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OBJECTIVES: Computed tomographic perfusion (CTP) can play an auxiliary role in the selection of patients with acute ischemic stroke for endovascular treatment. However, data on CTP in non-stroke patients with intracranial arterial stenosis are scarce. We aimed to investigate images in patients with asymptomatic intracranial arterial stenosis to determine the detection accuracy and interpretation time of large/medium-artery stenosis or occlusion when combining computed tomographic angiography (CTA) and CTP images. METHODS: We retrospectively reviewed 39 patients with asymptomatic intracranial arterial stenosis from our hospital database from January 2021 to August 2023 who underwent head CTP, head CTA, and digital subtraction angiography (DSA). Head CTA images were generated from the CTP data, and the diagnostic performance for each artery was assessed. Two readers independently interpreted the CTA images before and after CTP, and the results were analyzed. RESULTS: After adding CTP maps, the accuracy (area under the curve) of diagnosing internal carotid artery (R1: 0.847 vs. 0.907, R2: 0.776 vs. 0.887), middle cerebral artery (R1: 0.934 vs. 0.933, R2: 0.927 vs. 0.981), anterior cerebral artery (R1: 0.625 vs. 0.750, R2: 0.609 vs. 0.750), vertebral artery (R1: 0.743 vs. 0.764, R2: 0.748 vs. 0.846), and posterior cerebral artery (R1: 0.390 vs. 0.575, R2: 0.390 vs. 0.585) occlusions increased for both readers (p < 0.05). Mean interpretation time (R1: 72.4 ± 6.1 s vs. 67.7 ± 6.4 s, R2: 77.7 ± 3.8 s vs. 72.6 ± 4.7 s) decreased when using a combination of both images both readers (p < 0.001). CONCLUSIONS: The addition of CTP images improved the accuracy of interpreting CTA images and reduced the interpretation time in asymptomatic intracranial arterial stenosis. These findings support the use of CTP imaging in patients with asymptomatic intracranial arterial stenosis.
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AVC Isquêmico , Humanos , Estudos Retrospectivos , Constrição Patológica/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Angiografia por Tomografia Computadorizada/métodos , Perfusão , Angiografia Cerebral/métodosRESUMO
OBJECTIVE: Gastric cancer (GC) ranks fifth in incidence and fourth for mortality worldwide. The response to immune checkpoint blockade (ICB) therapy in GC is heterogeneous due to tumour-intrinsic and acquired immunotherapy resistance. We developed an immunophenotype-based subtyping of human GC based on immune cells infiltration to develop a novel treatment option. DESIGN: A algorithm was developed to reclassify GC into immune inflamed, excluded and desert subtypes. Bioinformatics, human and mouse GC cell lines, syngeneic murine gastric tumour model, and CTLA4 blockade were used to investigate the immunotherapeutic effects by restricting receptor tyrosine kinase (RTK) signalling in immune desert (ICB-resistant) type GC. RESULTS: Our algorithm restratified subtypes of human GC in public databases and showed that immune desert-type and excluded-type tumours are ICB-resistant compared with immune-inflamed GC. Moreover, epithelial-mesenchymal transition (EMT) signalling was highly enriched in immune desert-type GC, and syngeneic murine tumours exhibiting mesenchymal-like, compared with epithelial-like, properties are T cell-excluded and resistant to CTLA4 blockade. Our analysis further identified a panel of RTKs as potential druggable targets in the immune desert-type GC. Dovitinib, an inhibitor of multiple RTKs, strikingly repressed EMT programming in mesenchymal-like immune desert syngeneic GC models. Dovitinib activated the tumour-intrinsic SNAI1/2-IFN-γ signalling axis and impeded the EMT programme, converting immune desert-type tumours to immune inflamed-type tumours, sensitising these mesenchymal-like 'cold' tumours to CTLA4 blockade. CONCLUSION: Our findings identified potential druggable targets relevant to patient groups, especially for refractory immune desert-type/ 'cold' GC. Dovitinib, an RTK inhibitor, sensitised desert-type immune-cold GC to CTLA4 blockade by restricting EMT and recruiting T cells.
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BACKGROUND: IgG4-related disease (IgG4-RD) is a newly discovered systemic disease that can affect any organ or tissue in the body. IgG4-related kidney disease (IgG4-RKD) is relatively rare but essential to IgG4-RD. However, there are few reports of IgG4-RD mimicking malignant ureteral tumors leading to hydronephrosis. We report here a rare case of IgG4-RD involving the ureter. CASE PRESENTATION: An 87-year-old man presented to our nephrology department with anorexia, nausea, and acute kidney injury in November 2020. Urinary computed tomography (CT) examination revealed a right lower ureter mass with right renal and ureter hydronephrosis. The serum level of IgG4 was 1890 mg/dL, and the concurrently renal biopsy revealed extensive infiltration of IgG4-positive plasma cells in renal interstitium, which was diagnosed as IgG4-associated tubule-interstitial nephritis(IgG4-TIN). The renal function improved significantly after double-J tube implantation of the right ureter and moderate-dose hormone therapy. The serum IgG4 decreased to the normal range, and the right lower ureter mass almost disappeared after one year of low-dose hormone maintenance therapy. CONCLUSION: IgG4-RD can present as a mass in the renal pelvis and (or) ureter, leading to hydronephrosis. Therefore, early recognition of this disease is significant. Most patients respond well to hormonal therapy to avoid surgical treatment due to misdiagnosis as malignant tumors, causing secondary harm to patients.
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Hidronefrose , Doença Relacionada a Imunoglobulina G4 , Nefrite Intersticial , Obstrução Ureteral , Masculino , Humanos , Idoso de 80 Anos ou mais , Obstrução Ureteral/complicações , Doença Relacionada a Imunoglobulina G4/complicações , Doença Relacionada a Imunoglobulina G4/diagnóstico , Imunoglobulina G , Nefrite Intersticial/complicações , Nefrite Intersticial/diagnóstico , Nefrite Intersticial/patologia , Hidronefrose/complicações , HormôniosRESUMO
Sepsis is one of the most challenging health problems worldwide. Our previous study showed that chronic schistosoma japonica (SJ) infection might increase serum anti-inflammatory factors to play a protective role, thus improving the survival rate of septic mice. Further research revealed that SJ infection promoted J774A.1 macrophage differentiation into M2 macrophages; suppressed LPS-induced activation of M1 macrophages; up-regulated CD163, IL-10, and TGF-ß1 expression; inhibited TNF-α and iNOS expression; and blocked the effect of LPS-promoted TNF-α and iNOS expression. Furthermore, adoptive transfer of ex vivo programed M2 macrophages significantly increased the survival rate of septic mice. In vitro studies suggested that soluble egg antigen (SEA) from SJ played the same role as worm infection but had no impact on M1 macrophages. SEA reduced LPS-induced TNF-α and iNOS expression, decreased the inhibitory effect of LPS on IL-10 and TGF-ß1 expression, increased STAT6 phosphorylation, and up-regulated PI3K and Akt expression but inhibited SOCS1 expression. When PI3K inhibitors were added, SEA-induced expression of CD163, IL-10, and arg1 might be reduced. Therefore, worm infection has a protective effect in septic mice in which SEA may play a key role via the STAT6 and PI3K pathways. This finding may provide a favorable solution for the treatment of sepsis, especially early cases. J. Cell. Biochem. 118: 4230-4239, 2017. © 2017 Wiley Periodicals, Inc.
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Antígenos de Helmintos/imunologia , Citocinas , Macrófagos/metabolismo , Esquistossomose Japônica/complicações , Sepse/complicações , Transdução de Sinais , Animais , Macrófagos/imunologia , Camundongos , Óxido Nítrico Sintase Tipo II , Fosfatidilinositol 3-Quinases/metabolismo , Fator de Transcrição STAT6/metabolismo , Esquistossomose Japônica/imunologia , Esquistossomose Japônica/metabolismo , Sepse/mortalidade , Taxa de SobrevidaRESUMO
OBJECTIVE: To investigate the potential association between FADS1 rs174537 polymorphism and serum proteins in patients with aggressive periodontitis, which may provide benefits for diagnosis and treatment of aggressive periodontitis. METHODS: A total of 353 patients with aggressive periodontitis (group AgP) and 125 matched controls (group HP) were recruited in the study. Genotyping of FADS1 rs174537 and serum biochemical indexes were tested at the study's start. The relationships between the levels of TP, GLB, ALB, A/G and genotyping were analyzed. RESULTS: (1) The detection rate of allele G in group AgP was higher than that in group HP(68.1% vs. 61.2%, P=0.046,OR=1.35,95% CI 1.00-1.83); the detection rate of genotype GG in group AgP was higher than in group HP(45.5% vs. 34.4%,P=0.029, OR=1.60, 95% CI 1.05-2.44). (2) In group AgP, the patients with GG genotype exhibited significantly lower TP, GLB than the patients with GT+TT genotype [(77.08 ± 7.88) g/L vs. (79.00 ± 4.66) g/L, P=0.007; (28.17 ± 7.63) g/L vs.(29.88 ± 3.49) g/L,P=0.007) and the higher A/G(1.72 ± 0.22 vs.1.67 ± 0.22, P=0.040), but there was no significant difference in ALB between the patients with GG genotype and the patients with GT+TT genotype. In group HP, there were no significant differences in TP, GLB, A/G and ALB between individuals with genotype GT+TT and with genotype GG. (3)Compared with individuals with genotype GT+TT in group HP, the AgP patients with genotype GT+TT exhibited significantly higher TP, GLB [(79.00 ± 4.66) g/L vs. (75.20 ± 4.53) g/L, P<0.01; (29.88 ± 3.49) g/L vs.(26.55 ± 2.94) g/L, P<0.01) and the lower A/G(1.67 ± 0.22 vs. 1.88 ± 0.30, P<0.01), but there was no significant difference in ALB. There were no significant differences in TP, GLB, A/G and ALB the between the AgP patients with genotype GG and the healthy subjects with the same genotype either. CONCLUSION: FADS1 rs174537 polymorphism is associated with aggressive periodontitis. The patients with genotype GG in group AgP had relatively lower TP,GLB and higher A/G. Genotype GG might be a risk indicator for aggressive periodontitis by reducing host defense capability and contributing to inflammatory response in the occurrence and development of aggressive periodontitis.
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Periodontite Agressiva/genética , Proteínas Sanguíneas/metabolismo , Ácidos Graxos Dessaturases/genética , Alelos , Estudos de Casos e Controles , Dessaturase de Ácido Graxo Delta-5 , Genótipo , Humanos , Polimorfismo Genético , Fatores de RiscoRESUMO
Micrometam C is a core of novel marine compound isolated from the mangrove associates Micromelum falcatum. In this study, we investigated the protective effects of micrometam C in inflammation models in the transgenic zebrafish line Tg (corola: eGFP) and RAW264.7 macrophages. We found that micrometam C significantly suppressed the migration of immune cells in tail-cutting-induced inflammation in transgenic zebrafish and reduced lipopolysaccharide (LPS)-induced reactive oxygen species (ROS) in both zebrafish and macrophages. In addition, micrometam C also restored LPS-induced reduction of endogenous antioxidants, such as catalase (CAT), glutathione (GSH) and superoxide dismutase (SOD). The protective effects of micrometam C were in parallel to its inhibition of NADPH oxidase and nuclear factor-kappa-binding (NF-κB) activity. Thus, the present results demonstrate that micrometam C protects against LPS-induced inflammation possibly through its antioxidant property.
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Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Ácidos Cumáricos/química , Ácidos Cumáricos/farmacologia , Inflamação/tratamento farmacológico , Animais , Antioxidantes , Linhagem Celular , Regulação da Expressão Gênica/efeitos dos fármacos , Lipopolissacarídeos/toxicidade , Macrófagos , Camundongos , Estrutura Molecular , NADPH Oxidases/metabolismo , NF-kappa B/genética , NF-kappa B/metabolismo , Estresse Oxidativo , Explosão Respiratória , Cauda , Peixe-ZebraRESUMO
OBJECTIVE: To investigate the changes of osteoprotegerin (OPG) and receptor activator of nuclear factor kappa B ligand (RANKL) level in perio-implant crevicular fluid (PICF) and to monitor the development of the stability of Straumann® tissue-level implants by resonance frequency analysis (RFA) during the early phases of healing. METHODS: A total of 35 implants (length 10 mm) were placed. PICF samples were collected with filter paper strips at baseline, 1, 2, 3, 4, 6, 8, and 12 weeks post-surgery, respectively. The OPG, RANKL levels were determined by ELISA method. At the same time points, the implant stability quotient (ISQ) values were determined with Osstell™ mentor. RESULTS: During healing, PICF-OPG levels increased significantly 2 weeks after surgery when compared with the 4(th) -, 6(th) -, 8(th) - and 12(th) -week reevaluation (P<0.05). The OPG/RANKL ratio in PICF was significantly higher (P<0.05) than that in gingival crevicular fluid at 1 week post-surgery. ISQ slightly fluctuated within the first 4 weeks after installation. Following this, the ISQ values increased steadily for all the implants and up to 12 weeks. Significant differences were noted between the mean ISQ values at the 12th-week and other observation time points. CONCLUSION: The PICF-OPG levels may be effective in monitoring the process of osseointegration. All the ISQ values indicated the stability of Straumann® implants over a 12-week healing period. RFA is a reliable and effective assistant to monitor implant stability.
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Osso e Ossos/metabolismo , Implantação Dentária Endóssea , Implantes Dentários , Líquido do Sulco Gengival/química , Biomarcadores/química , Humanos , Osseointegração , Osteoprotegerina/metabolismo , Ligante RANK/metabolismo , CicatrizaçãoRESUMO
OBJECTIVE: To investigate the relationship between vitamin D receptor (VDR) gene polymorphisms and chronic periodontitis(CP). METHODS: Buccal swabs from 105 patients with mild/mode-rate CP and 85 severe CP were collected, DNA was extracted from these buccal swabs using the TIANamp Swab DNA Kit [TIANGEN Biotech (Beijing) CO.Ltd]. The VDR rs1544410 and rs731236 were genotyped by the Sequenom MassARRAY system (Shanghai Benegene Biotechnology Co. Ltd), which was based on MALDI-TOF (matrix-assisted laser desorption ionization time-of-flight) technology. The distribution of the genotypes and allele frequencies were analyzed. RESULTS: The frequencies of the rs1544410 A allele and AA+AG genotype were significantly higher in severe CP than in mild/moderate CP of all the patients and the female patients respectively (all the patients: P=0.006, 0.007; the female patients: P=0.001, 0.001). The frequencies of the rs731236 C allele and CC+CT genotype were significantly higher in severe CP than in mild/moderate CP of all the patients and the female patients respectively (all the patients: P=0.003, 0.004; the female patients: P<0.001, <0.001). CONCLUSION: Gene polymorphisms of VDR rs731236 and rs1544410 may be associated with severe CP in Chinese Han population.
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Periodontite Crônica/genética , Receptores de Calcitriol/genética , Alelos , China , Feminino , Frequência do Gene , Genótipo , Humanos , Masculino , Polimorfismo Genético , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por MatrizRESUMO
OBJECTIVE: To analyze the serum IgG titers to Aggregatibacter actinomycetemcomitans(Aa) and associated factors in patients with aggressive periodontitis (AgP). METHODS: Venous blood samples were collected from 62 AgP patients and 45 periodontal healthy controls, unstimulated whole saliva and pooled subgingival plaque samples of AgP patients were also collected for the detection of Aa (PCR method). Serum IgG titers to Aa serotype c were measured by enzyme-linked immunosorbnent assay (ELISA). RESULTS: The detection rates of serum IgG to Aa serotype c in the AgP patients and the healthy controls were both 100%. The AgP patients exhibited significantly higher IgG titers to Aa serotype c than the healthy controls (11.1±1.9 vs. 9.1±1.8, P<0.01). There was no significant difference in serum IgG levels to Aa serotype c and in the prevalence of high-responding patients to Aa serotype c between the incisor-first molar type AgP patients and generalized AgP patients. Serum IgG titers to Aa serotype c in the Aa-positive AgP patients (the patients who were Aa-positive in subgingival plaque or saliva) were significantly higher than those of the Aa-negative patients (11.9±1.3 vs. 10.7±2.1, P<0.05). CONCLUSION: Serotype c was the main serotype of Aa in Chinese patients with AgP. Serum IgG responses in generalized AgP patients were comparable to those in incisor-first molar type AgP patients.
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Aggregatibacter actinomycetemcomitans/classificação , Periodontite Agressiva/imunologia , Anticorpos Antibacterianos/sangue , Imunoglobulina G/sangue , Periodontite Agressiva/sangue , Estudos de Casos e Controles , Placa Dentária/microbiologia , Humanos , Saliva/microbiologia , SorogrupoRESUMO
OBJECTIVE: To assess the characteristics of establishing the different sample banks of plasma, leukocytes and DNA by sedimentation method of isolating from ethylene diamine tetraacetic acid(EDTA)-blood and to clarify the sedimentation method of leukocyte isolation and plasma volume by comparative data and recommended procedures for applicability. METHODS: In the study, 29 EDTA-bloods were obtained, the total amounts of leukocytes and the percentage of neutrophile granulocytes, and lymphocytes in the EDTA-blood detected as a control group and then assigned equally into 4 EP tubes with 1 mL EDTA-blood per tube as 4 test groups, then the 4 tubes were placed with the EDTA-blood at room temperature and the plasma layers were isolated at 0.5, 1, 2 and 3 h, receptively. The total amount of leukocytes and the percentage of neutrophile granulocytes, and lymphocytes were detected by automated hematology analyzer at the clinical laboratory. The volume of the plasma was also measured at the same time. RESULTS: The plasma volume at 0.5 h [(241.72 ± 101.52)µL] was substantially lower than those at 1 h[(317.24 ± 97.50)µL], at 2 h[(371.03 ± 91.66)µL], and at 3 h [(408.97 ± 97.43)µL] , P < 0.05. The plasma volume at 1 h was substantially lower than those at 2 h and 3 h (P < 0.05). The total amount of leukocytes in the plasma layer at 0.5 h (2.50 × 10(6) ± 1.48 × 10(6)) group was substantially higher than the amount of 2 or 3 h groups respectively (1.47 × 10(6) ± 7.19 × 105,1.21 × 10(6) ± 7.41 × 105), P < 0.05. Significant difference was not found between 0.5 h group and 1 h group (2.29 × 10(6)± 1.17 × 10(6)), P > 0.05. The total amount of leukocytes in the plasma layer in 1 h group was substantially higher than that in 2 h and 3 h groups (P < 0.05). There was no significant difference between 3 h group and 2 h group (P > 0.05). The total amount of leukocytes in the plasma layer of the 4 test groups was substantially lower than that in the control group (P < 0.05). The percentage of neutrophile granulocytes (54.14% ± 11.65%) in the plasma layer in 0.5 h group was substantially higher than those in 1 h, 2 h and 3 h groups (46.66% ± 12.70%,39.17% ± 12.33%,43.25% ± 14.54%), P < 0.05, respectively, which was the substantially lower than that in the control group (60.53% ± 8.46%), P < 0.05. The average value of the percentage of neutrophile granulocytes in the plasma layer in 1 h group was substantially higher than that in 2 h group (P < 0.05). There was no significant different between 3 h group and both 1 h, 2 h groups (P > 0.05). The mean percentage of lymphocytes in the plasma layer in 0.5 h group (35.09% ± 10.84%) was substantially lower than those in the plasma layer in 1 h, 2 h and 3 h groups, respectively ( 41.48% ± 12.20%, 47.96% ± 12.27%, 45.50% ± 13.71%), which was significant higher than that in the control group(30.98% ± 7.33%), P < 0.05. The average value of the percentage of lymphocytes in the plasma layer in 1 h group was substantially higher than those in the control group and 0.5 h group, but was substantially lower than those in 2 h and 3 h groups (P < 0.05). The average value of percentage of lymphocytes in the plasma layer in 2 h group was substantially higher than those in the control group, 0.5 h and 1 h groups (P < 0.05). There was no significant difference between 2 h and 3 h groups (P > 0.05). CONCLUSION: The best period of time in obtaining leukocytes is 0.5-1 h sedimentation of EDTA-blood. Both the plasma layer and leukocytes can be separated and obtained at the same time from the same sample by the sedimentation method of EDTA-blood. The sedimentation of EDTA-blood has the least interference of both chemical and physical factors, as well as a ready operation, which can establish the plasma, leukocytes and DNA sample banks for various aspects of research.
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Sedimentação Sanguínea , Ácido Edético , Leucócitos , Granulócitos , Humanos , Linfócitos , PlasmaRESUMO
BACKGROUND AND PURPOSE: Little research regarding genotypes and clopidogrel response related to acute ischemic stroke has been published. This study was conducted to investigate whether the polymorphisms of receptors or enzymes involved in the metabolic process of clopidogrel affect clopidogrel response and prognosis related to acute stroke. METHODS: A total of 259 patients with acute ischemic stroke were enrolled in this study; all received follow-up evaluations 3 and 6 months after clopidogrel treatment. CYP2C19, CYP3A4, and P2Y12 were screened. The adenosine diphosphate-induced platelet aggregation test, the National Institutes of Health Stroke Scale (NIHSS), and the modified Rankin Scale (mRS) were used, and blood vascular events were evaluated. RESULTS: The difference before and after clopidogrel treatment on adenosine diphosphate-induced platelet aggregation was significantly smaller in patients carrying 1 or 2 CYP2C19 loss-of-function alleles (*2, *3) compared with patients carrying none. Patients with none had better outcomes than patients with CYP2C19 loss-of-function alleles, as demonstrated by NIHSS and mRS scores at 3 and 6 months after treatment. Regression analysis showed that CYP2C19 was an independent predictor of clopidogrel resistance. CONCLUSIONS: CYP2C19 genotypes had significant impact on clopidogrel response and prognosis of patients with stroke. Clinical Trial Registration Information- URL: http://www.chictr.org/. Unique Identifier: ChiCTR-OCH-12002681.
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Hidrocarboneto de Aril Hidroxilases/genética , Povo Asiático/genética , Inibidores da Agregação Plaquetária/uso terapêutico , Polimorfismo de Nucleotídeo Único/genética , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/genética , Ticlopidina/análogos & derivados , Idoso , Alelos , Povo Asiático/etnologia , Estudos de Casos e Controles , China/epidemiologia , Clopidogrel , Citocromo P-450 CYP2C19 , Resistência a Medicamentos/genética , Feminino , Seguimentos , Testes Genéticos , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Farmacogenética , Prognóstico , Acidente Vascular Cerebral/etnologia , Ticlopidina/uso terapêutico , Resultado do TratamentoRESUMO
OBJECTIVE: To establish a predictive model for long-term tooth loss of patients with aggressive periodontitis (AgP) after periodontal treatment. METHODS: Patients diagnosed as AgP in Department of Periodontology, Peking University School and Hospital of Stomatology, who were re-evaluated 3 to 11 years after periodontal treatment were enrolled (n=85). Logistic regression was performed to select background, periodontal and radiographic factors which were related to long-term post-treatment tooth loss. A predictive model was built and analyzed by receiver operator characteristic (ROC) curve. RESULTS: After periodontal treatment, 55 teeth from 22 patients lost further. High prevalence of baseline bone loss, root abnormality, and residual severe bleeding sites, as well as poor compliance to maintenance were detected as risk factors in the predictive model. ROC analysis found the sensitivity and specificity of the model could reach up to 80% simultaneously. CONCLUSION: Predictive model for post-treatment tooth loss of patients with AgP is an important adjunct in clinical practice.
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Periodontite Agressiva/complicações , Perda de Dente/etiologia , Humanos , Modelos Logísticos , Curva ROC , Estudos Retrospectivos , Fatores de RiscoRESUMO
1. Histone deacetylase (HDAC) inhibitors exert neuroprotection in both cellular and animal models of ischaemic stroke. However, which HDAC isoform (or isoforms) mediates this beneficial effect has not yet been determined. 2. In the present study, gene levels of the HDAC isoforms were determined in the mouse cortex using reverse transcription-polymerase chain reaction (RT-PCR), whereas changes in the expression of individual zinc-dependent HDAC family members were evaluated by western blotting, 3, 12, 24 and 48 h after cerebral ischaemia induced by transient middle cerebral artery occlusion in male Kunming mice. 3. The HDAC isoforms HDAC1-11 were all expressed in the mouse cortex and differentially affected by cerebral ischaemia. Notably, there was a substantial increase in HDAC3, HDAC6 and HDAC11 expression during the early phases of experimental stroke, indicating their contribution to stroke pathogenesis. Furthermore, induction of HDAC3 and HDAC6 in cortical neurons by ischaemic stroke was confirmed in vivo and in vitro using double-labelled immunostaining and RT-PCR, respectively. Therefore, small hairpin (sh) RNAs were used to selectively knock down HDAC3 or HDAC6. This knockdown appreciably promoted the survival of cortical neurons subjected to oxygen and glucose deprivation. 4. The findings of the present study demonstrate the expression patterns of HDAC isoforms during experimental ischaemic stroke. Furthermore, HDAC3 and HDAC6 were identified as potential mediators in the neurotoxicity of ischaemic stroke, suggesting that specific therapeutic approaches may be considered according to HDAC subtype.
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Córtex Cerebral/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Histona Desacetilases/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Neurônios/metabolismo , Acidente Vascular Cerebral/metabolismo , Animais , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/patologia , Modelos Animais de Doenças , Embrião de Mamíferos , Desacetilase 6 de Histona , Inibidores de Histona Desacetilases/farmacologia , Inibidores de Histona Desacetilases/uso terapêutico , Histona Desacetilases/química , Histona Desacetilases/genética , Infarto da Artéria Cerebral Média/fisiopatologia , Isoenzimas/antagonistas & inibidores , Isoenzimas/genética , Isoenzimas/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos , Terapia de Alvo Molecular , Proteínas do Tecido Nervoso/antagonistas & inibidores , Proteínas do Tecido Nervoso/genética , Neurônios/efeitos dos fármacos , Neurônios/patologia , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Interferência de RNA , RNA Mensageiro/metabolismo , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/patologiaRESUMO
OBJECTIVE: To compare the granulocyte elastase (EA) levels in saliva and/or gingival crevicular fluid (GCF) of subjects with various periodontal conditions and analyze the relation between EA levels in GCF and in saliva. METHODS: GCF and salivary samples were collected from 17 subjects with healthy periodontium, 14 with gingivitis, 24 with chronic periodontitis (CP) and 24 with aggressive periodontitis (AgP). The EA levels in GCF and saliva were analyzed. RESULTS: The GCF-EA level in AgP were significantly higher than that in CP (0.485 3 ± 0.225 0 vs. 0.288 4 ± 0.193 1, P<0.01); the levels of EA in saliva of periodontitis patients (AgP and CP) were higher than those of healthy and gingivitis subjects (0.844 5 ± 0.660 6, 0.637 3 ± 0.648 9 vs. 0.031 6 ± 0.020 6, 0.012 2 ± 0.005 8, P<0.001). A positive correlation was found between EA levels in saliva and those in GCF (r=0.660). CONCLUSION: GCF-EA level may serve as a marker for clinical assessment of periodontal conditions. The measurement of EA levels in saliva may facilitate to overall screen periodontitis patients in epidemiological study or to monitor periodontal conditions in clinical practice.
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Periodontite Agressiva/enzimologia , Líquido do Sulco Gengival/enzimologia , Gengivite/enzimologia , Elastase de Leucócito/análise , Periodontite/enzimologia , Saliva/enzimologia , Adulto , Feminino , Humanos , MasculinoRESUMO
OBJECTIVE: To investigate the level of osteoprotegerin (OPG) and receptor activator of nuclear factor kappa B ligand (RANKL) in gingival crevicular fluid (GCF) during orthodontic retention and corresponding expression of OPG and RANKL in periodontal tissues. METHODS: Fifteen male Wistar rats (age, 6 weeks) were divided into three groups with 5 rats for each. GCF samples were collected at the baseline, 14 days after orthodontic force application, and 14 days after orthodontic force removal. enzyme linked immunosorbent assay (ELISA) was used to quantify the concentration of OPG and sRANKL (soluble receptor activator of nuclear factor kappa B ligand) in GCF. Immunohistochemical staining was performed to identify the OPG and RANKL expression in periodontal tissues. RESULTS: The concentration of sRANKL in GCF increased statistically significant from baseline to T2 (P<0.05) while decreased significantly from T2 to T3 (P<0.05). The concentration of OPG had minimum fluctuation from baseline to T3 without any statistical significance (P>0.05). The sRANKL/OPG ratio in GCF and that in periodontal tissues during the three time points were similar which showed a prominent increase in T2 (P<0.05 and P<0.01, respectively) and sharp decrease in T3 (P<0.05). CONCLUSION: sRANKL/OPG ratio may be one of the predictors reflecting the remodeling of periodontal tissues in orthodontic retention.
Assuntos
Remodelação Óssea/fisiologia , Líquido do Sulco Gengival/metabolismo , Osteoprotegerina/metabolismo , Ligante RANK/metabolismo , Técnicas de Movimentação Dentária , Processo Alveolar , Animais , Masculino , Aparelhos Ortodônticos , Ratos , Ratos WistarRESUMO
OBJECTIVE: To investigate the possible relationship between the preterm and/or low birth weight (PLBW) and three anaerobic microorganisms in saliva of their mothers, including Porphyromonas gingivalis (Pg), Tannerella forsythia (Tf), Treponema Denticola (Td). METHODS: 110 retrospective cases were collected from 4 hospitals in Beijing urban and suburban areas. PLBW group included 72 subjects and NBW group included 38 subjects. They were made up of 2:1 matched data. Nonstimulated saliva samples were collected from all the individuals. The periodontal examinations included plaque index (PLI), probing depth (PD), bleeding index (BI), and clinical attachment loss (CAL) were performed in 1-1.5 years after preterm. According to the PCR results in their saliva, they were divided into positive group and negative group of Pg, Tf, Td. RESULTS: CAL in PLBW and NBW groups were 0.18 (0.00, 4.97) mm and 0.08 (0.00, 1.81) mm respectively which was significantly different (P<0.05). The detection rates of Pg in PLBW and NBW groups were 94.4% and 78.9% respectively (P<0.05). The detection rates of Tf were 84.7% and 94.7% respectively (P>0.05). The detection rates of Td were 86.1% and 89.5% respectively (P>0.05). The clinical parameters of CAL [2.25(0.54, 4.00) mm, 1.44(0.63, 3.80) mm], PD[(2.47 ± 0.43) mm, (1.94 ± 0.39) mm], PLI (1.80 ± 0.44, 1.36 ± 0.34) in Pg positive group was significantly higher than those in Pg negative group. The birth weight of Pg positive group [(2 482.95 ± 813.17) g] was significantly lower than Pg negative group [(3 425.00 ± 1 024.36) g]. CAL [0.14(0.00,4.9) mm, 0.03(0.00,0.44) mm], PD[(2.44 ± 0.46) mm, (2.17 ± 0.38) mm] were significantly different between Tf positive and negative group. PD [(2.44 ± 0.46) mm, (2.14 ± 0.43) mm] and BI (2.31 ± 0.86, 1.83 ± 0.68) were significantly different between Td positive and negative group. CONCLUSION: There is higher level of Pg, Tf and Td in the saliva of both PLBW and NBW groups. The detection of Pg may be related to PLBW.
Assuntos
Bactérias Anaeróbias/isolamento & purificação , Recém-Nascido de Baixo Peso , Doenças Periodontais/microbiologia , Complicações Infecciosas na Gravidez , Nascimento Prematuro , Saliva/microbiologia , Adulto , Placa Dentária/microbiologia , Feminino , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Doenças Periodontais/complicações , Porphyromonas gingivalis/isolamento & purificação , Gravidez , Complicações Infecciosas na Gravidez/microbiologia , Nascimento Prematuro/etiologia , Inquéritos e Questionários , Treponema denticola/isolamento & purificação , Adulto JovemRESUMO
OBJECTIVE: To explore the protective effect of human 14-3-3 γ gene transfer on dopaminergic cells against rotenone-induced injury. METHODS: Adenovirus vector carrying the gene of 14-3-3 γ (Ad/14-3-3 γ) was employed to transfect PC12 cells. Then the cells were exposed to rotenone as a model of Parkinson's disease. Methyl thiazolyl tetrazolium (MTT) was used to assay the viability of PC12 cells. The 4',6-diamidino-2-phenylindole (DAPI) staining was used to analyze the apoptotic ratio of PC12 cells among the groups of control, Ad/14-3-3 γ, Ad-null and Rotenone. And high performance liquid chromatography (HPLC) was performed to detect the secreting functions of PC12 cells. The aggregates of α-Synuclein protein were detected under confocal microscopy. RESULTS: MTT showed that the cell absorbance A(570) of Ad/14-3-3 γ group (0.46 ± 0.09) was higher than that of Ad-null group (0.19 ± 0.08) and rotenone group (0.16 ± 0.07), but lower than that of normal control (0.63 ± 0.11), (all P < 0.01); HPLC-ECD showed that the levels of dopamine (189 ± 11) ng/ml and noradrenalin (55 ± 8) ng/ml in the culture fluid of Ad/14-3-3 γ group were higher than those of Ad-null group (79 ± 12, 38 ± 7) ng/ml and rotenone group (81 ± 13, 39 ± 7) ng/ml (all P < 0.01). DAPI staining showed that cell apoptosis ratio of group Ad/14-3-3 γ (27% ± 64%) was lower than that of group Ad-null (53% ± 10%) and rotenone group (56% ± 12%, P < 0.01), but higher than that of control group (10% ± 5%, P < 0.01). Under confocal microscopy, the aggregates of α-synuclein protein in PC12 cells were detected more in Ad-null group and rotenone group than that in Ad/14-3-3 γ group. CONCLUSION: Gene transfer of Ad/14-3-3 γ has a protective effect on dopaminergic cells against rotenone-induced injury.
Assuntos
Proteínas 14-3-3/genética , Adenoviridae/genética , Neurônios Dopaminérgicos/efeitos dos fármacos , Neurônios Dopaminérgicos/metabolismo , Rotenona/efeitos adversos , Animais , Sobrevivência Celular , Técnicas de Transferência de Genes , Vetores Genéticos , Humanos , Células PC12 , RatosRESUMO
OBJECTIVE: To improve cost-efficiency, discriminant functions in stepwise method was founded for the differential diagnosis of angina pectoris by detecting the serum level of high-sensitivity C-reactive protein (hs-CRP), macrophage migration inhibitory factor (MIF), interleukin-4 (IL-4) and interleukin-10 (IL-10) in patients with stable angina pectoris (SAP) and unstable angina pectoris (UAP). METHODS: Thirty-nine SAP patients and 47 UAP patients were enrolled into the study, while 39 healthy volunteers were enrolled into the controlled group forming the entire set of training samples. The serum levels of hs-CRP, MIF, IL-4 and IL-10 were measured by enzyme linked immunosorbent assay (ELISA). Data was analyzed by software to define discriminant functions in the ways of "entering" and "stepwise". Both functions were evaluated by the results of validation. RESULTS: By the way of "enter independent together", the following discriminant functions were defined based on the data of training samples' age, hs-CRP, MIF, IL-4, IL-10: healthy control group =-129.858 + 2.869×age -2.451×hs-CRP + 1.393×MIF + 6.001×IL-4 + 4.848×IL-10; SAP group=-161.037 + 2.896×age-2.022×hs-CRP + 1.662×MIF + 6.703×IL-4 + 6.287×IL-10; UAP group=-199.087 + 2.468×age-1.440×hs-CRP + 3.404×MIF-13.875×IL-4 + 7.752×IL-10. Retrospective validation showed 4.8% of total miss-grouping, while cross-validation showed 5.6% of total miss-grouping. By the way of "stepwise", the above data was screened by software and training samples' age, MIF and IL-10 were suggested to define the following functions: healthy control group = - 125.218 + 2.659 × age + 0.599×MIF + 5.040 × IL-10; SAP group=-157.864 + 2.721×age + 1.008×MIF + 6.468×IL-10; UAP group=- 197.327 + 2.360×age + 2.932×MIF + 7.640×IL-10. Both retrospective and cross validation showed 6.4% of total miss-grouping. Both sets of discriminant functions had the same efficiency (100%) for differential diagnosis of SAP and UAP. CONCLUSION: The discriminant functions based on samples' age, MIF and IL-10, which were screened and suggested by stepwise method, may contribute to the differential diagnosis of atypical SAP and UAP, and therefore demonstrate better cost-efficiency.
Assuntos
Angina Pectoris/sangue , Angina Pectoris/diagnóstico , Proteína C-Reativa/metabolismo , Interleucina-10/sangue , Idoso , Angina Pectoris/classificação , Estudos de Casos e Controles , Análise Discriminante , Feminino , Humanos , Inflamação , Interleucina-4/sangue , Oxirredutases Intramoleculares/sangue , Fatores Inibidores da Migração de Macrófagos/sangue , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
OBJECTIVE: To evaluate the effects of microRNA-155 (miR-155) on liver injury in mice with sepsis. METHODS: One hundred and twenty BALB/c mice were randomly divided into two groups of equal number according to random number table. Sepsis was induced by intraperitoneal injection of lipopolysaccharide (LPS,20 mg/kg). The mice were sacrificed at the time-points of 0, 2, 6, 12, 24, 48 hours. Blood and liver tissue were collected, and the levels of tumor necrosis factor- α (TNF- α ), interleukin (IL-6, IL-10) in serum and liver homogenate and alanine transaminase (ALT) in serum were determined by enzyme linked immunosorbent assay(ELISA). The injury of liver tissue was evaluated by histopathology. The expression of miR-155 in liver tissue was assessed by fluorescent quantitation reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: The levels of TNF- α , IL-6 and IL-10 in serum and liver homogenate of septic mice increased with passage of time, and then the levels of TNF-α and IL-6 lowered after reaching the peak value, but remained higher than that of control group.TNF-α (ng/L) reached the peak value at 2 hours post-LPS-injection (serum: 1538.46 ± 102.12 vs. 64.52 ± 18.44,liver homogenate: 255.26 ± 41.23 vs. 60.21 + 13.55, both P<0.05). The level of IL-6 (µg/L) reached the peak value at 6 hours post-LPS-injection (serum: 875.33 ± 102.37 vs. 153.72 ± 20.67, liver homogenate: 9.22 + 0.82 vs. 3.35 ±0.36, both P<0.05), and that of IL-10 (ng/L) reached the peak value at 48 hours post-LPS-injection (serum: 520.13 ± 88.52 vs. 23.43 3.01, liver homogenate: 260.12 + 50.38 vs. 16.37 ± 3.71, both P<0.05). There were significant differences in above indexes between septic and control group (all P<0.05). The serum level of ALT (U/L) rose with passage of time, reaching the peak value at 48 hours post-LPS-injection (603.26 + 70.21 vs. 45.84 + 5.64, P<0.05). The values showed significant differences between septic and control group (P<0.05). A large number of leucocytic infiltration was found in liver. Hepatic tissue showed architectural distortion. Hepatocyte vacuolation and nodular necrosis were obvious at 12 hours post-LPS-injection. Relative expression of miR-155 was found to be increased at 2 hours post-LPS-injection, reaching its peak value at 12 hours post-LPS-injection [(72.96 ± 9.34)-fold of control group, P<0.05]. CONCLUSION: The increase in miR-155 expression might play an important role in the mechanism of liver injury during sepsis.
Assuntos
Fígado/metabolismo , MicroRNAs/metabolismo , Sepse/metabolismo , Animais , Fígado/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Sepse/patologiaRESUMO
Chronic obstructive pulmonary disease (COPD) is a common chronic pulmonary disease with multiple etiologies and pathological changes. PYK2 expression is significantly increased in lipopolysaccharide-induced lung injury, but it mediates chronic lung inflammation. The mechanism of its occurrence remains unclear. Quanzhenyiqitang is often used in clinical treatment of COPD, so this study explored the mechanism of its treatment of lipopolysaccharide-induced lung injury. In this study, transfection, flow cytometry, QRT-PCR, and Western blotting methods were used to study the mechanism of Quanzhenyiqitang lipopolysaccharide-induced lung injury. The results showed that the mechanism of occurrence remains unclear. Our novel observations imply that the PYK2/p38MAPK/HDAC2/CK2 pathway is one of the fundamental underlying mechanisms that mediate the pathogenic progression of COPD, and Quanzhenyiqitang may be the therapeutic drug to prevent chronic inflammation and delay the progression of COPD by inhibiting PYK2 signaling pathways.