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1.
J Org Chem ; 89(3): 1858-1863, 2024 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-38215471

RESUMO

Salpratone A (1), a novel abietane diterpenoid containing a unique cis-fused A/B ring, was isolated from Salvia prattii. Bioactivity studies showed that 1 has potent activity in inhibiting platelet aggregation induced by multiple agonists as well as antithrombotic efficacy in the FeCl3-induced rat in vivo thrombosis model. Furthermore, a bioinspired synthesis of 1 from the abundant natural product ferruginol was achieved in 6 steps with a 22% overall yield. The key steps include a stereoselective allyl oxidation and a subsequent regioselective Meinwald rearrangement.


Assuntos
Abietanos , Salvia , Animais , Ratos , Salvia/química , Abietanos/síntese química
2.
Bioorg Chem ; 140: 106834, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37677855

RESUMO

Eleven new abietane-type diterpene lactones, salpratlactones D-N (1-11), including five 11,12-seco-11-nor-abietane diterpenes (1-5), four 11,12-seco-abietane diterpenes (6-9), two 20(10 â†’ 5)-abeo-4,5;11,12-bis-seco-abietane diterpenes (10-11), and two known analogues (12-13), were characterized from Salvia prattii. Notably, compounds 1-3 were characterized by a unique linear 6/6/6 tricyclic skeleton. The structures were established by spectroscopic data interpretation, calculated NMR-DP4+ and electronic circular dichroism analysis, as well as single-crystal X-ray diffraction. A bioactivity study showed that 1, 2, 5, 11, and 12 can potently inhibit platelet aggregation induced by arachidonic acid (AA), with IC50 values of 5.66-16.10 µg/ml, stronger than aspirin. In addition, the lactate dehydrogenase assay showed that they had no effect on platelet integrity. Structurally, the same 1,2-benzopyrone fragments of 1, 2, and 5 should be the important pharmacophore for antiplatelet activity.


Assuntos
Abietanos , Inibidores da Agregação Plaquetária , Salvia , Abietanos/farmacologia , Aspirina , Lactonas/farmacologia , Ensaios Enzimáticos , Inibidores da Agregação Plaquetária/química , Inibidores da Agregação Plaquetária/farmacologia
3.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 31(4): 1044-1049, 2023 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-37551475

RESUMO

OBJECTIVE: To explore the diagnostic value of 18F-FDG PET/CT in bone marrow infiltration (BMI) of newly diagnosed diffuse large B-cell lymphoma (DLBCL), compared with the results of bone marrow biopsy (BMB) and investigate whether the BMI diagnosed by 18F-FDG PET/CT and other factors have independent prognostic values. METHODS: Ninety-four newly diagnosed DLBCL patients who underwent PET/CT in Clinical Medical College of Shanghai General Hospital of Nanjing Medical University were included. BMB was performed within 2 weeks before or after PET/CT, and standardized treatment was performed after PET/CT. The manifestations of bone marrow (BM) FDG uptake were recorded. The diagnostic criteria of BMI were BMB positive or focal BM FDG uptake confirmed by imaging follow-up. The relationship between clinical features and BM FDG uptake and the values of PET/CT and BMB in the diagnosis of BMI was analyzed. The progression-free survival (PFS) was analyzed by Kaplan-Meier survival curves, log-rank test was used to compare PFS rate, and Cox regression model was used to analyze the independent risk factors affecting PFS. RESULTS: Among 94 DLBCL patients, 34 patients showed focal BM uptake (fPET), 7 patients showed super BM uptake (sBMU), 11 patients showed diffuse homogenous uptake higher than liver (dPET), and the other 42 patients had normal BM uptake (nPET) (lower than liver). BMB positive was found in all sBMU patients, in 20.6%(7/34) of fPET patients, and in 27.3% (3/11) of dPET patients. All nPET patients had negative BMB results. dPET patients were associated with lower hemoglobin level and leukocyte count compared with nPET group (P < 0.001, P =0.026). Compared with fPET patients, sBMU patients were more likely to have B symptoms and elevated lactate dehydrogenase (LDH). A total of 44 patients were diagnosed BMI, including 17 cases with BMB+. The sensitivity and specificity of BMB in the diagnosis of BMI was 38.6% (17/44) and 100% (50/50), respectively. Using fPET and sBMU as criteria of PET BMI, the diagnostic sensitivity and specificity of PET/CT was 93.2% (41/44) and 100% (50/50), respectively. Kaplan-Meier analysis showed that there was no significant difference in 2-year PFS rate between nPET and dPET patients (P >0.05), while sBMU patients had lower 2-year PFS rate compared with fPET patients (P < 0.001). Multivariate analysis showed that higher Ann Arbor stage (HR=9.010, P =0.04) and sBMU (HR=3.964, P =0.002) were independent risk factors affecting PFS. CONCLUSIONS: Increased BM FDG uptake of DLBCL can be manifested as dPET, fPET and sBMU. fPET and sBMU can replace BMB to diagnose BMI. Although dPET cannot completely exclude the possibility of BMI, it does not affect the prognosis, so it can be diagnosed as PET BMI negative. sBMU is an independent prognostic risk factor.


Assuntos
Linfoma Difuso de Grandes Células B , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Fluordesoxiglucose F18 , Prognóstico , Medula Óssea/patologia , Estudos Retrospectivos , China , Tomografia por Emissão de Pósitrons/métodos , Linfoma Difuso de Grandes Células B/diagnóstico por imagem , Linfoma Difuso de Grandes Células B/patologia , Biópsia
4.
Acta Pharmacol Sin ; 43(10): 2562-2572, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35948751

RESUMO

Tax1 banding protein 1 (Tax1bp1) was originally identified as an NF-κB regulatory protein that participated in inflammatory, antiviral and innate immune processes. Tax1bp1 also functions as an autophagy receptor that plays a role in autophagy. Our previous study shows that Tax1bp1 protects against cardiomyopathy in STZ-induced diabetic mice. In this study we investigated the role of Tax1bp1 in heart failure. Pressure overload-induced heart failure model was established in mice by aortic banding (AB) surgery, and angiotensin II (Ang II)-induced heart failure model was established by infusion of Ang II through osmotic minipump for 4 weeks. We showed that the expression levels of Tax1bp1 in the heart were markedly increased 2 and 4 weeks after AB surgery. Knockdown of Tax1bp1 in mouse hearts significantly ameliorated both AB- and Ang II infusion-induced heart failure parameters. On the contrary, AB-induced heart failure was aggravated in cardiac-specific Tax1bp1 transgenic mice. Similar results were observed in neonatal rat cardiomyocytes (NRCMs) under Ang II insult. We demonstrated that the pro-heart failure effect of Tax1bp1 resulted from its interaction with the E3 ligase ITCH to promote the transcription factor P73 ubiquitination and degradation, causing enhanced BCL2 interacting protein 3 (BNIP3)-mediated cardiomyocyte apoptosis. Knockdown ITCH or BNIP3 in NRCMs significantly reduced Ang II-induced apoptosis in vitro. Similarly, BNIP3 knockdown attenuated heart failure in cardiac-specific Tax1bp1 transgenic mice. In the left ventricles of heart failure patients, Tax1bp1 expression level was significantly increased; Tax1bp1 gene expression was negatively correlated with left ventricular ejection fraction in heart failure patients. Collectively, the Tax1bp1 increase in heart failure enhances ITCH-P73-BNIP3-mediated cardiomyocyte apoptosis and induced cardiac injury. Tax1bp1 may serve as a potent therapeutic target for the treatment of heart failure.• Cardiac Tax1bp1 transgene mice were more vulnerable to cardiac dysfunction under stress.• Cardiac Tax1bp1 transgene mice were more vulnerable to cardiac dysfunction under stress.• Knockout of Tax1bp1 in mouse hearts ameliorated heart failure induced by pressure overload.• Tax1bp1 interacts with the E3 ligase Itch to promote P73 ubiquitination and degradation, causing enhanced BNIP3-mediated apoptosis.• Tax1bp1 may become a target of new therapeutic methods for treating heart failure.


Assuntos
Diabetes Mellitus Experimental , Insuficiência Cardíaca , Angiotensina II/farmacologia , Animais , Antivirais/farmacologia , Apoptose , Diabetes Mellitus Experimental/complicações , Insuficiência Cardíaca/metabolismo , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Knockout , Camundongos Transgênicos , Proteínas Mitocondriais , Miócitos Cardíacos , NF-kappa B/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos , Volume Sistólico , Ubiquitina-Proteína Ligases/metabolismo , Função Ventricular Esquerda
5.
Proc Natl Acad Sci U S A ; 119(9)2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-35217599

RESUMO

Percolation theory has been widely used to study phase transitions in network systems. It has also successfully explained various macroscopic spreading phenomena across different fields. Yet, the theoretical frameworks have been focusing on direct interactions among nodes, while recent empirical observations have shown that indirect interactions are common in many network systems like social and ecological networks, among others. By investigating the detailed mechanism of both direct and indirect influence on scientific collaboration networks, here we show that indirect influence can play the dominant role in behavioral influence. To address the lack of theoretical understanding of such indirect influence on the macroscopic behavior of the system, we propose a percolation mechanism of indirect interactions called induced percolation. Surprisingly, our model exhibits a unique anisotropy property. Specifically, directed networks show first-order abrupt transitions as opposed to the second-order continuous transition in the same network structure but with undirected links. A mix of directed and undirected links leads to rich hybrid phase transitions. Furthermore, a unique feature of the nonmonotonic pattern is observed in network connectivities near the critical point. We also present an analytical framework to characterize the proposed induced percolation, paving the way to further understanding network dynamics with indirect interactions.

6.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(3): 731-734, 2021 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-34105465

RESUMO

OBJECTIVE: To explore the value of interim 18F-FDG PET/CT in the prognosis of patients with extranodal NK/T-cell lymphoma, nasal type (ENKTL). METHODS: Twenty-one patients with ENKTL who were pathologically diagnosed at Shanghai General Hospital of Nanjing Medical University (Shanghai General Hospital) from January 2015 to December 2018 were retrospectively collected, and 18F-FDG PET/CT imaging was performed before and during treatment (3 weeks after 2-4 chemotherapy courses or 6 weeks after radiotherapy). The complete clinical data of the patients were followed up. The progression-free survival (PFS) and overall survival (OS) were analyzed by the Korean prognostic index (KPI), Deauville score (DS) and the maximum standard uptake reduction rate (ΔSUVmax). The independent risk factors affecting survival were evaluated by COX regression. RESULTS: After treatment, 11 patients had complete remission (CR), 3 had partial remission (PR), 1 had stable disease (SD), and 6 had disease progression (PD). The CR patients' △SUVmax was significantly higher than non-CR patients ï¼»(66.07±22.33)% vs (36.87±23.28)%, t=2.927, P=0.009ï¼½. Calculated from the receiver operating curve (ROC), the optimal cut-off point of ΔSUVmax was 51.45%. The median follow-up time was 32 months. Kaplan-Meier survival analysis showed that KPI, DS and ΔSUVmax had significance in predicting PFS and OS (P<0.05). COX regression analysis showed that DS was an independent risk factor affecting PFS (P<0.05), and KPI and ΔSUVmax were independent risk factors affecting OS (P<0.05). CONCLUSION: Interim 18F-FDG PET/CT imaging has some value in the prognostic evaluation of patients with ENKTL.


Assuntos
Fluordesoxiglucose F18 , Linfoma Extranodal de Células T-NK , China , Intervalo Livre de Doença , Humanos , Linfoma Extranodal de Células T-NK/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Prognóstico , Estudos Retrospectivos
7.
Rev Cardiovasc Med ; 21(4): 615-625, 2020 12 30.
Artigo em Inglês | MEDLINE | ID: mdl-33388007

RESUMO

The novel coronavirus disease (COVID-19) has spread all over the world in a short time. Information about the differences between COVID-19 patients with and without hypertension is limited. To explore the characteristics and outcomes differences between COVID-19 patients with and without hypertension, the medical records and cardiac biomarkers of 414 patients were analyzed. A total of 149 patients had a history of hypertension, while 265 patients did not have hypertension, and the groups were compared based on their clinical characteristics and laboratory findings as well as the hazard risk for composite outcomes, including intensive care unit (ICU) admission, mechanical ventilation, or death. The results are as follows. On admission, 22.1% of patients in hypertension group had elevated high sensitivity troponin I (hs-TNI > 26 pg/mL), which was higher than the proportion in the nonhypertension group (6.4%). Median NT-proBNP levels in patients with hypertension (141.9 pg/mL) were higher than those in patients without hypertension (77.3 pg/mL). Patients in the hypertension group had a higher risk for in-hospital death [HR: 2.57, 95% CI (1.46~4.51)]. However, the impact of hypertension on the prognosis was not significant after adjusting for age and sex. Multivariate Cox hazard regression confirmed that NT-proBNP levels in the highest tertile (upper 75 % of patients with hypertension) was an independent risk factor for in-hospital death in all COVID-19 patients. Taken together, hypertension per se had a modest impact on the prognosis in COVID-19 patients. In COVID-19 patients with and without hypertension, NT-proBNP may be a better predictor of prognosis than hs-TNI.


Assuntos
COVID-19/epidemiologia , Hipertensão/epidemiologia , Pandemias , SARS-CoV-2 , Idoso , Comorbidade , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco
8.
Eur J Med Chem ; 187: 111961, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31865017

RESUMO

Accumulation of tau protein aggregation plays a crucial role in neurodegenerative diseases, such as Alzheimer's disease (AD). Uncontrollable neuroinflammation and tau pathology form a vicious circle that further aggravates AD progression. Herein, we reported the synthesis of usnic acid derivatives and evaluation of their inhibitory activities against tau-aggregation and neuroinflammation. The inhibitory activity of the derivatives against the self-fibrillation of the hexapeptide AcPHF6 was initially screened by ThT fluorescence assay. Using circular dichroism and transmission electron microscopy, compound 30 showed the most potent inhibitory activity against AcPHF6 self-fibrillation. Compound 30 was further confirmed to inhibit the aggregation of full-length 2N4R tau protein by a heparin-induced mechanism. In addition, we investigated the anti-inflammatory activity of compound 30, and showed that compared with sodium usnate, it reduced NO release in LPS-stimulated mouse microglia BV2 cells. More importantly, 30 showed significant protective effects against okadaic acid-induced memory impairment in rats. Thus, 30 was a novel tau-aggregation and neuroinflammation inhibitor that represented a potential therapeutic candidate for AD.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Benzofuranos/farmacologia , Inflamação/tratamento farmacológico , Aprendizagem em Labirinto/efeitos dos fármacos , Proteínas tau/antagonistas & inibidores , Doença de Alzheimer/metabolismo , Animais , Benzofuranos/síntese química , Benzofuranos/química , Linhagem Celular Tumoral , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Humanos , Inflamação/metabolismo , Lipopolissacarídeos/antagonistas & inibidores , Lipopolissacarídeos/farmacologia , Masculino , Camundongos , Modelos Moleculares , Estrutura Molecular , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico/biossíntese , Agregados Proteicos/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Relação Estrutura-Atividade , Proteínas tau/metabolismo
9.
Endocrine ; 66(2): 254-265, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31317522

RESUMO

OBJECTIVES: For patients with differentiated thyroid carcinoma (DTC), distant metastases are commonly identified in the lungs and bones. However, they are relatively rare in other distant organs, such as the liver, kidneys, or brain. The aim of the current study was to describe the clinical outcomes and evaluate the prognostic factors of patients with no less than three different distant organ system metastases from DTC. METHODS: This study retrospectively identified 717 patients diagnosed with DTC with distant metastases between January 2005 and December 2017. Patient response to radioactive iodine (RAI) therapy was monitored by changes in serum thyroglobulin levels and imaging changes. Five-year and 10-year overall survival (OS) rates were calculated by the Kaplan-Meier methods and Cox proportional hazards. RESULTS: Among the 717 participants, 37 (5.16%) patients had no less than three different distant organ system metastases from DTC. Five-year and 10-year OS were 45.9% and 37.8% in patients with three or more distant organ system metastases while 74.5% and 64.9% in individuals with one or two distant organ system metastases, respectively. RAI avidity and RAIR-DTC were main independent prognostic factors influencing the clinical outcomes for both groups of patients. The presence of 3 or more different distant organ system metastases was the only independent prognostic factors for 10-year OS by multivariate analysis. CONCLUSIONS: Patients with no less than three distant organ system metastases from DTC had poor prognosis. RAI avidity and RAIR-DTC were main factors influencing overall survival for patients with distant metastases from DTC in both groups.


Assuntos
Adenocarcinoma/secundário , Neoplasias Ósseas/secundário , Radioisótopos do Iodo/uso terapêutico , Neoplasias Pulmonares/secundário , Neoplasias da Glândula Tireoide/patologia , Adenocarcinoma/mortalidade , Adenocarcinoma/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/radioterapia , Feminino , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/radioterapia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Neoplasias da Glândula Tireoide/mortalidade , Neoplasias da Glândula Tireoide/radioterapia , Resultado do Tratamento , Adulto Jovem
10.
Eur J Med Chem ; 179: 736-743, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31284083

RESUMO

The formation of amyloid-ß (Aß) plaques in the brain is one of the main pathological features of Alzheimer's disease (AD). The imaging probes, capable of detecting Aß deposition, are important tools for early diagnosis of AD. In this article, we designed, synthesized and evaluated a cyanine-based near-infrared fluorescence (NIRF) probe ZT-1 for the detection of Aß deposits in the brain. The probe had excellent fluorescent properties with an emission maximum above 720 nm upon binding to Aß aggregates with affinity of 445.0 nM (Kd). Furthermore, ZT-1 exhibited good biostability, photostability, and binding selectivity toward Aß1-42 aggregates by in vitro fluorescence staining experiments. In vivo NIRF imaging result also revealed that our probe could efficiently differentiate transgenic and wild-type mice. All these studies indicated that ZT-1 is a promising fluorescent probe for Aß plaques in the AD brains.


Assuntos
Doença de Alzheimer/diagnóstico por imagem , Carbocianinas/química , Imagem Óptica , Placa Amiloide/química , Animais , Carbocianinas/síntese química , Relação Dose-Resposta a Droga , Raios Infravermelhos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos ICR , Estrutura Molecular , Relação Estrutura-Atividade
11.
Org Biomol Chem ; 17(11): 2877-2882, 2019 03 13.
Artigo em Inglês | MEDLINE | ID: mdl-30789160

RESUMO

We described the chemical synthesis of a sulfated trisaccharide repeating unit of fucosylated chondroitin sulfate (FCS), which has significant anticoagulant activity. Well-functionalized monosaccharides were readily prepared, and highly efficient glycosylations using a common activator (NIS/TfOH) were also presented. The synthesized trisaccharide 4 could be used to extend oligosaccharide sequences.

12.
Phys Rev E ; 99(1-1): 012317, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30780290

RESUMO

Previously, the controllability problem of a linear time-invariant dynamical system was mapped to the maximum matching (MM) problem on the bipartite representation of the underlying directed graph, and the sizes of MMs on random bipartite graphs were calculated analytically with the cavity method at zero temperature limit. Here we present an alternative theory to estimate MM sizes based on the core percolation theory and the perfect matching of cores. Our theory is much more simplified and easily interpreted, and can estimate MM sizes on random graphs with or without symmetry between out- and in-degree distributions. Our result helps to illuminate the fundamental connection between the controllability problem and the underlying structure of complex systems.

13.
Int J Mol Med ; 42(6): 3386-3394, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30272348

RESUMO

The present study investigated the underlying molecular mechanism by which Buthus martensii Karsch chlorotoxin (BmK CT) inhibits the invasion and metastasis of glioma cells and the possibility of 131I­labeled BmK CT (131I­BmK CT) as a novel targeted agent for the treatment of glioma. The impact of BmK CT with and without 131I radiolabeling on the invasion and metastasis of glioma cells in vitro was studied. Cell viability was assessed using Cell Counting Kit­8 and plate colony formation assays in order to confirm the cytotoxicity of BmK CT and 131I­BmK CT at different concentrations. Transwell invasion and wound­healing assays were conducted in order to investigate the inhibitory effects BmK CT and 131I­BmK CT on cell migration and invasion. Furthermore, western blotting, ELISA immunofluorescence and a gelatin zymography assay were performed to evaluate changes in the protein expression levels of glioma cells following treatment with BmK CT or 131I­BmK CT. The results indicated that BmK CT inhibits the invasion and metastasis of glioma cells via regulation of tissue inhibitor of metalloproteinase­2 expression and that 131I­BmK CT has the potential to be a novel targeted therapeutic drug for glioma.


Assuntos
Glioma/metabolismo , Venenos de Escorpião/farmacologia , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Humanos , Microscopia Confocal , Cicatrização/efeitos dos fármacos
14.
Nat Prod Res ; 32(20): 2418-2423, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29258353

RESUMO

A new abietane diterpenoid, tripterregeline A (1), together with six known diterpenoids (2-7), were isolated from the roots of Tripterygium regelii. The structure of 1 was elucidated by extensive spectroscopic methods and the known compounds were identified by comparison with data reported in the literature. All isolated compounds were evaluated for their cytotoxicities against five human cancer cell lines: HL-60, SMMC-7721, A-549, MCF-7 and SW480 in vitro. Compounds 1-7 showed significant inhibitory effects against various human cancer cell lines with IC50 values ranging from 0.58 to 21.06 µM.


Assuntos
Abietanos/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Tripterygium/química , Células A549 , Abietanos/isolamento & purificação , Antineoplásicos Fitogênicos/isolamento & purificação , China , Células HL-60 , Humanos , Células MCF-7 , Estrutura Molecular , Raízes de Plantas/química
15.
Asian Pac J Allergy Immunol ; 35(4): 196-202, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28364410

RESUMO

BACKGROUND: Atopic dermatitis (AD) and other atopic diseases often share some common genetic and pathogenic bases. Recent genome-wide association studies (GWAS) have identified several loci associated with atopic diseases, allergic sensitization and asthma in different populations. The aim of this study was to investigate whether these susceptibility loci were related to AD in Chinese Han population. METHODS: Eight single nucleotide polymorphisms (SNPs) from recent atopic diseases and allergic sensitization GWAS were genotyped in 3,013 AD patients and 5,483 healthy controls in Chinese Han population using Sequenom MassArray system. Data was analyzed with PLINK 1.07 software. RESULTS: We identified that the susceptibility loci at 5q31 (RAD50/IL13, rs2158177, P = 1.08×10-3, OR = 1.15) and 5q22.1 (TSLP, rs1837253, P = 2.66×10-3, OR = 0.91) were significantly associated with AD. Genotype-based association testing revealed that the dominant model provided the best fit for both rs2158177 (P = 3.75×10-3) and rs1837253 (P = 5.30×10-3). Pathway analysis conformed that both loci were associated with the JAK-STAT signaling pathway. CONCLUSIONS: We identified two susceptibility loci 5q31 and 5q22.1 for AD that might bear candidate genes conferring susceptibility to AD.


Assuntos
Cromossomos Humanos Par 5/genética , Dermatite Atópica/genética , Loci Gênicos/genética , Genótipo , Adolescente , Adulto , Estudos de Casos e Controles , China , Biologia Computacional , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Adulto Jovem
16.
Inflammation ; 40(3): 1006-1011, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28303415

RESUMO

Schisandrin B (Sch B), a dibenzocyclooctadiene lignan isolated from Schisandra chinensis (Turcz.) Baill, has been shown to have anti-inflammatory effect. The purpose of this study was to evaluate the effect of Sch B on LPS-induced inflammation in microglia and to investigate the molecular targets of Sch B. BV2 cells were stimulated by LPS in the presence or absence of Sch B. The results showed that the levels of TNF-α, IL-6, IL-1ß, and PGE2 upregulated by LPS were significantly suppressed by Sch B. LPS-induced NF-κB activation was also inhibited by Sch B. Furthermore, Sch B was found to upregulate the expression of PPAR-γ in a concentration-dependent manner. In addition, the inhibition of Sch B on TNF-α, IL-6, IL-1ß, and PGE2 production were reversed by PPAR-γ antagonist GW9662. In conclusion, these results suggested that Sch B inhibited LPS-induced inflammatory response by activating PPAR-γ.


Assuntos
Lignanas/farmacologia , Microglia/efeitos dos fármacos , PPAR gama/metabolismo , Compostos Policíclicos/farmacologia , Anti-Inflamatórios/farmacologia , Linhagem Celular , Ciclo-Octanos/farmacologia , Ativação Enzimática/efeitos dos fármacos , Humanos , Inflamação/tratamento farmacológico , Inflamação/prevenção & controle , Lipopolissacarídeos
17.
Nan Fang Yi Ke Da Xue Xue Bao ; 36(8): 1123-8, 2016 Aug 20.
Artigo em Chinês | MEDLINE | ID: mdl-27578584

RESUMO

OBJECTIVE: To explore the value of (18)F-FDG PET/CT in the diagnosis and treatment evaluation in patients with pretreatment or recurrent extranodular natural killer/T-cell lymphoma nasal type (ENTCL). METHODS: (18)F-FDG PET/CT images and clinical records of 35 cases (67 scans) of pathologically confirmed ENTCL treated in our hospital within the last 9 years were analyzed. The imaging characteristics of the upper aerodigestive tract (UAT) and the non-aerodigestive tract (NUAT) lesions were analyzed. Lesion distribution, clinical stages, SUVmax and patient survival data were compared between pretreatment and recurrent cases. RESULTS: s All the ENTCL lesions were hypermetabolic. The UAT lesions involved mainly the nasal cavity and pharynx, while the NUAT lesions may involve the lymph nodes and all the organs. UAT lesions were more common in pretreatment cases while NUAT lesions tended to increase in recurrent cases. The SUVmax of pretreatment and recurrent lesions were 10.4∓4.4 and 9.6∓5.2, and showed no significant difference among patients with different lesion distribution patterns, clinical stages, or treatment history. The tumor remission rate evaluated by PET/CT were higher in cases with an initial diagnosis than in those with recurrence [(89.5% (17/19) vs 33.3% (5/15), P<0.005)]. Cox regression analysis revealed no significant differences in the survival rates among patients with different treatment history, clinical stages, lesion distribution patterns, or SUVmax levels (P>0.05). CONCLUSION: (18)F-FDG PET/CT can sensitively detect the pretreatment or recurrent lesions in ENTCL patients and helps in accurate tumor staging and curative effect evaluation.


Assuntos
Linfoma Extranodal de Células T-NK/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Fluordesoxiglucose F18 , Humanos , Recidiva Local de Neoplasia , Estadiamento de Neoplasias
18.
Asian Pac J Allergy Immunol ; 34(2): 109-14, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27007831

RESUMO

BACKGROUND: Recent genome-wide association studies (GWAS) and a meta-analysis of GWAS for atopic dermatitis (AD) have identified some AD genetic loci in European and Japanese populations. OBJECTIVE: To investigate whether some novel susceptibility loci are associated with AD in the Chinese Han population. METHODS: We first selected eight novel susceptibility loci to replicate in 2,205 AD patients and 2,116 healthy controls using the Sequenom platform. Data were analyzed with PLINK 1.07 software. RESULTS: We found that rs12634229 (3q13.2), rs7927894 (11p13.5) and rs878860 (11p15.4) showed a slight association with AD (P = 0.012, P = 0.033, P = 0.020, respectively); rs6780220 (3p21.33) was preferentially related to AD with keratosis pilaris, but did not reach the threshold of significance after correction. The frequency of rs7927894 allele T was significantly different between AD patients with a positive and negative family history of atopy. CONCLUSION: The loci rs7927894 (11p13.5) are related to AD with a positive family history of atopy in Chinese Han population, providing novel insight into the genetic pathogenesis of AD.


Assuntos
Povo Asiático/genética , Cromossomos Humanos Par 11 , Dermatite Atópica/genética , Polimorfismo de Nucleotídeo Único , Adolescente , Adulto , Estudos de Casos e Controles , Criança , Pré-Escolar , China/epidemiologia , Dermatite Atópica/diagnóstico , Dermatite Atópica/etnologia , Feminino , Frequência do Gene , Estudos de Associação Genética , Loci Gênicos , Predisposição Genética para Doença , Humanos , Lactente , Recém-Nascido , Masculino , Linhagem , Fenótipo , Fatores de Risco , Índice de Gravidade de Doença , Adulto Jovem
19.
Zhongguo Dang Dai Er Ke Za Zhi ; 17(6): 565-9, 2015 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-26108314

RESUMO

OBJECTIVE: To evaluate the psychological state of children with epilepsy and analyze its influencing factors. METHODS: The Mental Health Scale for Child and Adolescent was used to survey 113 children with epilepsy and 114 normal children to evaluate and compare their psychological state. Questionnaires were used to investigate the general status of all subjects and the disease condition and treatment of children with epilepsy. The possible influencing factors for the psychological state of children with epilepsy were analyzed. RESULTS: The mental health status of children with epilepsy was poorer than that of normal children in cognition, thinking, emotion, will-behavior, and personality traits (P<0.05). Multivariate logistic regression analysis showed that family education, family relations, seizure frequency, seizure duration, EEG epileptiform discharges in the last six months, and number of types of antiepileptic drugs were correlated with the psychological state of children with epilepsy. CONCLUSIONS: There is a wider range of psychological health problems in children with epilepsy than in normal children. Poor family living environment, poor seizure control, and use of many antiepileptic drugs are the risk factors affecting the psychological state of children with epilepsy. Improving family living environment, controlling seizures, and monotherapy help to improve the psychological state of children with epilepsy.


Assuntos
Epilepsia/psicologia , Adolescente , Criança , Epilepsia/tratamento farmacológico , Feminino , Humanos , Modelos Logísticos , Masculino , Transtornos da Memória/etiologia
20.
Nat Prod Res ; 29(14): 1372-5, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25573271

RESUMO

Fifteen known compounds including four triterpenoids (1-4), one sterol (5), one diketopiperazine alkaloid (6) and nine phenolics (7-15) were isolated from the stems of Piper wallichii. Their structures were elucidated by means of spectroscopic analysis, and acidic hydrolysis in case of the 2-oxo-3ß,19α,23-trihydroxyurs-12-en-28-oic acid ß-D-glucopyranosyl ester (1). The structure of compound 1 was fully assigned by 1D and 2D NMR experiments for the first time. All isolates were tested for their antibacterial, antifungal, anti-inflammatory and antiplatelet aggregation bioactivities.


Assuntos
Alcaloides/química , Fenóis/química , Fitosteróis/química , Piper/química , Triterpenos/química , Animais , Bactérias/efeitos dos fármacos , Plaquetas/efeitos dos fármacos , Linhagem Celular/efeitos dos fármacos , Fungos/efeitos dos fármacos , Camundongos , Estrutura Molecular , Caules de Planta/química , Coelhos
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