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1.
Mil Med ; 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32239167

RESUMO

INTRODUCTION: Psychological stress is associated with sedentary behavior, which may impair exercise performance. The aim of our study was to examine the association between psychological stress and physical fitness in military personnel. METHOD: A military cohort of 4080 subjects in Taiwan was used for the analysis. The Brief Symptoms Rating Scale (BSRS-5) includes items of anxiety, depression, hostility, interpersonal sensitivity, and insomnia measured by a five-point Likert-type scale of 0-4. Psychological stress was defined as normal (n = 3657), slight (n = 314), and great (n = 109) by BSRS-5 score ≤5, 6-9, and ≥10, respectively. Aerobic fitness and anaerobic fitness were evaluated by the time of 3000-meter running and the numbers of 2-min sit-ups and 2-min push-ups, respectively. Multiple linear and logistic regression analyses were used to determine the relationship. RESULTS: As compared with normal stress, slight and great stress were positive dose-dependently correlated with 3000-meter running time (ß = 9.09 and 14.44; P = 0.0032 and 0.048, respectively) after adjusting for age, sex, service specialty, body mass index, systolic blood pressure, cigarette smoking, alcohol intake, hemoglobin levels, and exercise frequency. Similarly, those with slight stress were more likely to be the worst 10% performers in the 3000-meter run test relative to the normal individuals (odds ratio and 95% confidence intervals: 1.50, 1.00-2.24). By contrast, there was no relationship of psychological stress with the numbers of 2-min sit-ups and 2-min push-ups. CONCLUSIONS: Our findings suggest that the presence of higher psychological stress on military personnel may reduce their cardiorespiratory fitness but not affect the anaerobic fitness.

2.
Neurol Res ; 42(4): 308-318, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32151238

RESUMO

Objectives: miR-199a can regulate autophagy, its underlying mechanisms remain unknown. The purpose of this study was to investigate the mechanisms of miR-199a involved in regulating autophagy in a 1-methyl-4-phenylpyridine (MPP+)-induced in vitro model of PD.Methods: PC12 cells were incubated in MPP+, and the expression levels of miR-199a were bidirectionally regulated via either transfection of an miR-199a mimic or incubation in miR-199a inhibitors. The experimental manipulations were divided into four groups, including the control group, MPP+ group, MPP+ + miR-199a mimic group, and MPP+ + miR-199a inhibitor group. MTT, CCK-8, qRT-PCR, Western blotting and linear correlation analysis were performed to evaluate various experimental indicators.Results: At increasing MPP+ concentrations, the following results were found: the expression levels of miR-199a, phosphorylated AKT and mTOR proteins expression decreased; the expression levels of phosphatase and tensin homologue (PTEN), GSK3ß, Beclin1, and LC3II increased; PC12 autophagy increased; and cellular viability and survival rates decreased. Transfection of an miR-199a mimic increased miR-199a expression and induced all of the following: the expression levels of PTEN, GSK3ß, Beclin1, and LC3II decreased; the expression levels of phosphorylated AKT and mTOR proteins expression increased; PC12 autophagy decreased; and cellular viability and survival rates increased.Discussion: In this in vitro study, we found that increasing miR-199a expression in PC12 cells reduced protein levels of Beclin1 and LC3II, decreased autophagy, enhanced cellular viability, increased survival rate, and ameliorated MPP+-induced parkinsonian-like cellular pathologies by targeting pro-autophagic pathways and GSK3ß to activate PTEN/AKT/mTOR signaling.

3.
BMC Complement Med Ther ; 20(1): 88, 2020 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-32178661

RESUMO

BACKGROUND: Sedum sarmentosum is traditionally used to treat various inflammatory diseases in China. It has protective effects against acute liver injury, but the exact mechanism of such effects remains unclear. This study investigated the protective effects of S. sarmentosum extract on lipopolysaccharide (LPS)/D-galactosamine (D-GalN)-induced acute liver injury in mice and the mechanism of such effects. METHODS: Mice were randomly divided into control, treatment, model, and model treatment groups. Acute liver injury was induced in model mice via intraperitoneal injection of LPS and D-GalN with doses of 10 µg/kg of LPS and 500 mg/kg, respectively. The mRNA expression levels of miR-124, Hedgehog, Patched (Ptch), Smoothened (Smo), and glioma-associated oncogene homolog (Gli) in liver tissues were determined through RT-PCR, and the protein levels of Hedgehog, Ptch, Smo, Gli, P13k, Akt, HMGB1, TLR4, IkB-α, p-IkB-α, and NF-kB65 were evaluated via Western blot analysis. The serum levels of IL-6, TNF-α, CRP, IL-12, and ICAM-1 were determined via ELISA. TLR4 and NF-κBp65 activity and the levels of DNA-bound NF-KB65 and TLR4 in LPS/D-GalN-induced liver tissues were also determined. We recorded the time of death, plotted the survival curve, and calculated the liver index. We then observed the pathological changes in liver tissue and detected the levels of liver enzymes (alanine aminotransferase [ALT] and aspartate transaminase [AST]) in the serum and myeloperoxidase (MPO) and plasma inflammatory factors in the liver homogenate. Afterward, we evaluated the protective effects of S. sarmentosum extracts on acute liver injury in mice. RESULTS: Results showed that after S. sarmentosum extract was administered, the expression level of miR-124 increased in liver tissues. However, the protein expression levels of Hedgehog, Ptch, Smo, Gli, P13k, p-Akt, HMGB1, TLR4, p-IκB-α, and NF-κB65 and the mRNA expression levels of Hedgehog, Ptch, Smo, and Gli decreased. The MPO level in the liver, the IL-6, TNF-α, CRP, IL-12, and MMP-9 levels in the plasma, and the serum ALT and AST levels also decreased, thereby reducing LPS/D-GalN-induced liver injury and improving the survival rate of liver-damaged animals within 24 h. CONCLUSIONS: S. sarmentosum extract can alleviate LPS/D-GalN-induced acute liver injury in mice and improve the survival rate of mice. The mechanism may be related to the increase in miR-124 expression, decrease in Hedgehog and HMGB1 signaling pathway activities, and reduction in inflammatory responses in the liver. Hedgehog is a regulatory target for miR-124.

4.
Int J Behav Med ; 2020 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-32096097

RESUMO

BACKGROUND: Adverse childhood experiences (ACEs) have been linked to long-term health outcomes, while the impact of such experience has not been investigated among Zambian youth. This study examined the associations of ACEs with individual and clusters of health risk behavior among college students in Zambia. METHOD: A total of 624 college students participated in this cross-sectional study. A self-administered questionnaire was used to collect information on their ACEs and health risk behaviors. RESULTS: There were 58.3% (364) reporting some forms of ACEs, with 27.6% (172), 16.3% (102), and 14.4% (90) being exposed to 1, 2, and ≥ 3 ACEs, respectively. The prevalence of health risk behaviors ranged from 6.0 to 34.2%. Overall, ACEs were associated with increased risk of smoking, binge drinking, suicide attempt, risky sexual behaviors, and illicit drug use. Logistic regression suggested that participants with ≥ 3 ACEs (OR, 3.62; 95% CI, 2.14-6.13) were more likely to engage in the unhealthy cluster, characterized by the presence of any health risk behavior, than those without ACE. CONCLUSION: ACEs were associated with individual and clustering of health risk behaviors among Zambia college students. Our study suggests that early intervention is needed to prevent long-term adverse health consequences in this population.

5.
Am J Prev Med ; 58(2): 294-301, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31735481

RESUMO

INTRODUCTION: Evidence on the combined effect of fruit and vegetable intake and total fat intake on hypertension is scarce. This study aimed to explore the relationship among fruit and vegetable intake, fat intake, and hypertension risk among Chinese adults. METHODS: Individuals who participated in the China Health and Nutrition Survey (2004, 2006, 2009, and 2011) and were free of hypertension at baseline (n=4,368) were categorized into quartiles (Q1, lowest; Q4, highest) according to their dietary fruit and vegetable intake and fat intake. Generalized estimation equation models, adjusted for confounders, were used to explore the relationship of fat intake with hypertension and systolic and diastolic blood pressure among all adults and within quartiles of fruit and vegetable intake. Data analyses were performed in 2018. RESULTS: A total of 1,086 adults developed hypertension during follow-up. In the total population, the OR of the highest quartile of fat intake was 1.40 (95% CI=1.12, 1.75) compared with the lowest. Among individuals with low fruit and vegetable intake, the odds of hypertension for those in Q3 (OR=1.97, 95% CI=1.37, 2.83) and Q4 (OR=1.81, 95% CI=1.14, 2.90) of fat intake, compared with individuals in Q1, were even higher than for the overall sample. For each 50-gram increase in FI per day, the ORs of hypertension increased from fat intake Q1 to Q4 among all respondents and those with low fruit and vegetable intake, but not among those with high fruit and vegetable intake. Systolic blood pressure increased by 1.08 mm Hg (95% CI=0.03, 2.13) per 50-gram fat intake per day increment in the fruit and vegetable intake Q1 group, whereas the association was not significant in the fruit and vegetable intake Q2-Q4 groups. CONCLUSIONS: Fruit and vegetable intake modifies the relationship between fat intake and hypertension, whereby high fruit and vegetable intake may offset the detrimental effect of fat intake on hypertension. Increased fruit and vegetable intake and controlled fat intake are recommended to prevent hypertension in Chinese adults.

6.
J Affect Disord ; 261: 172-180, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31634676

RESUMO

BACKGROUND: Fruit and vegetable intake (FVI) has been inversely associated with the risk of depression. However, there is a gap in evidence from low- and middle-income countries (LMICs) and among adolescents. Further, little is known about FVI in relation to the risk of anxiety. Therefore, we examined these associations among adolescents in 25 LMICs. METHODS: Data from the Global School-based Student Health Survey were analyzed in 65267 adolescents aged 12-15 years (mostly nationally representative). Depressive and anxiety symptoms during the past 12 months were self-reported. Frequencies of FVI during the past 30 days were collected. Multivariable logistic regression and meta-analyses of country-wise estimates were undertaken. RESULTS: The prevalence of depressive and anxiety symptoms were 30.3% and 9.8%, respectively. A meta-analysis indicated that FVI of <5 times/d (vs. higher) was associated with an increased risk of depressive symptoms (OR = 1.10; 95% CI = 1.02-1.18). The pooled estimate for anxiety symptoms was insignificant. When examined separately, fruit intake was significantly associated with both lower risks of depressive and anxiety symptoms; vegetable intake was significantly associated with a lower risk of depressive symptoms, but not with anxiety. LIMITATIONS: Only adolescents attending school were included; the cross-sectional design cannot reveal causality; outcomes were not measured against the gold-standard diagnostic criteria. CONCLUSIONS: Our study provides multi-national evidence of the protective effect of FVI against depressive and anxiety symptoms among adolescents in LMICs, enabling key stakeholders to address mental health issues among adolescents globally.

7.
Phys Rev E ; 99(3-1): 032416, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30999422

RESUMO

We study pattern formation of skin cancers by means of numerical simulation of a binary system consisting of cancer and healthy cells. We extend the conventional model H for macrophase separations by considering a logistic growth of cancer cells and also a mechanical friction between dermis and epidermis. Importantly, our model exhibits a microphase separation due to the proliferation of cancer cells. By numerically solving the time evolution equations of the cancer composition and its velocity, we show that the phase separation kinetics strongly depends on the cell proliferation rate as well as on the strength of hydrodynamic interactions. A steady-state diagram of cancer patterns is established in terms of these two dynamical parameters and some of the patterns correspond to clinically observed cancer patterns. Furthermore, we examine in detail the time evolution of the average composition of cancer cells and the characteristic length of the microstructures. Our results demonstrate that different sequence of cancer patterns can be obtained by changing the proliferation rate and/or hydrodynamic interactions.


Assuntos
Modelos Biológicos , Neoplasias Cutâneas/fisiopatologia , Proliferação de Células , Simulação por Computador , Derme/patologia , Derme/fisiopatologia , Progressão da Doença , Epiderme/patologia , Epiderme/fisiopatologia , Humanos , Hidrodinâmica , Neoplasias Cutâneas/patologia , Fatores de Tempo
8.
J Am Coll Health ; : 1-6, 2019 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-30849021

RESUMO

OBJECTIVE: This study aimed to assess the impact of a health education intervention on health behaviors, self-efficacy, and well-being among college students. PARTICIPANTS: Between March and October 2016, a total of 532 undergraduates participated. METHODS: A theory-based intervention was conducted at Wuhan University, China. Participants were assigned to a control or intervention group (IG). The IG attended a 7-week health education class on knowledge, attitude, and practice of health behaviors. RESULTS: Participants in the IG, compared with those in the control group (CG), reported significantly increased prevalence of high physical activity and regular breakfast, as well as lower screen time, sugar beverage intake, and Internet addiction tendency. Furthermore, intervention students improved in health behavior scores (p = 0.040), compared with the CG, while the changes in subjective well-being and self-efficacy remained similar between the two groups. CONCLUSIONS: Health education may promote health behaviors among Chinese college students.

9.
BMC Pulm Med ; 19(1): 35, 2019 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-30744607

RESUMO

BACKGROUND: Reactive oxygen species (ROS) levels largely determine pulmonary fibrosis. Antioxidants have been found to ameliorate lung fibrosis after long-term paraquat (PQ) exposure. The effects of antioxidants, however, on the signalling pathways involved in PQ-induced lung fibrosis have not yet been investigated sufficiently. Here, we examined the impacts of ligustrazin on lung fibrosis, in particular ROS-related autophagy and pro-fibrotic signalling pathways, using a murine model of PQ-induced lung fibrosis. METHODS: We explored the effects of microRNA-193 (miR-193a) on Hedgehog (Hh) and PI3K/Akt/mTOR signalling and oxidative stress in lung tissues. Levels of miR-193a, protein kinase B (Akt), phosphoinositide 3-Kinase (PI3K), ceclin1, mammalian target of rapamycin (mTOR), sonic hedgehog (SHH), myosin-like Bcl2 interacting protein (LC3), smoothened (Smo), and glioma-associated oncogene-1 (Gli-1) mRNAs were determined with quantitative real-time PCR. Protein levels of PI3K, p-mTOR, p-Akt, SHH, beclin1, gGli-1, LC3, smo, transforming growth factor-ß1 (TGF-ß1), mothers against DPP homologue-2 (Smad2), connective tissue growth factor (CTGF), collagen I, collagen III, α-smooth muscle actin (α-SMA) nuclear factor erythroid 2p45-related factor-2 (Nrf2), and p-Smad2 were detected by western blotting. In addition, α-SMA, malondialdehyde, ROS, superoxide dismutase (SOD), oxidised and reduced glutathione, hydroxyproline, and overall collagen levels were identified in lung tissues using immunohistochemistry. RESULTS: Long-term PQ exposure blocked miR-193a expression, reduced PI3K/Akt/mTOR signalling, increased oxidative stress, inhibited autophagy, increased Hh signalling, and facilitated the formation of pulmonary fibrosis. Ligustrazin blocked PI3K/Akt/mTOR and Hh signalling as well as reduced oxidative stress via increasing miR-193a expression and autophagy, all of which reduced pulmonary fibrosis. These effects of ligustrazin were accompanied by reduced TGF-ß1, CTGF, and Collagen I and III expression. CONCLUSIONS: Ligustrazin blocked PQ-induced PI3K/Akt/mTOR and Hh signalling by increasing miR-193a expression, thereby attenuating PQ-induced lung fibrosis.


Assuntos
Autofagia/efeitos dos fármacos , MicroRNAs/metabolismo , Fibrose Pulmonar/metabolismo , Pirazinas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Células A549 , Animais , Colágeno Tipo I/metabolismo , Feminino , Humanos , Camundongos , MicroRNAs/genética , Estresse Oxidativo/efeitos dos fármacos , Paraquat/toxicidade , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/patologia , Espécies Reativas de Oxigênio/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Fator de Crescimento Transformador beta1/metabolismo
10.
Curr Alzheimer Res ; 16(14): 1269-1275, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31902363

RESUMO

BACKGROUND: The Angiotensin-Converting Enzyme (ACE) gene has drawn attention for its possible role in regulating the degradation of ß-amyloid (Aß), yet its role in affecting the cognitive and psychiatric symptoms of Alzheimer`s Disease (AD) patients has yet to be elucidated. OBJECTIVE: This study aimed to investigate whether the ACE gene acts as a risk factor of Behavioral and Psychological Symptoms of Dementia (BPSD) in the AD population. METHODS: The genotyping of ACE and Apolipoprotein E gene with allele ε4(APOEε4) was determined among 360s clinically diagnosed AD patients. Symptoms and severity of BPSD were evaluated annually via Neuropsychiatric Inventory (NPI). RESULTS: At the base measurement of the first year of patient recruitment, there were no significant contributory risk factors to NPI score. In the two-year follow-up, ACE insertion polymorphism showed a significant risk (adjusted odds ratio=1.65, 95% CI=1.1- 2.5, p=0.019) of progression of NPI total score. CONCLUSION: ACE gene is involved in aggravating BPSD among AD patients.

11.
Eur J Nutr ; 57(7): 2639-2647, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29663080

RESUMO

PURPOSE: Fruit and vegetable intake has been inversely associated with the risk of hypertension; however, there is inconsistent evidence on the long-term association. Given this gap in the literature, it is necessary to identify evidence from large prospective studies, especially in China, where insufficient evidence exists. Thus, we examined the association of fruit and vegetable intake with incident hypertension in Chinese adults. METHODS: We conducted analyses among 5659 Chinese adults aged 18-64 years, free of cardiovascular disease, cancer, and hypertension in the 2006 wave of the China Health and Nutrition Survey. Fruit and vegetable intake was assessed using consecutive 24-h recalls. Incident hypertension was identified from the 2011 wave of the survey. RESULTS: A total of 866 participants developed incident hypertension. The relative risks (RRs) and 95% confidence intervals (CIs) of hypertension were 0.74 (0.55-0.99), 0.65 (0.48-0.88), 0.68 (0.50-0.92), and 0.73 (0.53-0.99) comparing each quintile group of fruit and vegetable intake with the lowest quintile group. These associations attenuated for the change of intake but remained significant for the fourth quintile, of which the RR (95% CI) was 0.65 (0.47-0.89). The magnitude of association was stronger among those who were younger, female, overweight and had prehypertension. When examined separately, fruit intake was more strongly and significantly associated with lowering BP than vegetable intake. Adding body mass index to the models attenuated all associations. CONCLUSIONS: Greater long-term intake and increased intake of fruit and vegetables may reduce the risk of developing hypertension in Chinese adults.


Assuntos
Frutas , Hipertensão/epidemiologia , Verduras , Adolescente , Adulto , Idoso , China/epidemiologia , Dieta , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Inquéritos Nutricionais , Razão de Chances , Estudos Prospectivos , Fatores de Risco , Inquéritos e Questionários , Adulto Jovem
12.
BMC Complement Altern Med ; 18(1): 51, 2018 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-29402262

RESUMO

BACKGROUND: In China, Panax notoginseng has been used to treat oxidative stress-related diseases for a long time. Panax notoginseng saponins is an extract from Panax notoginseng Ledeb. Its therapeutic potential is related to antioxidant activity, but related mechanisms are still unclear. The study aims to assess the protection effects of Panax notoginseng saponins in the taurocholate-induced rat model of acute pancreatitis (AP) and explore underlying mechanisms. METHODS: A rat model of severe acute pancreatitis (SAP) was established in rats induced with taurocholate. Panax notoginseng saponins was firstly administered in the treatment group via intravenous injection. After 2 h, taurocholate administration was performed. After 24 h, the expression levels of miR-181b, Beclin1, LC3-II, Akt and mTOR from pancreas tissues were measured by Western Blotting and RT-PCR. Then the expression levels of Caspase-3 and Blc-2 were determined by immunohistochemistry. Apoptosis was assessed by the TUNEL assay. Amylase and lipase in serum were determined by ELISA and pancreatic water contents in pancreatic tissue were measured. After eosin and hematoxylin staining, the histologic analysis was performed. RESULTS: After SAP induction by taurocholate and the treatment with Panax notoginseng saponins for 24 h, we detected the up-regulated miR-181b, the reduced Bcl-2 expression, the increased activity of mTOR/Akt, the blocked Beclin1 and LC3-II expressions, and the enhanced Caspase-3 expression. Serum lipase and amylase levels were significantly decreased in the treatment group of Panax notoginseng saponins compared to the control group. Histological analysis results verified the attenuation effects of Panax notoginseng saponins on taurocholate-induced pancreas injury, apoptosis, and autophagy. CONCLUSION: By up-regulating the miR-181b expression level, Panax notoginseng saponins significantly reduced taurocholate-induced pancreas injury and autophagy and increased apoptosis. The significant protection effects of Panax notoginseng saponins suggested its potential in treating taurocholate induced-acute pancreatitis.


Assuntos
Caspase 3/metabolismo , MicroRNAs/metabolismo , Panax notoginseng , Pancreatite/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Saponinas/farmacologia , Serina-Treonina Quinases TOR/metabolismo , Animais , Linhagem Celular , Modelos Animais de Doenças , Masculino , MicroRNAs/genética , Pâncreas/efeitos dos fármacos , Pâncreas/patologia , Pancreatite/patologia , Extratos Vegetais , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Ácido Taurocólico/efeitos adversos
13.
PLoS One ; 12(11): e0188533, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29161331

RESUMO

BACKGROUND: Unbalanced dietary intake and insufficient physical activity (PA) have been recognized as risk factors for metabolic syndrome (MetS). We aimed to examine the independent and combined effects of fruit and vegetables (FV) intake and PA on MetS. METHODS AND FINDINGS: A cross-sectional survey was conducted among residents of China in 2009, with fasting blood samples collected. Participants were divided into sufficient/insufficient FV intake and adequate/ inadequate PA groups according to self-reported questionnaires. MetS was defined using the NCEP-ATPIII criteria. The difference of individual MetS components was compared across different PA or FV groups. Multivariable logistic regression was used to assess association between FV/PA and the risk of MetS. A total of 7424 adults were included in the current study. MetS was prevalent in 28.7% of participants, with 24.7% and 32.9% in male and female, respectively. Compared with those with inadequate PA and insufficient FV intake, participants with the combination of adequate PA and sufficient FV intake had the lowest risk of MetS (OR = 0.69,95%CI: 0.59-0.82), following by the group with adequate PA time but insufficient FV intake (OR = 0.74, 95%CI:0.65-0.83). CONCLUSION: Findings of the current study show that the combination of sufficient FV intake and adequate PA was significantly associated with reduced MetS risk among adult residents of China.


Assuntos
Exercício Físico/fisiologia , Frutas , Síndrome Metabólica/dietoterapia , Verduras , Adulto , Idoso , China , Ingestão de Alimentos , Feminino , Humanos , Masculino , Síndrome Metabólica/patologia , Síndrome Metabólica/prevenção & controle , Pessoa de Meia-Idade , Fatores de Risco
14.
Exp Ther Med ; 14(2): 917-930, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28810543

RESUMO

Airway remodeling in asthma contributes to airway hyperreactivity, loss of lung function and persistent symptoms. Current therapies do not adequately treat the structural airway changes associated with asthma. Statin drugs have improved respiratory health and their therapeutic potential in asthma has been tested in clinical trials. However, the mechanism of action of statins in this context has remained elusive. The present study hypothesized that atorvastatin treatment of ovalbumin-exposed mice attenuates early features of airway remodeling via a mevalonate-dependent mechanism. BALB/c mice were sensitized with ovalbumin and atorvastatin was delivered via oral gavage prior to each ovalbumin exposure. Reverse transcription-semi-quantitative polymerase chain reaction (RT-semi-qPCR), ELISA and western blot analysis were used to assess the expression of a number of relevant genes, including tissue transglutaminase (tTG), triggering receptor expressed on myeloid cells (TREM)-1, nuclear factor erythroid 2-related factor (Nrf) 2, hypoxia-inducible factor (HIF)-1α, transforming growth factor (TGF)-ß1, matrix metalloproteinase (MMP)-9 and tissue inhibitors of metalloproteinases (TIMP)-1 in lung tissue. α-Smooth muscle actin (α-SMA) activity was measured by immunohistochemistry. Airway hyperresponsiveness, lung collagen deposition, airway wall area, airway smooth muscle thickness and lung pathology were also assessed. Atorvastatin treatment led to downregulation of tTG and TREM-1 expression in lung tissue after ovalbumin sensitization, blocked the activity of MMP-9, vascular endothelial growth factor, nuclear factor-κB p65, α-SMA, HIF-α and TGF-ß1 and up-regulated Nrf2 expression. Furthermore, the number of lymphocytes and eosinophils in the atorvastatin group was significantly lower than that in the control group. In addition, airway hyperresponsiveness, lung collagen deposition, airway wall area, airway smooth muscle thickness and pathological changes in the lung were significantly decreased in the atorvastatin group, and tumor necrosis factor-α, interleukin (IL)-8, IL-13 and IL-17 in serum were significantly decreased. Histological results demonstrated the attenuating effect of atorvastatin on ovalbumin-induced airway remodeling in asthma. In conclusion, the present study indicated that atorvastatin significantly alleviated ovalbumin-induced airway remodeling in asthma by downregulating tTG and TREM-1 expression. The marked protective effects of atorvastatin suggest its therapeutic potential in ovalbumin-induced airway remodeling in asthma treatment.

15.
Int J Mol Med ; 38(5): 1419-1432, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27666960

RESUMO

Xuebijing injection (XBJ) has long been used to treat infectious diseases in China. The therapeutic effect of XBJ is probably associated with anti-inflammatory effects. However, the precise mechanisms responsible for the effects of XBJ remain unknown. The present study was conducted in order to evaluate the protective effects of XBJ in a rat model of D-galactosamine (D-Gal)- and lipopolysaccharide (LPS)­induced acute liver injury. In the present study, the rats were injected with D-Gal and LPS intraperitoneally to induce acute liver injury. Two hours prior to D-Gal and LPS administration, the treatment group was administered XBJ by intravenous infusion. The effects of XBJ on D-Gal- and LPS-induced expression of tumor necrosis factor (TNF)­alpha­induced protein 8-like 2 (TIPE2), nuclear factor-κB (NF-κB), matrix metalloproteinase-9 (MMP-9) and heme oxygenase-1 (HO-1) as well as mitogen-activated protein kinase (MAPK) signaling was examined using reverse transcription-quantitative polymerase chain reaction (RT-qPCR), western blot analysis, immunofluorescence, as well as by analysing the serum levels of pro-inflammatory cytokines and the transaminases, alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Myeloperoxidase (MPO), malondialdehyde (MDA) and superoxide dismutase (SOD) levels in the rat liver tissues were also measured. For histological analysis, hematoxylin and eosin (H&E)-stained liver samples were evaluated. The results showed that XBJ upregulated TIPE2 and HO-1 expression, reduced the expression of NF-κB65 and MMP-9, inhibited the LPS-induced gene expression of c-jun N-terminal kinase (JNK) and p38 MAPK, decreased the generation of pro-inflammatory cytokines [interleukin (IL)-6, IL-13 and TNF-α], inhibited ALT and AST activity, and ameliorated D-Gal- and LPS-induced liver injury. The histological results also demonstrated that XBJ attenuated D-Gal- and LPS-induced liver inflammation. It was found that XBJ may prevent LPS-induced pro-inflammatory gene expression through inhibiting the NF-κB and MAPK signaling pathways by upregulating TIPE2 expression, thereby attenuating LPS-induced liver injury in rats. The marked protective effects of XBJ suggest that it has the potential to be used in the treatment of LPS-induced liver injury.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Medicamentos de Ervas Chinesas/farmacologia , Heme Oxigenase-1/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Western Blotting , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/genética , Citocinas/sangue , Medicamentos de Ervas Chinesas/administração & dosagem , Galactosamina/administração & dosagem , Galactosamina/toxicidade , Regulação da Expressão Gênica/efeitos dos fármacos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Lipopolissacarídeos/administração & dosagem , Lipopolissacarídeos/toxicidade , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Masculino , Malondialdeído/metabolismo , Peroxidase/metabolismo , Fitoterapia , Substâncias Protetoras/administração & dosagem , Substâncias Protetoras/farmacologia , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Superóxido Dismutase/metabolismo , Análise de Sobrevida , Proteínas Quinases p38 Ativadas por Mitógeno/genética
16.
Gait Posture ; 45: 103-9, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26979890

RESUMO

People with type II diabetes mellitus (DM) are at a high risk of falling especially during more challenging locomotor tasks such as obstacle-crossing. The current study aimed to identify the risk factors for tripping in these patients during trailing-limb obstacle-crossing. Fourteen patients with type II DM with or without mild peripheral neuropathy (PN) and 14 healthy controls walked and crossed obstacles of three different heights while their motion data were measured using a motion capture system and two forceplates. The DM group was found to cross obstacles with significantly reduced trailing toe clearance (p<0.05), increasing the probability of the foot hitting the obstacle, and thus the risk of tripping. This altered end-point control was associated with significantly reduced knee flexion and hip adduction of the trailing swing limb (p<0.05), as well as significantly increased ankle plantarflexor moments in the leading stance limb (p<0.05). Therefore, reduced knee flexion and hip adduction of the swing limb are identified as risk factors for tripping during obstacle-crossing. Increased mechanical demands on the ankle plantarflexors suggest that weakness of these muscles may further reduce the already compromised performance of obstacle-crossing in these patients. The current results showed that obstacle-crossing can be used to detect gait deviations and to identify the associated risk of tripping in patients with type II DM without or at an early stage of PN.


Assuntos
Acidentes por Quedas/prevenção & controle , Articulação do Tornozelo/fisiopatologia , Diabetes Mellitus Tipo 2/fisiopatologia , Terapia por Exercício/métodos , Marcha/fisiologia , Articulação do Joelho/fisiopatologia , Caminhada/fisiologia , Fenômenos Biomecânicos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/reabilitação , Feminino , Pé/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco
17.
BMC Complement Altern Med ; 16: 11, 2016 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-26758514

RESUMO

BACKGROUND: Puerarin, extracted from Radix puerariae, was reported to ameliorate airway inflammation, lung injury and lung fibrosis induced by paraquat (PQ) in mice. However, effects of Radix puerariae extracts (RPEs) on lung fibrosis or signalling pathways in PQ-induced lung injury have not been well studied. Therefore, the goals of our study were to investigate whether Radix puerariae extracts are antifibrotic in a paraquat (PQ) induced lung fibrosis model in mice and to propose possible mechanisms of action of the RPE effects. METHODS: We used a long-term exposure model of PQ-induced lung fibrosis in mice to evaluate effects of antioxidant-containing RPE. We examined effects of miR-21 on follistatin-like 1 (Fstl 1) pathways and oxidative stress in the lung. Gene expression levels of miR-21, Fstl 1, transforming growth factor-ß1 (TGF-ß1), connective tissue growth factor (CTGF), collagen-1 and collagen III were measured by real-time PCR. Protein expression levels of Fstl 1(FSTL1), heme oxygenase-1 (HO-1), nuclear factor erythroid 2p45-related factor-2 (Nrf2), Smad2/3, p38MAPK, nuclear factor-κB 65 (NF-κB65), and matrix metalloproteinase-9 were detected by western blotting. FSTL1 andalpha-smooth muscle actin (α-SMA) in lung tissue were detected by immunohistochemistry. Malondialdehyde, superoxide dismutase (SOD), reduced (GSH) and oxidised (GSSH) glutathione and reactive oxygen species levels, hydroxyproline and total lung collagen were also determined. RESULTS: Long-term challenge with PQ enhanced miRNA-21 (miR-21), Fstl 1 pathways, oxidative stress and development of fibrotic features in the lungs. RPE reduced features of lung fibrosis by blocking Fstl 1 pathways and oxidative stress through decreased miR-21 expression. This was accompanied by suppression of CTGF, TGF-ß1, vascular endothelial growth factor, collagen I, and collagen III. In addition, PQ-induced activation of NF-κB, Nrf2 and α-SMA were enhanced by puerarin. We also found that puerarin increased HO-1, SOD and GSH levels. CONCLUSIONS: These findings demonstrated that RPEs blocked PQ-induced Fstl 1 pathways and oxidative stress by inhibiting miR-21 expression, leading to attenuation of PQ-induced lung fibrosis.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Proteínas Relacionadas à Folistatina/metabolismo , Herbicidas/toxicidade , MicroRNAs/metabolismo , Paraquat/toxicidade , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/tratamento farmacológico , Animais , Antioxidantes/metabolismo , Antioxidantes/uso terapêutico , Colágeno/metabolismo , Modelos Animais de Doenças , Regulação para Baixo , Técnicas de Silenciamento de Genes , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/genética , Fator 2 Relacionado a NF-E2/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos
18.
Int J Mol Med ; 36(2): 386-98, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26063084

RESUMO

In recent years, several studies have shown that Rhodiola rosea can enhance cellular immunity and humoral immune function in mice, and thus, it has become a research hotspot. However, its underlying mechanism of action has remained elusive. The present study investigated whether Rhodiola rosea was able to downregulate the expression of tumor necrosis factor-α-inducible protein 8-like 2 (TIPE2), thereby inhibiting the expression of apoptotic genes, attenuating T-lymphocyte apoptosis and improving immunity in septic mice. A mouse model of caecal ligation and puncture (CLP)-induced sepsis was established, and animals in the treatment group were pre-treated with an intraperitoneal injection of Rhodiola rosea extract, while animals in the control group and sham-operated group were injected with an equivalent amount of normal saline. TIPE2, B-cell lymphoma 2 (Bcl-2), Fas and Fas ligand (FasL) mRNA and protein levels in thymic T cells were determined using reverse transcription quantitative polymerase chain reaction and western blot analysis, respectively. Furthermore, the thymus T-lymphocyte apoptosis rate, thymus T-lymphocyte count and thymus T-lymphocyte sub-sets were assessed using flow cytometry. Levels of T-helper cell type 1 (Th1) cytokines [Interleukin (IL)-2, IL-12 and interferon (IFN)-γ] and Th2 cytokines (IL-4 and IL-10) were determined using ELISA. The results showed that, compared to that in the CLP group, the expression of TIPE2, Fas and FasL in the treatment group was significantly decreased, while the expression of Bcl-2 was increased (P<0.05). The thymus lymphocyte count in the CLP group was significantly higher compared with that in the treatment group (P<0.05). Furthermore, the apoptotic rate of thymus T-lymphocytes in the treatment group was significantly lower than that in the CLP group (P<0.05). In addition, treatment with Rhodiola rosea rescued decreased in the counts of the CD3(+) T and CD4(+) T sub-sets of thymus T lymphocytes in the CLP group (P<0.05), while not affecting the increased levels of Th2 cytokines (IL-4 and IL-10) in the CLP group compared with those in the control groups. In addition, the Th1 cytokines (IL-12, IL-2 and IFN-γ) were significantly increased (P<0.05) in the CLP group, and treatment with Rhodiola rosea led to further increases. The thymus index of septic mice treated with Rhodiola rosea as well as their survival rate were improved as compared with those in the CLP group. These findings suggested that Rhodiola rosea has protective effects against sepsis by decreasing apoptosis, increasing Th1 cytokines and enhancing the host's immunity via the regulation of TIPE2 expression.


Assuntos
Fatores Imunológicos/uso terapêutico , Peptídeos e Proteínas de Sinalização Intracelular/genética , Extratos Vegetais/uso terapêutico , Rhodiola/química , Sepse/tratamento farmacológico , Linfócitos T/efeitos dos fármacos , Timo/efeitos dos fármacos , Animais , Antígenos CD/análise , Antígenos CD/imunologia , Apoptose/efeitos dos fármacos , Citocinas/análise , Citocinas/imunologia , Regulação para Baixo/efeitos dos fármacos , Feminino , Deleção de Genes , Fatores Imunológicos/química , Fatores Imunológicos/farmacologia , Peptídeos e Proteínas de Sinalização Intracelular/imunologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Ratos , Sepse/genética , Sepse/imunologia , Sepse/patologia , Linfócitos T/imunologia , Linfócitos T/metabolismo , Linfócitos T/patologia , Timo/imunologia , Timo/metabolismo , Timo/patologia
19.
Mol Med Rep ; 11(5): 3308-16, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25571852

RESUMO

A typical indicator of sepsis is the development of progressive subcutaneous and body­cavity edema, which is caused by the breakdown of endothelial barrier function, leading to a marked increase in vascular permeability. Microvascular leakage predisposes to microvascular thrombosis, breakdown of microcirculatory flow and organ failure, which are common events preceding mortality in patients with severe sepsis. Melilotus suaveolens (M. suaveolens) is a Traditional Tibetan Medicine. Previous pharmacological studies have demonstrated that an ethanolic extract of M. suaveolens has powerful anti­inflammatory activity and leads to an improvement in capillary permeability. However, the mechanisms underlying its pharmacological activity remain elusive. The present study aimed to assess the impact of M. suaveolens extract tablets on pulmonary vascular permeability, and their effect on regulating lung inflammation and the expression of vascular endothelial growth factor (VEGF) in the lung tissue of rats with sepsis. A cecal ligation and puncture (CLP) sepsis model was established for both the control and treatment groups. ~2 h prior to surgery, 25 mg/kg of M. suaveolens extract tablet was administered to the treatment group. Polymerase chain reaction and western blot analyses were used to assess the expression of nuclear factor (NF)­κB and VEGF in the lung tissue, and ELISA was applied to detect changes in serum tumor necrosis factor­α as well as interleukins (IL) ­1, ­4, ­6, and ­10. The lung permeability, wet/dry weight ratio and lung pathology were determined. The results demonstrated that in the lung tissue of CLP­rats with sepsis, M. suaveolens extract inhibited the expression of NF­κB, reduced the inflammatory response and blocked the expression of VEGF, and thus significantly decreased lung microvascular permeability. The effects of M. Suaveolens extract may be of potential use in the treatment of CLP­mediated lung microvascular permeability.


Assuntos
Permeabilidade Capilar/efeitos dos fármacos , Melilotus/química , Microcirculação/efeitos dos fármacos , Extratos Vegetais/farmacologia , Sepse/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Lesão Pulmonar Aguda/etiologia , Lesão Pulmonar Aguda/metabolismo , Lesão Pulmonar Aguda/patologia , Animais , Citocinas/metabolismo , Modelos Animais de Doenças , Regulação da Expressão Gênica/efeitos dos fármacos , Mediadores da Inflamação/metabolismo , Masculino , Microcirculação/genética , NF-kappa B/metabolismo , Ratos , Sepse/complicações , Sepse/genética , Fator A de Crescimento do Endotélio Vascular/genética
20.
Mol Med Rep ; 11(3): 1675-84, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25405912

RESUMO

As a Traditional Chinese Medicine, Melilotus extracts have been reported to function as an anti­inflammatory agent, antioxidant and inhibitor of capillary permeability. The present study aimed to identify the mechanisms by which Melilotus interferes with inflammation­associated and oxidative stress pathways during sepsis. An animal model of cecal ligation­perforation (CLP)­induced sepsis was established. Two hours prior to surgery, animals in the treatment group were administered 25 mg/kg Melilotus extract tablets and subsequently every 8 h. At 24 h post­administration, pathological modifications in lung tissue and expression levels of tumor necrosis factor­α­induced protein­8­like 2 (TIPE2) expression, nuclear factor (NF)­κB, toll­like receptor 4 (TLR4), heme oxygenase­1 (HO­1), inhibitor of κB kinase (IκB), pro­inflammatory mediators (interleukin­6 and tumor necrosis factor­α), myeloperoxidase (MPO), malondialdehyde (MDA) and superoxide dismutase (SOD), were examined. The results showed that Melilotus extract had a marked effect on the pathological manifestation of lung tissue and lung inflammatory response, the upregulation of TIPE2, HO­1 and IκB expression, and the inhibition of TLR4 and NF­κB activities. In addition, following treatment with Melilotus extract, the model animals demonstrated decreased levels of MPO and MDA as well as increased levels of SOD. In conclusion, these results indicated that Melilotus extract may be a potential therapeutic agent for the treatment of CLP­induced lung injury, the mechanism of which proceeded via inflammation­ and oxidation­associated pathways by increasing TIPE2 expression.


Assuntos
Peptídeos e Proteínas de Sinalização Intracelular/genética , Lesão Pulmonar/etiologia , Extratos Vegetais/farmacologia , Sepse/complicações , Sepse/genética , Animais , Citocinas/metabolismo , Modelos Animais de Doenças , Regulação da Expressão Gênica , Heme Oxigenase-1/metabolismo , Mediadores da Inflamação/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/deficiência , Lesão Pulmonar/tratamento farmacológico , Lesão Pulmonar/patologia , Melilotus , Camundongos , Camundongos Knockout , NF-kappa B/genética , NF-kappa B/metabolismo , Peroxidase/metabolismo , Extratos Vegetais/administração & dosagem , Sepse/metabolismo , Superóxido Dismutase/metabolismo , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
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