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Peptidoglycan (PGN), as the major components of the bacterial cell wall, is known to cause excessive proinflammatory cytokine production. Toll-like receptor 2 (TLR2) is abundantly expressed on immune cells and has been shown to be involved in PGN-induced signaling. Although more and more evidences have indicated that PGN is recognized by TLR2, the role of TLR2 PGN recognition is controversial. Mannan-binding lectin (MBL), a plasma C-type lectin, plays a key role in innate immunity. More and more evidences show that MBL could suppress the amplification of inflammatory signals. Whether MBL can alter PGN-elicited cellular responses through TLR2 in macrophages is still unknown, and possible mechanism underlying it should be investigated. In this study, we found that MBL significantly attenuated PGN-induced inflammatory cytokine production, including TNF-α and IL-6, in PMA-stimulated THP-1 cells at both mRNA and protein levels. The expression of TLR2 was strongly induced by PGN stimulation. Furthermore, the administration of TLR2-neutralized antibody effectively suppressed PGN-induced TNF-α and IL-6 expression. These results supplied the evidence that PGN from Saccharomyces cerevisiae could be recognized by TLR2. In addition, we also found that MBL decreased PGN-induced TLR2 expression and suppressed TLR2-mediated downstream signaling, including the phosphorylation of IκBα, nuclear translocation of NF-κBp65, and phosphorylation of MAPK p38 and ERK1/2. Administration of MBL alone did not have an effect on the expression of TLR2. Finally, our data showed that PGN-mediated immune responses were more severely suppressed by preincubation with MBL and indicated that MBL can combine with both TLR2 and PGN to block the inflammation cytokine expression induced by PGN. All these data suggest that MBL could downregulate inflammation by modulating PGN/TLR2 signaling pathways. This study supports an important role for MBL in immune regulation and signaling pathways involved in inflammatory responses.
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Lectina de Ligação a Manose/metabolismo , Peptidoglicano/farmacologia , Receptor 2 Toll-Like/metabolismo , Transporte Ativo do Núcleo Celular , Citocinas/metabolismo , Regulação da Expressão Gênica , Humanos , Inflamação/metabolismo , Interleucina-6/metabolismo , Macrófagos/metabolismo , Subunidade p50 de NF-kappa B/metabolismo , Fosforilação , Saccharomyces cerevisiae , Transdução de Sinais , Células THP-1 , Fator de Necrose Tumoral alfa/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
The present study was designed to investigate the role of opioid receptors in the vasorelaxation effect of chronic intermittent hypobaric hypoxia (CIHH) in thoracic aorta rings and the underlying mechanism in rats. Adult male Sprague-Dawley (SD) rats were randomly divided into 2 groups: CIHH treatment group and control group. The rats in CIHH group were exposed to hypoxia in a hypobaric chamber (simulated 5 000 m altitude) for 28 days, 6 h per day. The rats in control group were kept in the same environment as CIHH rats except no hypoxia exposure. The relaxation of thoracic aorta rings was recorded by organ bath perfusion technique, and expression of opioid receptors was measured by Western blot. Results are shown as follows. (1) The acetylcholine (ACh)-induced endothelium-dependent relaxation of thoracic aorta in CIHH rats was increased obviously in a concentration-dependent manner compared with that in control rats (P < 0.05). (2) This enhancement of ACh-induced relaxation in CIHH rats was abolished by naloxone, a non-specific opioid receptor blocker (P < 0.05). (3) The expressions of δ, µ and κ opioid receptors in thoracic aorta of CIHH rats were up-regulated compared with those in control rats (P < 0.05). (4) The enhancement of CIHH on relaxation of thoracic aorta was reversed by glibenclamide, an ATP-sensitive potassium channel (KATP) blocker (P < 0.05). The results suggest that opioid receptors are involved in CIHH-enhanced ACh-induced vasorelaxation of thoracic aorta through KATP channel pathways.
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Acetilcolina/farmacologia , Aorta Torácica/efeitos dos fármacos , Hipóxia/fisiopatologia , Receptores Opioides/metabolismo , Altitude , Animais , Glibureto/farmacologia , Canais KATP/antagonistas & inibidores , Masculino , Ratos , Ratos Sprague-Dawley , VasodilataçãoRESUMO
Reaction-boned silicon carbide (RB-SiC) is considered a new material for large lightweight ground-based space telescopes due to its high specific stiffness, low thermal deformation, and excellent optical quality. The excellent mechanical properties of RB-SiC result in the low efficiency of traditional polishing and mechanical polishing. In this paper, a polishing method for RB-SiC based on a femtosecond laser is proposed to improve surface quality. A theoretical heat conduction model was established in the process of femtosecond laser irradiation of SiC. We analyzed the ablation type and calculated the single-pulse ablation threshold of SiC, which verified the feasibility of femtosecond laser polishing. Further, the effects of polishing parameters on the polished surface quality were analyzed by a series of experiments, and the optimal parameters were selected. It was observed to improve polishing efficiency and can replace the intermediate steps of traditional mechanical polishing.
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OBJECTIVE: To observe the effect of acupuncture at "Feishu" (BL 13) + "Dingchuan" (EX-B 1) and "Kongzui" (LU 6) + "Yuji" (LU 10) for the airway remodeling in asthma rats based on the transforming growth factor-ß1 (TGF-ß1)/ Smad family member 3 (Smad3) signaling pathway; and explore the efficacy difference between the two acupoint combinations. METHODS: Forty SPF male SD rats, aged 4 weeks, were randomly divided into a blank group (n = 10) and a modeling group (n = 30). The ovalbumin (OVA) sensitization method was used to establish asthma model in the modeling group. After successful model preparation, the rats of the modeling group were randomized into a model group, an acupuncture at "Feishu" (BL 13) + "Dingchuan" (EX-B 1) (AAF) group, and acupuncture at "Kongzui" (LU 6)+"Yuji" (LU 10) (AAK) group, with 10 rats in each one. Starting from day 15 of the experiment, 5 min after motivating, acupuncture was applied to "Feishu" (BL 13) + "Dingchuan" (EX-B 1) and "Kongzui" (LU 6)+"Yuji" (LU 10) in the AAF group and the AAK group respectively. The intervention was delivered for 30 min each time, once daily, lasting 3 weeks consecutively. Using lung function detector, the airway resistance (RL) and dynamic compliance (Cdyn) of the lungs were detected. The histomorphology of lung tissues was detected with HE staining and Masson staining, and the mRNA and protein expression of TGF-ß1 and Smad3 in lung tissues was detected with the real-time PCR and Western blot methods. RESULTS: Compared with the blank group, RL was increased and Cdyn was decreased in the rats of the model group (P<0.01); and RL was reduced and Cdyn was increased in the AAF group and the AAK group when compared with those in the model group (P<0.01, P<0.05). The rats of the model group had bronchial lumen stenosis, inflammatory cell infiltration, collagen fibre hyperplasia and thickened smooth muscle in the lung tissues when compared with those in the blank group; and in comparison with the model group, all of the above morphological changes were attenuated in the AAF group and the AAK group. Besides, these morphological changes of the lung tissues were more alleviated in the AAF group when compared with those in the AAK group. In comparison with the blank group, the mRNA and protein expression of TGF-ß1 and Smad3 of the lung tissues was increased in the model group (P<0.01), and it was reduced in the AAF group and the AAK group when compared with that in the model group (P<0.05, P<0.01). The mRNA expression of TGF-ß1 and Smad3 was lower in the AAF group when compared with that in the AAK group (P<0.05). CONCLUSION: Acupuncture at either "Feishu" (BL 13)+"Dingchuan" (EX-B 1) or "Kongzui" (LU 6)+"Yuji" (LU 10) reduces the airway remodeling in the rats with asthma, which may be related to the down-regulation of mRNA and protein expression of TGF-ß1 and Smad3. The better efficacy is obtained with acupuncture at "Feishu" (BL 13)+"Dingchuan" (EX-B 1).
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Terapia por Acupuntura , Antiasmáticos , Asma , Masculino , Animais , Ratos , Ratos Sprague-Dawley , Fator de Crescimento Transformador beta1/genética , Remodelação das Vias Aéreas , Transdução de Sinais , Asma/genética , Asma/terapia , Constrição PatológicaRESUMO
OBJECTIVE: P-type atypical lymphocytes may play important roles in the aetiology and therapy of schizophrenia. However, there is merely a direct immunological characterisation of it. The aim of this study is to explore the surface antigens of these cells and their comparative ultrastructure in schizophrenia. METHODS: We recruited 25 age-and gender-matched patients with unmedicated schizophrenia, other mental diseases and healthy individuals. Peripheral venous blood was smeared and stained. CD4+, CD8+ and CD19+ cell surface antigen- positive lymphocytes were purified using magnetic beads and prepared for light microscopy and electron microscopy. RESULTS: The percentages of P-type atypical lymphocytes (34.53% ± 9.92%) were significantly higher (p < 0.0001) in schizophrenia than that of other mental diseases (9.79% ± 3.45%). These cells could present CD4+, CD8+ and CD19+ surface antigens. Their relative ultrastructure differed from that of normal lymphocytes, especially in mitochondria, which showed abundant, aggregated and quite irregular mitochondria; for example, slight dilation of the foci, swelling, degeneration, and even cavity. CONCLUSIONS: P-type atypical lymphocytes could be found among CD4+, CD8+, and CD19 + lymphocytes with schizophrenia. Their abnormal ultrastructure of mitochondria implied that energy metabolism might play an important role in the aetiology of schizophrenia.
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Esquizofrenia , Humanos , Antígenos de Superfície , Linfócitos , Antígenos CD19 , MitocôndriasRESUMO
The present study is aimed to investigate the effect of chronic intermittent hypobaric hypoxia (CIHH) on contractile activities in isolated thoracic aorta and pulmonary artery rings and the underlying mechanism in rats. Sprague-Dawley (SD) rats were randomly divided into 4 groups: control group (CON), 14 days CIHH treatment group (CIHH14), 28 days CIHH treatment group (CIHH28) and 42 days CIHH treatment group (CIHH42). CIHH rats were exposed to hypoxia in a hypobaric chamber simulating 5 000 m altitude, 6 h daily for 14, 28 and 42 d, respectively. After artery rings were prepared from pulmonary artery and thoracic aorta, the contractile activity of the artery rings was recorded using organ bath technique. Results are shown as follows. (1) There were no significant differences of noradrenaline (NA)- and KCl-induced contractions in thoracic aorta and pulmonary artery rings among CIHH and CON rats. (2) Angiotensin â ¡ (ANGâ ¡)-induced contraction in thoracic aorta rings, not in pulmonary artery rings, of CIHH rats was decreased compared with that in CON rats. There was no significant difference of ANGâ ¡-induced contraction in thoracic aorta rings among CIHH rats. (3) Inhibitory effect of CIHH on ANGâ ¡-induced contraction in thoracic aorta rings was endothelium-independent, and was reversed by glibenclamide (Gli), an ATP-sensitive potassium channels (K(ATP)) blocker, and L-NAME, a NO synthase inhibitor, but not by indomethacin (Indo), a cyclooxygenase inhibitor. These results suggest that CIHH attenuates the contraction induced by ANGâ ¡ in thoracic aorta rings of rat, which is related to the opening of K(ATP) channel and the increased production of NO.
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Aorta Torácica/fisiopatologia , Hipóxia/fisiopatologia , Músculo Liso Vascular/fisiopatologia , Artéria Pulmonar/fisiopatologia , Vasoconstrição/fisiologia , Angiotensina II/farmacologia , Animais , Canais KATP/metabolismo , Masculino , Contração Muscular/fisiologia , Óxido Nítrico/biossíntese , Ratos , Ratos Sprague-DawleyRESUMO
BACKGROUND: Pain is a common complication after mixed hemorrhoids, which seriously affects the recovery of patients and prolongs the length of hospital stay. Acupoint catgut embedding has advantages in improving a variety of acute and chronic pain diseases, but there is still a lack of rigorous randomized controlled studies to verify its efficacy and safety in the treatment of postoperative pain of mixed hemorrhoids. Therefore, the purpose of this randomized controlled trial is to evaluate the clinical efficacy of acupoint catgut embedding in the treatment of postoperative pain of mixed hemorrhoids. METHODS: This is a prospective randomized controlled trial to study the efficacy and safety of acupoint catgut embedding in the treatment of postoperative pain of mixed hemorrhoids. Approved by the clinical research ethics committee of our hospital, the patients were randomly divided into observation group and control group according to 1:1. The observation group received acupoint catgut embedding before the operation, while the control group received no special treatment. The efficacy and safety indexes were concerned after the operation, and the observation indexes included: resting state and visual analogue scale (VAS) score during defecation, postoperative hospitalization time, total amount of analgesic use, adverse reactions, etc. Finally, we carried on the data statistical analysis through the SPSS version 19.0. DISCUSSION: This study will evaluate the efficacy and safety of acupoint catgut embedding in the treatment of postoperative pain of mixed hemorrhoids, and the results of this study will provide a new idea for the selection of postoperative analgesia for mixed hemorrhoids resection. TRIAL REGISTRATION: OSF Registration number: DOI 10.17605/OSF.IO/T2ZGY.
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Pontos de Acupuntura , Terapia por Acupuntura/métodos , Hemorroidas/cirurgia , Dor Pós-Operatória/terapia , Adolescente , Adulto , Idoso , Categute , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Estudos Prospectivos , Projetos de Pesquisa , Índice de Gravidade de Doença , Método Simples-Cego , Adulto JovemRESUMO
Phosphatidylethanolamine-binding protein (PEBP) is a highly conserved group of multifunctional proteins found in a variety of different species. In the same species, it is expressed in numerous tissues and cell types. PEBP plays a pivotal modulatory role in several signal transduction pathways. PEBP inhibits the MAPK pathway through interacting with Raf-1, so it's also known as Raf-1 kinase inhibitor protein (RKIP). PEBP is involved in the regulation of PKC, G-protein-coupled receptor and NF-kappaB signaling pathway as well. In clinical researches, it was found that as the precursor of hippocampal cholinergic neurostimulating peptide (HCNP), PEBP has an important effect on the development of Alzheimer's disease. Recent evidence imply that PEBP function as a metastasis suppressor gene because it can suppress metastasis and promote apoptosis in tumor cells. In colorectal cancer, high methylation of the promoter region of PEBP gene results in the non-expression of PEBP, that maybe the molecular basis of tumor metastasis. The latest studies demonstrate that PEBP regulates the spindle checkpoint in cell cycle and loss of PEBP can leads to chromosomal abnormalities.
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Proteína de Ligação a Fosfatidiletanolamina , Doença de Alzheimer , Animais , Pontos de Checagem do Ciclo Celular , Humanos , Neoplasias , Transdução de SinaisRESUMO
The above article published in Medicinski Glasnik online on 26 June 2014 by the Medical Association of Zenica-Doboj Canton (http://www.ljkzedo.com.ba/index.php/u-sljedecem-broju) and in Volume 11, Issue 2, pages 276-282, has been retracted by agreement between the authors, the journal Editor-in-Chief, Professor Selma Uzunovic, and the Medical Association of Zenica-Doboj Canton. The reasons for this retraction are as follows: The work reported in the paper was about the role of duodenal eosinophils and mast cells in the pathogenesis of functional dyspepsia. Most of the experiments were carried out by a former member of the authors' team named Yuan Haipeng, who has left the team for more than two years. A high proportion of data in the paper had been reported in the doctoral dissertation of Yuan Haipeng in 2012, and the paper was published without the knowledge or permission of Yuan. Besides the data previously reported in the doctoral dissertation of Yuan Haipeng, the authors calculated the other data in the paper before the submission. However, it has come to the authors' attention that they had made quite a few mistakes due to a loss of the original data, which was not described in details in the dissertation. REFERENCE Shijun Song, Yan Song, Haishan Zhang, Gaiqin Li, Xiaopei Li, Xiaohong Wang, Zhen Liu. Increased counts and degranulation of duodenal mast cells and eosinophils in functional dyspepsia- a clinical study. Med Glas (Zenica) 2014; 11(2):276-82.
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OBJECTIVE: To investigate the effects of mannan-binding lectin (MBL) on the maturation and cytokine secretion of human dendritic cells (DC) induced by Candida albicans (C. albicans). METHODS: The plastic-adherent mononuclear cells were prepared from the blood of healthy adult volunteers. The human peripheral blood mononuclear cells-derived dendritic cells (MNC-DC) were induced by 5-day-culture in medium supplemented with rhGM-CSF and rhIL-4, and then cultured for 2 days in presence or absence of C. albicans at varying concentration of human MBL ranging from 1 to 20 mg/L. DC's shape and characters were observed under inverted microscopy, the expression of CD83 and CD86 on DC was analyzed by FACS. The levels of TNF-α and IL-6 were detected by ELISA. FACS also was used to investigate the interaction of MBL with immature DC(imDC) and C. albicans. Western blot was used to detect C. albicans-induced IκBα phosphorylation and p65/NF-κB translocation in DC. RESULTS: MBL at higher concentrations (10-20 mg/L) down-regulated the expression of CD83 and CD86 on the monocyte-derived dentritic cells(MoDC) induced by C. albicans, and inhibited the production of TNF-α and IL-6 induced by C. albicans. FACS showed that MBL could not only bind to C. albicans but also bind to imDCs in a Ca2+-dependent manner. Western blot showed that MBL could decrease the phosphorylation of IκBα and the nuclear translocation of p65/ NF-κB. CONCLUSION: MBL may inhibit TNF-α and IL-6 production induced by C. albicans in DC through NF-κB signaling pathways, suggesting that MBL can play some roles in the regulation of C. albicans-induced immune response.
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Candida albicans , Células Dendríticas , Diferenciação Celular , Citocinas , Humanos , Lectina de Ligação a Manose , NF-kappa B , Transporte ProteicoRESUMO
OBJECTIVE: To determine the clinical significance of silent mating type information regulation 2 homolog 1 (SIRT1) expression in Hepatocellular Carcinoma (HCC) and its association with P53 and Yes-associated protein 2 (YAP2) expression. STUDY DESIGN: Observational study. PLACE AND DURATION OF STUDY: Department of General Surgery, China-Japan Union Hospital of Jilin University, Changchun, China, from January 2000 to January 2010. METHODOLOGY: Tissue microarray technique and immunohistochemistry were conducted to detect the expression of SIRT1, P53 and YAP2 proteins in 300 self-paired HCC samples. Associations with clinicopathologic manifestations were analyzed, overall survival analysis and multivariate analysis were performed. RESULTS: By tissue microarray technique and immunohistochemistry on 300 self-paired HCC samples, it was found that SIRT1, P53 and YAP2 were significantly overexpressed in HCC tumor tissues compared with adjacent non-tumor tissues. SIRT1 immunostaining localized both in the nucleus (145/300, 48.3%) and the cytoplasm (70/300, 23.3%), and the overexpression of nuclear SIRT1 was positively related to the overexpression of P53 and YAP2. Survival analysis showed that nuclear SIRT1, P53 and YAP2 overexpression predicted poor overall survival while cytoplasmic SIRT1 overexpression predicted longer overall survival. Multivariate analysis showed nuclear SIRT1 and P53 overexpression as independent tumor promoters while cytoplasmic SIRT1 overexpression as an independent tumor suppressor. CONCLUSION: SIRT1 was overexpressed in HCC and the expression was positively related to P53 and YAP2 expression. As the nuclear SIRT1 functions as a tumor promoter and cytoplasmic SIRT1 functions as a tumor suppressor, the role of SIRT1 in HCC should be reconsidered.
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Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Fosfoproteínas/metabolismo , Sirtuína 1/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Adolescente , Adulto , Idoso , Biomarcadores Tumorais , Carcinoma Hepatocelular/genética , China , Feminino , Seguimentos , Regulação Neoplásica da Expressão Gênica/fisiologia , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/genética , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Fosfoproteínas/genética , Estudos Retrospectivos , Sirtuína 1/genética , Análise de Sobrevida , Análise Serial de Tecidos , Fatores de Transcrição , Proteína Supressora de Tumor p53/genética , Proteínas de Sinalização YAP , Adulto JovemRESUMO
AIM: Immune factors, especially mast cells and eosinophils, play an important role in the pathogenesis of functional dyspepsia. However, the role of these cells in the duodenum has not been fully understood in patients with functional dyspepsia. We aimed to investigate the infiltration and activation of mast cells and eosinophils in the duodena of subjects with functional dyspepsia. METHODS: Duodenal biopsies obtained in 48 patients with functional dyspepsia and 21 healthy volunteers were collected for the study. Eosinophils in the bulb (D1) and the descending part (D2) of the duodenum were identified and counted by hematoxylin and eosin (H and E) staining. Major basic protein immunostaining was used to evaluate eosinophil degranulation, as well as mast cells and mast cell degranulation was identified by toluidine blue staining. RESULTS: In the D2 area, compared to controls, functional dyspepsia patients showed a marked increase in eosinophil cell numbers (p=0.008) and eosinophil degranulation rate (p=0.005). Mast cell numbers were significantly increased in patients compared with controls in the D1 (p=0.002) and D2 areas (p less than 0.001), and the degranulation rates of mast cells were significantly increased in functional dyspepsia patients in the D1 (p=0.028) and D2 areas (p=0.044). CONCLUSION: Duodenal eosinophils and mast cells may be involved in the pathogenesis of functional dyspepsia.
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Duodeno/patologia , Dispepsia/patologia , Eosinófilos/patologia , Mastócitos/patologia , Adulto , Degranulação Celular/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Candida albicans (C. albicans), the most common human fungal pathogen, can cause fatal systemic infections under certain circumstances. Mannan-binding lectin (MBL),a member of the collectin family in the C-type lectin superfamily, is an important serum component associated with innate immunity. Toll-like receptors (TLRs) are expressed extensively, and have been shown to be involved in C. albicans-induced cellular responses. We first examined whether MBL modulated heat-killed (HK) C. albicans-induced cellular responses in phorbol 12-myristate 13-acetate (PMA)-activated human THP-1 macrophages. We then investigated the possible mechanisms of its inhibitory effect. METHODOLOGY/PRINCIPAL FINDING: Enzyme-linked immunosorbent assay (ELISA) and reverse transcriptasepolymerase chain reaction (RT-PCR) analysis showed that MBL at higher concentrations (10-20 µg/ml) significantly attenuated C. albicans-induced chemokine (e.g., IL-8) and proinflammatory cytokine (e.g., TNF-α) production from PMA-activated THP-1 cells at both protein and mRNA levels. Electrophoretic mobility shift assay (EMSA) and Western blot (WB) analysis showed that MBL could inhibit C. albicans-induced nuclear factor-κB (NF-κB) DNA binding and its translocation in PMA-activated THP-1 cells. MBL could directly bind to PMA-activated THP-1 cells in the presence of Ca(2+), and this binding decreased TLR2 and TLR4 expressions in C. albicans-induced THP-1 macrophages. Furthermore, the binding could be partially inhibited by both anti-TLR2 monoclonal antibody (clone TL2.1) and anti-TLR4 monoclonal antibody (clone HTA125). In addition, co-immunoprecipitation experiments and microtiter wells assay showed that MBL could directly bind to the recombinant soluble form of extracellular TLR2 domain (sTLR2) and sTLR4. CONCLUSIONS/SIGNIFICANCE: Our study demonstrates that MBL can affect proinflammatory cytokine and chemokine expressions by modifying C. albicans-/TLR-signaling pathways. This study supports an important role for MBL on the regulation of C. albicans-induced cellular responses.
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Candida albicans/imunologia , Lectina de Ligação a Manose/metabolismo , Receptor 2 Toll-Like/metabolismo , Receptor 4 Toll-Like/metabolismo , Candida albicans/patogenicidade , Linhagem Celular , DNA/metabolismo , Expressão Gênica , Humanos , Imunidade Inata , Interleucina-8/biossíntese , Interleucina-8/genética , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , NF-kappa B/metabolismo , Ligação Proteica , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Acetato de Tetradecanoilforbol/farmacologia , Receptor 2 Toll-Like/antagonistas & inibidores , Receptor 2 Toll-Like/genética , Receptor 4 Toll-Like/antagonistas & inibidores , Receptor 4 Toll-Like/genética , Fator de Necrose Tumoral alfa/biossíntese , Fator de Necrose Tumoral alfa/genéticaRESUMO
OBJECTIVE: To observe the effects of Coptis Chinensis on vasoconstrictive activity of isolated thoracic aorta rings of normoxic and chronic intermittent hypobaric hypoxic (CIHH) rats, and to investigate the underlying mechanisms. METHODS: Young male Sprague-Dawley rats were randomly divided into normoxic group and CIHH group: the fonnrmer were not given any special treatment; the latter were exposed to hypoxia in a hypobaric chamber simulating 5000 m altitude (PB = 404 mmHg, PO2 = 84 mmHg, 11.1% O2), 6 hours daily for 28 days. The isolated thoracic aorta rings of rats were prepared and perfused in thermostat, and the effects of Coptis on vasoconstrictive activity of aorta rings were recorded, the mechanisms were investigated simultaneouly. RESULTS: Coptis Chinensis significantly decreased NE and KC-induced vasoconstriction of normoxic and CIHH rats' isolated aortic rings, but the inhibitive effects had no obvious discrepancy between the two groups. The contractive amplitude had no marked change after the removal of endothelium. When calculated by Logit Loglinear analysis, IC50 of NE and KCl-induced contractive amplitude in normoxic group were respectively 2.99 g/L and 6.14 g/L, while they were 3.45 g/L and 5.81 g/L in CIHH group. The inhibitive effect of Coptis on vasoconstrictive activity of both groups could be partly decreased by Glibenclamide and nitro-L-arginine methyl ester; Indomethacin suppressed the effect on normoxic group as well. Also Coptis significantly inhibited NE-induced both intracellular and extracellular calciumion-depended vasoconstriction. CONCLUSION: Coptis Chinensis obviously relaxes isolated thoracic aorta rings of normoxic and CIHH rats, but the effects are endothelium-independent and have no marked discrepancy between the two groups. The mechanisms of the effects may be related to the opening of ATP-sensitive K+ channel, raise of nitric oxide concentration in both groups, and the increasing of PGI2 in normoxic group. Besides, Coptis may inhibit sarcoplasmic reticulum releasing Ca2+ and decrease the inflow of extracellular Ca2+ via cell membrane.
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Aorta Torácica/fisiopatologia , Coptis/química , Medicamentos de Ervas Chinesas/farmacologia , Hipóxia/fisiopatologia , Vasoconstrição/efeitos dos fármacos , Animais , Cálcio/metabolismo , Técnicas In Vitro , Canais KATP/efeitos dos fármacos , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
AIM: To investigate the effect of Honeysuckle flower (HF) and Scutellaria Baicalensis Georgi (SBG) on contraction and electric activity of small intestine smooth muscle in rabbit and the underlying mechanisms. METHODS: Using organ bath technique to observe the effect of HF and SBG on contractive and electric activity of small intestine smooth muscle in rabbit. RESULTS: HF and SBG significantly decreased the amplitude, frequency and area under the curve of contractive, as well as electric activity in a dose-depended manner. IC50 of the contractive amplitude was 6.30 g/L and 1.56 g/L by Logit Loglinear analysis. The inhibitive effect of HF and SBG on contractive activity could be partly decreased by beta-receptor blocker Propranolol, NO synthase inhibitor L-NAME, and K+ channel blocker Glibenclamide. Also HF and SBG inhibited acetylcholine-induced both intracellular and extracellular calcium-depended contraction significantly. CONCLUSION: HF and SBG obviously inhibit the contractive and electric activity of small intestine smooth muscle of rabbit. The mechanisms are related to several pathways.
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Potenciais de Ação/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Lonicera/química , Músculo Liso/fisiologia , Scutellaria baicalensis/química , Animais , Depressão Química , Feminino , Flores/química , Técnicas In Vitro , Intestino Delgado/fisiologia , Masculino , Contração Muscular/efeitos dos fármacos , CoelhosRESUMO
AIM: To investigate the relationship between the spatial learning and memory and hippocampal ERK1/2 pathway activity in ovariectomized rats. METHODS: Female SD rats were randomly divided into sham operated group (Sham group) and ovariectomized group (OVX group), and fed 4 months. Then spatial learning and memory of rats were evaluated by the Morris water maze task. Rats in each group were randomly divided into training group and untraining group before the test. Induced activity of ERK 1/2 stimulated by learning and memory was detected in the training group, and basic activity of ERK 1/2 was detected in the untraining group. The protein expression of p-ERK 1/2 and Raf kinase inhibitor protein (RKIP) were assayed by Western blotting respectively. RESULTS: (1) During the training session the OVX rats held longer escape latenci than the sham rats did (P < 0.05). (2) The relative level of pERK1/2 protein in training rats of the both groups was higher than that in untraining rats (P < 0.05). (3) The relative level of p-ERK1/2 protein both training and untraining rats in OVX group was lower than that in sham group correspondingly (P < 0.05). (4) Compared with sham group, the relative expression of RKIP in OVX group was significantly higher (P < 0.05). CONCLUSION: Spatial learning and memory deficits in ovariectomized rats might be correlated with the decreased basic and induced activity of ERK1/2 pathway and increased expression of RKIP in the CA1/CA2 region of hippocampus.