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1.
J Appl Genet ; 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38780866

RESUMO

This study aims to harness bioinformatics to identify prognostic immune-related genes in clear cell renal cell carcinoma (ccRCC), focusing particularly on LILRB3. It evaluates LILRB3's expression in ccRCC, its association with patient prognosis, and its potential as a biomarker for predicting survival, thereby providing a preliminary basis for the diagnosis of ccRCC. Utilizing The Cancer Genome Atlas (TCGA) datasets and an immune gene set, we sought immune-related genes with elevated expression in ccRCC. Seventy-two normal tissue samples and 531 ccRCC samples were analyzed, and differential genes were identified with a screening criterion of fold change (FC) > 2 and P value < 0.01. Survival analysis and receiver operating characteristic (ROC) curve analysis were employed to discover genes of prognostic and diagnostic relevance to ccRCC. Pearson correlation analysis with a cutoff of |r|≥ 0.5, facilitated by cBioPortal, assessed genes co-expressed with LILRB3. The DAVID online tool conducted functional and pathway enrichment analyses for LILRB3-coexpressed genes. The TIMER and TCIA databases were utilized to explore LILRB3's influence on immune infiltration in the tumor microenvironment and its relation to key immunological checkpoints. Screening the TCGA database revealed 3719 up-regulated differential genes in ccRCC, with 355 overlapping immune-related genes. Survival analysis of these 355 genes revealed 100 with significant survival impact. ROC curve analysis pinpointed the top 10 genes, including LILRB3, with the highest diagnostic efficiency. LILRB3 emerged as an independent risk factor from the Cox risk regression model. GO and KEGG analyses linked LILRB3 to various biological processes, including chemokine signaling pathways, immunological response, antigen processing and presentation, inflammatory response, T cell co-stimulation, and signal transduction. LILRB3 significantly affected ccRCC immune infiltration and correlated positively with several immunological checkpoints, such as PD-1, LAG3, IDO1, PD-L1, CTLA4, TIM3, TIGIT, and VISTA. LILRB3 shows higher expression levels in ccRCC than in normal tissues and correlates with poor patient prognosis. Its impactful role in the immune infiltration of the RCC microenvironment suggests that LILRB3 could serve as a novel target for ccRCC treatment and prognosis, underlining its diagnostic and prognostic significance.

2.
Int J Infect Dis ; 134: 187-194, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37352912

RESUMO

OBJECTIVES: To investigate the challenges of patients with spinal muscular atrophy (SMA) during the Omicron variant COVID-19 pandemic. DESIGN: A cross-sectional survey was conducted in China from January 02, 2023, to January 12, 2023, using a questionnaire that covered three aspects: (1) Demographic information; (2) SMA-related information; and (3) COVID-19-related information. We recruited patients with SMA from 33 provinces. The prevalence, course, and clinical manifestations of COVID-19 were calculated. The relationships between independent and outcome variables were investigated. RESULTS: In total, 677 patients (male: 349; female: 328) were included in this study (average age = 11.40 years); 534 (78.88%) suffered from COVID-19. The most common symptoms were fever (95.51%), cough (57.87%), and sputum (49.44%). Of the infected patients, 91.57% recovered with at-home care, and 8.43% were hospitalized; 1.31% were admitted to the intensive care unit (ICU). A positive correlation was observed between the SMA severity and hospitalization rate. The ICU stay rate in patients with SMA type I was significantly higher than that in other SMA types. CONCLUSION: This is the first large sample survey to timely reveal the living situation of patients with SMA during the COVID-19 pandemic's Omicron variant. Patients with SMA type I should be paid more attention in terms of hospitalization and ICU stay.


Assuntos
COVID-19 , Atrofia Muscular Espinal , Humanos , Feminino , Masculino , Criança , Pandemias , Estudos Transversais , Doenças Raras , COVID-19/epidemiologia , SARS-CoV-2 , Atrofia Muscular Espinal/epidemiologia , China/epidemiologia
3.
PLoS One ; 17(4): e0265311, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35363791

RESUMO

Deer genera around the globe are threatened by anthropogenic interference. The translocation of alien species and their subsequent genetic introgression into indigenous deer populations is particularly harmful to the species of greatest conservation concern. Products derived from deer, including venison and antler velvet, are also at risk of fraudulent labeling. The current molecular markers used to genetically identify deer species were developed from genome sequences and have limited applicability for cross-species amplification. The absence of efficacious diagnostic techniques for identifying deer species has hampered conservation and wildlife crime investigation efforts. Expressed sequence tag-simple sequence repeat (EST-SSR) markers are reliable tools for individual and species identification, especially in terms of cross-species genotyping. We conducted transcriptome sequencing of sambar (Rusa unicolor) antler velvet and acquired 11,190 EST-SSRs from 65,074 newly assembled unigenes. We identified a total of 55 unambiguous amplicons in sambar (n = 45), which were selected as markers to evaluate cross-species genotyping in sika deer (Cervus nippon, n = 30) and red deer (Cervus elaphus, n = 46), resulting in cross-species amplification rates of 94.5% and 89.1%, respectively. Based on polymorphic information content (>0.25) and genotyping fidelity, we selected 16 of these EST-SSRs for species identification. This marker set revealed significant genetic differentiation based on the fixation index and genetic distance values. Principal coordinate analysis and STRUCTURE analysis revealed distinct clusters of species and clearly identified red-sika hybrids. These markers showed applicability across different genera and proved suitable for identification and phylogenetic analyses across deer species.


Assuntos
Chifres de Veado , Cervos , Animais , Cervos/genética , Etiquetas de Sequências Expressas , Repetições de Microssatélites/genética , Filogenia
4.
Zhongguo Gu Shang ; 34(1): 80-5, 2021 Jan 25.
Artigo em Chinês | MEDLINE | ID: mdl-33666025

RESUMO

OBJECTIVE: To investigate the clinical effect of anterior cervical Hybrid surgery in the treatment of cervical degenerative diseases (CDD) and observe the incidence of heterotopic ossification of disc replacement segment at 1 year after surgery. METHODS: From January 2015 to April 2018, 35 patients who received anterior cervical hybrid surgery met the inclusion and exclusion criteria and the complete clinical follow up data were analyzed retrospectively. Complete imaging follow-up data were obtained from 24 patients. There were 15 males and 20 females, aged from 39 to 70(55.57±7.73) years old. The amount of bleeding was for 20 to 100 (40.29±18.39) ml, and the hospitalstay was for 4 to 28(11.03±4.63) days, and the follow-up time was(12.97±1.36) months. Clinical outcomes were assessed by the Tanaka Yasushi cervical spondylitis symptom scale 20 score (YT20), and Japanese Orthopaedic Association (JOA) score. The occurrence of heterotopic ossification after Hybrid surgery was evaluated by X-ray according to McAfee standard one year after operation. Patients with or without heterotopic ossificationwere divided into two groups and their clinical effects were compared. RESULTS: At the final follow up, the mean YT20 score and JOA score were significantly higher than those before operation (P <0.05), and the average improvement rate of JOA was (70.66 ±0.44)%. One year after operation, the heterotopic ossification occurred in 10 of 24 segments, with incidence of 41.70%(10/24), including 29.20% in gradeⅠand 12.50% in gradeⅡ. The results of clinical efficacy comparison between patients with and without heterotopic ossification were as follows:there was no significant difference in JOA score before and after operation (P>0.05);there was no significant difference in YT20 score before operation (P>0.05), and YT20 score in patients with heterotopic ossification was significantly lower than that in patients without heterotopic ossification(P<0.05). CONCLUSION: The short-term clinical effect of Hybrid surgery is satisfactory for cervical degenerative diseases, and the cause of heterotopic ossification still needs tobe further explored.


Assuntos
Degeneração do Disco Intervertebral , Substituição Total de Disco , Adulto , Idoso , Vértebras Cervicais/cirurgia , Feminino , Seguimentos , Humanos , Degeneração do Disco Intervertebral/cirurgia , Masculino , Pessoa de Meia-Idade , Amplitude de Movimento Articular , Estudos Retrospectivos , Resultado do Tratamento
5.
J Cell Mol Med ; 25(6): 2909-2917, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33497543

RESUMO

Melatonin is well-documented to have the ability of reducing nerve inflammation and scavenging free radicals. However, the therapeutic effect of melatonin on spinal cord injury has not been fully described. In this study, we assessed the effect of melatonin on T9 spinal cord injury established by Allen method in rats. Melatonin deficiency significantly delayed the recovery of sensory and motor functions in SCI rats. Treatment with melatonin significantly alleviated neuronal apoptosis and accelerated the recovery of spinal cord function. These results suggest that melatonin is effective to ameliorate spinal cord injury through inhibition of neuronal apoptosis and promotion of neuronal repair.


Assuntos
Melatonina/metabolismo , Traumatismos da Medula Espinal/etiologia , Traumatismos da Medula Espinal/metabolismo , Animais , Apoptose/efeitos dos fármacos , Biomarcadores , Modelos Animais de Doenças , Suscetibilidade a Doenças , Expressão Gênica , Imuno-Histoquímica , Melatonina/farmacologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/patologia , Corpos de Nissl/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Ratos , Recuperação de Função Fisiológica/efeitos dos fármacos , Traumatismos da Medula Espinal/tratamento farmacológico , Traumatismos da Medula Espinal/patologia
6.
Front Pharmacol ; 12: 723913, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35095480

RESUMO

Methylprednisolone (MP) is the drug of choice for treating spinal cord injury (SCI), but the aggressive dosage regimen used often results in adverse side effects. Therefore, MP should be combined with other drugs to lower the required dose. Melatonin is effective in alleviating nerve damage and inhibiting axonal degeneration. The combination of melatonin and half-dose methylprednisolone (HMP) for spinal cord injury treatment has never been reported. In this study, we established a rat model of T9 spinal cord injury by the Allen's method and assessed the synergistic therapeutic effects of melatonin and HMP by factorial design. Our results demonstrated that melatonin could synergize with HMP to ameliorate acute SCI through PI3K-AKT1 pathway. Combining melatonin with HMP significantly reduced the standard-dose of methylprednisolone and limited its adverse reactions, representing a promising option for treating acute SCI.

7.
Biomed Pharmacother ; 118: 109383, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31545251

RESUMO

Given studies have shown that Artemisinin (ART) reduces cancer cell proliferation, migration, invasion, tumorigenesis and metastasis. In this study, we evaluated the roles of ART in clear cell renal cell carcinoma (ccRCC) progression. We measured the eff ;ects of ART on cancer cell proliferation, colony formation, migration, invasion and tumorigenesis. CCK-8 assay demonstrated that ART inhibited cell growth with IC50 values 31.30 ±â€¯0.73 µM in UMRC-2 and 23.97 ±â€¯0.92 µM in CAKI-2, respectively. Colony formation assay shown that ART inhibited cell colony formation. Transwell migration and invasion assay shown that ART inhibited RCC migration and invasion. Realtime-qPCR assay shown that ART decreased the mRNA levels of proliferation related genes c-Myc, cyclin D1 and PCNA, and reduced the mRNA levels of mesenchymal genes N-cadherin, Vimentin and Snail, but increased the mRNA levels of epithelial marker E-cadherin. Moreover, ART inhibited AKT signaling pathway. In the presence of AKT inhibitor VIII, a pan-AKT inhibitor, ART reduced more cell proliferation, migration and invasion than in the absence of AKT inhibitor VIII, suggesting combination of ART and AKT inhibitor enhanced the anti-cancer effects of ART. Furthermore, the in vivo xenograft tumor model results suggested that ART decreased tumor size and weight, and suppressed AKT signaling. Taken together, our results indicated that ART inhibited ccRCC cell proliferation, colony formation, migration, invasion and tumorigenesis. Combination of ART and AKT inhibitor enhanced the anti-cancer cell proliferation, migration and invasion.


Assuntos
Antineoplásicos/uso terapêutico , Artemisininas/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Animais , Antineoplásicos/farmacologia , Artemisininas/química , Artemisininas/farmacologia , Carcinogênese/efeitos dos fármacos , Carcinogênese/genética , Carcinoma de Células Renais/patologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Humanos , Neoplasias Renais/patologia , Masculino , Camundongos Nus , Invasividade Neoplásica , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Ensaio Tumoral de Célula-Tronco
8.
Brain Behav ; 9(8): e01339, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31225705

RESUMO

INTRODUCTION: In this study, the effects of omega-3 fatty acids were examined in a rat model of spinal cord injury. METHODS: The rats were classified into sham, control, spinal cord injury plus 50 mg/kg Omega-3 fatty acids and spinal cord injury plus 100 mg/kg Omega-3 fatty acids. The levels of oxidative, apoptotic, and inflammatory markers were examined in each of these groups. RESULTS: Altered lipid peroxidation, reduced glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (Gpx), and catalase were normalized. Omega-3 fatty acid supplementation decreased tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) levels by >50%. TNF-α and IL-6 mRNA expression were reduced. Caspase-3, p53, bax, and pro-NGF mRNA expression levels were increased by 1.3-, 1.4-, 1.2-, and 0.9-fold, respectively, whereas bcl-2 mRNA expression was decreased by 0.77-fold in control rats. Omega-3 fatty acid supplementation decreased p53, caspase-3, bax, and pro-NGF mRNA expression by >40%, while the level of bcl-2 mRNA expression was increased by 286.9%. Omega-3 fatty acid supplementation decreased caspase-3 and p53 protein expression by >30%. CONCLUSION: Taken together, our results suggested that omega-3 fatty acid supplementation reduced oxidative stress, apoptosis, and the levels of inflammatory markers in ischemia-reperfusion-induced rats.


Assuntos
Apoptose/efeitos dos fármacos , Ácidos Graxos Ômega-3/farmacologia , Inflamação , Estresse Oxidativo/efeitos dos fármacos , Traumatismos da Medula Espinal , Animais , Antioxidantes/farmacologia , Modelos Animais de Doenças , Inflamação/sangue , Inflamação/tratamento farmacológico , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Fármacos Neuroprotetores/farmacologia , Ratos , Traumatismos da Medula Espinal/tratamento farmacológico , Traumatismos da Medula Espinal/metabolismo , Resultado do Tratamento , Fator de Necrose Tumoral alfa/metabolismo
9.
J Cell Mol Med ; 23(7): 4582-4591, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31044535

RESUMO

Congenital scoliosis (CS) is the result of anomalous vertebrae development, but the pathogenesis of CS remains unclear. Long non-coding RNAs (lncRNAs) have been implicated in embryo development, but their role in CS remains unknown. In this study, we investigated the role and mechanisms of a specific lncRNA, SULT1C2A, in somitogenesis in a rat model of vitamin A deficiency (VAD)-induced CS. Bioinformatics analysis and quantitative real-time PCR (qRT-PCR) indicated that SULT1C2A expression was down-regulated in VAD group, accompanied by increased expression of rno-miR-466c-5p but decreased expression of Foxo4 and somitogenesis-related genes such as Pax1, Nkx3-2 and Sox9 on gestational day (GD) 9. Luciferase reporter and small interfering RNA (siRNA) assays showed that SULT1C2A functioned as a competing endogenous RNA to inhibit rno-miR-466c-5p expression by direct binding, and rno-miR-466c-5p inhibited Foxo4 expression by binding to its 3' untranslated region (UTR). The spatiotemporal expression of SULT1C2A, rno-miR-466c-5p and Foxo4 axis was dynamically altered on GDs 3, 8, 11, 15 and 21 as detected by qRT-PCR and northern blot analyses, with parallel changes in Protein kinase B (AKT) phosphorylation and PI3K expression. Taken together, our findings indicate that SULT1C2A enhanced Foxo4 expression by negatively modulating rno-miR-466c-5p expression via the PI3K-ATK signalling pathway in the rat model of VAD-CS. Thus, SULT1C2A may be a potential target for treating CS.


Assuntos
Fatores de Transcrição Forkhead/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Longo não Codificante/metabolismo , Escoliose/congênito , Escoliose/genética , Transdução de Sinais , Regiões 3' não Traduzidas/genética , Animais , Sequência de Bases , Regulação para Baixo/genética , Embrião de Mamíferos/metabolismo , Fatores de Transcrição Forkhead/genética , Regulação da Expressão Gênica no Desenvolvimento , Genes Reporter , Células HEK293 , Humanos , Luciferases/metabolismo , MicroRNAs , Modelos Biológicos , Organogênese/genética , RNA Longo não Codificante/genética , Ratos Sprague-Dawley , Somitos/embriologia , Deficiência de Vitamina A/embriologia , Deficiência de Vitamina A/genética
10.
Mol Med ; 23: 34-39, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28283678

RESUMO

α7 nicotinic acetylcholine receptor (α7 nAChR, coded by Chrna7) is indispensible in dampening proinflammatory responses. However, whether α7 nAChR would play a role in regulating bleomycin (BLM)-induced lung fibrosis is less investigated. Here, we intratracheally challenged wildtype and Chrna7-/- mice with BLM to elicit lung fibrosis. Taken advantage of this model, we measured body weight loss, lung fibrogenic genes (Acta2, Col1a1, Fsp1, and Fstl1), histology, Masson's trichrome staining, hydroxyproline levels, and expression of α-SMA at protein levels in the BLM-challenged lung for evaluating severity of lung fibrosis. We also pretreated human fibroblasts (MRC5 cell line) and isolated mouse lung fibroblasts with GTS-21 (an α7 nAChR agonist) to study its effects on TGF-ß-stimulated profibrotic profiles. We found that lung Chrna7 expression and CD4+CHAT+ (Choline acetyltransferase, an enzyme for local acetylcholine synthesis) cells were 12-fold and 4.5-fold respectively elevated in the early stage of lung fibrosis. Deletion of Chrna7 prevented body weight loss and reduced lung fibrogenic genes (Acta2, Col1a1, Fsp1, and Fstl1) and Arg 1 (coding arginase 1). Deletion of Chrna7 attenuated lung arginase 1+Ly6C+ cells, Masson's trichrome staining, hydroxyproline levels, and expression of α-SMA at protein levels in BLM-challenged mice. Mechanistically, activation of α7 nAChR in human fibroblasts increased TGF-ß-induced phosphorylation of Smad2/3 and transcription of fibrogenic genes (Acta2, Col1a1). In isolated mouse lung fibroblasts, activation of α7 nAChR also enhanced TGF-ß induced-transcription of fibrogenic genes; however, deletion of Chrna7 diminished these effects. Taken together, deficiency of α7 nAChR could suppress the development of BLM-induced lung fibrosis. Thus, α7 nAChR might be a novel therapeutic target for treating lung fibrosis.


Assuntos
Fibrose Pulmonar/metabolismo , Receptor Nicotínico de Acetilcolina alfa7/deficiência , Animais , Bleomicina , Linhagem Celular , Humanos , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fibrose Pulmonar/induzido quimicamente , Fator de Crescimento Transformador beta/metabolismo , Receptor Nicotínico de Acetilcolina alfa7/genética
11.
Mitochondrial DNA A DNA Mapp Seq Anal ; 27(3): 1650-1, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-25228374

RESUMO

The complete mitochondrial genome of Viverricula indica taivana, exclusive of tandem repeats within the control region, is 16,583 bp in length, with a total base composition of: 33.18% A, 28.93% T, 24.88% C, and 13.00% G in H-strand. The genome contains 37 genes, including 13 protein-coding genes, 2 ribosomal RNA genes, 22 transfer RNA genes, and 1 control region.


Assuntos
Genoma Mitocondrial/genética , Viverridae/genética , Animais , Composição de Bases/genética , DNA Mitocondrial/genética , RNA Ribossômico/genética , RNA de Transferência/genética , Análise de Sequência de DNA , Sequências de Repetição em Tandem/genética , Viverridae/classificação
12.
ACS Appl Mater Interfaces ; 6(15): 12495-504, 2014 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-25017583

RESUMO

A facile method was found to incorporate a mussel-inspired adhesive moiety into synthetic polymers, and mussel mimetic polyurethanes were developed as adhesive hydrogels. In these polymers, a urethane backbone was substituted for the polyamide chain of mussel adhesive proteins, and dopamine was appended to mimic the adhesive moiety of adhesive proteins. A series of mussel mimetic polyurethanes were created through a step-growth polymerization based on hexamethylene diisocyanate as a hard segment, PEG having different molecular weights as a soft segment, and lysine-dopamine as a chain extender. Upon a treatment with Fe(3+), the aqueous mussel mimetic polyurethane solutions can be triggered by pH adjustment to form adhesive hydrogels instantaneously; these materials can be used as injectable adhesive hydrogels. Upon a treatment with NaIO4, the mussel mimetic polyurethane solutions can be cured in a controllable period of time. The successful combination of the unique mussel-inspired adhesive moiety with a tunable polyurethane structure can result in a new kind of mussel-inspired adhesive polymers.


Assuntos
Biomimética/métodos , Bivalves/química , Hidrogel de Polietilenoglicol-Dimetacrilato/química , Hidrogel de Polietilenoglicol-Dimetacrilato/síntese química , Poliuretanos/química , Poliuretanos/síntese química , Animais , Catecóis/química , Reagentes de Ligações Cruzadas/química , Dopamina/química , Ésteres/química , Concentração de Íons de Hidrogênio , Iodatos/química , Ferro/química , Ligantes , Lisina/química , Peso Molecular , Oxirredução , Espectroscopia de Prótons por Ressonância Magnética , Reologia , Espectrofotometria Ultravioleta , Espectroscopia de Infravermelho com Transformada de Fourier , Termogravimetria , Fatores de Tempo
13.
PLoS One ; 9(3): e93003, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24671173

RESUMO

CFTR (cystic fibrosis transmembrane conductance regulator) is expressed by both neutrophils and platelets. Lack of functional CFTR could lead to severe lung infection and inflammation. Here, we found that mutation of CFTR (F508del) or inhibition of CFTR in mice led to more severe thrombocytopenia, alveolar neutrocytosis and bacteriosis, and lower lipoxin A4/MIP-2 (macrophage inhibitory protein-2) or lipoxin A4/neutrophil ratios in the BAL (bronchoalveolar lavage) during acute E. coli pneumonia. In vitro, inhibition of CFTR promotes MIP-2 production in LPS-stimulated neutrophils; however, lipoxin A4 could dose-dependently suppress this effect. In LPS-induced acute lung inflammation, blockade of PSGL-1 (P-selectin glycoprotein ligand-1) or P-selectin, antagonism of PAF by WEB2086, or correction of mutated CFTR trafficking by KM11060 could significantly increase plasma lipoxin A4 levels in F508del relevant to wildtype mice. Concurrently, F508del mice had higher plasma platelet activating factor (PAF) levels and PAF-AH activity compared to wildtype under LPS challenge. Inhibiting hydrolysis of PAF by a specific PAF-AH (PAF-acetylhydrolase) inhibitor, MAFP, could worsen LPS-induced lung inflammation in F508del mice compared to vehicle treated F508del group. Particularly, depletion of platelets in F508del mice could significantly decrease plasma lipoxin A4 and PAF-AH activity and deteriorate LPS-induced lung inflammation compared to control F508del mice. Taken together, lipoxin A4 and PAF are involved in E. coli or LPS-induced lung inflammation in CFTR-deficient mice, suggesting that lipoxin A4 and PAF might be therapeutic targets for ameliorating CFTR-deficiency deteriorated lung inflammation.


Assuntos
Regulador de Condutância Transmembrana em Fibrose Cística/deficiência , Lipoxinas/metabolismo , Fator de Ativação de Plaquetas/metabolismo , Pneumonia/metabolismo , Animais , Lavagem Broncoalveolar , Quimiocina CXCL2/metabolismo , Regulador de Condutância Transmembrana em Fibrose Cística/metabolismo , Escherichia coli , Lipopolissacarídeos , Lipoxinas/sangue , Camundongos Endogâmicos CFTR , Mutação/genética , Selectina-P/metabolismo , Contagem de Plaquetas , Pneumonia/sangue , Pneumonia/patologia , Trombocitopenia/genética
14.
Chest ; 141(2): 374-380, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21778258

RESUMO

BACKGROUND: A prolonged QRS duration ( ≥ 120 milliseconds) predicts outcomes in patients with left-sided heart failure, but the impact in idiopathic pulmonary arterial hypertension (IPAH) and right-sided heart failure is unknown. We assessed the prognostic value of a prolonged ECG QRS duration in patients with IPAH in China. METHODS: We retrospectively analyzed the initial 12-lead ECG for QRS duration in 212 consecutive patients with IPAH seen at our center between 2007 and 2009. Patients were divided according to QRS duration < 120 milliseconds or ≥ 120 milliseconds. The baseline characteristics and survival of the two groups were compared. RESULTS: Thirty-five patients with IPAH (16.5%) had a QRS duration ≥ 120 milliseconds, including 21 (9.9%) with right bundle-branch block and 14 (6.6%) with nonspecific intraventricular conduction delay. Prolongation of the QRS duration was associated with a worse World Health Organization functional class and 6-min walk test distance and higher serum uric acid when compared with patients with normal QRS duration (P < .05). Prolonged QRS duration was an independent predictor of mortality and was associated with a 2.5-fold increased risk of death (P = .024). CONCLUSION: Prolongation of the QRS duration is associated with clinical severity in patients with IPAH. In addition, QRS prolongation has an independent association with cardiopulmonary mortality and could be a new predictor of adverse outcome in patients with IPAH.


Assuntos
Fibrilação Atrial/fisiopatologia , Sistema de Condução Cardíaco/fisiopatologia , Insuficiência Cardíaca/fisiopatologia , Adulto , Fibrilação Atrial/diagnóstico por imagem , Fibrilação Atrial/mortalidade , Distribuição de Qui-Quadrado , China/epidemiologia , Ecocardiografia , Eletrocardiografia , Feminino , Insuficiência Cardíaca/diagnóstico por imagem , Insuficiência Cardíaca/mortalidade , Hemodinâmica , Humanos , Masculino , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Estatísticas não Paramétricas , Taxa de Sobrevida
15.
Inflammation ; 32(6): 347-56, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19669395

RESUMO

Dendritic cells (DCs) and renin-angiotensin system (RAS) have both been reported to contribute to the pathogenesis of atherosclerosis. Recently researches find the RAS expression on DCs and its effect on DCs' differentiation and proinflammatory function. The pattern of RAS expression on DCs derived from normal monocytes vs that on DCs derived from cornoary artery diease was investigated. In 82 coronary artery disease (CAD) patients and healthy controls (CTL), expressions of angiotensin I-converting enzyme (ACE), angiotensin AT1 receptor and DC-specific ICAM-3-grabbing nonintegrin (DC-SIGN) on DCs were measured by western-blot: CAD patients had an increased expression of ACE, AT1 receptor and DC-SIGN compared to controls especially in acute myocardial infarction (AMI). Cardiovascular risk factors of cardiovascular disease and circulating anigotensin II (Ang II) were assessed and found increased in AMI compared with CTL. The DC-SIGN and high-sensitivity C-reactive protein (hsCRP) also had significant correlations with RAS expression on DCs. Our research demonstrated the RAS expressions on DCs and their increase in CAD especially AMI. The RAS activation on DCs may cause a series of changes such as enhancing recruitment of DCs, activating the T cells and increasing their proinflammtory functions. The recruitment and T cells contact ability of DCs increases through DC-SIGN may be one of pathogenesis of atherosclerosis and this function may promoted by tissue RAS. CRP may also have some effect to the local RAS exprssion on DCs.


Assuntos
Doença da Artéria Coronariana/imunologia , Doença da Artéria Coronariana/patologia , Células Dendríticas/imunologia , Células Dendríticas/patologia , Regulação da Expressão Gênica/imunologia , Sistema Renina-Angiotensina/genética , Idoso , Células Cultivadas , Doença da Artéria Coronariana/genética , Doença da Artéria Coronariana/fisiopatologia , Células Dendríticas/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sistema Renina-Angiotensina/imunologia
18.
Zhonghua Yi Xue Za Zhi ; 88(12): 835-9, 2008 Mar 25.
Artigo em Chinês | MEDLINE | ID: mdl-18756989

RESUMO

OBJECTIVE: To investigate the effect of pioglitazone (Pio) on dendritic cell-(DC) specific intercellular adhesion molecule-3 grabbing nonintegrin (DC-SIGN) expression in DCs and explore the possible mechanism of Pio inhibiting DC adhesion and transmigration. METHODS: DCs derived from human peripheral blood mononuclear cells were cultured and divided into 6 groups: blank control group, Pio 0.1 micromol/L group, Pio 1.0 micromol/L group, Pio 10 micromol/L group, GW9662, a peroxisome proliferator activated receptor (PPAR)-gamma antagonist, 10 micromol/L group, and GW9662 10 micromol/L + Pio 10 micromol/L group. Western blotting was used to detect the protein expression of DC-SIGN 24 h later. Human umbilical vein endothelial cells (HUVECs) were obtained and co-cultured with the DCs undergoing different treatments. Immunofluorescence test was used to detect the protein expression of DC-SIGN. DCs labeled with 5-chloromethylfluorescein diacetate (CMFDA) were added into the monocellular layer of fused ECs. Blank DCs and DCs pretreated with anti-DC-SIGN antibody were used as blank and experimental groups. Laser confocal microscopy was used to observe the adhesion ability of the DCs. HUVECs were inoculated into the upper chamber of Transwell plate and CMFDA-labeled DCs of above mentioned groups were added to the mono-cellular layer of these ECs. Serum-free culture medium with monocyte chemoattractant protein-1 was added into the lower chamber. Eight hours later the transmigration ability was observed. RESULTS: Western blotting showed that the DC-SIGN protein expression levels of the DCs of the Pio 1.0 micromol/L and Pio 10 micromol/L group were 0.96 +/- 0.09 and 0.80 +/- 0.08 respectively, both significantly lower than that of the blank control group (1.25 +/- 0.23, P < 0.05 and P < 0.01); and the DC-SIGN protein expression level of the GW9662 10 micromol/L + Pio 10 micromol/L group was 1.10 +/- 0.12, significantly higher than that of the Pio 10 micromol/L group (P < 0.05). Immunofluorescence test showed that the DC-SIGN protein expression levels of the DCs of the Pio 1.0 micromol/L and Pio 10 micromol/L group were 22.3 +/- 5.4 and 14.4 +/- 2.3 respectively, both significantly lower than that of the control group (29.5 +/- 5.1, P < 0.05 and P < 0.01), and the DC-SIGN protein expression level of the GW9662 10 micromol/L + Pio 10 micromol/L group was 24.9 +/- 4.3, significantly higher than that of the Pio 10 micromol/L group (P < 0.01), and not significantly different from that of the blank control group (P > 0.05). The adhesion rates of the Pio 1.0 micromol/L and Pio 10 micromol/L groups were 10.8% +/- 2.0% and 7.6% +/- 1.5% respectively, both significantly lower than that of the control group (13.4% +/- 2.1%, P < 0.05 and P < 0.01); and the adhesion rate of the GW9662 + Pio 10 micromol/L group was 12.1% +/- 1.9%, significantly higher than that of the Pio 10 micromol/L group (P < 0.01), and not significantly different from that of the blank control group (P > 0.05). The transmigration inhibition rate of DCs of the Pio 0.1, 1.0, and 10 micromol/L groups were 4.1%, 12.9%, and 17.2% compared with the transmigration rate of the blank control group (P < 0.05, P < 0.05, and P < 0.01). The transmigration rate of the GW9662 + Pio 10 micromol/L group was significantly higher than that of the Pio 10 micromol/L group (P < 0.05), and not significantly different from that of the blank control group (P > 0.05). The transmigration rate of the anti-DC-SIGN intervention group was lower by 17.8% than that of the control group (P < 0.01). CONCLUSION: Pio down-regulates the DC-SIGN protein expression and inhibits DC adhesion and transmigration through the pathway of PPAR-gamma.


Assuntos
Moléculas de Adesão Celular/metabolismo , Movimento Celular/efeitos dos fármacos , Células Dendríticas/efeitos dos fármacos , Lectinas Tipo C/metabolismo , Receptores de Superfície Celular/metabolismo , Tiazolidinedionas/farmacologia , Anilidas/farmacologia , Western Blotting , Adesão Celular/efeitos dos fármacos , Linhagem Celular , Células Cultivadas , Técnicas de Cocultura , Células Dendríticas/citologia , Células Dendríticas/metabolismo , Regulação para Baixo , Células Endoteliais/citologia , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Humanos , Microscopia Confocal , Pioglitazona
19.
Int Immunopharmacol ; 7(9): 1241-50, 2007 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-17630203

RESUMO

Elevated plasma homocysteine (Hcy) is an independent risk factor for atherosclerosis, which is recognized as inflammatory and immune responses. The purpose of this study was to investigate the effect of Hcy on the interaction between dendritic cells (DCs) and endothelial cells (ECs) by upregulating the expression of DC-specific ICAM-3-grabbing nonintegrin (DC-SIGN) in cultured DCs. The immunophenotype of Hcy-treated DCs was monitored by flow cytometry. Then, they were coincubated with cultured human umbilical vein endothelial cells, and adhesion of DCs to ECs, and migration of DCs through an endothelial monolayer growing on the insert of a transwell plate, were assessed using a confocal microscope and a multi-detection microplate reader. The expression of DC-SIGN on Hcy-stimulated DCs was assessed by Western blot and immunofluorescence staining. The presence of Hcy did not change the phenotype of immature and mature DCs. Hcy promoted adhesion of DCs to ECs and migration in a concentration-dependent fashion. This effect was inhibited by an anti-DC-SIGN monoclonal antibody. The expression of DC-SIGN on DCs was significantly upregulated by Hcy in a concentration-dependent manner. Taken together, our results show for the first time that Hcy can potentiate the adhesion of DCs to ECs and migration by upregulating the expression of DC-SIGN on DCs, suggesting a novel role of Hcy in the pathogenesis of human vascular disease.


Assuntos
Moléculas de Adesão Celular/fisiologia , Movimento Celular/fisiologia , Células Dendríticas/metabolismo , Células Endoteliais/metabolismo , Homocisteína/fisiologia , Lectinas Tipo C/fisiologia , Receptores de Superfície Celular/fisiologia , Adesão Celular/fisiologia , Células Cultivadas , Células Dendríticas/patologia , Células Endoteliais/patologia , Homocisteína/toxicidade , Humanos
20.
Cancer Epidemiol Biomarkers Prev ; 14(7): 1697-702, 2005 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-16030104

RESUMO

BACKGROUND: Evidence of the chemopreventive effects of the dietary antioxidants alpha-tocopherol (vitamin E) and l-selenomethionine (selenium) comes from secondary analysis of two phase III clinical trials that found treatment with these antioxidants reduced the incidence of prostate cancer. To determine the effects of selenium and vitamin E in blood and prostate tissue, we undertook a preoperative feasibility study complementary to the currently ongoing Selenium and Vitamin E Cancer Prevention Trial. METHODS: Forty-eight patients with clinically localized prostate cancer enrolled on this 2 x 2 factorial design study were randomized to take selenium, vitamin E, both, or placebo for 3 to 6 weeks before prostatectomy. Sera were collected from patients before and after dietary supplementation. Thirty-nine patients were evaluable, and 29 age-matched disease-free men served as controls. Mass profiling of lipophilic serum proteins of lower molecular weight (2-13.5 kDa) was conducted, and mass spectra data were analyzed using custom-designed software. RESULTS: Weighted voting analyses showed a change in sera classification from cancerous to healthy for some patients with prostate cancer after dietary intervention. ANOVA analysis showed significantly different treatment effects on prediction strength changes among the four groups at a 95% confidence level. Eliminating an outlying value and performing post hoc analysis using Fisher's least significant difference method showed that effects in the group treated with the combination were significantly different from those of the other groups. CONCLUSION: In sera from patients with prostate cancer, selenium and vitamin E combined induced statistically significant proteomic pattern changes associated with prostate cancer-free status.


Assuntos
Antioxidantes/uso terapêutico , Neoplasias da Próstata/prevenção & controle , Selenometionina/uso terapêutico , Vitamina E/uso terapêutico , Análise de Variância , Método Duplo-Cego , Humanos , Masculino , Pessoa de Meia-Idade , Cuidados Pré-Operatórios , Prostatectomia , Neoplasias da Próstata/sangue , Proteômica
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