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1.
World J Gastrointest Oncol ; 16(5): 1787-1795, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38764817

RESUMO

BACKGROUND: Individuals diagnosed with gastrointestinal tumors are at an increased risk of developing cardiovascular diseases. Among which, ventricular arrhythmia is a prevalent clinical concern. This suggests that ventricular arrhythmias may have predictive value in the prognosis of patients with gastrointestinal tumors. AIM: To explore the prognostic value of ventricular arrhythmias in patients with gastrointestinal tumors receiving surgery. METHODS: We retrospectively analyzed data from 130 patients undergoing gastrointestinal tumor resection. These patients were evaluated by a 24-h ambulatory electrocardiogram (ECG) at the Sixth Affiliated Hospital of Sun Yat-sen University from January 2018 to June 2020. Additionally, 41 general healthy age-matched and sex-matched controls were included. Patients were categorized into survival and non-survival groups. The primary endpoint was all-cause mortality, and secondary endpoints included major adverse cardiovascular events (MACEs). RESULTS: Colorectal tumors comprised 90% of cases. Preoperative ambulatory ECG monitoring revealed that among the 130 patients with gastrointestinal tumors, 100 (76.92%) exhibited varying degrees of premature ventricular contractions (PVCs). Ten patients (7.69%) manifested non-sustained ventricular tachycardia (NSVT). The patients with gastrointestinal tumors exhibited higher PVCs compared to the healthy controls on both conventional ECG [27 (21.3) vs 1 (2.5), P = 0.012] and 24-h ambulatory ECG [14 (1.0, 405) vs 1 (0, 6.5), P < 0.001]. Non-survivors had a higher PVC count than survivors [150.50 (7.25, 1690.50) vs 9 (0, 229.25), P = 0.020]. During the follow-up period, 24 patients died and 11 patients experienced MACEs. Univariate analysis linked PVC > 35/24 h to all-cause mortality, and NSVT was associated with MACE. However, neither PVC burden nor NSVT independently predicted outcomes according to multivariate analysis. CONCLUSION: Patients with gastrointestinal tumors exhibited elevated PVCs. PVCs > 35/24 h and NSVT detected by 24-h ambulatory ECG were prognostically significant but were not found to be independent predictors.

2.
Materials (Basel) ; 16(20)2023 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-37895649

RESUMO

This study established a comprehensive framework for evaluating the lifetime performance of precast prestressed concrete frames exposed to chloride environments. The proposed analytical framework enabled a scientifically grounded and rational assessment of both the service life and residual load-carrying capacity of precast prestressed concrete frames in chloride environments. It further served as the foundational basis for making informed decisions regarding the repair and maintenance of pertinent structures. Based on Fick's second law, this evaluation framework established the probability distribution of the corrosion initiation time and cracking time of reinforced concrete structures due to corrosion expansion in a chloride environment. Additionally, based on the fragility analysis model and results of a precast prestressed concrete frame in a chloride environment, a practical method for evaluating the time-varying seismic performance of the precast structure considering the influence of corrosion was proposed. Furthermore, by employing the path probability model and reliability theory, time-varying reliability models were proposed to predict the three limit states of the precast prestressed concrete frame. According to the analysis results of a four-story planar frame, it could be seen that the corrosion initiation time and normal service limit state were highly sensitive to the chloride ion diffusion coefficient of the composite layer in precast concrete structures. Compared to cast-in-place structures, the presence of a composite layer in precast concrete structures could lead to more severe degradation of the time-varying seismic performance of the precast prestressed concrete frame.

3.
Entropy (Basel) ; 25(8)2023 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-37628177

RESUMO

Over the past few years, chaotic image encryption has gained extensive attention. Nevertheless, the current studies on chaotic image encryption still possess certain constraints. To break these constraints, we initially created a two-dimensional enhanced logistic modular map (2D-ELMM) and subsequently devised a chaotic image encryption scheme based on vector-level operations and 2D-ELMM (CIES-DVEM). In contrast to some recent schemes, CIES-DVEM features remarkable advantages in several aspects. Firstly, 2D-ELMM is not only simpler in structure, but its chaotic performance is also significantly better than that of some newly reported chaotic maps. Secondly, the key stream generation process of CIES-DVEM is more practical, and there is no need to replace the secret key or recreate the chaotic sequence when handling different images. Thirdly, the encryption process of CIES-DVEM is dynamic and closely related to plaintext images, enabling it to withstand various attacks more effectively. Finally, CIES-DVEM incorporates lots of vector-level operations, resulting in a highly efficient encryption process. Numerous experiments and analyses indicate that CIES-DVEM not only boasts highly significant advantages in terms of encryption efficiency, but it also surpasses many recent encryption schemes in practicality and security.

4.
BMC Cardiovasc Disord ; 23(1): 109, 2023 02 25.
Artigo em Inglês | MEDLINE | ID: mdl-36841792

RESUMO

BACKGROUND: Recent studies indicated that the prognosis of patients with gastrointestinal tumors is frequently influenced by its complications, notably myocardial injury. The main object is to investigate the occurrence and risk factors of myocardial injury in patients with gastrointestinal tumor. METHODS: 1126 patients who received gastrointestinal tumor related surgery from May 2018 to June 2020 in the Sixth Affiliated Hospital of Sun Yat-sen University were retrospectively collected and divided into the non-myocardial injury group and the myocardial injury group (high-sensitive cardiac troponin I (hs-cTnI) ≥ 0.028 ng/ml). The occurrence and risk factors of myocardial injury in patients with gastrointestinal tumor are analyzed. The influence of myocardial injury on the ICU detention time in gastrointestinal tumor patients is also studied. RESULTS: In total, 78 (6.93%) patients developed myocardial injuries. Compared with patients in the non-myocardial injury group, patients in the myocardial injury group have a higher prevalence of cardiovascular risk factors (including advanced age and higher smoking ratio), a higher prevalence of comorbidities (such as previous coronary artery disease, hypertension, atrium fibrillation and diabetes), and a higher rate of premedication (such as anticoagulation, ß-blocker, Angiotensin-converting enzyme inhibitor/Angiotensin II receptor blocker, and diuretic) (all with P-value < 0.05). In addition, patients in the myocardial injury group also presented with a higher revised cardiac risk index (Lee index), higher neutrophil granulocyte ratio, lower hemoglobin, and higher likelihood of impaired cardiac structure and function (all with P-value < 0.05). There was a trend of statistical significance in the ICU detention time between the myocardial injury group and the non-myocardial injury group (1[1,3] vs. 2[1,10], P = 0.064). In this study, there were 7 patients presented with clinical symptoms in the myocardial injury group (chest discomfort in 4 cases, non-compressive precordial chest pain in 1 case, dyspnea in 2 cases). In the multivariate analysis, advanced age, increased Lee index score, increased neutrophil granulocyte ratio, decreased left ventricular ejection fraction (LVEF), increased interventricular septum were independent risk factors for myocardial injury. CONCLUSION: In conclusion, advanced age, increased Lee index, increased neutrophil granulocyte ratio, decreased left ventricular ejection fraction, and increased ventricular septum were independent risk factors for preoperative myocardial injury in patients with gastrointestinal tumors. The proportion of clinical symptoms in gastrointestinal tumor patients with myocardial injury was low, indicating the necessity to closely monitor the cardiac status of individuals with gastrointestinal tumors.


Assuntos
Doença da Artéria Coronariana , Neoplasias Gastrointestinais , Traumatismos Cardíacos , Humanos , Volume Sistólico , Estudos Retrospectivos , Função Ventricular Esquerda , Fatores de Risco
5.
Front Pharmacol ; 13: 970812, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36278222

RESUMO

Background: Previous studies have demonstrated that activated endothelial epithelial sodium channel (EnNaC) impairs vasodilatation, which contributes to salt-sensitive hypertension. Here, we investigate whether mesenteric artery (MA) EnNaC is involved in cold exposure-induced hypertension (CIH) and identify the underlying mechanisms in SD rats. Methods: One group of rats was housed at room temperature and served as control. Three groups of rats were kept in a 4°C cold incubator for 10 h/day; among which two groups were administrated with either benzamil (EnNaC blocker) or eplerenone (mineralocorticoid receptor antagonist, MR). Blood pressure (BP), vasodilatation, and endothelial function were measured with tail-cuff plethysmography, isometric myograph, and Total Nitric Oxide (NO) Assay kit, respectively. A cell-attached patch-clamp technique, in split-open MA, was used to determine the role of EnNaC in CIH rats. Furthermore, the plasma aldosterone levels were detected using an ELISA kit; and Western blot analysis was used to examine the relative expression levels of Sgk1 and Nedd4-2 proteins in the MA of SD rats. Results: We demonstrated that cold exposure increased BP, impaired vasodilatation, and caused endothelial dysfunction in rats. The activity of EnNaC significantly increased, concomitant with an increased level of plasma aldosterone and activation of Sgk1/Nedd4-2 signaling. Importantly, CIH was inhibited by either eplerenone or benzamil. It appeared that cold-induced decrease in NO production and impairment of endothelium-dependent relaxation (EDR) were significantly ameliorated by either eplerenone or benzamil in MA of CIH rats. Moreover, treatment of MAs with aldosterone resulted in an activation of EnNaC, a reduction of NO, and an impairment of EDR, which were significantly inhibited by either eplerenone or GSK650394 (Sgk1 inhibitor) or benzamil. Conclusion: Activation of EnNaC contributes to CIH; we suggest that pharmacological inhibition of the MR/Sgk1/Nedd4-2/EnNaC axis may be a potential therapeutic strategy for CIH.

6.
Lipids Health Dis ; 21(1): 89, 2022 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-36123743

RESUMO

BACKGROUND: Alcohol-related liver disease (ALD) is a major chronic liver ailment caused by alcohol overconsumption and abuse. Apolipoprotein H (APOH) participates in lipid metabolism and might have a potential regulatory role in ALD. Therefore, this study aimed to explore the effects of ApoH on alcohol-induced liver injury and gut microbiota dysbiosis. METHODS: ApoH-/- mice were generated and the synergic alcoholic steatohepatitis mouse model was constructed, which were used to assess liver function and pathological changes. RESULTS: ApoH-/- mice clearly exhibited spontaneous steatohepatitis. Severe hepatic steatosis was observed in alcohol-fed WT and ApoH-/- mice, in which ApoH expression was reduced post alcohol consumption. Moreover, RNA-seq and KEGG pathway analyses indicated that differential expression genes enriched in lipid metabolism and oxidation-reduction process between in alcohol-fed ApoH-/- mice and pair-fed control mice. Finally, gut microbiota diversity and composition were assessed by 16S rRNA Illumina next-generation sequencing. Alpha diversity of enterobacteria was lower in ApoH-/- mice with ethanol feeding than in ethanol-fed WT mice and all control-fed mice (P < 0.05). Moreover, KEGG enrichment analysis, using PICRUSt software, revealed that metabolic functions were activated in the gut microorganisms of ApoH-/- mice with ethanol feeding (P < 0.05). CONCLUSIONS: Alcohol-downregulated ApoH expression, leading to the progress of fatty liver disease and gut microbiota dysbiosis.


Assuntos
Alcoolismo , Fígado Gorduroso , Microbioma Gastrointestinal , Hepatopatias , Animais , Regulação para Baixo , Disbiose/genética , Disbiose/microbiologia , Etanol/toxicidade , Fígado Gorduroso/genética , Camundongos , RNA Ribossômico 16S/genética , beta 2-Glicoproteína I/farmacologia
7.
Eur J Pharm Sci ; 170: 106102, 2022 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-34958883

RESUMO

This study test was designed to investigate the possible modulatory effect of rapamycin combined with HO-3867 in monocrotaline(MCT)-induced pulmonary arterial hypertension in rats. We hypothesized that combined treatment with rapamycin and HO-3867 is superior to either alone in attenuating MCT-induced rat pulmonary arterial hypertension (PAH). Pulmonary arterial hypertension was induced by a single intraperitoneal injection of monocrotaline (60 mg/kg). 2 weeks later, rapamycin (2 mg/kg i.p.) and HO3867 (10 mg/kg i.h.) were administered daily, alone and in combination, for 2 weeks. Right ventricular systolic pressure, echocardiography were recorded and then rats were sacrificed. Histological analysis of pulmonary arteries medial wall thickness, right ventricular hypertrophy index (RVHI), the ratio of right ventricular to body weight, and collagen volume fraction (CVF) of right ventricular were performed. Moreover, the expression of t-STAT3, p-STAT3, t-Akt, p-Akt in lung and t-STAT3, p-STAT3, t-S6, p-S6 in right ventricular were examined. The result showed that combined treatment provided a considerable improvement toward maintaining hemodynamic changes, lung vascular remodeling as well as amending RV remodeling and function. Furthermore, Combined treatment can normalize the protein levels of two signal pathways in lung and heart tissue, where p-S6 or p-Akt significantly decreased compared to HO-3867 alone, or p-STAT3 significantly reduced compared to rapamycin alone. In conclusion, combined treatment with rapamycin and HO-3867 is superior to either alone in attenuating MCT-induced PAH in rats.


Assuntos
Hipertensão Pulmonar , Monocrotalina , Animais , Modelos Animais de Doenças , Hipertensão Pulmonar/induzido quimicamente , Hipertensão Pulmonar/tratamento farmacológico , Piperidonas , Artéria Pulmonar , Ratos , Ratos Sprague-Dawley , Sirolimo
8.
EClinicalMedicine ; 40: 101128, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34522874

RESUMO

BACKGROUND: The incidence of cardiovascular events in perioperative period of gastrointestinal tumor surgery cannot be ignored, and studies have shown that level of postoperative troponin is related to the postoperative risk of non-cardiac surgery. However, the relationship between pre-operative troponin levels and perioperative risk of gastrointestinal tumor surgery is unclear. Thus, we aimed to evaluate the value of high-sensitive cardiac troponin I (hs-cTnI) prior to gastrointestinal tumor surgery for perioperative risk assessment. METHODS: In this retrospective cohort study, 1259 patients who underwent gastrointestinal tumor surgery and had been tested for hs-cTnI on admission within 7 days prior to surgery were retrospectively recruited from January 2018 to June 2020. The primary combined endpoint including in-hospital all-cause mortality, acute myocardial infarction, cardiac arrest or ventricular fibrillation and acute decompensated heart failure. The secondary endpoint included total hospital stay and requirement of intensive care treatment. FINDINGS: Compared with patients with normal hs-cTnI, those with elevated hs-cTnI (> 0·028 ng/ml) were more likely to experience the combined endpoint (28·2% versus 2·7%, P < 0·001) and there was also an increasing rate of in mortality in elevated hs-cTnI group (2·4% versus 0·3%, P = 0·057). The length of total hospital stay was significantly longer in patients with elevated hs-cTnI (24·8 ± 16·3 versus 19·5 ± 7·9, P = 0·003) and the number of patients requiring intensive care treatment was also higher (22·6% versus 4·2%, P < 0·001). The area under the ROC curve assessing hs-cTnI in predicting in-hospital mortality was 0·787 [95% confidence interval (CI) 0·612-0·963, P = 0·015] and for combined endpoint was 0·822 [95% CI 0·766-0·879, P < 0·001]. Hs-cTnI > 0·028 ng/ml was associated with significantly higher cardiovascular event rate in patients with the revised cardiac index ≤ 1. The positive likelihood ratio of hs-cTnI (> 0·028 ng/ml) for predicting combined endpoint reaches 10.5 in patients with Lee index = 0. In multivariate logistic analyses, hs-cTnI was one of the best predictors for the combined endpoint [odds ratio (OR) 5·924 (95%CI: 2·869-12·233), P < 0·001]. INTERPRETATION: Hs-cTnI provides powerful prognostic information for patients undergoing gastrointestinal tumor surgery, and therefore provides reliable prognostic information incremental to revised cardiac index.

9.
J Hazard Mater ; 419: 126406, 2021 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-34175708

RESUMO

Traditional disposal techniques for the spent layered adsorbents after capturing organics suffer from intractable obstacles, such as resource waste and secondary pollution. To address this diploma, we here developed the "resource-utilization" strategy, i.e., converting the organic layered double hydroxide (as representative) to magnetic sulfur (S)-doped graphene-like carbon-supported layered double oxide (MG/S-LDO) to be reutilized in water purification. The as-prepared MG/S-LDO exhibited outstanding remediation ability toward methyl orange (MO) and lead(II), with the adsorption capacity of 1456 and 656 mg g-1, respectively. Specifically, the residue concentration of Pb2+ was reduced to 0.15 mg L-1 within 1 h, which met the discharge limit of the secondary industrial wastewater. MG/S-LDO could also maintain the preeminent adsorption capability under various interferences (such as wide pH and co-existing ions), even in the authentic water matrices. The removal mechanisms were systematically investigated to unveil that MO removal was dominated by metal-complexation, "memory effect", and π-π electron donor-acceptor (EDA). While for Pb2+ removal, besides the released OH- from LDO as precipitate agent, the vacancy defect resulting from the S doping played a crucial role in electron interaction between Pb2+ and S-doped graphene. Additionally, the MG/S-LDO was further confirmed as an eco-friendly adsorbent with excellent reusability via the acute toxicity tests using green algae and multiple cycle experiments. This work provides a novel resource-utilization strategy for organic layered wastes to construct the functional eco-friendly materials in wastewater purification realm.


Assuntos
Grafite , Poluentes Químicos da Água , Purificação da Água , Adsorção , Compostos Azo , Carbono , Chumbo , Fenômenos Magnéticos , Óxidos , Enxofre
10.
J Hepatocell Carcinoma ; 8: 451-465, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34046369

RESUMO

BACKGROUND: Emerging evidences have highlighted the roles of neutrophils, as the major host microenvironment component, in the development of hepatocellular carcinoma (HCC). Neutrophils extracellular traps (NETs) produced in the infection can strengthen the behavior of cancer metastasis. Here, we investigated the roles of NETs in HCC metastasis and further explore the underlying mechanism of how NETs interact with cancer. METHODS: The neutrophils were isolated from whole blood of HCC patients and used to evaluate the formation of NETs. NET markers were detected in tissue samples, plasma and cell climbing slice. Mouse models were used to evaluate the roles of NETs in HCC metastasis in vivo, and the corresponding mechanisms were explored using in vivo and in vitro assays. RESULTS: An increase in the release of NETs in patients with HCC, particularly those with portal vein tumor thrombosis (PVTT). The presence of NETs in HCC tumor tissues closely correlated with a poor prognosis. Functionally, the invasion ability of HCC cells was enhanced by co-culture with HCC neutrophils, through NETs formation, while the neutrophils from a healthy donor (HD) exhibited the inhibition of the invasion ability. Furthermore, we observed an enhanced ability of forming NETs in neutrophils from HCC patients in vitro, especially patients with PVTT or extra-hepatic metastasis. An in-vivo animal study demonstrated that neutrophils of HCC facilitated the metastatic behavior towards the lung. The further mechanistic investigation unveiled that HCC cells-derived cytokine IL-8 triggered NETs formation in an NADPH oxidase-dependent manner, and NETs-associated cathepsin G (cG) promoted HCC metastasis in vitro as well as vivo. Clinically, the expression of the cG protein in tumor tissues displayed a close correlation with the disease prognosis of HCC patients. CONCLUSION: Our findings implicated that the induction of NETs by HCC cells is a critical metastasis-supporting cancer-host interaction and that NETs may serve as an immune-based potential therapeutic target against HCC progression.

11.
Environ Res ; 195: 110719, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33549622

RESUMO

Coexisting ammonium (NH4+-N) and phosphate (PO43--P) in wastewater is one of the main causes of eutrophication, which poses severe risks to aquatic ecosystem and human health worldwide. Herein, magnesium-rich tricalcium aluminate (Mg/C3A), which was constructed by incorporating Mg into cement-based material C3A via solid-state reaction, was employed in the simultaneous removal of NH4+-N and PO43--P. Considering the wastewater with unbalanced N/P ratio and fluctuant pH, the effect of multiple factors (Mg/C3A dosage, pH, initial contaminant concentration, and temperature) on the removal of both ions were systematically investigated by employing response surface methodology technique. The results demonstrated that the impact order of the factors on the NH4+ removal by Mg/C3A was: temperature > Mg/C3A dosage > initial NH4+ concentration > pH > initial PO43- concentration; the impact order on the PO43- removal was: initial PO43- concentration > Mg/C3A dosage > temperature > pH > initial NH4+ concentration. The maximum removal amount of NH4+ (54.13 mg g-1) and PO43- (56.47 mg g-1) were obtained at: Mg/C3A dosage = 3 g L-1, initial NH4+ concentration = 160 mg L-1, initial PO43- concentration = 160 mg L-1, temperature = 308 K, and pH = 7. In addition, the possible interactive influence mechanisms were elucidated in depth. Mg2+ played a major role in the PO43- removal by forming struvite (MgNH4PO4·6H2O) and newberyite (MgHPO4·3H2O). OH- released from Mg/C3A hydration mainly contributed to NH4+ removal. This work showed that Mg-rich C3A is a promising candidate for simultaneous removal of NH4+ and PO43-, shedding light on practical water remediation.


Assuntos
Compostos de Amônio , Fósforo , Ecossistema , Humanos , Magnésio , Fosfatos , Estruvita
12.
Brain Struct Funct ; 223(8): 3813-3840, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30083997

RESUMO

The inability to control or inhibit emotional distractors characterizes a range of psychiatric disorders. Despite the use of a variety of task paradigms to determine the mechanisms underlying the control of emotional interference, a precise characterization of the brain regions and networks that support emotional interference processing remains elusive. Here, we performed coordinate-based and functional connectivity meta-analyses to determine the brain networks underlying emotional interference. Paradigms addressing interference processing in the cognitive or emotional domain were included in the meta-analyses, particularly the Stroop, Flanker, and Simon tasks. Our results revealed a consistent involvement of the bilateral dorsal anterior cingulate cortex, anterior insula, left inferior frontal gyrus, and superior parietal lobule during emotional interference. Follow-up conjunction analyses identified correspondence in these regions between emotional and cognitive interference processing. Finally, the patterns of functional connectivity of these regions were examined using resting-state functional connectivity and meta-analytic connectivity modeling. These regions were strongly connected as a distributed system, primarily mapping onto fronto-parietal control, ventral attention, and dorsal attention networks. Together, the present findings indicate that a domain-general neural system is engaged across multiple types of interference processing and that regulating emotional and cognitive interference depends on interactions between large-scale distributed brain networks.


Assuntos
Encéfalo/fisiologia , Cognição/fisiologia , Conflito Psicológico , Emoções/fisiologia , Função Executiva/fisiologia , Mapeamento Encefálico , Humanos , Imageamento por Ressonância Magnética , Vias Neurais/fisiologia , Teste de Stroop
13.
Neuropharmacology ; 110(Pt A): 25-36, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27424103

RESUMO

The role of prelimbic (PrL) 5-HT6 receptors in depression is poorly understood, particularly in Parkinson's disease-related depression. Here we reported that 6-hydroxydopamine lesions in rats decreased sucrose preference and increased immobility time as measured by the sucrose preference and forced swim tests when compared to sham-operated rats, indicating the induction of depressive-like behaviors. Intra-PrL injection of 5-HT6 receptor agonist WAY208466 induced depressive-like responses in sham-operated rats, and produced antidepressant-like effects in the lesioned rats. However, 5-HT6 receptor antagonist SB258585 produced antidepressant-like effects in sham-operated rats, and increased the expression of depressive-like behaviors in the lesioned rats. Neurochemical results showed that intra-PrL injection of WAY208466 and SB258585 decreased or increased dopamine (DA) and noradrenaline (NA) levels in the medial prefrontal cortex, amygdala, habenula and ventral hippocampus in sham-operated and the lesioned rats, respectively. WAY208466 increased the firing rate of PrL glutamate neurons in the two groups of rats, while SB258585 decreased the firing rate of the neurons. Compared to sham-operated rats, the duration of WAY208466 and SB258585 action on the firing rate of glutamate neurons was markedly prolonged in the lesioned rats. The lesion did not change the co-localization of 5-HT6 receptor and glutamate neurons in the PrL. These findings indicate that 5-HT6 receptors in the PrL are involved in the regulation of depressive-like behaviors, which attribute to changes in DA and NA levels in the limbic and limbic-related brain regions. Additionally, the results suggest that the lesion leads to a supersensitization of 5-HT6 receptors on glutamate neurons in the PrL.


Assuntos
Depressão/metabolismo , Transtornos Parkinsonianos/metabolismo , Córtex Pré-Frontal/metabolismo , Receptores de Serotonina/metabolismo , Antagonistas da Serotonina/administração & dosagem , Agonistas do Receptor de Serotonina/administração & dosagem , Animais , Depressão/induzido quimicamente , Depressão/prevenção & controle , Injeções Intraventriculares , Masculino , Metilaminas/administração & dosagem , Oxidopamina/toxicidade , Transtornos Parkinsonianos/induzido quimicamente , Piperazinas/administração & dosagem , Córtex Pré-Frontal/efeitos dos fármacos , Piridinas/administração & dosagem , Ratos , Ratos Sprague-Dawley , Sulfonamidas/administração & dosagem
15.
Chembiochem ; 17(9): 799-803, 2016 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-26854280

RESUMO

Thienodolin (THN) features a tricyclic indole-S-hetero scaffold that encompasses two unique carbon-sulfur bonds. Although its biosynthetic gene cluster has been recently identified in Streptomyces albogriseolus, the essential enzymes for the formation of C-S bonds have been relatively unexplored. Here, we isolated and characterized a new biosynthetic gene cluster from Streptomyces sp. FXJ1.172. Heterologous expression, systematic gene inactivation, and in vitro biochemical characterization enable us to determine the minimum set of genes for THN synthesis, and an aminotransferase (ThnJ) for catalyzing the downstream conversion of tryptophan chlorination. In addition, we evaluated (and mainly excluded) a previously assumed pivotal intermediate by feeding experiments. With these results, we narrowed down four enzymes (ThnC-F) that are responsible for the two unprecedented C-S bond formations. Our study provides a solid basis for further unraveling of the unique C-S mechanisms.


Assuntos
Carbono/metabolismo , Indóis/metabolismo , Enxofre/metabolismo , Tiofenos/metabolismo , Carbono/química , Cromatografia Líquida de Alta Pressão , Indóis/química , Família Multigênica , Streptomyces/enzimologia , Streptomyces/genética , Enxofre/química , Tiofenos/química , Transaminases/genética , Transaminases/metabolismo
16.
Cell Biochem Biophys ; 70(2): 1433-8, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24989681

RESUMO

The catecholaminergic neurotoxin 6-hydroxydopamine has been widely used to mimic the lesions in dopaminergic neurons to develop Parkinson's disease. The present study was aimed to evaluate the combined treatment with Curcumin and desferrioxamine (DFO) on 6-OHDA-induced neurotoxicity in the striatum of rats. Rat models with 6-OHDA-induced Parkinson's disease were treated with curcumin, DFO, or both and the effect of different treatments on dopamine level was examined. Moreover, the effect of different treatments on the levels of PCC, SOD, and GSH was also assessed to elucidate the underlying mechanisms of the neuroprotective effects of combined treatment of curcumin and DFO.


Assuntos
Curcumina/farmacologia , Desferroxamina/farmacologia , Fármacos Neuroprotetores/farmacologia , Oxidopamina/toxicidade , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/etiologia , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Curcumina/uso terapêutico , Desferroxamina/uso terapêutico , Modelos Animais de Doenças , Dopamina/metabolismo , Interações Medicamentosas , Masculino , Fármacos Neuroprotetores/uso terapêutico , Doença de Parkinson/metabolismo , Ratos , Ratos Sprague-Dawley
17.
J Agric Food Chem ; 60(43): 10844-9, 2012 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-23057589

RESUMO

This study enzymatically acrylates two flavonoids from bamboo-leaf extracts, isoorientin and isovitexin, with different fatty acids as acyl donors using Candida antarctica lipase B (CALB). The conversion yield ranged from 35 to 80% for fatty acids with different chain lengths. Higher isoorientin and isovitexin conversion yields (>75%) were obtained using lauric acid in tert-amyl-alcohol as the reaction medium. (1)H and (13)C nuclear magnetic resonance spectroscopy analysis showed that, in the presence of CALB, acylation occurred at the isoorientin and isovitexin primary hydroxyl group of glucose moiety and only monoesters were detected. Introducing an acyl group into isoorientin and isovitexin significantly improved their lipophilicity but reduced their antiradical activity.


Assuntos
Apigenina/química , Bambusa/química , Sequestradores de Radicais Livres/química , Proteínas Fúngicas/química , Lipase/química , Luteolina/química , Extratos Vegetais/química , Folhas de Planta/química , Acilação , Biocatálise , Ácidos Graxos/química , Estrutura Molecular
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