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1.
Inflammation ; 2020 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-32535666

RESUMO

Interleukin (IL)-35, which has an anti-inflammatory role in acute respiratory distress syndrome (ARDS)/acute lung injury (ALI), is relatively promising as a drug target. Studies have shown that curcumin may play a therapeutic role in ALI and enhance the suppressive function of regulatory T cells (Tregs). To illustrate the effect of curcumin on the regulation of Treg cell differentiation and expression of IL-35, we built a cecal ligation and puncture (CLP)-induced acute lung injury mouse mode with curcumin pretreatment. The expression of IL-35 in serum, severity of lung injury, IL-17A in lung tissue, survival rate, Treg-related cytokines levels in serum, nuclear factor-kappa B (NF-κB)'s nuclear translocation in lung tissue, and splenic CD4+CD25+FOXP3+ Tregs were assessed. Furthermore, the proportion of Tregs, STAT5, and IL-35 expression during naïve CD4+ T cell differentiation in vitro was measured. Compared with the CLP group, the increased IL-35 expression in CLP with the curcumin pretreatment (CLP + Cur) group was consistent with the decreased severity of lung injury, IL-17A protein levels in lung tissue, and Treg-related cytokines levels. Pretreatment with curcumin, the survival rate climbed to 50%, while the mortality rate was 100% in the CLP group. In addition, splenic CD4+CD25+FOXP3+ Treg cells increased in the CLP + Cur group. In vitro, CD4+CD25+FOXP3+ Treg cells from naïve CD4+ T cells, STAT5 proportion, and IL-35 expression increased after curcumin treatment. These findings showed that curcumin might regulate IL-35 by activating the differentiation of Treg cells to control the inflammation in acute lung injury.

2.
Mediators Inflamm ; 2020: 9704327, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32565732

RESUMO

Progranulin (PGRN), which plays an anti-inflammatory role in acute lung injury (ALI), is promising as a potential drug. Studies have shown that regulatory T cells (Tregs) and interleukin- (IL-) 10 can repress inflammation and alleviate tissue damage during ALI. In this study, we built a lipopolysaccharide- (LPS-) induced ALI mouse model to illustrate the effect of PGRN on regulation of Treg differentiation and modulation of IL-10 promoting macrophage polarization. We found that the proportion of Tregs in splenic mononuclear cells and peripheral blood mononuclear cells was higher after treatment with PGRN. The increased proportion of Tregs after PGRN intratracheal instillation was consistent with the decreased severity of lung injury, the reduction of proinflammatory cytokines, and the increase of anti-inflammatory cytokines. In vitro, the percentages of CD4+CD25+FOXP3+ Tregs from splenic naïve CD4+ T cells increased after PGRN treatment. In further research, it was found that PGRN can regulate the anti-inflammatory factor IL-10 and affect the polarization of M1/M2 macrophages by upregulating IL-10. These findings show that PGRN likely plays a protective role in ALI by promoting Treg differentiation and activating IL-10 immunomodulation.

3.
J Gene Med ; : e3216, 2020 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-32410261

RESUMO

BACKGROUND: The present study aimed to determine the role and mechanism of miR-23 with respect to regulating the osteogenic differentiation of human bone marrow mesenchymal stem cells (hBMSCs). MATERIALS: The expression of miR-23 and MEF2C was measured in osteoporosis (OP) patients and healthy controls by a quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). The correlation between miR-23 and MEF2C was determined by the Pearson correlation coefficient. Moreover, bioinformatic analysis was performed using public databases. Target gene function and potential pathways were further examined. Then, we used a miR-23 mimic or inhibitor to further explore the potential mechanism of miR-23. RESULTS: miR-23 is found to be up-regulated and MEF2C is down-regulated in OP patients compared to healthy controls. miR-23 had a negative correlation with MEF2C (r = -0.937, p = 0.001). Bioinformatic analysis revealed that a total of 664 overlapping target genes were found in the TargetScan (http://www.targetscan.org), miRDB (http://mirdb.org) and miRanda (http://www.microrna.org/microrna/home.do) databases. Moreover, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated that miR-23 may regulate the mitogan-activated protein kinase (MAPK) signaling pathway. miR-23 is down-regulated and MEF2C is significantly up-regulated in the osteogenic differentiation of hBMSCs. MEF2C was significantly up-regulated in the osteogenic differentiation of hBMSCs. Overexpression of miR-23 significantly down-regulated alkaline phosphatase (ALP) activity and calcium deposition, whereas the miR-23 inhibitor had the opposite effects. Moreover, overexpression of miR-23 significantly decreased osteoblast-related markers (Runx2, Osx, ALP and OCN). Further experiments confirmed that MEF2C is a direct target of miR-23. Moreover, the miR-23 mimic enhanced the expression of p-p38 but had no effect on p-JNK. CONCLUSIONS: miR-23 decreases the osteogenic differentiation of hBMSCs through the MEF2C/MAPK signaling pathway.

4.
BMC Cardiovasc Disord ; 20(1): 170, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32293300

RESUMO

BACKGROUND: Systemic inflammation is an important feature of post-cardiac arrest syndrome (PCAS). This study was designed to determine whether the plasma concentrations of some circulating pro-inflammatory cytokines (interleukin-17 [IL-8], IL-22, IL-23 and IL-33) are of value in predicting the outcome of patients after return of spontaneous circulation (ROSC) during the post-cardiac arrest period. METHODS: This was a prospective observational clinical study. In total, 21 patients (survivors, n = 10; non-survivors, n = 11) who experienced cardiac arrest and successful ROSC with expected survival of at least 7 days were consecutively enrolled from January 2016 to December 2017. Of the 21 enrolled patients, ten survived were designated "survivors". The other eleven patients died between 2 days and 1 months post ROSC. Venous blood was drawn at three time-points: baseline (< 1 h post ROSC), 2 days post ROSC and 7 days post ROSC. Plasma IL-8, IL-22, IL-23 and IL-33 were determined using commercial enzyme-linked immunosorbent assays. RESULTS: Plasma creatinine levels, but aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels, were elevated in non-survivors compared with survivors. Plasma levels of IL-17, IL-22, IL-23 and IL-33 of the 21 total patients did not change at 2 or 7 days post ROSC compared to baseline. In survivors, the plasma levels of IL-17 and IL-23 at 2 or 7 days post ROSC were lower than baseline. In non-survivors, plasma levels of IL-17 increased compared with baseline. Receiver operating characteristic curve analysis showed that the plasma levels of IL-17 and IL-23 at 2 or 7 days post ROSC were able to predict the mortality of PCAS patients, and positively correlated with Acute Physiology and Chronic Health Evaluation (APACHE)-II score and time to ROSC. CONCLUSION: These results provide the first evidence that the elevated plasma IL-17 and IL-23 levels are associated with poor outcome in PCAS patients. The role of IL-17/IL-23 axis post ROSC is worth paying attention to in PCAS patients. TRIAL REGISTRATION: Clinicaltrial.govNCT02297776, 2014-11-21.

5.
Biomed Pharmacother ; 125: 109946, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32004976

RESUMO

OBJECTIVES: Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is one type of respiratory failure characterized by rapid onset of widespread inflammation in the lungs. Curcumin has been reported to be an anti-inflammatory factor through enhancing the function of regulatory T cells (Tregs). This study aimed to explore the effect of curcumin on the differentiation of Tregs and the role of curcumin in ALI/ARDS. METHODS: A cecal ligation and puncture (CLP)-induced acute lung injury mouse model was used to explore the effect of curcumin in ALI/ARDS. The severity of lung injury was evaluated. Immunohistochemistry of IL-17A and MPO in lung tissue was examined. Treg-related cytokine levels in serum and bronchoalveolar lavage fluid (BALF) were tested. The expression of nuclear factor-kappa B (NF-κB) in lung tissue was detected. Macrophages in lung tissue were detected by immunofluorescence. Splenic CD4+CD25+FOXP3+ Tregs were quantified, and the differentiation of Tregs from naïve CD4 + T cell and STAT5 was evaluated. The expression of IL-10 during naïve CD4 + T cell differentiation in vitro was tested. RESULTS: Curcumin alleviated lung injury in the induced CLP mouse model and suppressed inflammation. IL-17A, MPO-producing neutrophils, and NF-κB p65 expression in lungs of CLP mice decreased significantly after pretreatment with curcumin. We found curcumin could regulate M1/M2 macrophage levels in lungs of CLP mice. This may have been through regulating the differentiation of Tregs and the production of Treg-derived IL-10. Treg-derived IL-10 is the main factor that could affect macrophage polarization. We found curcumin could increase Treg proportions in vivo and up-regulate IL-10 expression in serum and BALF of CLP mice. In our in vitro experiments, we found curcumin could promote Treg differentiation and increase the production of IL-10. CONCLUSIONS: Curcumin can reduce the degree of severity of ALI and uncontrolled inflammation through promoting the differentiation of naïve CD4 + T cells to CD4+ CD25+ FOXP3+ Tregs. Curcumin promotes the conversion of macrophages from M1 to M2. The differentiation of Tregs induced by curcumin may be one source of IL-10 immune modulation.

6.
Dis Markers ; 2020: 9608276, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32015774

RESUMO

Background: Adipokines are a group of cytokines or peptides secreted by adipose tissue to exert numerous biological functions. In the present study, we measured the plasma levels of four adipokines (adiponectin, leptin, fatty acid-binding protein 4 (FABP4), and visfatin) in cardiac arrest patients following return of spontaneous circulation (ROSC). Methods: Totally, 21 patients who experienced cardiac arrest and successful ROSC with expected survival of at least 48 hours (from January 2016 to December 2017) were consecutively enrolled into this prospective observational clinical study. Of the 21 enrolled patients, ten survived, and other eleven died between 2 days and 6 months post ROSC. Venous blood was drawn at three time points: baseline (<1 hour post ROSC), 2 days post ROSC, and 7 days post ROSC. Plasma concentrations of adiponectin, leptin, FABP4, and visfatin were determined using commercial enzyme-linked immunosorbent assays. Results: The plasma visfatin levels at 2 or 7 days post ROSC increased significantly compared with the baseline (P < 0.01), while plasma levels of adiponectin, leptin, and FABP4 did not change. Moreover, plasma visfatin levels in survivors at 2 or 7 days post ROSC were higher than those in nonsurvivors (P < 0.01). Plasma visfatin levels at 2 or 7 days post ROSC were negatively correlated with Acute Physiology and Chronic Health Evaluation (APACHE) II score and time to ROSC. Moreover, receiver operating characteristic curve analysis showed that the plasma visfatin levels at 2 or 7 days post ROSC were good predictors for survival of the patients. Conclusion: Elevated plasma visfatin levels may be a marker for better outcome of cardiac arrest patients post ROSC.

7.
Exp Gerontol ; 119: 128-137, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30710682

RESUMO

BACKGROUND: Androgen has been implicated in aging-related cardiac remodeling, but its precise role in aging heart remains controversial. We aimed to investigate the role of testosterone in the development of aging-related cardiac remodeling and the mechanisms involved. METHODS: Wild type and Axl knockout mice (Axl-/-) were randomized into three groups: the young group (n = 30, 3 months old), the aging group (n = 30, 18 months old), the testosterone undecanoate treatment group (TU, n = 30, 18 months old). Mice in the TU group were given testosterone undecanoate (39 mg/kg) by subcutaneous injection on the back at fifteen-months-old, once a month, a total of three times. The old group received solvent reagent (corn oil) by the same method. RESULTS: The aging mice exhibited a decrease in serum testosterone, and Gas6 levels and an increase in apoptosis, and manifested cardiac fibrosis. Testosterone injection to wild type mice increased the levels of testosterone and Gas6 in serum and decreased cardiac apoptosis and fibrosis. Axl-/-mice receiving testosterone injection exhibited no obvious improvement in cardiac remodeling although the levels of testosterone and Gas6 in serum elevated. CONCLUSIONS: These data indicated that testosterone replacement therapy (TRT) alleviates cardiac fibrosis and apoptosis, at least in part by enhancing Gas6 expression. Moreover, deletion of Axl disables testosterone, which indicated that Axl is an important downstream regulator of testosterone. TRT would improve aging-related cardiac remolding via Gas6/Axl signaling pathway, implicating its therapeutic potential to treat aging-related heart disease.

8.
Biomed Environ Sci ; 31(7): 515-526, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30145986

RESUMO

OBJECTIVE: To identify potential serum biomarkers for distinguishing between latent tuberculosis infection (LTBI) and active tuberculosis (TB). METHODS: A proteome microarray containing 4,262 antigens was used for screening serum biomarkers of 40 serum samples from patients with LTBI and active TB at the systems level. The interaction network and functional classification of differentially expressed antigens were analyzed using STRING 10.0 and the TB database, respectively. Enzyme-linked immunosorbent assays (ELISA) were used to validate candidate antigens further using 279 samples. The diagnostic performances of candidate antigens were evaluated by receiver operating characteristic curve (ROC) analysis. Both antigen combination and logistic regression analysis were used to improve diagnostic ability. RESULTS: Microarray results showed that levels of 152 Mycobacterium tuberculosis (Mtb)-antigen- specific IgG were significantly higher in active TB patients than in LTBI patients (P < 0.05), and these differentially expressed antigens showed stronger associations with each other and were involved in various biological processes. Eleven candidate antigens were further validated using ELISA and showed consistent results in microarray analysis. ROC analysis showed that antigens Rv2031c, Rv1408, and Rv2421c had higher areas under the curve (AUCs) of 0.8520, 0.8152, and 0.7970, respectively. In addition, both antigen combination and logistic regression analysis improved the diagnostic ability. CONCLUSION: Several antigens have the potential to serve as serum biomarkers for discrimination between LTBI and active TB.


Assuntos
Tuberculose Latente/diagnóstico , Análise Serial de Proteínas/métodos , Proteômica/métodos , Adolescente , Adulto , Idoso , Anticorpos Antibacterianos , Especificidade de Anticorpos , Antígenos de Bactérias , Biomarcadores/sangue , Feminino , Humanos , Tuberculose Latente/sangue , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Mycobacterium tuberculosis , Proteoma/genética , Curva ROC , Adulto Jovem
9.
Clin Exp Pharmacol Physiol ; 44(5): 586-594, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28079261

RESUMO

Ropivacaine is one of the most common but toxic local anaesthetics, and the mechanisms underlying its neurotoxicity are still largely unknown. This study was conducted to prepare a ropivacaine-induced neuronal injury model and research the effects of ropivacaine on PARP-1 activation and nicotinamide adenine dinucleotide (NAD)+ depletion. The cell death and apoptosis of ropivacaine-induced SH-SY5Y cells were detected with flow cytometry. The lactate dehydrogenase cycling reaction measured the NAD+ level, and western blots were used to analyze the expression levels of PARP-1 and apoptosis-inducing factor (AIF) after ropivacaine treatments with different concentrations and durations. A PARP-1 inhibitor (PJ-34) was used to confirm the relationship between PARP-1 activation and NAD+ depletion. Hoechst 33258 nuclear staining and a mitochondrial membrane potential (Δψm) assay were used to detect the role of exogenous NAD+ in ropivacaine-induced neuronal injury. Ropivacaine-induced SH-SY5Y cell death and apoptosis, PARP-1 activation, and AIF increase as well as intracellular NAD+ depletion occurred in a time- and concentration-dependent manner (P<.05). PARP-1 activation led to NAD+ depletion (P<.05). Exogenous NAD+ impaired ropivacaine-induced nuclear injury (P<.05). Ropivacaine treatment induced PARP-1 activation and NAD+ depletion (P<.05). Parthanatos (PARP-1-dependent cell death) was definitely involved in ropivacaine-induced neuronal injury, and exogenous NAD+ may be a novel therapeutic method for parthanatos-dependent neuronal injury.


Assuntos
Amidas/administração & dosagem , Anestésicos Locais/administração & dosagem , Apoptose/efeitos dos fármacos , NAD/administração & dosagem , NAD/metabolismo , Poli(ADP-Ribose) Polimerase-1/metabolismo , Apoptose/fisiologia , Morte Celular/efeitos dos fármacos , Morte Celular/fisiologia , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Interações Medicamentosas/fisiologia , Humanos , Fenantrenos/administração & dosagem , Poli(ADP-Ribose) Polimerase-1/antagonistas & inibidores , Ropivacaina
10.
Age (Dordr) ; 38(3): 60, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27206970

RESUMO

Testosterone deficiency is associated with a higher incidence of cardiovascular diseases in men. However, its effect on cell senescence, which plays a causal role in vascular aging, remains unclear. Here, we tested the hypothesis that testosterone alleviated vascular smooth muscle cell (VSMC) senescence and collagen synthesis via growth arrest-specific protein 6 (Gas6)/Axl- and Akt/FoxO1a-dependent pathways. Testosterone significantly ameliorated angiotensin II-induced VSMC senescence and collagen overexpression. In addition, testosterone inhibited angiotensin II-induced matrix metalloproteinase-2 (MMP-2) activity, which played a pivotal role in facilitating age-related collagen deposition. Testosterone increased the expression of tissue inhibitor of metalloproteinase-2 but decreased the expression of MMP-2 and membrane type-1 metalloproteinase which contributed to increase MMP-2 activity. The effects on VSMCs senescence and collagen synthesis were mediated by restoration of angiotensin II-induced downregulation of Gas6 and Axl expression and a subsequent reduction of Akt and FoxO1a phosphorylation. The effects of testosterone were reversed by a Gas6 blocker, Axl-Fc, and a specific inhibitor of Axl, R428. Treatment of VSMCs with PI3K inhibitor LY294002 abrogated the downregulating effect of testosterone on MMP-2 activity. Furthermore, when FoxO1a expression was silenced by using a specific siRNA, the inhibitory effect of testosterone on MMP-2 activity was revered as well, that indicated this process was Akt/FoxO1a dependence. Taken together, Gas6/Axl and Akt/FoxO1a were involved in protective effects of testosterone on VSMCs senescence and collagen synthesis. Our results provide a novel mechanism underlying the protective effect of testosterone on vascular aging and may serve as a theoretical basis for testosterone replacement therapy.


Assuntos
Envelhecimento/genética , Colágeno/biossíntese , Regulação da Expressão Gênica no Desenvolvimento , Peptídeos e Proteínas de Sinalização Intercelular/genética , Músculo Liso Vascular/efeitos dos fármacos , Proteínas Proto-Oncogênicas/genética , Receptores Proteína Tirosina Quinases/genética , Testosterona/farmacologia , Androgênios/farmacologia , Animais , Apoptose , Western Blotting , Bovinos , Células Cultivadas , Senescência Celular , Colágeno/antagonistas & inibidores , DNA/genética , Ensaio de Imunoadsorção Enzimática , Peptídeos e Proteínas de Sinalização Intercelular/biossíntese , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Músculo Liso Vascular/citologia , Músculo Liso Vascular/metabolismo , Reação em Cadeia da Polimerase , Proteínas Proto-Oncogênicas/biossíntese , Receptores Proteína Tirosina Quinases/biossíntese , Transdução de Sinais/efeitos dos fármacos
11.
Guang Pu Xue Yu Guang Pu Fen Xi ; 36(4): 1017-20, 2016 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-30048104

RESUMO

Water-soluble CdZnTe quantum dots (QDs) were firstly synthesized by using 3-mercaptopropionic acid (MPA) as modifier in aqueous phase. Then, CdZnTe quantum dots were capped with polyethyleneimine (PEI) with electrostatic interaction and condensation reaction between carboxyl group on the surface of QDs and amino group of PEI, and several metal ions were tested to check if they affect the fluorescence properties of CdZnTe QDs in the paper. A novel method to detect trace Pb2+ has been developed based on the selective fluorescence quenching Pb2+ to PEI-CdZnTe QDs. Fluorescence quenching effect of PEI-CdZnTe QDs had been studied by increasing the Pb2+ concentration. The study results show that fluorescence quenching process of Pb2+ can be described well by Stern-Volmer fluorescence quenching equation. There is a good linear relationship between the fluorescence intensity F0/F and the concentration of Pb2+ when the concentration of Pb2+ is in the ranges of 0.05~3.0 µg·mL-1. The linear correlation coefficient and the detection limits are 0.998 8 and 0.01 µg·mL-1, respectively. The proposed fluorescence method of detection is simple, rapid and sensitive, which has been successfully applied to the detection of Pb2+ in tap water.

12.
Zhongguo Zhong Yao Za Zhi ; 41(8): 1397-1404, 2016 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-28884530

RESUMO

This paper was aimed to compare the acute toxicity of 999 Ganmaoling grain and its different ingredients, and investigate the influence of routine diet on the hepatic toxicity induced by Ganmaoling in mice, so as to provide experimental basis for the clinical safety evaluation. Mice were given a single dose of Ganmaoling grain or its different ingredients respectively by gavage, and then observed for 14 days. LD50 values of Ganmaoling grain or its chemical ingredient and the maximal tolerated dose of its herb ingredient were determined. Mice were divided into starvation and diet group, a single dose of Ganmaoling grain was administered by gavage. LD50 values were estimated after 14 day observation. Mice were divided into starvation and diet group. At the same time,control group was set up for each. A single dose of Ganmaoling grain was given. Serum biochemical indexes were detected, liver weight index was calculated and liver tissue morphological change was observed after 6 h. LD50 values were 4.42, 0.64 g•kg⁻¹ for Ganmaoling grain group and chemical ingredient group, respectively. The maximal tolerated dose of the herb ingredient group was close to 24.24 g•kg⁻¹. The toxic symptom was basically similar in the Ganmaoling grain and the chemical ingredient group. The body weight and food intake were decreased to a certain extent in both groups. There were pathological changes of liver and heart tissue in some of the surviving animals. The animals in the Ganmaoling grain group exhibited a lighter toxicity and recovered faster than that in the chemical ingredient group. LD50 values of Ganmaoling grain were 2.56, 6.93 g•kg⁻¹ for starvation and diet group respectively. TD50 values were 1.29, 6.31 g•kg⁻¹ for starvation and diet group respectively. The toxicity of 999 Ganmaoling was less, which may be related to the reduction of toxicity after the combination of herb and chemical ingredients. Compared with starvation group, the values of LD50 and TD50 of diet group was significantly increased, and toxicity was decreased. From the point of view of safety, it is safer to use Ganmaoling in the absence of hunger or after meal. The above tests provide experimental basis for the clinical safety use of Ganmaoling.


Assuntos
Dieta , Medicamentos de Ervas Chinesas/toxicidade , Fígado/efeitos dos fármacos , Animais , Doença Hepática Induzida por Substâncias e Drogas/patologia , Dose Letal Mediana , Fígado/patologia , Camundongos , Inanição , Testes de Toxicidade Aguda
13.
World J Emerg Med ; 6(2): 137-41, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26056545

RESUMO

BACKGROUND: Noninvasive monitoring of intra-abdominal pressure (IAP) by measuring abdominal wall tension (AWT) was effective and feasible in previous postmortem and animal studies. This study aimed to investigate the feasibility of the AWT method for noninvasively monitoring IAP in the intensive care unit (ICU). METHODS: In this prospective study, we observed patients with detained urethral catheters in the ICU of Shanghai Tenth People's Hospital between April 2011 and March 2013. The correlation between AWT and urinary bladder pressure (UBP) was analyzed by linear regression analysis. The effects of respiratory and body position on AWT were evaluated using the paired samples t test, whereas the effects of gender and body mass index (BMI) on baseline AWT (IAP<12 mmHg) were assessed using one-way analysis of variance. RESULTS: A total of 51 patients were studied. A significant linear correlation was observed between AWT and UBP (R=0.986, P<0.01); the regression equation was Y=-1.369+9.57X (P<0.01). There were significant differences among the different respiratory phases and body positions (P<0.01). However, gender and BMI had no significant effects on baseline AWT (P=0.457 and 0.313, respectively). CONCLUSIONS: There was a significant linear correlation between AWT and UBP and respiratory phase, whereas body position had significant effects on AWT but gender and BMI did not. Therefore, AWT could serve as a simple, rapid, accurate, and important method to monitor IAP in critically ill patients.

14.
Cell Physiol Biochem ; 35(3): 1151-66, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25766527

RESUMO

BACKGROUND/AIMS: Growth arrest-specific protein 6 (Gas6) is a cytokine that can be synthesized by a variety of cell types and secreted into the extracellular matrix. Previous studies have confirmed that Gas6 is involved in certain pathophysiological processes of the cardiovascular system through binding to its receptor, Axl. In the present study, we investigated the role of Gas6 in cellular senescence and explored the mechanisms underlying its activity. METHODS: We used vascular smooth muscle cells (VSMCs) to create two cellular senescence models, one for replicative senescence (RS) and one for induced senescence (IS), to test the hypothesis that Gas6 delays senescence. RESULTS: Gas6-treated cells appear relatively younger compared with non-Gas6-treated cells. In particular, Gas6-treated cells displayed decreased staining for SA-ß-Gal, fewer G1 phase cells, and decreased levels of p16(INK4a) and p21(Cip1) expression; conversely, Gas6-treated cells displayed more S phase cells and significantly increased proliferation indexes. Furthermore, in both the IS and RS models with Gas6 treatment, the levels of PI3K, p-Akt, and p-FoxO3a decreased following Axl inhibition by R428; similarly, the levels of p-Akt and p-FoxO3a also decreased following PI3K inhibition by LY294002. CONCLUSION: Gas6/Axl signaling is essential for delaying the cellular senescence process regulated by the PI3K/Akt/FoxO signaling pathway.


Assuntos
Senescência Celular/genética , Fatores de Transcrição Forkhead/biossíntese , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Músculo Liso Vascular/metabolismo , Proteínas Proto-Oncogênicas/biossíntese , Receptores Proteína Tirosina Quinases/biossíntese , Animais , Benzocicloeptenos/administração & dosagem , Senescência Celular/efeitos dos fármacos , Cromonas/administração & dosagem , Proteína Forkhead Box O3 , Fatores de Transcrição Forkhead/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Peptídeos e Proteínas de Sinalização Intercelular/administração & dosagem , Camundongos , Morfolinas/administração & dosagem , Músculo Liso Vascular/efeitos dos fármacos , Miócitos de Músculo Liso/efeitos dos fármacos , Miócitos de Músculo Liso/metabolismo , Fosfatidilinositol 3-Quinases/genética , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Receptores Proteína Tirosina Quinases/metabolismo , Transdução de Sinais/efeitos dos fármacos , Triazóis/administração & dosagem
15.
Int J Mol Med ; 35(3): 763-70, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25543888

RESUMO

Dilated cardiomyopathy (DCM), the most common form of primary myocardial disease, is an important cause of sudden cardiac death and heart failure and is the leading indication for heart transplantation in children and adults worldwide. Recent studies have revealed a strong genetic basis for idiopathic DCM, with many distinct genes causally implicated. Nevertheless, DCM is a genetically heterogeneous disorder and the genetic determinants underlying DCM in a substantial proportion of patients remain unclear. In this study, the whole coding exons and flanking introns of the GATA binding protein 5 (GATA5) gene, which codes for a zinc-finger transcription factor essential for cardiovascular development and structural remodeling, were sequenced in 130 unrelated patients with idiopathic DCM. The available relatives of the index patient carrying an identified mutation and 200 unrelated ethnically matched healthy individuals used as the controls were genotyped for GATA5. The functional characteristics of the mutant GATA5 were analyzed in contrast to its wild-type counterpart by using a dual-luciferase reporter assay system. As a result, a novel heterozygous GATA5 mutation, p.G240D, was identified in a family with DCM inherited in an autosomal dominant pattern, which co-segregated with DCM in the family with complete penetrance. The missense mutation was absent in 400 reference chromosomes and the altered amino acid was completely conserved evolutionarily across species. Functional analyses revealed that the GATA5 mutant was associated with significantly diminished transcriptional activity. This study firstly links GATA5 mutation to DCM, which provides novel insight into the molecular mechanisms of DCM, suggesting a potential molecular target for the prenatal prophylaxis and allele-specific treatment of DCM.


Assuntos
Cardiomiopatia Dilatada/genética , Fator de Transcrição GATA5/genética , Mutação , Adulto , Sequência de Aminoácidos , Substituição de Aminoácidos , Cardiomiopatia Dilatada/metabolismo , Cardiomiopatia Dilatada/fisiopatologia , Estudos de Casos e Controles , Análise Mutacional de DNA , Feminino , Fator de Transcrição GATA5/química , Fator de Transcrição GATA5/metabolismo , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Linhagem , Fenótipo , Alinhamento de Sequência , Transcrição Genética
16.
Eur Arch Otorhinolaryngol ; 271(6): 1667-72, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24487458

RESUMO

Postoperative sore throat (POST) is one of the main postoperative complaints. This study was to evaluate the efficacy of budesonide inhalation suspension (BIS) in reducing the incidence and severity of POST. One hundred and twenty patients scheduled for thyroid surgery with general anesthesia were enrolled and randomized into three groups. Group A received 200 mcg BIS 10 min prior to the tracheal intubation and received the same treatment 6 and 24 h after extubation. Group B received 200 mcg BIS 6 and 24 h after extubation. Control group received the same scheduled treatment as Group A, but the BIS was replaced with 2 ml normal saline. The patients were evaluated for sore throat and hoarseness 1, 24 and 48 h after extubation. The status of laryngopharynx was also recorded. There was no statistically significant difference in the incidence of sore throat among three groups. However, hoarseness occurred significantly less frequently in Group A (P < 0.05). One hour after extubation, Group A exhibited significantly less severe sore throat and hoarseness compared to the other two groups (P < 0.05), which disappeared 24 h later. The mucositis scores of laryngopharynx at 1, 24 and 48 h post-extubation were significantly lower in Group A (P < 0.05). BIS can reduce the incidence and severity of the POST prophylactically.


Assuntos
Anestesia Geral , Anti-Inflamatórios/uso terapêutico , Budesonida/uso terapêutico , Rouquidão/prevenção & controle , Intubação Intratraqueal , Faringite/prevenção & controle , Complicações Pós-Operatórias/prevenção & controle , Glândula Tireoide/cirurgia , Administração por Inalação , Adolescente , Adulto , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto Jovem
17.
Eur J Clin Pharmacol ; 69(10): 1855-60, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23748751

RESUMO

BACKGROUND: Statins are widely prescribed to reduce cholesterol levels in the prevention of atherosclerotic cardiovascular disease. However, the debate about the effect of statins on cancer risk remains unsettled. The aim of this study was to investigate the association of utilization of statins with the risk of gastric cancer by carrying out a meta-analysis. METHODS: A literature search was performed on PubMed and EMBASE up to March 2013 to identify the cohort or case-control studies or randomized controlled trials (RCTs) that examined the relationship between statins use and the risk of gastric cancer. The bibliographies of the retrieved articles were also reviewed to identify additional studies. A random-effects model was used to calculate the summary relative risks (RRs) with 95 % confidence intervals (CIs). RESULTS: Three post-hoc analyses of 26 RCTs involving 290 gastric cancers and eight observational studies totaling 7,321 gastric cancers were included. Statins use was shown to be significantly associated with a 27 % reduction in the risk of gastric cancer (RR = 0.73, 95 % CI = 0.58-0.93), with considerable heterogeneity among studies (I (2) = 88.9 %). Excluding one study in which all subjects are diabetic patients obtained an attenuated, but homogeneous result (RR = 0.85, 95 % CI = 0.80-0.91, I (2) = 0.0 %). These findings were consistent in the subgroup analysis. CONCLUSION: A meta-analysis of existing evidence, primarily from observational studies, indicates that use of statins reduces the risk of gastric cancer.


Assuntos
Uso de Medicamentos/tendências , Inibidores de Hidroximetilglutaril-CoA Redutases , Neoplasias Gástricas/prevenção & controle , Uso de Medicamentos/estatística & dados numéricos , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Estudos Observacionais como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Neoplasias Gástricas/epidemiologia
18.
Mol Biol Rep ; 40(1): 535-43, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23104471

RESUMO

Transforming growth factor-ß (TGF-ß) protein has been supposed to be a risk factor for liver cirrhosis; however, the associations between its genes (TGF-ß -509C>T and +869T>C) and liver cirrhosis remained unclear. This study was to quantitatively analyze the correlations by using a meta-analysis. Pubmed, Embase, Wanfang databases were retrieved up to November 1st, 2011. Odds ratio (OR) and 95 % confidence interval (95 %CI) were used to demonstrate the strength of association, and P < 0.05 of Z test indicated statistical significance. Combined analyses were performed by using fixed or random-effect model, depending on between-study heterogeneity. Seven studies were for TGF-ß -509C>T polymorphism, and eight studies were for +869T>C polymorphism. Combined results indicated that neither TGF-ß -509C>T nor +869T>C polymorphisms were associated with risk of liver cirrhosis [OR (95 % CI): 0.79 (0.60-1.04) for CT vs. TT of -509C>T and 0.87 (0.68-1.12) for CT vs. CC of +869T>C], with no between-study heterogeneity. In addition, subgroups analyses still inferred that two polymorphisms were not associated with risk of liver cirrhosis for HBV-infected patients, Asians and for Population-based studies. This meta-analysis indicated that neither TGF-ß -509C>T nor +869T>C polymorphisms were associated with risk of liver cirrhosis, regardless of HBV infection or not.


Assuntos
Cirrose Hepática/genética , Polimorfismo de Nucleotídeo Único , Fator de Crescimento Transformador beta/genética , Alelos , Estudos de Casos e Controles , Heterogeneidade Genética , Predisposição Genética para Doença , Genótipo , Humanos , Razão de Chances , Viés de Publicação
19.
Artigo em Inglês | MEDLINE | ID: mdl-24779227

RESUMO

In practice, the dielectric constant of a material varies the applied frequency the material composition, particle size, purity, temperature, physical state (solid or liquid), and moisture content. All of these parameters might change during processing, therefore, it is difficult to predict how well a material will absorb microwave energy in a given process. When the temperature is measured by a digital thermometer, it could not accurately reflect the true temperature of the bulk materials, especially for mixed materials. Thus, in this paper we measured the microwave absorption characteristics of different materials by calorimetry. The microwave power levels, irradiation times, and masses of the materials were varied. It was difficult to predict the microwave energy absorption characteristics of reagent-grade inorganic compounds based on their color, metallic cation, or water stoichiometry. CuO, MnO2, Fe3O4, and MnSO4 x H2O (Taishan) strongly absorbed microwave energy. Most of the remaining inorganic compounds were poor absorbers, with silica hardly absorbing any microwave energy. Carbon-based materials had significantly different microwave absorption characteristics. Activated carbon and coke were especially sensitive to microwaves, but different types of coal were poor absorbers. The jamesonite concentrate absorbed microwave energy strongly, while the zinc concentrate was a poor absorber.

20.
Shanghai Kou Qiang Yi Xue ; 22(6): 708-10, 2013 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-24469140

RESUMO

PURPOSE: To evaluate the efficacy and safety of tacrolimus mouth rinse on the treatment of erosive and ulcerative oral lichen planus (OLP). METHODS: A randomized single-blind open trial of tacrolimus mouth rinse with dexamethasone as control was designed. The VAS and REU scoring system was utilized to compare the signs and symptoms. The scores and therapeutic effects were analyzed with SPSS 17.0 software package. RESULTS: There was no significant difference in effective rate between the treatment group and control group (X(2)=0.295,0.413, P>0.01) at 4-week and 12-week after treatment. There was significant difference in REU scores between the 2 groups (P<0.01) 4 weeks after treatment. CONCLUSIONS: Tacrolimus mouth rinse effects quickly and is worthy of application in the treatment of erosive and ulcerative OLP.


Assuntos
Líquen Plano Bucal , Tacrolimo , Administração Tópica , Humanos , Antissépticos Bucais , Método Simples-Cego
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