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1.
Artigo em Inglês | MEDLINE | ID: mdl-35001883

RESUMO

OBJECTIVES: To establish and evaluate a machine learning radiomics model based on grayscale and Sonazoid contrast enhanced ultrasound images for the preoperative prediction of microvascular invasion (MVI) in hepatocellular carcinoma (HCC) patients. METHODS: 100 cases of histopathological confirmed HCC lesions were prospectively included. Regions of interest were segmented on both grayscale and Kupffer phase of Sonazoid contrast enhanced (CEUS) images. Radiomic features were extracted from tumor region and region containing 5 mm of peritumoral liver tissues. Maximum relevance minimum redundancy (MRMR) and Least Absolute Shrinkage and Selection Operator (LASSO) were used for feature selection and Support Vector Machine (SVM) classifier was trained for radiomic signature calculation. Radiomic signatures were incorporated with clinical variables using univariate-multivariate logistic regression for the final prediction of MVI. Receiver operating characteristic curves, calibration curves and decision curve analysis were used to evaluate model's predictive performance of MVI. RESULTS: Age were the only clinical variable significantly associated with MVI. Radiomic signature derived from Kupffer phase images of peritumoral liver tissues (kupfferPT) displayed a significantly better performance with an area under the receiver operating characteristic curve (AUROC) of 0.800 (95% confidence interval: 0.667, 0.834), the final prediction model using Age and kupfferPT achieved an AUROC of 0.804 (95% CI: 0.723, 0.878), accuracy of 75.0%, sensitivity of 87.5% and specificity of 69.1%. CONCLUSIONS: Radiomic model based on Kupffer phase ultrasound images of tissue adjacent to HCC lesions showed an observable better predictive value compared to grayscale images and has potential value to facilitate preoperative identification of HCC patients at higher risk of MVI.

2.
Artigo em Inglês | MEDLINE | ID: mdl-34769613

RESUMO

Despite the significance of early detection of breast cancer through screening, the screening uptake in China remains relatively low. Protection motivation theory (PMT) suggested by Rogers is one of the theories concerning threat appeal. This study aimed to apply the protection motivation theory (PMT) in predicting breast cancer screening intention. In this cross-sectional study, a sample of Chinese urban women was recruited using the convenient sampling method from five communities in Wuhan. Data were collected using a self-report questionnaire that included demographic variables, knowledge about breast cancer, six PMT subconstructs, and screening intention. We used the structural equation modeling (SEM) to identify the predictor factors associated with screening intention. Of the total sample (n = 412), 86.65% had intention to participate in screening. Our data fit the hypothesized SEM model well (Goodness of fit index (GFI) = 0.91, adjusted GFI (AGFI) = 0.89, comparative fit index (CFI) = 0.91, root mean square error of approximation (RMSEA) = 0.05, standardized root mean residual (SRMR) = 0.06, and Chi-square/df = 2.01). Three PMT subconstructs (perceived severity, response cost, and self-efficacy) were significantly associated with screening intention. Knowledge, social status, and medical history had significantly indirect associations with screening intention through the mediating effect of PMT subconstructs. Considering the utility of PMT, intervention programs might be more effective based on the subconstructs of PMT, especially to improve self-efficacy, perceived severity, and knowledge, reduce response cost, as well as targeting specific demographic groups.


Assuntos
Neoplasias da Mama , Motivação , Neoplasias da Mama/diagnóstico , China , Estudos Transversais , Detecção Precoce de Câncer , Feminino , Humanos , Intenção , Inquéritos e Questionários
3.
Artigo em Inglês | MEDLINE | ID: mdl-34602462

RESUMO

AIM: Preoperative suspicion of malignancy in nonfunctioning pancreatic neuroendocrine tumors (pNETs) is mostly based on tumor size. We retrospectively analyzed the contrast enhanced ultrasound (CEUS) features of a series of histopathologically proved nonfunctioning pNETs. METHODS: In this retrospective study, 37 surgery and histologically proved nonfunctioning pNETs were included. All pNETs lesions were incidentally detected by transabdominal ultrasound. B mode ultrasound (BMUS) and CEUS features were reviewed and analyzed. 52 histopathologically proved pancreatic ductal adenocarcinoma (PDACs) lesions were included as a control group. RESULTS: All nonfunctioning pNETs patients showed no typical clinical symptoms. No significant differences were observed in size, echogenicity or internal color flow imaging signal between pNETs and PDAC patients (P >  0.05). Most of nonfunctioning pNETs showed a well-defined tumor margin. The presence of pancreatic duct dilatation was less frequently observed in nonfunctioning pNETs patients (P <  0.05). After injection of ultrasound contrast agents, homogeneous enhancement was more commonly observed in nonfunctioning pNETs group (P <  0.05). During arterial phase of CEUS, most of nonfunctioning pNETs were hyper- or isoenhanced (32/37, 86.5%), whereas most of PDACs were hypoenhanced (34/52, 65.4%) (P <  0.05). Nonenhanced necrosis area was more commonly detected in PDACs (P = 0.012). CONCLUSIONS: CEUS features are helpful for preoperative non-invasive differential diagnosis of nonfunctioning pNETs, assisting further clinical decision-making process.

4.
Pancreatology ; 21(8): 1498-1505, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34580017

RESUMO

OBJECTIVES: The aim of this study was to quantitatively evaluate the stiffness of pancreatic parenchyma and solid focal pancreatic lesions (FPLs) by virtual touch tissue imaging and quantification (VTIQ) technique and to investigate the potential usefulness of VTIQ method in the prediction of post-operative pancreatic fistula (POPF) after pancreatectomy. METHODS: In this prospective study, patients who scheduled to undergo pancreatectomy were initially enrolled and received VTIQ assessment within one week before surgery. VTIQ elastography (Siemens ACUSON Sequoia, 5C-1 transducer) was used to measure the shear wave velocity (SWV) value of FPLs and the body part pancreatic parenchyma. The palpation stiffness of pancreas was qualitatively evaluated during operation by surgeons. POPF was finally diagnosed and graded through a three-weeks post-operative follow-up according to international study group of pancreatic fistula (ISGPF). SWV values were compared between POPF positive and negative group. Receiver operating characteristic (ROC) analysis was used to evaluate the diagnostic efficacy of SWV value in predicting POPF. RESULTS: From December 2020 to June 2021, 44 patients were finally enrolled in this study, among which, 26 patients were identified to develop POPF after pancreatectomy. The SWV value of pancreatic parenchyma in POPF positive group was significantly lower than that in POPF negative group (P = 0.001). However, there was no significant difference in palpation stiffness between the two groups (P = 0.124). Besides, neither the SWV value of FPL nor the SWV ratio between FPL to surrounding pancreatic parenchyma differ significantly between POPF positive and negative group (P > 0.05). Taking SWV value of pancreatic parenchyma >1.10 m/s as a cut-off value for predicting POPF, area under the receiver operating characteristic curve (AUROC) was 0.864 with 72.2% sensitivity, 92.3% specificity, 86.7% positive predictive value (PPV) and 82.8% negative predictive value (NPV), respectively. CONCLUSIONS: VTIQ technique might be a potential non-invasive imaging method to predict POPF before pancreatectomy in future clinical practice.

5.
Pharm Biol ; 59(1): 275-286, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33651969

RESUMO

CONTEXT: Poria coco F.A.Wolf (Polyporaceae) dispels dampness and promotes diuresis implying hypouricaemic action. OBJECTIVE: To examine hypouricaemic action of Poria coco. MATERIALS AND METHODS: Ethanol extract (PCE) was prepared by extracting the sclerotium of P. cocos with ethanol, and the water extract (PCW) was produced by bathing the remains with water. PCE and PCW (50, 100 and 200 mg/kg, respectively) were orally administered to hyperuricemic Kunming mice (n = 8) to examine its hypouricaemic effect. Also, molecular docking was performed. RESULTS: P. cocos showed excellent hypouricaemic action, decreasing the serum uric acid of hyperuricaemia (HUA) control (526 ± 112 µmol/L) to 178 ± 53, 153 ± 57 and 151 ± 62 µmol/L (p < 0.01) by PCE and 69 ± 23, 63 ± 15 and 62 ± 20 µmol/L (p < 0.01) by PCW, respectively. According to SCrs, BUNs and H&E staining, PCE and PCW partially attenuated renal dysfunction caused by HUA. They presented no negative effects on ALT, AST and ALP activities. They elevated ABCG2 (ATP-binding cassette super-family G member 2) mRNA and protein expression in comparison to HUA control. In molecular docking, compound 267, 277, 13824, 15730 and 5759 were predicted as the top bioactives of P. cocos against HUA, which even presented better scores than the positive compound, oestrone 3-sulfate. DISCUSSION AND CONCLUSIONS: This paper demonstrated the hypouricaemic and nephroprotective effects of P. cocos in hyperuricemic mice by up-regulating ABCG2. These results may be useful for the development of a hypouricaemic agent.


Assuntos
Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/genética , Hiperuricemia/tratamento farmacológico , Extratos Vegetais/farmacologia , Wolfiporia/química , Animais , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Etanol/química , Hiperuricemia/complicações , Nefropatias/etiologia , Nefropatias/prevenção & controle , Masculino , Camundongos , Simulação de Acoplamento Molecular , Extratos Vegetais/administração & dosagem , Regulação para Cima/efeitos dos fármacos , Ácido Úrico/sangue , Água/química
6.
Front Cardiovasc Med ; 8: 617391, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33763457

RESUMO

Objective: To investigate the value of high-frame rate vector flow imaging technique (V flow) in evaluating the hemodynamic changes of carotid stenosis caused by atherosclerotic plaques. Methods and Materials: In this prospective study, patients with stenosis rate (diameter) ≥30% caused by carotid atherosclerotic plaques were included. Degrees of carotid stenosis were graded according to North American Symptomatic Carotid Endarterectomy Trial criteria: moderate (30-69%) or severe (70-99%). Mindray Resona 7s ultrasound machine with a linear array transducer (3-11 MHz) was used for ultrasound examinations. The mean WSS value of carotid arteries was measured at the proximal, narrowest region and distal of carotid stenosis. The mean WSS values were correlated with peak systolic velocity (PSV) measured by color Doppler flow imaging and stenosis degree detected by digital subtraction angiography (DSA). The vector arrows and flow streamline detected by V flow dynamic imaging were analyzed. Imaging findings of DSA in carotid arteries were used as the gold standard. Results: Finally, 51 patients were included. V flow measurements were performed successfully in 17 patients (100%) with moderate-grade stenosis and in 30 patients (88.2%) with severe-grade stenosis. Dynamic V flow imaging showed yellow or red vectors at the stenotic segment, indicating fast speed blood flow (up to 260.92 cm/s). Changes of streamlines were detected in the stenotic segment. The mean WSS value measured at the narrowest region of the carotid artery had a moderately positive correlation with stenosis degree (r = 0.58, P < 0.05) and PSV value (r = 0.54, P < 0.05), respectively. Significant difference was detected in mean WSS value at the narrowest region of the carotid artery between severe carotid stenosis (1.47 ± 0.97 Pa) and moderate carotid stenosis (0.96 ± 0.44 Pa) (P < 0.05). Conclusion: The hemodynamic changes detected by V flow of the carotid stenosis might be a potential non-invasive imaging tool for assessing the degree of carotid stenosis.

7.
Clin Hemorheol Microcirc ; 77(4): 461-469, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33459703

RESUMO

OBJECTIVE: To investigate the clinical value of dynamic contrast enhanced ultrasound (D-CEUS) in predicting the microvascular invasion (MVI) of hepatocellular carcinoma (HCC). PATIENTS AND METHODS: In this retrospective study, 16 patients with surgery and histopathologically proved HCC lesions were included. Patients were classified according to the presence of MVI: MVI positive group (n = 6) and MVI negative group (n = 10). Contrast enhanced ultrasound (CEUS) examinations were performed within a week before surgery. Dynamic analysis was performed by VueBox® software (Bracco, Italy). Three regions of interests (ROIs) were set in the center of HCC lesions, at the margin of HCC lesions and in the surrounding liver parenchyma accordingly. Time intensity curves (TICs) were generated and quantitative perfusion parameters including WiR (wash-in rate), WoR (wash-out rate), WiAUC (wash-in area under the curve), WoAUC (wash-out area under the curve) and WiPi (wash-in perfusion index) were obtained and analyzed. RESULTS: All of HCC lesions showed arterial hyperenhancement (100 %) and at the late phase as hypoenhancement (75%) in CEUS. Among all CEUS quantitative parameters, the WiAUC and WoAUC were higher in MVI positive group than in MVI negative group in the center HCC lesions (P < 0.05), WiAUC, WoAUC and WiPI were higher in MVI positive group than in MVI negative group at the margin of HCC lesions. WiR and WoR were significant higher in MVI positive group. CONCLUSIONS: D-CEUS with quantitative perfusion analysis has potential clinical value in predicting the existence of MVI in HCC lesions.


Assuntos
Carcinoma Hepatocelular/diagnóstico por imagem , Meios de Contraste/uso terapêutico , Neoplasias Hepáticas/diagnóstico por imagem , Ultrassonografia/métodos , Idoso , Carcinoma Hepatocelular/patologia , Feminino , Humanos , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
8.
Clin Hemorheol Microcirc ; 77(3): 323-333, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33252067

RESUMO

PURPOSE: To evaluate the feasibility of dynamic contrast enhanced ultrasound (DCE-US) in predicting treatment response of high-intensity focused ultrasound (HIFU) in patients with locally advanced pancreatic cancer (LAPC) lesions. PATIENTS AND METHODS: In this prospective study, 10 patients with pathologically confirmed LAPC lesions (7 men, 3 women; average age, 61.13±5.80 years) were prospectively enrolled. All patients received HIFU treatment with peak intensity at 12000 W/cm2. Contrast enhanced ultrasound (CEUS) was performed with an ACUSON Oxana 2 ultrasound equipment and a 6 C-1 transducer (1-6 Hz). A dose of 2.4 ml SonoVue was injected for each examination. Time intensity curves (TICs) were generated and quantitative analyses were performed by SonoLiver software. B mode ultrasound (BMUS) features, CEUS enhancement patterns, TICs, CEUS quantitative parameters and serum carcinoma antigen 19-9 (CA19-9) levels were compared before and 4 weeks after HIFU treatment. Statistical analyses were performed with SPSS Version 20.0 and GraphPad Prism 5. RESULTS: While comparing before and after HIFU, no significant difference was obtained on mean size of lesion, BMUS or CEUS features. After HIFU treatment, TICs showed decreased and delayed enhancement. Among all CEUS quantitative parameters, significant decrease could be found in maximum intensity (MI) (60.66±23.95% vs 41.31±26.74%) and mean transit time (mTT) (76.66±47.61 s vs 38.42±28.35 s). CA19-9 level decreased significantly after HIFU (2747.92±4237.41 U/ml vs 715.08±1773.90 U/ml) (P = 0.05). CONCLUSION: DCE-US combining with quantitative analysis might be a useful imaging method for early treatment response evaluation of HIFU in LAPC lesions.


Assuntos
Meios de Contraste/uso terapêutico , Tratamento por Ondas de Choque Extracorpóreas/métodos , Neoplasias Pancreáticas/tratamento farmacológico , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento
9.
Respir Care ; 66(2): 307-315, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32900917

RESUMO

BACKGROUND: Although studies have confirmed the safety and feasibility of early active mobilization, its implementation status is still unsatisfactory. The most important obstacle is ensuring patient safety. Comprehensively assessing the physical condition of patients considered for mobilization is the basis of safety. However, appropriate guidance is lacking. We performed a systematic review to extract and summarize current safety assessment criteria for the early active mobilization of mechanically ventilated patients in the ICU. METHODS: A systematic literature search was conducted using English and Chinese databases according to the PRISMA checklist and guidelines to identify relevant original studies that evaluated safety assessment variables and specific parameters. RESULTS: A total of 24 medium- and high-quality articles involving a total of 4,842 subjects were included in the analysis. Among these studies, there were 15 randomized controlled trials involving 1,777 subjects (888 in the control groups, 889 in the interventional groups) and 9 cohort studies involving 3,065 subjects (1,240 in the control groups, 1,825 in the exposure groups). There were 5 safety assessment criteria, including cardiovascular, respiratory, neurological, musculoskeletal, and other. Within these were 17 different variables and 48 specific parameters. CONCLUSIONS: The safety assessment criteria should focus on cardiac reserve, respiratory reserve, consciousness, and muscle strength. It is especially important to note whether the parameters are stable because parameter stability can be more representative of a patient's condition than absolute values. We provide a flow diagram for clinical safety assessments; however, some limitations exist, and this assessment requires further validation and optimization.


Assuntos
Unidades de Terapia Intensiva , Respiração Artificial , Deambulação Precoce , Humanos , Força Muscular , Segurança do Paciente
11.
Int J Mol Sci ; 19(10)2018 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-30340390

RESUMO

Inonotus obliquus is an edible mushroom and also a remedy against various diseases, especially metabolic syndrome. In this paper we report the actions of an ethanol extract of I. obliquus (IOE) against hyperuricemia in hyperuricemic mice, and the screen of bioactives. The extract (IOE) was prepared by extracting I. obliquus at 65 °C with ethanol, and characterized by HPLC. IOE at low, middle, and high doses reduced serum uric acid (SUA) of hyperuricemic mice (353 µmol/L) to 215, 174, and 152 µmol/L (p < 0.01), respectively, showing similar hypouricemic effectiveness to the positive controls. IOE showed a non-toxic impact on kidney and liver functions. Of note, IOE suppressed xanthine oxidase (XOD) activity in serum and liver, and also down-regulated renal uric acid transporter 1 (URAT1). Four compounds hit highly against XOD in molecular docking. Overall, the four compounds all occupied the active tunnel, which may inhibit the substrate from entering. The IC50 of betulin was assayed at 121.10 ± 4.57 µM, which was near to that of allopurinol (148.10 ± 5.27 µM). Betulin may be one of the anti-hyperuricemia bioactives in I. obliquus.


Assuntos
Basidiomycota/química , Produtos Biológicos/química , Produtos Biológicos/farmacologia , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Hiperuricemia/enzimologia , Modelos Moleculares , Xantina Oxidase/química , Animais , Descoberta de Drogas , Hiperuricemia/sangue , Hiperuricemia/tratamento farmacológico , Camundongos , Relação Quantitativa Estrutura-Atividade , Xantina Oxidase/antagonistas & inibidores
12.
Molecules ; 23(10)2018 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-30336599

RESUMO

Conventionally, benzophenone-type molecules are beneficial for alleviating the UV exposure of humans. More importantly, various compounds with this skeleton have demonstrated various biological activities. In this paper, we report the anti-hyperuricemic effect of the benzophenone compound 2-hydroxy-4-methoxybenzophenone-5-sulfonic acid (HMS). Preliminarily, its molecular docking score and xanthine oxidase (XOD) inhibition suggested a good anti-hyperuricemic effect. Then, its anti-hyperuricemic effect, primary mechanisms and general toxicity were examined on a hyperuricemic mouse model which was established using potassium oxonate and hypoxanthine together. HMS demonstrated a remarkable anti- hyperuricemic effect which was near to that of the control drugs, showing promising perspective. General toxicity was assessed and it showed no negative effects on body weight growth and kidney function. Moreover, anti-inflammatory action was observed for HMS via spleen and thymus changes. Its anti-hyperuricemic mechanisms may be ascribed to its inhibition of XOD and its up-regulation of organic anion transporter 1 (OAT1) and down-regulation of glucose transporter 9 (GLUT9).


Assuntos
Benzofenonas/administração & dosagem , Proteínas Facilitadoras de Transporte de Glucose/genética , Hiperuricemia/tratamento farmacológico , Proteína 1 Transportadora de Ânions Orgânicos/genética , Xantina Oxidase/genética , Animais , Benzofenonas/química , Peso Corporal/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Hiperuricemia/patologia , Hipoxantina/administração & dosagem , Rim/efeitos dos fármacos , Camundongos , Simulação de Acoplamento Molecular , Ácido Oxônico/administração & dosagem , Baço/efeitos dos fármacos , Timo/efeitos dos fármacos , Xantina Oxidase/antagonistas & inibidores
13.
Int J Mol Sci ; 19(5)2018 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-29735945

RESUMO

Searching novel hypouricemic agents of high efficacy and safety has attracted a great attention. Previously, we reported the hypouricemic effect of Ganoderma applanatum, but its bioactives, was not referred. Herein, we report the hypouricemic effect of 2,5-dihydroxyacetophenone (DHAP), a compound screened from Ganoderma applanatum computationally. Serum parameters, such as uric acid (SUA), xanthine oxidase (XOD) activity, blood urea nitrogen (BUN), and creatinine were recorded. Real-time reverse transcription PCR (RT-PCR) and Western blot were exploited to assay RNA and protein expressions of organic anion transporter 1 (OAT1), glucose transporter 9 (GLUT9), uric acid transporter 1 (URAT1), and gastrointestinal concentrative nucleoside transporter 2 (CNT2). DHAP at 20, 40, and 80 mg/kg exerted excellent hypouricemic action on hyperuricemic mice, reducing SUA from hyperuricemic control (407 ± 31 μmol/L, p < 0.01) to 180 ± 29, 144 ± 13, and 139 ± 31 μmol/L, respectively. In contrast to the renal toxic allopurinol, DHAP showed some kidney-protective effects. Moreover, its suppression on XOD activity, in vivo and in vitro, suggested that XOD inhibition may be a mechanism for its hypouricemic effect. Given this, its binding mode to XOD was explored by molecular docking and revealed that three hydrogen bonds may play key roles in its binding and orientation. It upregulated OAT1 and downregulated GLUT9, URAT1, and CNT2 too. In summary, its hypouricemic effect may be mediated by regulation of XOD, OAT1, GLUT9, URAT1, and CNT2.


Assuntos
Acetofenonas/química , Acetofenonas/uso terapêutico , Ganoderma/química , Supressores da Gota/química , Supressores da Gota/uso terapêutico , Hiperuricemia/tratamento farmacológico , Animais , Nitrogênio da Ureia Sanguínea , Hiperuricemia/sangue , Masculino , Camundongos , Simulação de Acoplamento Molecular , Ácido Úrico/sangue , Xantina Oxidase/sangue
14.
Am J Chin Med ; 46(3): 585-599, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29595077

RESUMO

Ethanol and water extracts of Armillaria mellea were prepared by directly soaking A. mellea in ethanol (AME) at 65[Formula: see text]C, followed by decocting the remains in water (AMW) at 85[Formula: see text]C. Significantly, AME and AMW at 30, 60 and 120[Formula: see text]mg/kg exhibited excellent hypouricemic actions, causing remarkable declines from hyperuricemic control (351[Formula: see text][Formula: see text]mol/L, [Formula: see text]) to 136, 130 and 115[Formula: see text][Formula: see text]mol/L and 250, 188 and 152[Formula: see text][Formula: see text]mol/L in serum uric acid, correspondingly. In contrast to the evident renal toxicity of allopurinol, these preparations showed little impacts. Moreover, they showed some inhibitory effect on XOD (xanthine oxidase) activity. Compared with hyperuricemic control, protein expressions of OAT1 (organic anion transporter 1) were significantly elevated in AME- and AMW-treated mice. The levels of GLUT9 (glucose transporter 9) expression were significantly decreased by AMW. CNT2 (concentrative nucleoside transporter 2), a key target for purine absorption in gastrointestinal tract was involved in this study, and was verified for its innovative role. Both AME and AMW down-regulated CNT2 proteins in the gastrointestinal tract in hyperuricemic mice. As they exhibited considerable inhibitory effects on XOD, we selected XOD as the target for virtual screening by using molecular docking, and four compounds were hit with high ranks. From the analysis, we concluded that hydrogen bond, Pi-Pi and Pi-sigma interactions might play important roles for their orientations and locations in XOD inhibition.


Assuntos
Armillaria/química , Regulação para Baixo/efeitos dos fármacos , Hiperuricemia/tratamento farmacológico , Hiperuricemia/genética , Proteínas de Membrana Transportadoras/genética , Proteínas de Membrana Transportadoras/metabolismo , Proteína 1 Transportadora de Ânions Orgânicos/genética , Proteína 1 Transportadora de Ânions Orgânicos/metabolismo , Fitoterapia , Extratos Vegetais/uso terapêutico , Animais , Etanol , Trato Gastrointestinal/metabolismo , Expressão Gênica/efeitos dos fármacos , Proteínas Facilitadoras de Transporte de Glucose/genética , Proteínas Facilitadoras de Transporte de Glucose/metabolismo , Ligação de Hidrogênio , Hiperuricemia/metabolismo , Masculino , Camundongos , Extratos Vegetais/farmacologia , Ácido Úrico/sangue , Água , Xantina Oxidase/antagonistas & inibidores , Xantina Oxidase/metabolismo
15.
J Pharm Pharmacol ; 70(6): 760-767, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29484657

RESUMO

OBJECTIVES: This study aimed to investigate the cardioprotective effects of melatonin on heat stroke (HS) induced acute myocardial infarction in rats and to explore the underlying mechanisms. METHODS: Myocardial injury was induced by subjecting the anaesthetized rats to a high ambient temperature of 43°C for 70 min. Such a high ambient temperature caused hyperthermia, hypotension and myocardial injury in rats. Rats were treated with melatonin (3 mg/kg) intravenously one hour before and followed by an additional dose immediately after heat stress. KEY FINDINGS: At the onset of HS, animals displayed myocardial injury evidenced by increased levels of cardiac damage indicators (e.g. total lactate dehydrogenase, cardiac troponin I and creatine kinase-MB), increased cardiac damage scores and suppressed left ventricular performance. Animals with HS also had increased cardiac oxidative stress evidenced by increased levels of lipid peroxidation (e.g. increased thiobarbituric acid reactive substances) and decreased levels of antioxidant enzymes (e.g. superoxide dismutase, catalase and reduced glutathione) and activated inflammation (e.g. increased levels of interleukin-6 and tumour necrosis factor-α). Pretreatment with melatonin significantly reversed the HS-induced myocardial injury, cardiac oxidative stress and cardiac inflammation. CONCLUSIONS: Melatonin may protect against HS-induced myocardial injury in male rats by mitigating oxidative stress and inflammation.


Assuntos
Golpe de Calor/complicações , Melatonina/farmacologia , Infarto do Miocárdio/etiologia , Infarto do Miocárdio/prevenção & controle , Animais , Cardiotônicos/farmacologia , Inflamação/prevenção & controle , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos
16.
Front Microbiol ; 9: 58, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29422889

RESUMO

Recently, we've reported the anti-hyperuricemic effects of Cordyceps militaris. As a characteristic compound of C. militaris, we hypothesized that cordycepin may play a role in preventing hyperurecimia. Remarkably, cordycepin produced important anti-hyperuricemic actions, decreasing SUA (serum uric acid) to 216, 210, and 203 µmol/L (P < 0.01) at 15, 30, and 60 mg/kg in comparison of hyperuricemic control (337 µmol/L), closing to normal control (202 µmol/L). Elisa, RT-PCR and western blot analysis demonstrated that the actions may be attributed to its downregulation of uric acid transporter 1 (URAT1) in kidney. Serum creatinine levels and blood urine nitrogen and liver, kidney, and spleen coefficients demonstrated that cordycepin may not impact liver, renal, and spleen functions. In addition, we used computational molecular simulation to investigate the binding mechanism of cordycepin. Of which, van der Waals interaction dominated the binding. Residues TRP290, ARG17, ALA408, GLY411, and MET147 contributed mainly on nonpolar energy. This provided the theoretical guidance to rationally design and synthesis novel URAT1 inhibitors.

17.
Chem Biol Interact ; 265: 47-54, 2017 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-28104348

RESUMO

Heat stroke is characterized by hyperthermia, systemic inflammation, and multiple organ failure including arterial hypotension. This definition can be fulfilled by a rat model of heat stroke used in the present study. Anesthetized animals were exposed to heat exposure (43 °C for 70 min) and then returned to room temperature (26 °C) for recovery. One hour before heat exposure, an intraperitoneal dose of quercetin (30 mg/kg) or vehicle (normal saline 1 ml/kg) was administered to the experimental groups of rats. Additional injection was administered immediately after the onset of heat stroke. Immediately after the onset of heat stroke. Vehicle-treated rats displayed (i) hyperthermia; (ii) suppressed left ventricular function; (iii) decreased contents of cardiac total antioxiant capacity (e.g., superoxide dismutase, glutathione peroxidase, catalase); (iv) increased contents of cardiac oxidative capacity malondialdehyde and thiobarbituric acid reactive substances; (v) increased cardiac levels of pro-inflammatory cytokines tumor necrosis factor-α and interleukin-6; and (vi) decreased cardiac levels of an anti-inflammatory cytokine interleukin 10. Histopathologic and survival observation provided supportive evidence for biochemical analyses. These heat stroke reactions all can be significantly attenuated by quercetin therapy. Our data suggest that quercetin therapy might improve outcomes of heat stroke in rats by attenuating excessive hyperthermia as well as myocardial injury. The protective effects of quercetin could be attributed to anti-lipid peroxidative, anti-oxidant, and anti-inflammatory properties.


Assuntos
Cardiomiopatias/prevenção & controle , Golpe de Calor/complicações , Quercetina/farmacologia , Animais , Cardiomiopatias/etiologia , Cardiomiopatias/metabolismo , Cardiomiopatias/fisiopatologia , Citocinas/metabolismo , Hemodinâmica , Mediadores da Inflamação/metabolismo , Masculino , Estresse Oxidativo , Ratos , Ratos Sprague-Dawley
18.
Front Pharmacol ; 8: 996, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29379442

RESUMO

Ganoderma applanatum (G. applanatum) dispels wind to eliminate dampness and exhibited nephron- and liver-protective effects as noted in Chinese herbal classic literature; it might also affect hyperuricemia. Therefore, we examined the hypouricemia effects and mechanisms underlying G. applanatum on chemical-induced hyperuricemia in mice. Ethanol (GAE) and water (GAW) extracts were prepared by extracting G. applanatum in ethanol (GAE), followed by bathing the remains in water to yield GAW. GAE and GAW were administered orally at different doses to hyperuricemia mice, while allopurinol and benzbromarone served as positive controls. Both GAE and GAW showed remarkable hypouricemia activities, rendering a substantial decline in the SUA (serum uric acid) level in hyperuricemia control (P < 0.01). Moreover, the urine uric acid (UUA) levels were enhanced by GAE and GAW. In contrast to the evident renal toxicity of allopurinol, GAE and GAW did not show a distinct renal toxicity. Almost no suppressing effect was observed on the XOD activities. However, compared to the hyperuricemia control, OAT1 was elevated remarkably in mice drugged with GAE and GAW, while GLUT9 was significantly decreased. Similar to benzbromarone, GAE decreased the URAT1 protein levels significantly (P < 0.01), while GAW did not display a similar effect. GAE and GAW downregulated the level of CNT2 proteins in the gastrointestinal tract of hyperuricemia mice. Thus, G. applanatum produced outstanding hypouricemic effects, mediated by renal OAT1, GLUT9, and URAT1 and gastrointestinal CNT2 that might elevate urine uric secretions and decline in the absorption of purine in the gastrointestinal tracts. G. applanatum showed little negative influence on inner organs. By docking screening, four top-ranked compounds were identified that necessitated further investigation. Compounds: potassium oxonate, hypoxanthine, allopurinol, benzbromarone.

19.
Zhen Ci Yan Jiu ; 42(6): 527-32, 2017 Dec 25.
Artigo em Chinês | MEDLINE | ID: mdl-29318861

RESUMO

OBJECTIVE: To observe the clinical effect of heat sensitive moxibustion (HSM) and its regularity of acupoint heat-sensitization in the treatment of allergic rhinitis (AR) patients. METHODS: Seventy patients with AR were randomly divided into HSM and manual acupuncture groups (n=35/group). For patients of the HSM group, acupoints Yintang (EX-HN 3), bilateral Yingxiang (LI 20), Shangxing (GV 23), Tongtian (BL 7), Feishu (BL 13), Hegu (LI 4), etc. were used, and for patients of the manual acupuncture group, bilateral LI 20 and LI 4, Bitong (EX-HN 8) and EX-HN 3 were needled and stimulated with uniform reinforcing-reducing needling method. The treatment was conducted once every other day, for 20 days, with 3 days' interval between two 10 days. The symptoms of sneezing, running nose, nasal obstruction, and nasal itching were scored as 1, 2 and 3 points according to their severity. The signs of turbinate-nose cavity bottom/nasal septum correlation, morphological state (swelling or not) of inferior nasal concha and color of nasal mucosa, appearance (deviation or polyp) of the middle turbinate and nasal septum were scored as 1, 2 and 3 points according to their severity. The total score equaled to symptom score plus nasal sign score. The distribution of heat sensitization acupoints for effectively improving AR were recorded. RESULTS: The total effective rate of 82.86%(29/35) in the HSM group had no marked difference in comparison with that of 74.29%(26/35) in the manual acupuncture group (P>0.05). After the treatment, the total scores of symptoms and nasal signs of both HSM and manual acupuncture groups were significantly reduced in comparison with their own individual pre-treatment (P<0.01), and those in the HSM group were significantly decrased than those in the manual acupuncture group (P<0.05). In 35 patients of the HSM group, among the detected 57 acupoints, the most frequently sensitive acupoints were LI 20, EX-HN 3, EX-HN 8, Shangyintang, BL 13, Shenque(CV 8), GV 23, Fengchi(GB 20), Die'e and Dazhui (GV 14) in sequence, mainly covering the Governor Vessel, Large Intestine Meridian of Hand-yangming(LI), and Bladder Meridian of Foot-taiyang(BL), and characterized by heat conduction, heat diffusion, diathermancy, non-thermal (mainly itching) sensation, thermal sensation mainly in the deep tissue and in the distant part rather than in the body surface and the local part. CONCLUSIONS: HSM has a positive effect on improvement of AR, when applied, acupoints LI 20, EX-HN 3, EX-HN 8, Shangyintang, BL 13, CV 8, GV 23, GB 20, Die'e and GV 14 are highly recommended.


Assuntos
Terapia por Acupuntura , Moxibustão , Rinite Alérgica , Temperatura Alta , Humanos , Rinite Alérgica/terapia
20.
Artigo em Chinês | MEDLINE | ID: mdl-25434154

RESUMO

OBJECTIVE: To understand the schistosomiasis prevention knowledge of middle school students from areas with different endemic levels in Hubei Province. METHODS: The schistosomiasis endemic regions were divided into transmission controlled areas and endemic controlled areas in Hubei Province, middle school students from different types of areas were selected through stratified randomized cluster sampling and were investigated by questionnaire. RESULTS: A total of 3,204 students were selected and investigated. The awareness rate of schistosomiasis prevention and control knowledge among the students ranged from 65.1%-90.3%. Overall, the students from endemic controlled areas had higher knowledge rates of all the items than those from transmission controlled areas (all P <0.05). The middle school students acquired schistosomiasis prevention knowledge mainly from the teachers, parents, doctors and schistosomiasis staff. CONCLUSION: Health education to students should adopt different ways targeting at different endemic levels in the future.


Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Esquistossomose/prevenção & controle , Estudantes/estatística & dados numéricos , Inquéritos e Questionários , Adolescente , Criança , China/epidemiologia , Feminino , Humanos , Masculino , Esquistossomose/epidemiologia
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