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1.
Ann Clin Transl Neurol ; 7(2): 200-209, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32023010

RESUMO

OBJECTIVE: To describe the clinical and genetic features of two patients with different phenotypes due to various Dynactin 1 (DCTN1) gene mutations and further explore the phenotype-genotype relationship. METHODS: Patient 1 is a 23-year-old man with congenital foot deformity and life-long distal muscle weakness and atrophy. Patient 2 is a 48-year-old woman with adult-onset progressive weakness, lower limbs atrophy, and pyramid bundle signs. Electrophysiology test showed normal nerve conduction velocity of both patients and neurogenic changes in needle electromyography. Open sural nerve biopsy for Patient 1 showed slight loss of myelinated nerve fibers. Both patients were performed with whole-exome sequencing followed by functional study of identified variants. RESULTS: Two mutations in DCTN1 gene were identified in Patient 1 (c.626dupC) and Patient 2 (c.3823C>T), respectively. In vitro, the wild type mostly located in cytoplasm and colocalized with α-tubulin. However, c.626dupC tended to be trapped into nuclear and the c.3823C>T formed cytoplasmic aggregates, both losing colocalization with α-tubulin. Western blotting showed a truncated mutant with less molecular weight of c.626dupC was expressed. INTERPRETATION: We identify two novel DCTN1 mutations causing different phenotypes: (1) early-onset distal hereditary motor neuropathy plus congenital foot malformation and (2) amyotrophic lateral sclerosis, respectively. We provide the initial evidence that foot developmental deficiency probably arises from subcellular localizing abnormality of Dynactin 1, revealing DCTN1-related spectrum is still expanding.

2.
CNS Neurosci Ther ; 26(2): 155-166, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31503421

RESUMO

Alzheimer's disease (AD) is characterized by ß-amyloid (Aß) deposition and Tau phosphorylation, in which its pathogenesis has not been cleared so far. The metabolism of Aß and Tau is critically affected by the autophagy. Abnormal autophagy is thought to be involved in the pathogenesis of AD, regulating autophagy may become a new strategy for AD treatment. In the early stage of AD, the presence of Aß and Tau can induce autophagy to promote their clearance by means of mTOR-dependent and independent manners. As AD progress, the autophagy goes aberrant. As a result, Aß and Tau generate continually, which aggravates both autophagy dysfunction and AD. Besides, several related genes and proteins of AD can also adapt autophagy to make an effect on the AD development. There seems to be a bi-directional relationship between AD pathology and autophagy. At present, this article reviews this relationship from these aspects: (a) the signaling pathways of regulating autophagy; (b) the relationships between the autophagy and the processing of Aß; (c) Aß and Tau cause autophagy dysfunction; (d) normal autophagy promotes the clearance of Aß and Tau; (e) the relationships between the autophagy and both genes and proteins related to AD: TFEB, miRNAs, Beclin-1, Presenilin, and Nrf2; and (f) the small molecules regulating autophagy on AD therapy. All of the above may help to further elucidate the pathogenesis of AD and provide a theoretical basis for clinical treatment of AD.

3.
Int J Mol Med ; 45(1): 186-194, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31746354

RESUMO

Senescence of cardiomyocytes is considered a key factor for the occurrence of doxorubicin (Dox)­associated cardiomyopathy. The NOD­like receptor family pyrin domain­containing 3 (NLRP3) inflammasome is reported to be involved in the process of cellular senescence. Furthermore, thioredoxin­interactive protein (TXNIP) is required for NLRP3 inflammasome activation and is considered to be a key component in the regulation of the pathogenesis of senescence. Studies have demonstrated that pretreatment with honokiol (Hnk) can alleviate Dox­induced cardiotoxicity. However, the impact of Hnk on cardiomyocyte senescence elicited by Dox and the underlying mechanisms remain unclear. The present study demonstrated that Hnk was able to prevent Dox­induced senescence of H9c2 cardiomyocytes, indicated by decreased senescence­associated ß­galactosidase (SA­ß­gal) staining, as well as decreased expression of p16INK4A and p21. Hnk also inhibited TXNIP expression and NLRP3 inflammasome activation in Dox­stimulated H9c2 cardiomyocytes. When TXNIP expression was enforced by adenovirus­mediated gene overexpression, the NLRP3 inflammasome was activated, which led to inhibition of the anti­inflammation and anti­senescence effects of Hnk on H9c2 cardiomyocytes under Dox treatment. Furthermore, adenovirus­mediated TXNIP­silencing inhibited the NLRP3 inflammasome. Consistently, TXNIP knockdown enhanced the anti­inflammation and anti­senescence effects of Hnk on H9c2 cardiomyocytes under Dox stimulation. In summary, Hnk was found to be effective in protecting cardiomyocytes against Dox­stimulated senescence. This protective effect was mediated via the inhibition of TXNIP expression and the subsequent suppression of the NLRP3 inflammasome. These results demonstrated that Hnk may be of value as a cardioprotective drug by inhibiting cardiomyocyte senescence.

4.
J Nanosci Nanotechnol ; 20(2): 1013-1019, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31383099

RESUMO

Nanomaterial-based flexible strain sensors have developed rapidly in recent years. Here, we propose a flexible strain sensor based on polydimethylsiloxane with carbon nanotubes (CNTs) and graphene quantum dots (GQDs). Different weight ratios of CNTs and GQDs were used as the sensitive units of the strain sensors. After analyzing the results of current-voltage curves and the strain effects of the sensors, we concluded that the introduction of GQDs played an important role in improving the sensitivity of the sensors. The gauge factor of the as-prepared strain sensors ranges from 0 to 841.42.

5.
BMC Infect Dis ; 19(1): 1082, 2019 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-31881849

RESUMO

BACKGROUND: To investigate the clinical features of septic pulmonary embolism (SPE) cases and prognostic factors for in-hospital mortality in China. METHODS: A retrospective analysis was conducted of SPE patients hospitalized between January 2007 and June 2018 in the Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Guangxi Medical University. RESULTS: A total of 98 patients with SPE were identified. All patients had bilateral multiple peripheral nodules on chest computed tomography. The most common pathogen found in blood culture was Staphylococcus aureus (10/33, 30.3%). Transthoracic echocardiography was performed in 39 patients and 20 showed vegetations. Bronchoscopy was performed in 24 patients. Bronchoalveolar lavage fluid (BALF) was obtained from 15 patients (62.5%) and showed predominantly polymorphonuclear cell infiltration (52%, range of 48%~ 63%). Four patients received transbronchial lung biopsy, and histopathological examinations revealed suppurative pneumonia and organizing pneumonia. The in-hospital mortality rate was 19.4%. Age (odds ratio [OR] 1.100; 95% confidence interval [CI] 1.035-1.169), hypotension (OR 7.260; 95% CI 1.126-46.804) and ineffective or delay of empirical antimicrobial therapy (OR 7.341; 95% CI 1.145-47.045) were found to be independent risk factors for in-hospital mortality, whereas drainage treatment was found to be a protective factor (OR 0.33; 95% CI 0.002-0.677). CONCLUSIONS: SPE cases presented with nonspecific clinical manifestations and radiologic features. Blood cultures and bronchoscopy are important measures for early diagnosis and differential diagnosis. There is relationship between primary infection sites and the type of pathogen. Maintaining normal blood pressure and providing timely and appropriate initial antimicrobial therapy for effective control of the infection could improve prognosis.


Assuntos
Mortalidade Hospitalar , Embolia Pulmonar/diagnóstico , Embolia Pulmonar/mortalidade , Choque Séptico/diagnóstico , Choque Séptico/mortalidade , Infecções Estafilocócicas/diagnóstico , Infecções Estafilocócicas/mortalidade , Staphylococcus aureus/isolamento & purificação , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Líquido da Lavagem Broncoalveolar/microbiologia , Broncoscopia , China , Cuidados Críticos , Ecocardiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonia/diagnóstico por imagem , Pneumonia/tratamento farmacológico , Prognóstico , Embolia Pulmonar/tratamento farmacológico , Embolia Pulmonar/microbiologia , Estudos Retrospectivos , Choque Séptico/tratamento farmacológico , Choque Séptico/microbiologia , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Adulto Jovem
6.
Biosci Rep ; 39(1)2019 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-30498091

RESUMO

The aim of the present study was to understand the possible role of the Dihydromyricetin (DHM) in Alzheimer's disease (AD) rat model through regulation of the AMPK/SIRT1 signaling pathway. Rats were divided into Sham group, AD group, AD + DHM (100 mg/kg) group and AD + DHM (200 mg/kg) group. The spatial learning and memory abilities of rats were assessed by Morris Water Maze. Then, the inflammatory cytokines expressions were determined by radioimmunoassay while expressions of AMPK/SIRT1 pathway-related proteins by Western blot; and the apoptosis of hippocampal cells was detected by TdT-mediated dUTP nick end labeling assay. AD rats had an extended escape latency with decreases in the number of platform crossings, the target quadrant residence time, as well as swimming speed, and the inflammatory cytokines in serum and hippocampus were significantly elevated but AMPK/SIRT1 pathway-related proteins were reduced. Meanwhile, the apoptosis of hippocampal cells was significantly up-regulated with decreased Bcl-2 and increased Bax, as compared with Sham rats (all P<0.05). After AD rats treated with 100 or 200 mg/kg of DHM, the above effects were significantly reversed, resulting in a completely opposite tendency, and especially with 200 mg/kg DHM treatment, the improvement of AD rats was more obvious. DHM exerts protective role in AD via up-regulation of AMPK/SIRT1 pathway to inhibit inflammatory responses and hippocampal cell apoptosis and ameliorate cognitive function.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Doença de Alzheimer/tratamento farmacológico , Cognição/efeitos dos fármacos , Flavonóis/farmacologia , Nootrópicos/farmacologia , Sirtuína 1/metabolismo , Proteínas Quinases Ativadas por AMP/genética , Doença de Alzheimer/induzido quimicamente , Doença de Alzheimer/genética , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/administração & dosagem , Animais , Apoptose , Cognição/fisiologia , Citocinas/genética , Citocinas/metabolismo , Modelos Animais de Doenças , Regulação da Expressão Gênica , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Hipocampo/patologia , Injeções Intraperitoneais , Injeções Intraventriculares , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Aprendizagem em Labirinto/fisiologia , Memória/efeitos dos fármacos , Memória/fisiologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/patologia , Fragmentos de Peptídeos/administração & dosagem , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Sirtuína 1/genética , Técnicas Estereotáxicas
7.
Materials (Basel) ; 11(12)2018 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-30513628

RESUMO

Tiles are commonly used to cover the exteriors of buildings in Taiwan. However, older buildings in Taiwan encounter the problem of tiles falling off due to natural deterioration, which is unsightly, and more importantly, a threat to public safety. Nevertheless, no current method exists that can effectively detect flaws in building tiles in real time. This study combined the fields of civil engineering and automatic control to reduce risks caused by falling tiles by improving real-time detection of at-risk areas. Micro-resistance was combined with fuzzy theory as the logical foundation for evaluating tile status. String-type strain gauges were adopted as sensors to design a smart skin sensory system that could measure signs of deterioration in tile surface lesions. The design was found to be feasible. In the future, it can be further developed for facile real-time assessment of tile status.

8.
Biomed Pharmacother ; 108: 1651-1657, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30372867

RESUMO

Paeoniflorin-6'-O-benzene sulfonate (code: CP-25), is an active monomer obtained by modifying the structure of paeoniflorin (Pae). CP-25 can alleviate the course of adjuvant arthritis (AA) rats by regulating immune inflammatory response and reducing bone damage. In addition, our research has found that immune cells are important target cells for its anti-inflammatory and immunomodulatory effects. Therefore, it is of great significance to study the pharmacokinetics of CP-25 in immune cells. The aim of this study was to investigate the absorption and efflux of CP-25 in plasma and peripheral blood mononuclear cells (PBMCs) of rats. We established a sensitive ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) to rapidly determine CP-25 in plasma and PBMC of rat. We found that the transport amount of CP-25 in PBMC gradually decreased with the increase of time, and reached equilibrium after 1 h. Moreover, there is a certain correlation between the concentration of CP-25 in plasma and the concentration of CP-25 in PBMC. In addition, we used several transporter inhibitors to study their effects on the efflux of CP-25 in PBMC. The efflux of CP-25 in PBMC increased with the increase of time in the first 30 min, and the efflux of CP-25 decreased gradually after 30 min. Furthermore, after multiple administration of 50 mg/kg in rats, concentration of CP-25 in PBMC is similar to the change of concentration of CP-25 in plasma. Our results suggest that CP-25 may enter PBMC by passive transport, and P-glycoprotein (P-gp), multidrug resistance-associated protein 2 (MRP2) and breast cancer resistance protein (BCRP) may be involved in the efflux of CP-25 in PBMC. This research provides a basis and guidance for further study of the clinical application of CP-25.


Assuntos
Absorção Fisiológica , Glucosídeos/sangue , Leucócitos Mononucleares/metabolismo , Monoterpenos/sangue , Espectrometria de Massas em Tandem/métodos , Administração Oral , Animais , Transporte Biológico , Cromatografia Líquida de Alta Pressão , Glucosídeos/administração & dosagem , Glucosídeos/farmacocinética , Modelos Lineares , Masculino , Proteínas de Membrana/metabolismo , Monoterpenos/administração & dosagem , Monoterpenos/farmacocinética , Ratos Sprague-Dawley , Temperatura , Fatores de Tempo
9.
Curr Med Sci ; 38(2): 199-203, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30074176

RESUMO

Heart failure (HF) is the end stage of various kinds of cardiovascular diseases and leads to a high mortality worldwide. Numerous studies have demonstrated that frequencies of CD4+CD25+Foxp3+ regulatory T cells (Tregs) are reduced in HF patients and properly expanding Tregs attenuates HF progression. Histone deacetylase (HDAC) 9 has been revealed to contribute to several cardiovascular and cerebrovascular diseases. Plenty of studies showed that HDAC9 negatively regulated the number and function of Tregs. Thus, we aim to investigate the expression of HDAC 9 in patients with chronic heart failure (CHF) and the relationship among HDAC9, Tregs and CHF. Our research showed a reduced number of Tregs and an increased expression of HDAC9 mRNA in CHF patients. Patients with CHF were divided into two groups by heart function grade of New York Heart Association (NYHA), we found that the HDAC9 mRNA expression level in NYHA grade II-III group were lower than that in NYHA grade IV group. More importantly, the correlation study suggested that the expression of HDAC9 mRNA was negatively correlated to Tregs frequency and left ventricular ejection fraction (LVEF), whereas positively correlated to larger left ventricular end-diastolic dimension (LVEDD) and B-type natriuretic peptide (BNP) in patients with CHF. The correlation studies also showed a positive correlation between HDAC9 and the severity of CHF. Our research suggests that HDAC9 may be a new indicator for assessing CHF and it may offer a new direction for research of CHF.


Assuntos
Insuficiência Cardíaca/enzimologia , Insuficiência Cardíaca/imunologia , Histona Desacetilases/metabolismo , Proteínas Repressoras/metabolismo , Linfócitos T Reguladores/enzimologia , Idoso , Doença Crônica , Feminino , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo , Insuficiência Cardíaca/genética , Insuficiência Cardíaca/fisiopatologia , Testes de Função Cardíaca , Histona Desacetilases/genética , Humanos , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proteínas Repressoras/genética
10.
Int J Mol Med ; 42(3): 1327-1340, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29901179

RESUMO

Diabetes is associated with an increased risk of cardiovascular disease. A decrease in the number and functionality of endothelial progenitor cells (EPCs) leads to reduced endothelial repair and the development of cardiovascular disease. The aim of the present study was to explore the effect and underlying mechanisms of nuclear factor erythroid 2­related factor 2 (Nrf2) on EPC dysfunction caused by diabetic mellitus. The biological functions of EPCs in streptozotocin­induced diabetic mice were evaluated, including migration, proliferation, angiogenesis and the secretion of vascular endothelial growth factor (VEGF), stromal­derived growth factor (SDF) and nitric oxide (NO). Oxidative stress levels in diabetic EPCs were also assessed by detecting intracellular reactive oxygen species (ROS), superoxide dismutase (SOD) and malondialdehyde (MDA). EPC senescence was evaluated by measuring p16 and b­gal expression and observing the senescence­associated secretory phenotype. In addition, the function of EPCs and level of oxidative stress were assessed following Nrf2 silencing or activation. Nrf2 silencing resulted in a decrease of EPC biological functions, accelerated cell senescence and increased oxidative stress, as indicated by ROS and MDA upregulation accompanied with decreased SOD activity. Furthermore, Nrf2 silencing inhibited migration, proliferation and secretion in EPCs, while it increased oxidative stress and cell senescence. Nrf2 activation protected diabetic EPCs against the effects of oxidative stress and cell senescence, ameliorating the biological dysfunction of EPCs derived from mice with diabetes. In conclusion, Nrf2 overexpression protected against oxidative stress­induced functional damage in EPCs derived from diabetic mice by regulating cell senescence.


Assuntos
Diabetes Mellitus Experimental/metabolismo , Células Progenitoras Endoteliais/citologia , Células Progenitoras Endoteliais/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Animais , Movimento Celular/fisiologia , Células Cultivadas , Senescência Celular/fisiologia , Diabetes Mellitus Experimental/genética , Masculino , Malondialdeído/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Óxido Nítrico/metabolismo , Estresse Oxidativo/fisiologia , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo
11.
Chin Med J (Engl) ; 130(21): 2601-2607, 2017 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-29067959

RESUMO

OBJECTIVE: This review aimed to provide a current recommendation to multidisciplinary physicians for early detection, diagnosis, and treatment of corticosteroid-induced osteonecrosis of the femoral head (ONFH) based on a comprehensive analysis of the clinical literature. DATA SOURCES: For the purpose of collecting potentially eligible articles, we searched for articles in the PubMed, Cochrane Library, Embase, and CNKI databases up to February 2017, using the following key words: "corticosteroid", "osteonecrosis of the femoral head", "risk factors", "diagnosis", "prognosis", and "treatment". STUDY SELECTION: Articles on relationships between corticosteroid and ONFH were selected for this review. Articles on the diagnosis, prognosis, and intervention of earlier-stage ONFH were also reviewed. RESULTS: The incidence of corticosteroid-induced ONFH was associated with high doses of corticosteroids, and underlying diseases in certain predisposed individuals mainly occurred in the first 3 months of corticosteroid prescription. The enhanced awareness and minimized exposure to the established risk factors and earlier definitive diagnosis are essential for the success of joint preservation. When following up patients with ONFH, treatment should be started if necessary. Surgical treatment yielded better results than conservative therapy in earlier-stage ONFH. The ideal purpose of earlier intervention and treatment is permanent preservation of the femoral head without physical restrictions in daily living. CONCLUSIONS: Clinicians should enhance their precaution awareness of corticosteroid-induced ONFH. For high-risk patients, regular follow-up is very important in the 1st year after high-dose prescription of corticosteroids. Patients with suspected ONFH should be referred to orthopedists for diagnosis and treatment in its earlier stage to preserve the joint.


Assuntos
Corticosteroides/toxicidade , Osteonecrose/induzido quimicamente , Osteonecrose/diagnóstico , Feminino , Cabeça do Fêmur/efeitos dos fármacos , Cabeça do Fêmur/patologia , Necrose da Cabeça do Fêmur/induzido quimicamente , Necrose da Cabeça do Fêmur/diagnóstico , Humanos , Masculino , Fatores de Risco
12.
Chin Med Sci J ; 32(3): 177-184, 2017 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-28956745

RESUMO

Objective To investigate the association between the polymorphism of C-689T in the peroxisome proliferator-activated receptor-γ2 (PPARγ2) promoter and coronary heart disease (CHD). Methods This case-controlled study was conducted in nondiabetic Chinese Han people, which enrolled 455 patients with CHD (cases) and 693 subjects without CHD (controls). Data of clinical indexes were collected, including height, body weight, waist circumstance, systolic blood pressure (SBP), diastolic blood pressure (DBP), smoking, drinking, physical activity, as well as body mass index (BMI). Fasting blood glucose (FBG), plasma total cholesterol (TC) and triglyceride (TG) levels were measured. Polymerase chain reaction-restricted fragments length polymorphism (PCR-RFLP) was used to determine the PPARγ2 promoter C-689→T substitution. The genotype distribution of PPARγ2 promoter C-689T, allelic frequency, clinical indexes, and laboratorial measurements were compared between the two groups. The effect of genotype on the risk of CHD was assessed using univariate and multivariate regression model. Results The genotype frequencies of CC, CT and TT in PPARγ2 promoter C-689T were 89.7%, 9.9% and 0.4% in the case group, and 93.1%, 6.6% and 0.3% in the control group, respectively (CC vs. CT+TT, χ2= 6.243, P=0.041). Carriers of -689T allele (n=95) had significantly higher TC level than non-carriers (n=1053) (5.12±1.26 vs. 4.76±1.22 mmol/L, P=0.001). Male carriers of -689T allele (n=51) were significantly higher in waist circumference, body weight, TC and TG than male non-carriers (n=656) (all P<0.05). In subjects whose BMI was over 25 kg/m2, carriers of -689T allele (n=82) had significantly higher levels of waist circumference, BMI, SBP and TC than non-carriers (n=231) (all p<0.05). The -689T allele was an independent risk factor for CHD (OR=1.668, 95%CI: 1.031-2.705, P=0.037) after adjusting for age, gender, waist circumference, body weight, BMI, smoking, physical activities, SBP, DBP, FBG, TC and TG level. Conclusion These data support the hypothesis that the -689T allele is associated with an increased risk of CHD, in Chinese Han people and correlates significantly with the profiles of CHD-related risk factors.


Assuntos
Alelos , Doença das Coronárias/genética , Frequência do Gene , PPAR gama/genética , Polimorfismo de Fragmento de Restrição , Regiões Promotoras Genéticas , Fatores Etários , Idoso , Grupo com Ancestrais do Continente Asiático , China , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais
13.
Med Sci Monit ; 23: 4665-4667, 2017 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-28959004

RESUMO

BACKGROUND Hypoxic preconditioning may be a key influence on functions of endothelial progenitor cells (EPCs). MATERIAL AND METHODS To investigate the role and mechanism of the Notch-Jagged1 pathway on endothelial progenitor cells in hypoxic preconditioning, endothelial progenitor cells were randomly allocated into 5 groups: 1 Normoxic control group; 2 Hypoxic blank group; 3 Hypoxic+25 µM DAPT group; 4 Hypoxic+50 µM DAPT group; 5 Hypoxic+100 µM DAPT group. After reoxygenation, protein and mRNA levels of Jagged1 were measured by Western blot and quantitative RT-PCR. The MTT test was used to assess proliferation. ELISA was used to measure NO and VEGF secretion. RESULTS Hypoxic preconditioning treatment significantly upregulated both protein and mRNA levels of Jagged1 in endothelial progenitor cells. It also enhanced proliferation ability and elevated secretion of NO and VEGF. Furthermore, after blocking the Notch pathway by using DAPT, Jagged1 expression and EP proliferation, migration, and secretion of NO and VEGF were decreased in a dose-dependent manner. CONCLUSIONS Our results suggest the Notch-Jagged1 pathway enhances EPCs proliferation and secretion ability during hypoxic preconditioning.


Assuntos
Células Progenitoras Endoteliais/metabolismo , Células Progenitoras Endoteliais/patologia , Proteína Jagged-1/metabolismo , Receptores Notch/metabolismo , Transdução de Sinais , Hipóxia Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Forma Celular/efeitos dos fármacos , Dipeptídeos/farmacologia , Células Progenitoras Endoteliais/efeitos dos fármacos , Humanos , Óxido Nítrico/metabolismo , Transdução de Sinais/efeitos dos fármacos , Cordão Umbilical/citologia , Fator A de Crescimento do Endotélio Vascular/metabolismo
14.
Artigo em Inglês | MEDLINE | ID: mdl-28684969

RESUMO

Neuroinflammation has been suggested to be involved in the pathogenesis of postoperative cognitive dysfunction (POCD). Electroacupuncture (EA) is an irreplaceable method in traditional Chinese medicine that is used for treating neurodegenerative diseases in clinical and experimental studies. The aim of this study was to examine whether EA improves cognitive dysfunction caused by surgery and to investigate the pathological mechanism of TLR2 and TLR4 in the hippocampus of aged rats. A rat model of POCD was established and treated with EA or minocycline. Both EA- and minocycline-treated rats performed significantly better than untreated operated rats in spatial memory tasks of the Morris water maze (MWM) test, spending comparatively greater amounts of time in the target zone during the probe test. Additionally, decreased levels of proinflammatory cytokines (IL-1ß, IL-6, TNF-α, and HMGB1) and decreased TLR2 and TLR4 protein expression in the hippocampus of EA- and minocycline-treated rats were detected. Our data suggested that EA treatment alleviated the cognition performance deficit and neuroinflammation in aged rats following surgery, which may be mediated by inhibiting the expression of hippocampal neuroinflammatory cytokines through the microglia/TLR2/4 pathway.

15.
Environ Pollut ; 225: 232-243, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28388519

RESUMO

Short-chain chlorinated paraffins (SCCPs) are widely used chemicals in household products and might cause adverse human health effects. However, limited information is available on the occurrence of SCCPs in indoor environments and their exposure risks on humans. In this study the concentrations, profiles and human exposure of SCCPs in indoor dust from five different indoor environments, including commercial stores, residential apartments, dormitories, offices and laboratories were characterized. The SCCPs levels ranged from 10.1 to 173.0 µg/g, with the median and mean concentration of 47.2 and 53.6 µg/g, respectively. No significant difference was found on concentrations among the five microenvironments. The most abundant compounds in indoor dust samples were homologues of C13 group, Cl7 group and N20 (N is the total number of C and Cl) group. In the five microenvironments, commercial stores were more frequently exposed to shorter carbon chained and higher chlorinated homologues. Three potential sources for SCCPs were identified by the multiple linear regression of factor score model and correspondence analysis. The major sources of SCCPs in indoor dust were technical mixtures of CP-42 (42% chlorine, w/w) and CP-52 b (52% chlorine, w/w). The total daily exposure doses and hazard quotients (HQ) were calculated by the human exposure models, and they were all below the reference doses and threshold values, respectively. Monte Carlo simulation was applied to predict the human exposure risk of SCCPs. Infants and toddlers were at risk of SCCPs based on predicted HQ values, which were exceeded the threshold for neoplastic effects in the worst case. Our results on the occurrences, sources and human exposures of SCCPs will be useful to provide a better understanding of SCCPs behaviors in indoor environment in China, and to support environmental risk evaluation and regulation of SCCPs in the world.


Assuntos
Poluição do Ar em Ambientes Fechados/estatística & dados numéricos , Poeira/análise , Monitoramento Ambiental/métodos , Exposição por Inalação/estatística & dados numéricos , Poluição do Ar em Ambientes Fechados/análise , Carbono/análise , Pré-Escolar , China , Humanos , Hidrocarbonetos Clorados/análise , Lactente , Parafina/análise , Medição de Risco
16.
J Chromatogr A ; 1479: 137-144, 2017 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-27939601

RESUMO

Covalent-organic frameworks (COFs) are a newfangled class of intriguing microporous materials. Considering their unique properties, COFs should be promising as packing materials for high performance liquid chromatography (HPLC). However, the irregular shape and sub-micrometer size of COFs synthesized via the traditional methods render the main obstacles for the application of COFs in HPLC. Herein, we report the preparation of methacrylate-bonded COF monolithic columns for HPLC to overcome the above obstacles. The prepared COF bonded monolithic columns not only show good homogeneity and permeability, but also give high column efficiency, good resolution and precision for HPLC separation of small molecules including polycyclic aromatic hydrocarbons, phenols, anilines, nonsteroidal anti-inflammatory drugs and benzothiophenes. Compared with the bare polymer monolithic column, the COF bonded monolithic columns show enhanced hydrophobic, π-π and hydrogen bond interactions in reverse phase HPLC. The results reveal the great potential of COF bonded monoliths for HPLC and COFs in separation sciences.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Metacrilatos/química , Anti-Inflamatórios não Esteroides/isolamento & purificação , Cromatografia Líquida de Alta Pressão/instrumentação , Cromatografia de Fase Reversa , Interações Hidrofóbicas e Hidrofílicas , Fenóis/isolamento & purificação , Hidrocarbonetos Policíclicos Aromáticos/isolamento & purificação , Polímeros/química , Porosidade , Temperatura , Tiofenos/isolamento & purificação
17.
J Geriatr Cardiol ; 13(10): 846-854, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27928227

RESUMO

BACKGROUND: Our previous study showed that the combined Chinese herbs containing scutellaria baicalensis georgi and gardenia jasminoids ellis inhibited atherosclerosis. In this study, we sought to determine if baicalin and geniposide could inhibit atherosclerosis through Wnt1 and dickkopf-related protein-1 (DKK1). METHODS: The wild-type and ApoE-/- mice were treated with baicalin, geniposide, and baicalin plus geniposide daily by gavage for 12 weeks. Blood lipid levels were measured with an automatic biochemistry analyzer. Aortic atherosclerotic lesion areas were analyzed with Image-ProPlus software. The mRNA and protein expression of DKK1, Wnt1 and nuclear factor-κB (NF-κB) were measured with RT-PCR and Western Blot. Serum levels of interleukin-12 (IL-12) were quantified with ELISA. RESULTS: The baicalin or geniposide monotherapy as well as combination therapy inhibited the development of atherosclerotic lesions, increased Wnt1 and decreased DKK1 expression and elevated the ratio of Wnt1/DKK1 compared with high-lipid diet group. However, only baicalin or geniposide monotherapy decreased NF-κB expression. Moreover, baicalin and geniposide mono- or combination therapy lowered IL-12 levels. Geniposide reduced both serum total cholesterol and low density lipoprotein levels, while baicalin either alone or in combination with geniposide did not affect serum lipid levels. In human, umbilical vein endothelial cells stimulated by oxidized low density lipoprotein, baicalin and geniposide also increased Wnt1 and decreased DKK1 expression and elevated the ratio of Wnt1/DKK1. CONCLUSIONS: Baicalin and geniposide exert inflammation-regulatory effects and may prevent atherosclerotic lesions through enhancing Wnt1 and inhibiting DKK1 expression.

18.
Cell Physiol Biochem ; 38(6): 2247-60, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27188168

RESUMO

BACKGROUND/AIMS: Due to its antitumor and gastroprotective properties, cochinchina momordica seed (CMS), has been widely used to treat cancer patients in Asia. Our previous reports have shown that CMS is able to induce the differentiation of B16-F1 melanoma cells. However, its functional component and mechanism remain unclear and are addressed in this study. METHODS AND RESULTS: CMSP (p-hydroxycinnamaldehyde isolated from CMS) inhibited the proliferation, migration and invasiveness of B16-F1 cells both in vivo and in vitro. CMSP also induced the differentiation of B16-F1 cells, as characterized by dendrite-like outgrowth, increased melanogenesis and enhanced tyrosinase activity. Furthermore, CMSP treatment reduced the level of malignant markers of melanoma, specifically S-100B and melanoma-derived growth regulatory protein precursor (MIA), in a concentration-dependent manner. According to a western blot analysis, B16-F1 cells treated with CMSP exhibited a sustained increase in p-P38 and decreased activities of ERK and JNK. Our data further indicated that the downregulation of GTP-RhoA, which was mediated by increased cAMP release, was involved in CMSP-induced changes in MAPK, while LPA (Lysophosphatidic acid) partially reversed CMSP-induced B16 cell differentiation. CONCLUSION: These results demonstrated that CMSP-induced differentiation of B16F1 cells may occur through the RhoA-MAPK axis, which suggests a new potential strategy for melanoma treatment.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Diferenciação Celular/efeitos dos fármacos , Cinamatos/farmacologia , Melanoma Experimental/tratamento farmacológico , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proteína rhoA de Ligação ao GTP/metabolismo , Animais , Antineoplásicos Fitogênicos/química , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Cinamatos/química , Melanoma Experimental/metabolismo , Melanoma Experimental/patologia , Camundongos , Momordica/química , Monofenol Mono-Oxigenase/metabolismo , Sementes/química
19.
Int J STD AIDS ; 27(2): 127-32, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25725492

RESUMO

Bisexual men (men who have sex with men and women) are potential epidemiological bridges responsible for the spread of HIV and other sexually transmitted infections from men who have sex with men only to the heterosexual population. We aimed to estimate the prevalence of syphilis and HIV and the factors associated with syphilis infection among men who have sex with men and women and men who have sex with men only from Shijiazhuang, China. In 2011-2013, a cross-sectional cohort of 427 men who have sex with men was recruited by a snowball sampling method and tested for syphilis and HIV. Chi square and logistic regression were performed to identify syphilis risk factors. Among the 427 men who have sex with men, 71 (16.6%) cases were syphilis-positive and 16 cases (3.7%) were HIV-positive. The proportions of men who have sex with men and women and men who have sex with men only in the total sample were 31.4% and 68.6%, respectively. Men who have sex with men and women exhibited double the syphilis prevalence of men who have sex with men only and were more likely to practice insertive anal sex. Higher education level, being married, having more male partners, and both receptive and insertive anal sex roles were associated with syphilis among men who have sex with men and women. Residing in suburban areas, being married, being HIV positive, and an absence of desire to change sexual orientation were associated with syphilis among men who have sex with men only. Therefore, men who have sex with men and women represent an important sub-group in the syphilis epidemic and further interventions should be developed to reduce risk among different sub-sets of men who have sex with men.


Assuntos
Bissexualidade/estatística & dados numéricos , Infecções por HIV/epidemiologia , Homossexualidade Masculina/estatística & dados numéricos , Sífilis/epidemiologia , Adolescente , Adulto , Grupo com Ancestrais do Continente Asiático/estatística & dados numéricos , China/epidemiologia , Cidades , Preservativos/estatística & dados numéricos , Estudos Transversais , Feminino , Infecções por HIV/transmissão , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Assunção de Riscos , Parceiros Sexuais , Doenças Sexualmente Transmissíveis/epidemiologia , Sífilis/transmissão , Adulto Jovem
20.
Zhongguo Zhong Xi Yi Jie He Za Zhi ; 35(10): 1192-5, 2015 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-26677669

RESUMO

OBJECTIVE: To observe the clinical effect of Ziyin Huoxue Granule (ZHG) combined glucocorticoids and antibiotics in treatment of radiation pneumonitis. METHODS: Totally 70 radiation pneumonitis patients were assigned to the treatment group and the control group according to random digit table, 35 in each group. All patients received glucocorticoids and antibiotics. Patients in the treatment group additionally took ZHG, one dose per day for 4 successive weeks. Watters clinical-radiologic-physiologic (CRP) score, Karnofsky Performance Status Scale (KPS) , and acute radiation injury classification [set by Radiation Therapy Oncology Group (RTOG)] were observed in the two groups before and after treatment. The application time for antibiotics and glucocorticoids was compared between the two groups. RESULTS: All patients completed this trial, and nobody dropped out or died. There was no statistical difference in Watters-CRP scores, KPS, or RTOG between the two groups before treatment (P > 0.05). Compared with before treatment in the same group, RTOG classification was obviously improved in the two groups (P < 0.05). Compared with the control group, Watters-CRP scores decreased, KPS increased, the application time for antibiotics and glucocorticoids was reduced (P < 0.05). The efficacy of RTOG classification was better in the treatment group than in the control group, but with no statistical difference between the two groups (P > 0.05). CONCLUSION: ZHG combined glucocorticoids and antibiotics was superior in treating radiation pneumonitis to using glucocorticoids or antibiotics alone in elevating Watters-CRP scores, shortening the application time for glucocorticoids and antibiotics, and improving patients' physical conditions.


Assuntos
Antibacterianos/uso terapêutico , Quimioterapia Combinada/métodos , Medicamentos de Ervas Chinesas/uso terapêutico , Glucocorticoides/uso terapêutico , Pneumonite por Radiação/tratamento farmacológico , Humanos , Avaliação de Estado de Karnofsky
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