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1.
PeerJ ; 7: e8031, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31799071

RESUMO

Background: The Mosq-ovitrap (MOT) is currently used for routine surveillance of container-breeding Aedes in China. However, the effectiveness of monitoring Aedes albopictus using the MOT and other mosquito monitoring methods, such as the Ovitrap (OT) and the CO2-light trap (CLT), have not been extensively compared. Moreover, little is known about the spatial-temporal correlations of eggs with adult Ae. albopictus abundance among these three types of traps. Methods: Comparative field evaluation of MOT, OT and CLT for Ae. albopictus monitoring was conducted simultaneously at two city parks and three residential neighborhoods in downtown Shanghai for 8 months from April 21 to December 21, 2017. Results: Significantly more Ae. albopictus eggs were collected from both MOTs and OTs when traps remained in the field for 10 d or 7 d compared with 3 d (MOT: 50.16, 34.15 vs. 12.38 per trap, P < 0.001; OT: 3.98, 2.92 vs. 0.63 per trap, P < 0.001). Egg collections of MOTs were significantly greater than OTs for all three exposure durations (Percent positive: X 2 = 72.251, 52.420 and 51.429, P value all < 0.001; egg collections: t = 8.068, 8.517 and 10.021, P value all <0.001). Significant temporal correlations were observed between yields of MOT and CLT in all sampling locations and 3 different MOT exposure durations (correlation coefficient r ranged from 0.439 to 0.850, P values all < 0.05). However, great variation was found in the spatial distributions of Ae. albopictus density between MOT and CLT. MOT considerably underestimated Ae. albopictus abundances in areas with high Ae. albopictus density (>25.56 per day ⋅ trap by CLT). Conclusion: The MOT was more efficient than the OT in percent positive scores and egg collections of Ae. albopictus. The minimum length of time that MOTs are deployed in the field should not be less than 7 d, as Ae. albopictus collections during this period were much greater than for 3 d of monitoring. MOT considerably underestimated Ae. albopictus abundance in areas with high Aedes albopictus density compared to CLT. In areas with moderate Aedes albopictus densities, MOT results were significantly correlated with CLT catches.

2.
Shock ; 52(3): e1-e11, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-30192340

RESUMO

Mechanical ventilation (MV) is frequently employed to manage respiratory failure in sepsis patients and is required for the surgical management of intra-abdominal sepsis. The impact of MV varies dramatically depending on tidal volume, with even moderate tidal volume (MTV) ventilation leading to ventilator-induced lung injury, whereas low tidal volume (LTV) ventilation protects against sepsis-induced acute respiratory distress syndrome. Interleukin (IL)-33 is known to contribute to lung injury in sepsis and its release can be induced by mechanical stress. To determine the relationship between the IL-33-suppression of tumorigenicity 2 (ST2) pathway and patterns of lung injury associated with MV in sepsis, mice were subjected to cecal ligation and puncture (CLP) followed 6 h later by either MTV (10 mL/kg) or LTV (6 mL/kg) ventilation for 4 h. MTV and LTV ventilation alone for 4 h had no impact on lung injury. MTV markedly exacerbated lung injury and inflammation, while LTV significantly suppressed these parameters in septic mice. Lung and plasma levels of IL-33 ST2 were significantly elevated by CLP alone at 10 h. MTV caused further and significant increases in IL-33 and sST2 levels, while LTV significantly suppressed levels induced by CLP. Deletion of IL-33 or ST2 prevented the increase in lung injury and inflammation induced by MTV in septic mice, while administration of recombinant IL-33 in the airway reversed the protection seen with LTV. Taken together, these findings implicate the IL-33-ST2 pathway in the pro-inflammatory changes induced by the mechanical ventilation that leads to lung injury in the setting of intra-abdominal sepsis in a tidal volume-dependent manner.

3.
Inflammation ; 42(2): 485-495, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30317531

RESUMO

Mechanical ventilation (MV) can augment sepsis-induced organ injury. Previous studies indicate that human mesenchymal stem cells (hMSCs) have immune-modulatory effect. We hypothesize that human adipose tissue-derived stromal cells (hADSCs) could attenuate MV and sepsis-induced organ injury. Male C57BL/6 mice were randomized to five groups: Sham group; MV group; cecal ligation and puncture (CLP) group; CLP + MV group; and CLP + MV + hADSC group. Anesthetized mice were subjected to cecal ligation and puncture surgery. The mice then received mechanical ventilation (12 ml/kg), with or without the intervention of hADSCs. The survival rate, organ injury of the liver and kidney, total protein and cells in bronchoalveolar lavage fluid (BALF), and histological changes of the lung and liver were examined. The level of IL-6 in BALF was measured by ELISA. Real-time quantitative PCR was used to analyze mRNA of IL-6 and tumor necrosis factor-α (TNF-α). hADSC treatment increased survival rate of septic mice with MV. hADSCs attenuated dysfunction of the liver and kidney and decreased lung inflammation and tissue injury of the liver and lung. IL-6 level in BALF and TNF-α and IL-6 mRNA expression in the tissue of the lung, liver, and kidney were significantly reduced by hADSC treatment. MV with conventional tidal volume aggravates CLP-induced multiple organ injuries. hADSCs inhibited the compound injuries possibly through modulation of immune responses.


Assuntos
Insuficiência de Múltiplos Órgãos/terapia , Respiração Artificial/efeitos adversos , Sepse/complicações , Células Estromais/transplante , Tecido Adiposo/citologia , Animais , Líquido da Lavagem Broncoalveolar/química , Líquido da Lavagem Broncoalveolar/citologia , Citocinas/análise , Humanos , Rim/lesões , Fígado/lesões , Fígado/patologia , Pulmão/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Insuficiência de Múltiplos Órgãos/etiologia , Insuficiência de Múltiplos Órgãos/mortalidade , Respiração Artificial/mortalidade , Sepse/mortalidade , Taxa de Sobrevida
4.
Crit Care ; 22(1): 302, 2018 11 16.
Artigo em Inglês | MEDLINE | ID: mdl-30445996

RESUMO

BACKGROUND: High tidal volume ventilation of healthy lungs or exacerbation of existing acute lung injury (ALI) by more moderate mechanical ventilation (MTV) produces ventilator-induced lung injury. It is less clear whether extrapulmonary sepsis sensitizes the lung to MTV. METHODS: We used a two-hit model of cecal ligation and puncture (CLP) followed 12 h later by MTV (10 ml/kg; 6 h) to determine whether otherwise noninjurious MTV enhances CLP-induced ALI by contrasting wildtype and TLR4-/- mice with respect to: alveolar-capillary permeability, histopathology and intrapulmonary levels of WNT-inducible secreted protein 1 (WISP1) and integrin ß5; plasma levels of cytokines and chemokines (TNF-α, IL-6, MIP-2, MCP-1) and intrapulmonary neutrophil infiltration; and other inflammatory signaling via intrapulmonary activation of JNK, p38 and ERK. A separate cohort of mice was pretreated with intratracheal neutralizing antibodies to WISP1, integrin ß5 or IgG as control and the presented phenotyping repeated in a two-hit model; there were 10 mice per group in these first three experiments. Also, isolated peritoneal macrophages (PM) from wildtype and TLR4-/-, MyD88-/- and TRIF-/- mice were used to identify a WISP1-TLR4-integrin ß5 pathway; and the requisite role of integrin ß5 in WISP1-induced cytokine and chemokine production in LPS-primed PM was examined by siRNA treatment. RESULTS: MTV, that in itself did not cause ALI, exacerbated increases in alveolar-capillary permeability, histopathologic scoring and indices of pulmonary inflammation in mice that previously underwent CLP; the effects of this two-hit model were abrogated in TLR4-/- mice. Attendant with these findings was a significant increase in intrapulmonary WISP1 and integrin ß5 in the two-hit model. Anti-WISP1 or anti-integrin ß5 antibodies partially inhibited the two-hit phenotype. In PM, activation of TLR4 led to an increase in integrin ß5 expression that was MyD88 and NF-κB dependent. Recombinant WISP1 increased LPS-induced cytokine release in PM that was inhibited by silencing either TLR4 or integrin ß5. CONCLUSIONS: These data show for the first time that otherwise noninjurious mechanical ventilation can exacerbate ALI due to extrapulmonary sepsis underscoring a potential interactive contribution of common events (sepsis and mechanical ventilation) in critical care, and that a WISP1-TLR4-integrin ß5 pathway contributes to this phenomenon.


Assuntos
Proteínas de Sinalização Intercelular CCN/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Sepse/complicações , Receptor 4 Toll-Like/metabolismo , Lesão Pulmonar Induzida por Ventilação Mecânica/etiologia , Animais , Proteínas de Sinalização Intercelular CCN/sangue , Modelos Animais de Doenças , Citometria de Fluxo/métodos , Mediadores da Inflamação/efeitos adversos , Cadeias beta de Integrinas/sangue , Cadeias beta de Integrinas/imunologia , Cadeias beta de Integrinas/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Proto-Oncogênicas/sangue , Respiração Artificial/métodos , Sepse/sangue , Sepse/fisiopatologia , Receptor 4 Toll-Like/sangue , Lesão Pulmonar Induzida por Ventilação Mecânica/fisiopatologia
5.
Immunol Cell Biol ; 96(9): 935-947, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29672927

RESUMO

Sepsis is defined as infection with organ dysfunction due to a dysregulated immune response. The lung is one of the most vulnerable organs at the onset of sepsis. Interleukin (IL)-33 can be released by injured epithelial and endothelial cells in the lung and regulate immune activation and infiltration. Therefore, we postulated that IL-33 would contribute to the immune response in the lung during sepsis. Using the cecal ligation and puncture (CLP) sepsis model, we show here that IL-33 contributes significantly to both sepsis-induced inflammation in the lung and systemic inflammatory response in the early phase of sepsis. Despite the higher intra-peritoneal bacterial burden, the absence of IL-33 resulted in less infiltration of neutrophils and monocytes into the lungs in association with lower circulating, lung and liver cytokine levels as well as reduced lung injury at 6 h after sepsis. IL-33 was required for the upregulation of IL-5 in type 2 Innate Lymphoid Cells (ILC2), while IL-5 neutralization suppressed neutrophil and monocyte infiltration in the lungs during CLP sepsis. This reduction in leukocyte infiltration in IL-33-deficient mice was reversed by administration of recombinant IL-5. These results indicate that IL-33 plays a major role in the local inflammatory changes in the lung, in part, by regulating IL-5 and this axis contributes to lung injury early after the onset of sepsis.


Assuntos
Interleucina-33/imunologia , Interleucina-5/imunologia , Linfócitos/imunologia , Pneumonia/imunologia , Sepse/imunologia , Animais , Modelos Animais de Doenças , Imunidade Inata , Pulmão/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Infiltração de Neutrófilos
6.
J Int Med Res ; 46(2): 596-611, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28436302

RESUMO

Objective To explore stable and functional microRNA (miRNA)-disease relationships using a genome-wide expression profile pattern matching strategy. Methods We applied the ranked microarray pattern matching strategy Gene Set Enrichment Analysis to identify miRNA permutations with similar expression patterns to diseases. We also used quantitative reverse transcription PCR to validate the predicted expression levels of miRNAs in three diseases: inflammatory bowel disease (IBD), oesophageal cancer, and colorectal cancer. Results We found that hsa-miR-200 c was upregulated more than 40-fold in oesophageal cancer. The expression of miR-16 and miR-124 was not consistently upregulated in IBD or colorectal cancer. Conclusions Our results suggest that this expression profile matching strategy can be used to identify functional miRNA-disease relationships.


Assuntos
Neoplasias Colorretais/genética , Neoplasias Esofágicas/genética , Genoma Humano , Doenças Inflamatórias Intestinais/genética , MicroRNAs/genética , Adulto , Idoso , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Conjuntos de Dados como Assunto , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patologia , Feminino , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Estudo de Associação Genômica Ampla , Humanos , Doenças Inflamatórias Intestinais/diagnóstico , Doenças Inflamatórias Intestinais/metabolismo , Doenças Inflamatórias Intestinais/patologia , Masculino , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Família Multigênica , Análise de Sequência com Séries de Oligonucleotídeos , Reação em Cadeia da Polimerase Via Transcriptase Reversa
7.
Acta Biochim Biophys Sin (Shanghai) ; 49(10): 907-915, 2017 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-28981603

RESUMO

Saquinavir (SQV) is the first FDA approved HIV protease inhibitor. Previous studies showed that SQV can limit Toll-like receptor-4 (TLR4)-mediated inflammatory pathway and nuclear factor-κB (NF-κB) activation, thereby playing a protective role in many kinds of diseases. High-mobility group box 1 (HMGB1) has been identified as an inflammatory mediator and it might express its toxicity in a short period of time in ventilator-induced lung injury (VILI). In this study, C57BL/6 mice were randomly divided into four groups (n = 10): control group and control with SQV group (Con + SQV) were spontaneous breath. HTV group (HTV) received high tidal volume ventilation (HTV) for 4 h. HTV with SQV group (HTV + SQV) were pretreated with 5 mg/kg of SQV for 7 days before HTV. Mice were sacrificed after 4 h of HTV. Lung wet/dry weight (W/D) ratio, alveolar-capillary permeability to Evans blue albumin (EBA), cell counts, total proteins in bronchoalveolar lavage fluid (BALF), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) level in BALF and lung tissue, and lung histopathology were examined. Our results showed that HTV caused significant lung injury and NF-κB activation, which was correlated with the increase of TNF-α and IL-6 levels in BALF and plasma. SQV pretreatment significantly attenuated pulmonary inflammatory injury, as well as NF-κB activation. These findings indicate that the protective effect of SQV may be associated with the inhibition of NF-κB activation and HMGB1 expression in mice.


Assuntos
Proteína HMGB1/metabolismo , Substâncias Protetoras/farmacologia , Saquinavir/farmacologia , Lesão Pulmonar Induzida por Ventilação Mecânica/prevenção & controle , Animais , Líquido da Lavagem Broncoalveolar/química , Inibidores da Protease de HIV/farmacologia , Proteína HMGB1/genética , Interleucina-6/sangue , Interleucina-6/metabolismo , Pulmão/metabolismo , Pulmão/patologia , Pulmão/fisiopatologia , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Distribuição Aleatória , Volume de Ventilação Pulmonar , Fator de Necrose Tumoral alfa/sangue , Fator de Necrose Tumoral alfa/metabolismo , Lesão Pulmonar Induzida por Ventilação Mecânica/metabolismo , Lesão Pulmonar Induzida por Ventilação Mecânica/fisiopatologia
8.
Sci Rep ; 7: 34278, 2017 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-28198368

RESUMO

Acute lung injury is a life-threatening inflammatory response caused by severe infection. Toll-like receptors in alveolar macrophages (AMΦ) recognize the molecular constituents of pathogens and activate the host's innate immune responses. Numerous studies have documented the importance of TLR-TLR cross talk, but few studies have specifically addressed the relationship between TLR4 and TLR3. We explored a novel mechanism of TLR3 up-regulation that is induced by LPS-TLR4 signaling in a dose- and time-dependent manner in AMΦ from C57BL/6 mice, while the LPS-induced TLR3 expression was significantly reduced in TLR4-/- and Myd88-/- mice and following pretreatment with a NF-κB inhibitor. The enhanced TLR3 up-regulation in AMΦ augmented the expression of cytokines and chemokines in response to sequential challenges with LPS and Poly I:C, a TLR3 ligand, which was physiologically associated with amplified AMΦ-induced PMN migration into lung alveoli. Our study demonstrates that the synergistic effect between TLR4 and TLR3 in macrophages is an important determinant in acute lung injury and, more importantly, that TLR3 up-regulation is dependent on TLR4-MyD88-NF-κB signaling. These results raise the possibility that bacterial infections can induce sensitivity to viral infections, which may have important implications for the therapeutic manipulation of the innate immune system.


Assuntos
Lesão Pulmonar Aguda/patologia , Macrófagos Alveolares/imunologia , NF-kappa B/metabolismo , Transdução de Sinais , Receptor 3 Toll-Like/metabolismo , Receptor 4 Toll-Like/metabolismo , Regulação para Cima , Animais , Células Cultivadas , Relação Dose-Resposta Imunológica , Imunidade Inata , Lipopolissacarídeos/imunologia , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fator 88 de Diferenciação Mieloide/deficiência , Fator 88 de Diferenciação Mieloide/metabolismo , Receptor 4 Toll-Like/deficiência
9.
Sci Rep ; 6: 28841, 2016 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-27349568

RESUMO

We recently noted that the matricellular protein WISP1 contributes to sepsis induced acute lung injury (ALI) via integrin ß6. In the current study, we pursued further aspects of WISP1 modulation of TLR signaling in lungs of mice after sepsis and TLR4 mediated release of TNF-α in macrophages. After confirming that TLR4 and CD14 are critical in transducing sepsis mediated ALI, we now demonstrate that intrapulmonary αvß3 is increased by polymicrobrial sepsis in a TLR4, CD14 dependent fashion. Comparison of cultured macrophages revealed that WISP1 increased release of TNF-α from RAW264.7 cells with baseline expression of αvß3, but primary cultures of peritoneal macrophages (PMø) required activation of TLR4 to induce de novo synthesis of αvß3 enabling WISP1 to stimulate release of TNF-α. The specific requirement for ß3 integrin was apparent when the effect of WISP1 was lost in PMø isolated from ß3(-/-) mice. WISP1 enhanced TLR4 mediated ERK signaling and U0126 (an ERK inhibitor) blocked LPS induced ß3 integrin expression and WISP1 enhanced TNF-α release. Collectively these data suggest that WISP1-αvß3 integrin signaling is involved in TLR4 pathways in macrophages and may be an important contributor to TLR4/CD14 mediated inflammation in sepsis induced lung injury.


Assuntos
Lesão Pulmonar Aguda/metabolismo , Inflamação/metabolismo , Integrina alfaVbeta3/metabolismo , Sepse/metabolismo , Receptor 4 Toll-Like/metabolismo , Lesão Pulmonar Aguda/genética , Animais , Proteínas de Sinalização Intercelular CCN/genética , Proteínas de Sinalização Intercelular CCN/farmacologia , Células Cultivadas , Inflamação/genética , Integrina alfaVbeta3/genética , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Macrófagos Peritoneais/efeitos dos fármacos , Macrófagos Peritoneais/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas/farmacologia , Células RAW 264.7 , Proteínas Recombinantes/farmacologia , Sepse/genética , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Receptor 4 Toll-Like/genética , Fator de Necrose Tumoral alfa/metabolismo
10.
Exp Eye Res ; 151: 203-11, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27212443

RESUMO

This study was aimed to further investigate the possible mechanisms by which the glucagon like peptide 1 analogue, exendin-4 (EX4), protects rat retinal cells at the early stage of diabetes. EX4 was injected intravitreally into normal and early-stage streptozotocin-diabetic rats. Cell death, reactive oxygen species (ROS), and electroretinogram (ERG) were measured. Sirtuin (Sirt) mRNA and protein were analyzed. In retinas of diabetic rats 1 month after diabetes onset, cell death and ROS level increased significantly, and the b-wave amplitudes and OPs were significantly reduced. Four days after intravitreal EX4 treatment, retinal cell death and ROS level in retinas reduced significantly, and visual function was recovered. In the retinas of early-stage diabetic rats, the expressions of Sirt1 and Sirt3 were also found to be significantly decreased, and both were back to normal levels after intravitreal injection of EX4. In R28 cells, hydrogen peroxide (H2O2) treatment increased ROS and cell death and decreased Sirt1 and Sirt3. With the addition of EX4 into the culture system, the expressions of Sirt1 and Sirt3 were increased, and the H2O2-induced ROS and cell death were significantly reduced. These results confirm a mechanism for EX4 to protect retinal cells from diabetic damage and oxidative injury. EX4 reduces retinal cell death and ROS generation by upregulating Sirt1 and Sirt3 expressions in the retina of early-stage diabetic rats as well as in H2O2-treated R28 cells.


Assuntos
Retinopatia Diabética/prevenção & controle , Regulação da Expressão Gênica , Estresse Oxidativo/efeitos dos fármacos , Peptídeos/farmacologia , Células Ganglionares da Retina/patologia , Sirtuína 1/genética , Sirtuínas/genética , Peçonhas/farmacologia , Animais , Morte Celular , Células Cultivadas , Diabetes Mellitus Experimental , Retinopatia Diabética/metabolismo , Retinopatia Diabética/patologia , Eletrorretinografia , Exenatida , Peptídeo 1 Semelhante ao Glucagon/análogos & derivados , Hipoglicemiantes/farmacologia , Immunoblotting , Marcação In Situ das Extremidades Cortadas , Masculino , RNA Mensageiro/genética , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase em Tempo Real , Células Ganglionares da Retina/efeitos dos fármacos , Células Ganglionares da Retina/metabolismo , Sirtuína 1/biossíntese , Sirtuínas/biossíntese , Fatores de Tempo
11.
Clin J Pain ; 32(12): 1053-1061, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-26889623

RESUMO

OBJECTIVES: To investigate the efficacy and safety of magnesium sulfate as an adjuvant of local anesthetics in perineural nerve blocks. MATERIALS AND METHODS: Randomized controlled trials studying the effect and safety of magnesium sulfate in perineural nerve blocks were retrieved from online databases. The mean difference (MD), risk ratio, and their corresponding 95% confidence intervals (CIs) were calculated using RevMan 5.3 statistical software. RESULTS: Seven trials evaluating 493 patients were included. The pooled results from our meta-analysis showed that a combination of magnesium sulfate and local anesthetics in nerve blocks could result in longer postoperative duration time of analgesia (MD=124.66; 95% CI, 65.09-184.23; P<0.0001), longer duration time of sensory (MD=106.69; 95% CI, 60.93-152.45; P<0.00001) and motor block (MD=89.95; 95% CI, 50.89-129.00; P<0.0001). In addition, magnesium sulfate in nerve blocks was also associated with significantly quick onset of motor block (MD=-1.17; 95% CI, -1.73 to -0.60; P<0.0001). For onset time of sensory block, number of patients requiring supplementary analgesics, and incidence of postoperative nausea and vomiting, no statistically differences were observed between the 2 groups. DISCUSSION: The present study suggests that combined magnesium sulfate and local anesthetics in perineural nerve blocks provided better analgesic efficacy. For it prolongs the postoperative duration time of analgesia, sensory and motor block without increasing the short-term side effects. Magnesium sulfate may be a promising analgesic for perineural nerve blocks, but further studies are required to validate our results.


Assuntos
Analgésicos/uso terapêutico , Anestésicos Locais/uso terapêutico , Sulfato de Magnésio/uso terapêutico , Bloqueio Nervoso , Nervos Periféricos/efeitos dos fármacos , Quimioterapia Adjuvante , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto
12.
Sci Rep ; 6: 20141, 2016 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-26821752

RESUMO

Wnt-induced secreted protein-1 (WISP1) is an extracellular matrix protein that has been reported in cancer researches. Our previous studies on WISP1 implied it could be a harmful mediator in septic mice. However, its role in liver ischemia reperfusion (I/R) injury is unknown. This study investigated the effects of WISP1 on liver I/R damage. Male C57BL/6 wild-type mice were used to undergo 60 min segmental (70%) ischemia. WISP1 expression was measured after indicated time points of reperfusion. Anti-WISP1 antibody was injected intraperitoneally to mice. Toll-like receptor 4 (TLR4) knockout mice and TIR-domain-containing adaptor inducing interferon-ß (TRIF) knockout mice were adopted in this study. WISP1 was significantly enhanced after 6 h of reperfusion when compared with sham treated mice and significantly decreased either by TLR4 knockout mice or TRIF knockout mice. Anti-WISP1 antibody significantly decreased serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), pathological changes and pro-inflammatory cytokine levels in the mice following I/R. Furthermore, significantly increased serum transaminase levels were found in C57 wild-type mice treated with recombinant WISP1 protein, but not found in TLR4 knockout or TRIF knockout mice subjected to liver I/R. Taken together, WISP1 might contribute to hepatic ischemia reperfusion injury in mice and possibly depends on TLR4/TRIF signaling.


Assuntos
Proteínas de Sinalização Intercelular CCN/biossíntese , Regulação da Expressão Gênica , Fígado/metabolismo , Proteínas Proto-Oncogênicas/biossíntese , Traumatismo por Reperfusão/metabolismo , Transdução de Sinais , Receptor 4 Toll-Like/metabolismo , Proteínas Adaptadoras de Transporte Vesicular/genética , Proteínas Adaptadoras de Transporte Vesicular/metabolismo , Animais , Proteínas de Sinalização Intercelular CCN/genética , Fígado/patologia , Masculino , Camundongos , Camundongos Knockout , Proteínas Proto-Oncogênicas/genética , Traumatismo por Reperfusão/genética , Traumatismo por Reperfusão/patologia , Receptor 4 Toll-Like/genética
13.
Mol Med ; 22: 54-63, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26772774

RESUMO

Mechanical ventilation can improve hypoxemia, but can also cause the so-called ventilator-induced lung injury (VILI). Polyinosinic-polycytidylic acid (poly(I:C)), an analogue of natural double strand RNA virus, can induce lung inflammation. The purpose of this study was to determine whether moderate tidal volume mechanical ventilation (MTV) augments Poly(I:C)-induced lung injury, and if so, the mechanism responsible for it. Poly(I:C) (2µg/g) were instilled intratracheally in C57BL/6J wide type (WT) mice. They were then randomized to MTV (10ml/kg tidal volume) or spontaneous breath. Lung tissues and bronchoalveolar lavage fluid (BALF) were collected 4h later for various measurements. Our results showed that MTV did not cause significant injury in normal lungs, but augmented Poly(I:C)-induced lung injury. The expression level of WNT-induced secreted protein 1 (WISP1) was consistent with lung injury, and the amplification of lung injury by MTV can be alleviated by anti-WISP1 antibody treatment. MTV further increased Poly(I:C)-induced integrin ß3 expression in the lung. And co-immunoprecipitation (Co-IP) results suggested there was an interaction between WISP1 and ß3. WISP1 significantly increased Poly(I:C)-induced TNF-α production in macrophages isolated from WT mice but not in macrophages isolated from ß3 knock-out mice. Co-treatment with WISP1 and Poly(I:C) markedly increased the phosphorylation of extracellular signal-related kinase (ERK) in macrophages. Pretreating macrophages with an ERK inhibitor, U0126, dose-dependently antagonized WISP's synergistic effect on Poly(I:C)-induced TNF-α release. In conclusion, MTV exaggerates Poly(I:C)-induced lung injury in a WISP1 and integrin ß3 dependent manner, involving, at least part, the activation of the ERK pathway. The WISP1-integrin ß3 pathway could be an important target for novel therapy.

14.
Med Sci Monit ; 21: 3241-6, 2015 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-26498664

RESUMO

BACKGROUND: The aim of this study was to investigate and interpret the expression level and potential function of TCEA3 in gastric cancer. MATERIAL AND METHODS: qRT-PCR was used to determine the expression level of TCEA3 in gastric cancer tissues. Pearson χ2 test was performed to clarify the correlation between TCEA3 expression and patients' clinicopathologic characteristics. Biological function of TCEA3 was tested by proliferation assay and colony formation assay. Flow cytometry was used to study the potential function of TCEA3 in apoptosis induction. RESULTS: TCEA3 expression was significantly downregulated in gastric cancer tissues compared with paired normal tissues. Poor prognoses were observed in the low TCEA3 expression group of patients in contrast to the high TCEA3 expression group. Functionally, upregulation of TCEA3 inhibited gastric cancer cell proliferation and colony formation. We also found that TCEA3 may attenuate cell growth through apoptosis induction. CONCLUSIONS: Our findings suggest that TCEA3 attenuates the proliferation and induces apoptosis of gastric cancer cells.


Assuntos
Apoptose , Regulação Neoplásica da Expressão Gênica , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Fatores de Elongação da Transcrição/metabolismo , Idoso , Linhagem Celular Tumoral , Proliferação de Células , DNA Complementar/metabolismo , Feminino , Citometria de Fluxo , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Reação em Cadeia da Polimerase em Tempo Real
15.
Clinics (Sao Paulo) ; 70(9): 648-53, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26375568

RESUMO

Patients frequently experience postoperative pain after a total knee arthroplasty; such pain is always challenging to treat and may delay the patient's recovery. It is unclear whether local infiltration or a femoral nerve block offers a better analgesic effect after total knee arthroplasty.We performed a systematic review and meta-analysis of randomized controlled trials to compare local infiltration with a femoral nerve block in patients who underwent a primary unilateral total knee arthroplasty. We searched Pubmed, EMBASE, and the Cochrane Library through December 2014. Two reviewers scanned abstracts and extracted data. The data collected included numeric rating scale values for pain at rest and pain upon movement and opioid consumption in the first 24 hours. Mean differences with 95% confidence intervals were calculated for each end point. A sensitivity analysis was conducted to evaluate potential sources of heterogeneity.While the numeric rating scale values for pain upon movement (MD-0.62; 95%CI: -1.13 to -0.12; p=0.02) in the first 24 hours differed significantly between the patients who received local infiltration and those who received a femoral nerve block, there were no differences in the numeric rating scale results for pain at rest (MD-0.42; 95%CI:-1.32 to 0.47; p=0.35) or opioid consumption (MD 2.92; 95%CI:-1.32 to 7.16; p=0.18) in the first 24 hours.Local infiltration and femoral nerve block showed no significant differences in pain intensity at rest or opioid consumption after total knee arthroplasty, but the femoral nerve block was associated with reduced pain upon movement.


Assuntos
Analgesia/métodos , Anestesia Local/estatística & dados numéricos , Artroplastia do Joelho , Nervo Femoral , Bloqueio Nervoso/estatística & dados numéricos , Anestésicos Locais , Humanos , Medição da Dor , Ensaios Clínicos Controlados Aleatórios como Assunto
16.
Clinics ; 70(9): 648-653, Sept. 2015. tab, ilus
Artigo em Inglês | LILACS | ID: lil-759290

RESUMO

Patients frequently experience postoperative pain after a total knee arthroplasty; such pain is always challenging to treat and may delay the patient’s recovery. It is unclear whether local infiltration or a femoral nerve block offers a better analgesic effect after total knee arthroplasty.We performed a systematic review and meta-analysis of randomized controlled trials to compare local infiltration with a femoral nerve block in patients who underwent a primary unilateral total knee arthroplasty. We searched Pubmed, EMBASE, and the Cochrane Library through December 2014. Two reviewers scanned abstracts and extracted data. The data collected included numeric rating scale values for pain at rest and pain upon movement and opioid consumption in the first 24 hours. Mean differences with 95% confidence intervals were calculated for each end point. A sensitivity analysis was conducted to evaluate potential sources of heterogeneity.While the numeric rating scale values for pain upon movement (MD-0.62; 95%CI: -1.13 to -0.12; p=0.02) in the first 24 hours differed significantly between the patients who received local infiltration and those who received a femoral nerve block, there were no differences in the numeric rating scale results for pain at rest (MD-0.42; 95%CI:-1.32 to 0.47; p=0.35) or opioid consumption (MD 2.92; 95%CI:-1.32 to 7.16; p=0.18) in the first 24 hours.Local infiltration and femoral nerve block showed no significant differences in pain intensity at rest or opioid consumption after total knee arthroplasty, but the femoral nerve block was associated with reduced pain upon movement.


Assuntos
Humanos , Artroplastia do Joelho , Analgesia/métodos , Anestesia Local , Nervo Femoral , Bloqueio Nervoso , Anestésicos Locais , Medição da Dor , Ensaios Clínicos Controlados Aleatórios como Assunto
17.
Int J Clin Exp Med ; 8(1): 368-76, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25785007

RESUMO

Early post-operative mobilization is important both to reduce immobility-related complications and to get the best functional result following surgery on knee. We hypothesized that saphenous nerve block would reduce pain in this patient category compared with placebo injection. In this study, two reviewers independently searched the databases of PubMed, EMBASE, and Cochrane Library (last performed on 12 October, 2014) to retrieve eligible randomized controlled clinical trials. The primary outcomes were visual analog scale (VAS) pain scores within 24 hours after operation when at rest and at an active flexion of knee. Mean difference (MD) or odds ratio (OR) with 95% confidence intervals (CIs) was calculated for each end point. Subgroup analysis was calculated to evaluate potential sources of heterogeneity. Nine randomized controlled trials were retrieved and analyzed. We found that VAS pain scores at rest within postoperative 24 hours were significantly decreased in saphenous nerve block group than that in placebo group (MD = -0.79; 95% CI -1.35 to -0.22; P = 0.007), as well as VAS pain scores at an active flexion of knee within postoperative 24 hours (MD = -0.92; 95% CI -1.61 to -0.22; P = 0.010). In addition, compared to placebo injection group, saphenous nerve block resulted in significantly less morphine consumption during the first postoperative 24 hours (MD = -6.56; 95% CI -11.26 to -1.86; P = 0.006). To conclude, this meta-analysis suggests that saphenous nerve block has an advantage in pain relief both at an active flexion of knee and at rest after knee surgery. Further studies are still wanted to validate these conclusions.

18.
Shock ; 43(4): 352-60, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25526379

RESUMO

Acute lung injury is a common consequence of sepsis, a life-threatening inflammatory response caused by severe infection. In this study, we elucidate the attenuating effects of synthetic Arg-Gly-Asp-Ser peptides (RGDs) on acute lung injury in a sepsis mouse model. We further reveal that the beneficial effects of RGDs stem from their negative regulation of the Wisp1 (WNT1-inducible signaling pathway)-integrin ß6 pathway. After inducing sepsis using cecal ligation and puncture (CLP), mice were randomized into experimental and control groups, and survival rates were recorded over 7 days, whereas only 20% of mice subjected to CLP survived when compared with untreated controls; the addition of RGDs to this treatment regimen dramatically increased the survival rate to 80%. Histological analysis revealed acute lung injury in CLP-treated mice, whereas those subjected to the combined treatment of CLP and RGDs showed a considerable decrease in lung injury severity. The addition of RGDs also dramatically attenuated other common sepsis-associated effects, such as increased white blood cell number in bronchoalveolar lavage fluid and decreased pulmonary capillary barrier function. Furthermore, treatment with RGDs decreased the serum and bronchoalveolar lavage fluid levels of inflammatory cytokines such as tumor necrosis factor α and interleukin 6, contrary to the CLP treatment alone that increased the levels of these proteins. Interestingly, however, RGDs had no detectable effect on bacterial invasion following sepsis induction. In addition, mice treated with RGDs showed decreased levels of wisp1 and integrin ß6 when compared with CLP-treated mice. In the present study, a linkage between Wisp1 and integrin ß6 was evaluated in vivo. Most strikingly, RGDs resulted in a decreased association of Wisp1 with integrin ß6 based on coimmunoprecipitation analyses. These data suggest that RGDs ameliorate acute lung injury in a sepsis mouse model by inhibiting the Wisp1-integrin ß6 pathway.


Assuntos
Lesão Pulmonar Aguda/patologia , Proteínas de Sinalização Intercelular CCN/antagonistas & inibidores , Cadeias beta de Integrinas/metabolismo , Oligopeptídeos/farmacologia , Proteínas Proto-Oncogênicas/antagonistas & inibidores , Sepse/imunologia , Animais , Líquido da Lavagem Broncoalveolar , Capilares/patologia , Modelos Animais de Doenças , Imunoprecipitação , Interleucina-6/metabolismo , Pulmão/irrigação sanguínea , Pulmão/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Sepse/microbiologia , Sepse/fisiopatologia , Fator de Necrose Tumoral alfa/metabolismo
19.
Int J Clin Exp Med ; 7(9): 2504-10, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25356103

RESUMO

PURPOSE: Ketamine is currently the N-methyl-D-aspartate receptor channel blocker in clinical use. Morphine in pain management is usually limited by adverse effect such as nausea and vomiting. Adjuvant treatment with ketamine may be value in giving better analgesia with fewer adverse effects. The purpose of this meta-analysis was to evaluate the differences when patients received morphine with adjuvant ketamine (MK) compared with higher dose of morphine (MO) for acute pain. METHODS: The PubMed, EMBASE and the Cochrane Library databases were searched (Last search performed on July 1, 2014) by two reviewers independently. Data were extracted independently by the same two individuals who searched the studies. RESULTS: A total of 7 trials involving 492 patients were included in the current analysis. We found pain scores were lower in the MK group compared to the MO group [MD 2.19, 95% CI (1.24, 3.13) P<0.00001]. And more patients in the MO required diclofenac [OR 1.97, 95% CI (1.06, 3.67) P=0.03]. Furthermore, morphine plus ketamine can reduced post-operative nausea and vomiting (PONV) [OR 3.71, 95% CI (2.37, 5.80) P<0.00001]. Importantly, the wakefulness scores for the MK group were consistently and significantly better than those for the MO group [MD -1.53, 95% CI (-2.67, -0.40) P=0.008]. CONCLUSION: The use of ketamine plus 1/4~2/3 the dose of morphine is better than higher dose of morphine alone in reducing pain scores, and rescuing analgesic requirement. It also improved PONV and wakefulness.

20.
Int J Clin Exp Med ; 7(9): 2966-75, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25356170

RESUMO

BACKGROUND: The increasing use of the transversus abdominis plane (TAP) block, as a form of pain relief after laparoscopic surgery, warrants evaluation of its effectiveness, when compared with other analgesic techniques. METHODS: We searched online databases of MEDLINE, EMBASE, Google scholar and The Cochrane Database of Systematic Review. Mean differences (MD) were formulated for continuous data; odds ratios (OR) were calculated for dichotomous data. Results were produced with a random effects model with 95% confidence intervals (CI). RESULTS: 14 trials with a total of 905 patients were included for the analysis, TAP block resulted in significantly less postoperative analgesic consumption at 24 h (MD = -25.46, 95% CI [-32.22, -18.69], P < 0.00001), and less number of patients requiring analgesic postoperatively (OR = 0.16, 95% CI 0.03-0.87, P = 0.03). Meanwhile, pain sores were significantly different at 2 h (MD = -1.55, 95% CI [-2.50, -0.59], P < 0.00001), a borderline difference between the groups seen at 6 hours ( MD = -1.13, 95% CI [-1.69, -0.56], P = 0.05), and there was not affect pain at 24 h (MD = -0.33, 95% CI [-0.08, 0.15], P = 0.14) with TAP block groups compared with the groups without TAP block. There was a significant difference in postoperative nausea and vomiting (random effects model: OR = 2.04, 95% CI [1.19-3.48], P = 0.34). CONCLUSION: TAP block would result in less analgesic consumption, less requirement of analgesic, and less pain at 2 h and slightly at 6 h but at 24 h after laparoscopic surgery in comparison with usual care alone or placebo block. In addition TAP block can increase the incidence of postoperative nausea and vomiting.

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