the serum levels of ET-1 in NMOSD patients remain unknown. The purpose of this study was to measure the serum levels of ET-1 and other immune-related cytokines/chemokines in patients with NMOSD, and to investigate the correlation between serum ET-1 levels and clinical characteristics of NMOSD. METHODS: Thirty-eight patients with NMOSD and twenty-eight healthy controls (HCs) were recruited in this study. The serum concentrations of ET-1 and other cytokines/chemokines were measured, and their correlations to the clinical features of patients with NMOSD were analyzed. RESULTS: The serum levels of ET-1 in patients with NMOSD were significantly higher than those in HCs (P =  0.0001). The serum concentrations of ET-1 were positively correlated with the Expanded Disability Status Scale score (r = 0.428, P = 0.0183). High-dose intravenous methylprednisolone treatment significantly reduced the levels of ET-1 and interleukin (IL)-6 in blood, but significantly increased the serum concentrations of IL-10 in NMOSD patients. No correlations were found between serum ET-1 levels and the concentrations of other cytokines/chemokines in these patients. CONCLUSION: ET-1 and IL-6 might exert pro-inflammatory effects in the pathogenesis of NMOSD, whereas IL-10 played an anti-inflammatory role in this process. ET-1 might be a potential biomarker for predicting the severity of NMOSD. However, the serum levels of ET-1 were not correlated with the changes of other cytokines/chemokines in patients with NMOSD. The involvement of ET-1 in the development of NMOSD needs to be further studied.


Assuntos
Biomarcadores , Endotelina-1/sangue , Neuromielite Óptica/sangue , Neuromielite Óptica/diagnóstico , Citocinas/sangue , Citocinas/metabolismo , Suscetibilidade a Doenças , Regulação da Expressão Gênica , Humanos , MicroRNAs/genética , Monócitos/imunologia , Monócitos/metabolismo , Neuromielite Óptica/etiologia , Prognóstico , Índice de Gravidade de Doença , Transdução de Sinais
14.
Eur J Pharmacol ; 882: 173272, 2020 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-32535096

RESUMO

Dipeptidyl Peptidase-4 (DPP-4) is a specific enzyme hydrolyzing the incretin hormone glucagon like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) to reduce insulin secretion, meanwhile DPP-4 inhibitors play an important role in diabetic therapy. In present study, 14 potential inhibitors were screened with an inhibition over 50% on DPP-4 activity from Xiao-Ke-An formula (XKA) and 12 of them exhibited a dose-dependently inhibitory effect at concentrations of 5-50 µmol/l. We found 10 DPP-4 inhibitors restrained differentiation of 3T3-L1 pre-adipocytes as well as reducing the triglycerides and total cholesterol content in 3T3-L1 adipocytes. Furthermore, 7 DPP-4 inhibitors promoted the glucose consumption in insulin-resistance BNL CL.2 cells. Thereinto, ginsenoside Rk1 up-regulated the protein kinase B (AKT) and glycogen synthase kinase-3 (GSK-3ß) phosphorylation expression, while kukoamine B and coptisine hydrochloride obviously increased the phosphorylation of AKT protein and columbamine, panaxadiol, ginsenoside Ro, timosaponin AI significantly promoted the phosphorylation of GSK-3ß protein. It's our first effort to confirm those seven compounds could serve as DPP-4 inhibitors to attenuate DPP-4 activities, accompanied with the ability to adjust glucolipid metabolism. Moreover, activating the AKT/GSK-3ß signaling pathway to ameliorate insulin resistant may be the anti-diabetic mechanism of XKA.


Assuntos
Inibidores da Dipeptidil Peptidase IV/farmacologia , Medicamentos de Ervas Chinesas , Glucose/metabolismo , Glicogênio Sintase Quinase 3 beta/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Animais , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Colesterol/metabolismo , Dipeptidil Peptidase 4/metabolismo , Camundongos , Transdução de Sinais , Triglicerídeos/metabolismo
15.
Neurol Sci ; 41(10): 2859-2866, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32328833

RESUMO

BACKGROUND AND OBJECTIVE: Autoimmune longitudinal extensive transverse myelitis (LETM) is often combined with connective tissue disorders (CTD). The purpose of this study was to compare the clinical characteristics of autoimmune LETM with and without CTD. METHODS: Ninety-two patients diagnosed with autoimmune LETM were enrolled from our clinical database and divided into two groups depending on whether they had a concomitant diagnosis of CTD. Differences in clinical, serological, and imaging characteristics between the two groups were evaluated and compared. RESULTS: Fifty-nine LETM patients without CTD and 33 LETM patients with CTD were included. LETM patients with CTD had higher Kurtzke Expanded Disability Status Scale at nadir and more severe sensory dysfunction (p < 0.05) than those without CTD. It was also found that LETM patients with CTD, compared with those without CTD, had elevated levels of immune inflammation markers such as IgG, IgA, and globulins (p < 0.05). These abovementioned characteristics were more prominent in patients with aquaporin-4 antibodies (AQP4-ab) than in those without them. In addition, the most common type of CTD in LETM was Sjögren syndrome (SS), which was usually diagnosed at the time of LETM or later. CONCLUSION: LETM patients with CTD, especially those with AQP4-ab, had greater sensory dysfunction and higher levels of inflammatory markers than did LETM patients without CTD. Multicenter cooperation and long-term follow-up are necessary to further study the inherent implications and prognosis of the disease.


Assuntos
Mielite Transversa , Neuromielite Óptica , Aquaporina 4 , Autoanticorpos , Tecido Conjuntivo , Humanos , Imageamento por Ressonância Magnética , Mielite Transversa/complicações , Mielite Transversa/diagnóstico , Estudos Retrospectivos
16.
Neuromolecular Med ; 22(3): 335-340, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-31933131

RESUMO

As a type of stress, maternal separation (MS) has been one of the most widely used models in neuropsychiatric research. An increasing number of studies has found that MS not only affects the function of the hypothalamic-pituitary-adrenal axis and hippocampal 5-hydroxytryptamine system, but also causes dysfunction of the central dopamine (DA) system and increases the susceptibility of dopaminergic neurons to pathogenic factors of Parkinson's disease (PD), for instance, 6-hydroxydopamine, thus impairing motor function. We reviewed the impact of MS on the DA system and its correlation with PD and found the following: (1) discrepant effects of MS on the DA system have been reported; (2) MS is a good model to study the impact of stress on the occurrence and development of PD, however, unified modeling criteria of MS are required; (3) correlation between MS and PD may involve the impact of MS on the DA system, which however is not the only connection; (4) intervening measures can block pathways between MS and PD, which provides reference for the prevention of PD in specific populations such as left-behind children.


Assuntos
Dopamina/fisiologia , Sistema Hipotálamo-Hipofisário/fisiopatologia , Privação Materna , Doença de Parkinson/etiologia , Sistema Hipófise-Suprarrenal/fisiopatologia , Adulto , Experiências Adversas da Infância , Criança , Criança Abandonada , Corpo Estriado/fisiopatologia , Neurônios Dopaminérgicos/patologia , Feminino , Heterogeneidade Genética , Humanos , Modelos Neurológicos , Doença de Parkinson/fisiopatologia , Doença de Parkinson/prevenção & controle , Substância Negra/fisiopatologia
17.
Medicine (Baltimore) ; 98(44): e17826, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31689870

RESUMO

Current study was to evaluate the prevalence of guideline recommended medications adherence in myocardial infarction (MI) patients postpercutaneous coronary intervention (PCI) and the association of medication nonadherence and major adverse cardiovascular events (MACEs).MI patients who underwent PCI in the last 12 months were enrolled. Demographic and clinical characteristics were collected and guideline recommended medications were evaluated. Patients were divided into with and without MACEs groups.Compared to patients without MACEs, those with MACEs were older (54.8 ±â€Š16.4 vs 51.1 ±â€Š15.2 years), more likely to be smoker (40.2% vs 31.9%), have higher body mass index (BMI; 25.0 ±â€Š6.1 vs 23.8 ±â€Š5.7 kg/m), diabetes (47.5% vs 37.8%), ischemic stroke (34.4% vs 25.6%), and estimated lower glomerular filtration rate (85.4 ±â€Š9.6 vs 92.6 ±â€Š10.7 mL/minute/1.73 m). Patients with MACEs were also more likely to present with ST-elevation MI (STEMI; 54.1% vs 48.4%) and to undergo urgent PCI (62.3% vs 56.3%). Furthermore, patients with MACEs were less likely to adhere to dual antiplatelet therapy (77.9% vs 85.9%), renin-angiotensin system inhibitor (62.3% vs 69.7%), and beta-blocker (69.7% vs 72.8%) treatment. In unadjusted model, medication nonadherence was associated with 2-fold higher odds of MACEs. After adjustment for demographics, risk factors, comorbidities, and peri-PCI characteristics, medications nonadherence remained independently associated with MACEs, with odds ratio of 1.40 (95% confidence interval: 1.29-1.87).Medications adherence rate among MI patients post-PCI is suboptimal in China, which is independently associated with MACEs.


Assuntos
Fármacos Cardiovasculares/uso terapêutico , Doenças Cardiovasculares/epidemiologia , Adesão à Medicação/estatística & dados numéricos , Infarto do Miocárdio/tratamento farmacológico , Adulto , Idoso , China/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/cirurgia , Intervenção Coronária Percutânea , Prevalência
18.
Sci Total Environ ; 685: 856-866, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31247434

RESUMO

Oil spills are major threats to marine ecosystems. Here, we establish a three-dimensional oil spill model to simulate and project the short- and long-term trajectories of oil slicks and oil-contaminated water that leaked from the Sanchi wreckage. The pollution probability in surrounding areas for the period up to 180 days after the Sanchi sank is statistically analysed. The short-term simulations are consistent with synchronous SAR images and observational reports. The potentially polluted areas depend on the properties of the released oil. The coastal areas most likely to be affected by the bunker oil are located in the Ryukyu Island Chain, Tsushima Strait, on the south and east coasts of Japan. Approximately 50% to 70% of oil particles remain in the ocean and mainly expand along the Ryukyu Island Chain and the region southeast of the Sanchi wreck. Subsurface oil-contaminated water is likely to enter the Sea of Japan along the Tsushima Strait. Due to the rapid evaporation rate of condensate oil, the potentially polluted area is confined to regions within a 100 × 100 km area around the location of the shipwreck, and the contaminated region is closely associated with the surface wind.

19.
Opt Express ; 21(1): 1076-86, 2013 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-23389001

RESUMO

A three-layered Ag-low-permittivity (LP)-high-permittivity (HP) nanoshell is proposed as a plausible meta-atom for building the three-dimensional isotropic negative refractive index metamaterials (NIMs). The overlap between the electric and magnetic responses of Ag-LP-HP nanoshell can be realized by designing the geometry of the particle, which can lead to the negative electric and magnetic polarizabilities. Then, the negative refractive index is found in the random arrangement of Ag-LP-HP nanoshells. Especially, the modulation of the middle LP layer can move the negative refractive index range into the visible region. Because the responses arise from the each meta-atom, the metamaterial is intrinsically isotropic and polarization independent. It is further found with the increase of the LP layer thickness that the negative refractive index range of the random arrangement shows a large blue-shift and becomes narrow. With the decrease of the filling fraction, the negative refractive index range shows a blue-shift and becomes narrow while the maximum of the negative refractive index decreases.

20.
Opt Express ; 20(24): 26559-67, 2012 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-23187511

RESUMO

The influences of the symmetry-breaking on the plasmon resonance couplings in the isolated gold nanotube and the gold nanotube dimer have been investigated by means of the finite element method. It is found that the core offset of gold nanotubes leads to the red-shifts of the low energy modes and the enhanced near-field on the thin shell side of the symmetry-broken gold nanotube (SBGNT). In the weak coupling model of the SBGNT dimer, the interference of the bonding octupole mode of the dimer with the dipole modes causes a strong Fano-like resonance in scattering spectrum. The Fano dip shows a red-shift and becomes deep with the increase of the offset-value. In the strong coupling model of the SBGNT dimer, the coupling between two SBGNTs induces giant electric field enhancement at the gap of the dimer, which is much larger than that in the symmetry gold nanotube dimer. The SBGNT with larger offset-value exhibits stronger near-field at the "hot spot".


Assuntos
Simulação por Computador , Ouro/química , Luz , Modelos Teóricos , Polímeros/química , Ressonância de Plasmônio de Superfície/instrumentação , Dimerização , Humanos , Nanotubos
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