RESUMO
Natural resistance associated macrophage protein 5 (NRAMP5) is a key transporter for cadmium (Cd) uptake by rice roots; however, the effect of OsNRAMP5 on Cd translocation and redistribution in rice plants remains unknown. In this study, an extremely low Cd-accumulation mutant (lcd1) and wild type (WT) plants were utilized to investigate the effect of OsNRAMP5 mutation on Cd translocation and redistribution via the xylem and phloem and its possible physiological mechanism using field, hydroponic and isotope-labelling experiments. The results showed that OsNRAMP5 mutation reduced xylem and phloem transport of Cd, due to remarkably lower Cd translocation from roots to shoots and from the leaves â -â ¢ to their corresponding nodes, as well as lower Cd concentrations in xylem and phloem sap of lcd1 compared to WT plants. Mutation of OsNRAMP5 reduced Cd translocation from roots to shoots in lcd1 plants by increasing Cd deposition in cellulose of root cell walls and reducing OsHMA2-and OsCCX2-mediated xylem loading of Cd, and the citric acid- and tartaric acid-mediated long-distance xylem transport of Cd. Moreover, OsNRAMP5 mutation inhibited Cd redistribution from flag leaves to nodes and panicles in lcd1 plants by increasing Cd sequestration in cellulose and vacuoles, and decreasing OsLCT1-mediated Cd phloem transport in flag leaves.
Assuntos
Cádmio , Oryza , Cádmio/metabolismo , Oryza/genética , Oryza/metabolismo , Floema/metabolismo , Transporte Biológico , Xilema/metabolismo , Mutação , Celulose/metabolismo , Raízes de Plantas/metabolismoRESUMO
BACKGROUND: Bupleurum (Bup), is a traditional effective medicine to treat colds and fevers in clinics. Multiple studies have demonstrated that Bup exhibites various biological activities, including cardioprotective effects, anti-inflammatory, anticancer, antipyretic, antimicrobial, and antiviral effects, etc. Currently, the effects of Bup on cardiac electrophysiology have not been reported yet. METHODS: Electrocardiogram recordings were used to investigate the effects of Bup on aconitine-induced arrhythmias. Patch-clamp techniques were used to explore the effects of Bup on APs and ion currents. RESULTS: Bup reduced the incidence of ventricular fibrillation (VF) and delayed the onset time of ventricular tachycardia (VT) in mice. Additionally, Bup (40 mg/mL) suppressed DADs induced by high-Ca2+ and shortened action potential duration at 50 % completion of repolarization (APD50) and action potential duration at 90 % completion of repolarization (APD90) to 60.89 % ± 8.40 % and 68.94 % ± 3.24 % of the control, respectively. Moreover, Bup inhibited L-type calcium currents (ICa.L) in a dose-dependent manner, with an IC50 value of 25.36 mg/mL. Furthermore, Bup affected the gated kinetics of L-type calcium channels by slowing down steady-state activation, accelerating the steady-state inactivation, and delaying the inactivation-recovery process. However, Bup had no effects on the Transient sodium current (INa.T), ATX II-increased late sodium current (INa.L), transient outward current (Ito), delayed rectifier potassium current (IK), or inward rectifier potassium current (IK1). CONCLUSION: Bup is an antiarrhythmic agent that may exert its antiarrhythmic effects by inhibiting L-type calcium channels.
Assuntos
Bupleurum , Canais de Cálcio Tipo L , Camundongos , Animais , Bupleurum/metabolismo , Miócitos Cardíacos/metabolismo , Antiarrítmicos/efeitos adversos , Arritmias Cardíacas , Sódio/metabolismo , Potássio/farmacologia , Potenciais de AçãoRESUMO
In this study, 6229 brown rice grains from three major rice-producing regions were collected to investigate the spatial and variety distributions of heavy metals in rice grains in China. The potential sources of heavy metals in rice grains were identified using the Pearson correlation matrix and principal component analysis, and the health risks of dietary exposure to heavy metals via rice consumption were assessed using the hazard index (HI) and total carcinogenic risk (TCR) method, respectively. Moreover, 48 paired soil and rice samples from 11 cities were collected to construct a predicting model for Cd accumulation in rice grains using the multiple linear stepwise regression analysis. The results indicated that Cd and Ni were the main heavy metal pollutants in rice grains in China, with approximately 10% of samples exceeding their corresponding maximum allowable limits. The Yangtze River basin had heavier pollution of heavy metals than the Southeast Coastal Region and Northeast Plain, and the indica rice varieties had higher heavy metal accumulation abilities compared with the japonica rice. The Cu, Pb, and Cd mainly originated from anthropogenic sources, while As, Hg, Cr, and Ni originated from both natural and anthropogenic sources. The mean HI and TCR values of dietary exposure to heavy metals via rice consumption ranged from 2.92 to 4.31 and 9.74 × 10-3 to 1.44 × 10-2, respectively, much higher than the acceptable range, and As and Ni were the main contributor to the HI and TCR for Chinese adults and children, respectively. The available Si (ASi), total Cd (TCd), available Mo (AMo), and available S (AS) were the main soil factors determining grain Cd accumulation. A multiple linear stepwise regression model was constructed based on ASi, TCd, AMo, and AS in soils with good accuracy and precision, which could be applied to predict Cd accumulation in rice grains and guide safe rice production in contaminated paddy fields.
Assuntos
Metais Pesados , Oryza , Poluentes do Solo , Criança , Adulto , Humanos , Cádmio/análise , Poluentes do Solo/análise , Metais Pesados/análise , Medição de Risco , China , Solo , Receptores de Antígenos de Linfócitos T , Monitoramento AmbientalRESUMO
Circulating tumor cells (CTCs), which are shed from primary tumor or metastatic sites into the bloodstream and subsequently seed into distant tissues, are considered as the precursors of metastases. Gastric cancer (GC) is a highly heterogeneous malignant tumor. With regard to the diagnosis of GC, secondary pathological biopsy is difficult, while invasive examination is harmful to patients. In recent years, CTCs have made great progress in tumor diagnosis, prognosis prediction, efficacy detection and treatment guidance, but the research on the role of CTCs in GC remains limited. The following sections review the landmark studies demonstrating the technical approaches of CTCs monitoring in the field of GC. Moreover, we highlight the clinical application of CTCs numbers and phenotypes in monitoring the therapeutic efficacy and judging patient prognosis by sequential blood analyses.
Assuntos
Células Neoplásicas Circulantes , Neoplasias Gástricas , Humanos , Células Neoplásicas Circulantes/patologia , Neoplasias Gástricas/diagnóstico , Prognóstico , Biópsia , Biomarcadores TumoraisRESUMO
The reduction of oil uptake in vacuum-fried Pleurotus eryngii chips by ultrasound assisted pretreatment was investigated regarding the pore structure changes. Pore structure of P. eryngii chips with four pretreatments, such as blanching, blanching + osmosis, blanching + ultrasound and blanching + ultrasound assisted osmosis was determined by mercury intrusion porosimetry (MIP) and scanning electron microscopy (SEM). In addition, the quality parameters of vacuum-fried P. eryngii chips such as hardness, rehydration ratio, reducing sugar, protein and oil content were also measured. The results showed that the oil absorption of vacuum fried P. eryngii chips was affected by the porous structure. The oil content of vacuum fried P. eryngii chips was significantly and positively correlated with the pores with diameters above 50, 5-50, and 0.5-5 µm in the samples both before and after vacuum frying, while negatively correlated with the pores with diameters below 0.5 µm. Ultrasound pretreatment changed the microporous structure of P. eryngii chips, effectively hindering the oil absorption of samples. In particular, ultrasound assisted osmosis pretreatment induced the formation of more micropores. It was concluded that blanching + ultrasound assisted osmosis pretreatment is a promising method to reduce oil absorption and improve the quality of vacuum fried foods.
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Esophageal cancer is of high importance to occurrence, development, and treatment resistance. As evidenced by recent studies, pathways (e.g., Wnt/ß-catenin, AMPK, and Hippo) are critical to the proliferation, differentiation, and self-renewal of esophageal cancer. In addition, the above pathways play a certain role in regulating esophageal cancer and act as potential therapeutic targets. Over the past few years, the function of lipid metabolism in controlling tumor cells and immune cells has aroused extensive attention. It has been reported that there are intricate interactions between lipid metabolism reprogramming between immune and esophageal cancer cells, whereas molecular mechanisms should be studied in depth. Immune cells have been commonly recognized as a vital player in the esophageal cancer microenvironment, having complex crosstalk with cancer cells. It is increasingly evidenced that the function of immune cells in the tumor microenvironment (TME) is significantly correlated with abnormal lipid metabolism. In this review, the latest findings in lipid metabolism reprogramming in TME are summarized, and the above findings are linked to esophageal cancer progression. Aberrant lipid metabolism and associated signaling pathways are likely to serve as a novel strategy to treat esophageal cancer through lipid metabolism reprogramming.
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The effects of salicylic acid (SA) on cadmium (Cd) accumulation, Cd subcellular distribution, cell wall composition and Cd adsorption in Cd-stressed rice seedlings were examined. The interaction between SA and nitric oxide (NO) signaling in regulating cell wall composition under Cd exposure was also investigated. Our results showed that 5 µmol·L-1 Cd treatment significantly decreased plant height, root length and plant dry weight by 40.1%, 46.1% and 21.3% (p < 0.05), respectively, and the inhibitory effects of Cd on the growth parameters were alleviated by exogenous SA. Application of SA remarkably decreased Cd concentrations in roots and shoots of rice seedlings by 48.0% and 19.6%, respectively, and increased the distribution ratio of Cd in the root cell wall fraction (from 35.7% to 40.6%) compared with Cd treatment alone. The reduced Cd accumulation in rice plants could be attributed to that SA application promoted pectin synthesis and demethylesterification, thereby increasing Cd deposition in the root cell wall. Moreover, SA application promoted lignin biosynthesis to strengthen the cell wall and prevent Cd from entering the root cells. In addition, NO might be involved in SA-induced pectin synthesis, pectin demethylesterification and lignin biosynthesis as a downstream signaling molecule, contributing to reduced Cd accumulation in Cd-stressed rice seedlings. The results provide deep insights into the mechanisms of exogenous SA action in reducing Cd accumulation in rice plants.
Assuntos
Oryza , Poluentes do Solo , Cádmio/toxicidade , Parede Celular , Óxido Nítrico , Raízes de Plantas , Ácido Salicílico , Plântula , Poluentes do Solo/toxicidadeRESUMO
Management of nitrogen fertilizer is a good strategy for controlling cadmium (Cd) accumulation in plants. Some progress has already been made but much remains to be done. Here, we show that mutants with loss of function of nitrate transporter1.1 (NRT1.1) or nitrate transporter2.1 (NRT2.1) had lower Cd concentrations than wild-type plants under low-nitrate conditions. However, this was eliminated when plants were cultivated in nitrate-free medium or supplied with Cd and nitrate alternately. These findings indicate that inhibition of NRT1.1 or NRT2.1 activity reduces Cd accumulation in plants, and depends on the presence of nitrate. The results showing that nrt2.1-2 mutants had the lowest Cd concentrations compared with Col-0, nrt1.1 and nrt2.4 plants, proves that NRT2.1 is the major contributor to Cd uptake controlled by nitrate high-affinity transporters. NRT2.1 acts as the major contributor to nitrate uptake under Cd stress in low-nitrate conditions, and contributes about 50% to nitrate uptake, while NRT1.1 contributes only 10%, and little is known regarding the role of NRT2.2 and NRT2.4 on nitrate uptake in medium with 200 µM nitrate. Positive correlations between nitrate uptake and Cd concentration in plants were also observed. Collectively, NRT2.1 acts as the major contributor to Cd uptake by controlling nitrate uptake in nitrate high-affinity systems.
RESUMO
To observe the changes in NLR family pyrin domain containing 3 (NLRP3) inflammasome in a rat model of diabetes-induced lung injury, and investigate the effect of low-dose ethanol on the production of NLRP3 inflammasome. The type I diabetic mellitus (DM) rat model was established, and the rats were divided into four groups: normal control group (CON group), low-dose ethanol group (EtOH group), diabetes group (DM group) and DM+EtOH group. The rats were fed for 6 and 12 weeks, respectively. The ratio of lung wet weight/body weight (lung/body coefficient) was calculated, and the changes of pulmonary morphology and fibrosis were observed by HE and Masson staining. The changes in pulmonary ultra-structure were examined by electron microscopy. The expressions of mitochondrial acetaldehyde dehydrogenase 2 (ALDH2) and NLRP3 inflammasome key factors, NLRP3, ASC and caspase-1 proteins were detected by western blot. Compared with the CON group, the lung/body coefficient was increased (P<0.05), lung fibrosis occurred, ALDH2 protein expression was decreased, and NLRP3, ASC and caspase-1 protein expressions were increased in the DM rats (P<0.05). Compared with the DM group, the lung/body coefficient and fibrosis degree were decreased, ALDH2 protein expression was increased (P<0.05), and NLRP3, ASC and caspase-1 protein expressions were decreased in the DM+EtOH group (P<0.05). Hence, low-dose ethanol increased ALDH2 protein expression and alleviated diabetes-induced lung injury by inhibiting the production of NLRP3 inflammasome.
Assuntos
Complicações do Diabetes/fisiopatologia , Etanol/efeitos adversos , Inflamassomos/genética , Lesão Pulmonar/fisiopatologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Aldeído-Desidrogenase Mitocondrial/metabolismo , Animais , Complicações do Diabetes/induzido quimicamente , Relação Dose-Resposta a Droga , Inflamassomos/metabolismo , Inflamação/induzido quimicamente , Inflamação/genética , Lesão Pulmonar/induzido quimicamente , Masculino , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Distribuição Aleatória , Ratos , Ratos Sprague-DawleyRESUMO
STUDY OBJECTIVE: To propose a "3O" (obstruction, ureteric orifice, and outcome) subclassification system associated with obstructed hemivagina and ipsilateral renal anomaly (OHVIRA). DESIGN: Retrospective case series. SETTING: Xiangya Hospital, Central South University, Changsha, Hunan, China. PARTICIPANTS: A total of 26 women with obstructed hemivagina and ipsilateral renal anomaly (OHVIRA) over a 9-year period. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: In all cases, the obstruction, ureteric orifice, outcome and surgical strategy were reviewed. RESULTS: In our study, the "obstruction" category included 14 cases of blind hemivagina, 8 cases of buttonhole septum, 3 cases of cervical fistula, and 1 case of cervical atresia. A total of 25 patients with vaginal obstruction underwent resection of the vaginal septum. The patient with cervical atresia underwent a failed cervicoplasty, followed by hemi-hysterectomy. The "ureteric orifice" category included 24 cases of absent ureter with no orifice, as well as 2 cases of ureteric orifice emptying into the obstructed hemivagina. The 2 patients were treated with laparoscopic extirpation of the ectopic ureter and renal moiety. Regarding the "outcome" category, 5 patients with severe recurrent hematometra, hematosalpinx, and ovarian endometrioma underwent hemi-hysterectomy, salpingectomy, and cystectomy of the ovarian endometrioma. Both patients (1 with a septate uterus and 1 with a bicornuate uterus) who experienced recurrent abortion accepted uterine correction. CONCLUSION: We provide new insights into the anatomical variants of this rare syndrome with the relevant surgical implications. Magnetic resonance imaging is the most useful tool in 3O diagnosis.
Assuntos
Rim/anormalidades , Útero/anormalidades , Vagina/anormalidades , Adolescente , Adulto , Criança , Feminino , Humanos , Histerectomia , Rim/cirurgia , Gravidez , Estudos Retrospectivos , Síndrome , Ureter , Obstrução Ureteral/cirurgia , Útero/cirurgia , Vagina/cirurgia , Adulto JovemRESUMO
Cadmium (Cd) is a heavy metal that is toxic to plants and animals. Nitrogen (N), the most significant macro-nutrient and a common input for crop production, is often excessively applied than plants' demands by farmers to obtain more economic benefits. Understanding the regulatory mechanisms of N that control Cd uptake, translocation, and accumulation may enable the development of solutions regarding Cd pollution in the trophic chain, a major and global threat to agricultural sustainability and human health. In this review, we clarified that an increased amount of N, regardless of its form, enhances Cd uptake, translocation, and accumulation in plants, and nitrate promotes Cd uptake more than any other N form. We also described that N fertilizer alters the Cd exchange capacity and the bio-available Cd content in soil; regulates nitric oxide induced divalent cation gene expression of Nramp1, HMA2, and IRT1; and changes cell wall isolation, chelation capacity, and oxidative resistance to regulate Cd accumulation in plants. By revealing the integrated interaction effects between Cd accumulation and N fertiliser use, we propose new challenges to investigate the functions and mechanisms of N in Cd-contaminated croplands and develop suitable N-fertilisation protocols to practically reduce food health risks in agricultural food production.
Assuntos
Plantas , Animais , Cádmio , Fertilizantes , Humanos , Nitrogênio , Solo , Poluentes do SoloRESUMO
The variations in microRNA (miRNA) expression levels can be useful biomarkers for the diagnosis of different cancers. In this work, a label-free and sensitive fluorescent method for detection of miRNA-21 is described based on duplex-specific nuclease (DSN) assist target recycling and terminal deoxynucleotidyl transferase (TdT) induced copper nanoclusters (CuNCs). In the absence of target, the 3'-phosphorylated probe DNA cannot be hydrolyzed by DSN and extended by TdT, and failed to synthesizing fluorescent CuNCs. However, the target miRNA-21 can caused the digestion of probe DNA with DSN, releasing primer DNA with 3'-OH. After that, the primer DNA can forms long poly T with the assistance of TdT, leading to synthesize high fluorescent CuNCs. The fluorescence change of CuNCs can be used to identify the concentration of target miRNA-21. Under optimal experimental conditions, this strategy could quantitatively detect miRNA-21 down to 18.7 pM. We have also demonstrated the practical application of our proposed method for monitoring miRNA-21 expression levels in cancer cells. Moreover, this method show good specificity for miRNA-21 detection due to the strong preference of DSN for cutting perfectly matched DNA/RNA duplex, which holds great potential for highly specific quantification of biomarkers in bioanalysis and clinical diagnosis.
Assuntos
Biomarcadores Tumorais/análise , Cobre/química , Corantes Fluorescentes/química , Nanopartículas Metálicas/química , MicroRNAs/análise , Neoplasias/química , Técnicas Biossensoriais , Linhagem Celular Tumoral , DNA/química , DNA Nucleotidilexotransferase/metabolismo , Sondas de DNA/química , Endonucleases/metabolismo , Humanos , Limite de Detecção , Neoplasias/diagnóstico , Neoplasias/metabolismo , Hibridização de Ácido Nucleico , Poli T/química , Sensibilidade e Especificidade , Espectrometria de Fluorescência , Coloração e RotulagemRESUMO
The depression incidence is much higher in patients with diabetes mellitus (DM), and the majority of these cases remain under-diagnosed. Type 1 diabetes mellitus (T1D) is now widely thought to be an organ-specific autoimmune disease. As a chronic autoimmune condition, T1D is characterized by T cell-mediated selective loss of insulin-producing ß-cells. The age of onset of T1D is earlier than T2D, and T1D patients have an increased vulnerability to depression due to its diagnosis and treatment burden occurring in a period when the individuals are young. The literature has suggested that inflammatory cytokines play a wide role in both diseases. In this review, the mechanisms behind the initiation and propagation of the autoimmune response in T1D and depression are analyzed, and the contribution of cytokines to both conditions is discussed. This review outlines the immunological mechanism of T1D and depression, with a particular emphasis on the role of tumor necrosis factor-α (TNF-α), IL-1ß, and interferon-γ (IFN-γ) cytokines and their signaling pathways. The purpose of this review is to highlight the possible pathways of the cytokines shared by these two diseases via deciphering their cytokine cascades. They may provide a basic groundwork for future study of the possible mechanism that links these two diseases and to develop new compounds that target the same pathway but can conquer two diseases.
Assuntos
Citocinas/metabolismo , Depressão/imunologia , Diabetes Mellitus Tipo 1/imunologia , Diabetes Mellitus Tipo 1/metabolismo , Inflamação/imunologia , Depressão/metabolismo , Feminino , Humanos , Inflamação/metabolismo , MasculinoAssuntos
Carbono/administração & dosagem , Ressecção Endoscópica de Mucosa/métodos , Excisão de Linfonodo/métodos , Linfonodos/cirurgia , Mediastinoscopia/métodos , Nanopartículas/administração & dosagem , Cirurgia Endoscópica por Orifício Natural/métodos , Animais , Injeções , Mediastino , Modelos Animais , Sus scrofaRESUMO
Ustilaginoidea (U.) virens grows on rice grains and leads to significant rice yield losses in most of the major rice producing areas. Meanwhile, ustiloxins produced by U. virens are a serious hazard to human health and ecological safety of farmlands. The other key point is that ustiloxins have been regarded as a novel resource with their potential in the treatment of cancers. There is no better way to extract ustiloxins than from pure culture of the high ustilotoxin-producing strains. U. virens has become a key research organism. However, due to the presence of some interference components, it is a certain difficulty in the successful isolation of the strain from the false smut balls. We present here a detailed study based on the separation, screening and identification of high ustiloxins-producing strains of U. virens. Through this study, we got a satisfactory success rate of separation and provided a good solution to the problem of separation. At the same time, this study provides quality resources for researchers interested in ustiloxins as anticancer agents.
Assuntos
Hypocreales/isolamento & purificação , Micotoxinas/biossíntese , Oryza , Doenças das Plantas/microbiologia , Antineoplásicos/isolamento & purificação , Cromatografia Líquida , Meios de Cultura , DNA Fúngico/genética , DNA Espaçador Ribossômico/genética , Hypocreales/genética , Hypocreales/crescimento & desenvolvimento , Luz , Micotoxinas/classificação , Micotoxinas/isolamento & purificação , Análise de Sequência de DNA , Espectrometria de Massas em TandemRESUMO
Sulfur (S) fertilizer application in rice (Oryza sativa L.) is crucial in determining rice grain productivity and quality. However, little information is available concerning the effect of S supply on cadmium (Cd) uptake and translocation in rice. In this study, both hydroponic and soil experiments were conducted to investigate the influence of S supply on Cd accumulation in rice under two Cd levels (0 and 50⯵M), combined with three S concentrations (0, 2.64 and 5.28â¯mM). The moderate and excessive S supply (2.64 and 5.28â¯mM) tended to increase plant growth, root length, root and shoot dry weights of rice seedlings, and significantly decreased Cd concentrations in rice plants and grains in the absence or presence of Cd. The subcellular distribution and chemical forms of Cd in roots and shoots also varied with S supply levels. The decreased Cd uptake and translocation in rice grains could be ascribed to the enhanced formation of iron (Fe) plaque on the root surfaces and increased Cd chelation and vacuolar sequestration in roots, since Fe, Mn concentrations in Fe plaque, glutathione and phytochelatins contents, as well as phytochelatin synthase (OsPCS) and tonoplast heavy metal ATPase (OsHMA3) expressions in roots significantly increased with increased S supply. This work provides more insight into the mechanisms of Cd uptake and translocation in rice, and will be helpful for developing strategies to reduce rice grain Cd through S fertilizer application in Cd-contaminated soil.
Assuntos
Cádmio/metabolismo , Ferro/metabolismo , Oryza/metabolismo , Raízes de Plantas/crescimento & desenvolvimento , Plântula/metabolismo , Poluentes do Solo/metabolismo , Enxofre/farmacologia , Adenosina Trifosfatases/metabolismo , Aminoaciltransferases/metabolismo , Transporte Biológico/efeitos dos fármacos , Cádmio/análise , Grão Comestível/química , Fertilizantes/análise , Glutationa/metabolismo , Ferro/análise , Oryza/crescimento & desenvolvimento , Fitoquelatinas/metabolismo , Raízes de Plantas/metabolismo , Solo/química , Poluentes do Solo/análise , Enxofre/análiseRESUMO
Barbaloin (10-ß-D-glucopyranosyl-1,8-dihydroxy-3-(hydroxymethyl)-9(10H)-anthracenone) is extracted from the aloe plant and has been reported to have anti-inflammatory, antitumor, antibacterial, and other biological activities. Here, we investigated the effects of barbaloin on cardiac electrophysiology, which has not been reported thus far. Cardiac action potentials (APs) and ionic currents were recorded in isolated rabbit ventricular myocytes using whole-cell patch-clamp technique. Additionally, the antiarrhythmic effect of barbaloin was examined in Langendorff-perfused rabbit hearts. In current-clamp recording, application of barbaloin (100 and 200 µmol/L) dose-dependently reduced the action potential duration (APD) and the maximum depolarization velocity (Vmax), and attenuated APD reverse-rate dependence (RRD) in ventricular myocytes. Furthermore, barbaloin (100 and 200 µmol/L) effectively eliminated ATX II-induced early afterdepolarizations (EADs) and Ca2+-induced delayed afterdepolarizations (DADs) in ventricular myocytes. In voltage-clamp recording, barbaloin (10-200 µmol/L) dose-dependently inhibited L-type calcium current (ICa.L) and peak sodium current (INa.P) with IC50 values of 137.06 and 559.80 µmol/L, respectively. Application of barbaloin (100, 200 µmol/L) decreased ATX II-enhanced late sodium current (INa.L) by 36.6%±3.3% and 71.8%±6.5%, respectively. However, barbaloin up to 800 µmol/L did not affect the inward rectifier potassium current (IK1) or the rapidly activated delayed rectifier potassium current (IKr) in ventricular myocytes. In Langendorff-perfused rabbit hearts, barbaloin (200 µmol/L) significantly inhibited aconitine-induced ventricular arrhythmias. These results demonstrate that barbaloin has potential as an antiarrhythmic drug.
Assuntos
Antracenos/farmacologia , Arritmias Cardíacas/prevenção & controle , Canais de Potássio de Abertura Dependente da Tensão da Membrana/metabolismo , Aconitina/antagonistas & inibidores , Aconitina/farmacologia , Potenciais de Ação/efeitos dos fármacos , Animais , Arritmias Cardíacas/induzido quimicamente , Cálcio/farmacologia , Relação Dose-Resposta a Droga , Preparação de Coração Isolado , Miócitos Cardíacos/fisiologia , Técnicas de Patch-Clamp , Coelhos , Venenos de Escorpião/antagonistas & inibidores , Venenos de Escorpião/farmacologiaRESUMO
Traumatic brain injury (TBI), as a neurological injury, becomes a leading cause of disability and mortality due to lacking effective therapy. About 75% of TBI is mild traumatic brain injury (mTBI). However, the complex molecular mechanisms underlying mTBI pathophysiology remains to be elucidated. In this study, iTRAQ-based quantitative proteomic approach was employed to measure temporal-global proteome changes of rat brain tissues from different time points (1 day, 7 day and 6 months) post single mTBI (smTBI) and repetitive mTBI (rmTBI). A total of 5169 proteins were identified, of which, 237 proteins were significantly changed between control rats and mTBI model rats. Fuzzy c-means (FCM) clustering analysis classified these 237 proteins into six clusters according to their temporal pattern of protein abundance. Functional bioinformatics analysis and protein-protein interaction (PPI) network mapping of these FCM clusters showed that phosphodiesterase 10A (Pde10a) and guanine nucleotide-binding protein G (olf) subunit alpha (Gnal) were the node proteins in the cAMP signaling pathway. Other biological processes, such as cell adhesion, autophagy, myelination, microtubule depolymerization and brain development, were also over-represented in FCM clusters. Further Western Blot experiments confirmed that Pde10a and Gnal were acutely up-regulated in severity-dependent manner by mTBI, but these two proteins could not be down-regulated to basal level at the time point of 6 months post repetitive mTBI. Our study demonstrated that different severity of mTBI cause significant temporal profiling change at the proteomic level and pointed out the cAMP signaling pathway-related proteins, Pde10a and Gnal, may play important roles in the pathogenesis and recovery of mTBI.
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Lesões Encefálicas Traumáticas/genética , AMP Cíclico/metabolismo , Subunidades alfa de Proteínas de Ligação ao GTP/genética , Proteínas do Tecido Nervoso/isolamento & purificação , Diester Fosfórico Hidrolases/genética , Proteoma/isolamento & purificação , Animais , Encéfalo/metabolismo , Encéfalo/patologia , Lesões Encefálicas Traumáticas/metabolismo , Lesões Encefálicas Traumáticas/patologia , Cromatografia Líquida de Alta Pressão , Análise por Conglomerados , Biologia Computacional/métodos , Modelos Animais de Doenças , Subunidades alfa de Proteínas de Ligação ao GTP/metabolismo , Regulação da Expressão Gênica , Masculino , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Diester Fosfórico Hidrolases/metabolismo , Mapeamento de Interação de Proteínas , Proteólise , Proteoma/genética , Proteoma/metabolismo , Proteômica/métodos , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , Coloração e Rotulagem/métodos , Índices de Gravidade do TraumaRESUMO
BACKGROUND: Plant glutathione S-transferases (GSTs, EC 2.5.1.18) are multifunctional enzymes involved in heavy metal cellular detoxification by conjugating the tripeptide (g-Glu-Cys-Gly) glutathione to heavy metals. Previous studies demonstrated that individual rice GSTs were differentially induced by heavy metal exposure at the mRNA transcript level. However, little information is available concerning changes in protein concentration of rice GSTs under heavy metal stress. Because the correlation between changes in protein concentration and gene expression under abiotic stress is poor, direct determination of rice GSTs protein concentrations during cadmium (Cd) exposure is a more effective and reliable approach to explore possible mechanisms of rice Cd translocation and accumulation. RESULTS: This study established an optimized and advanced liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based targeted proteomics assay for quantification of OsGSTF14 and OsGSTU6 proteins in Cd-stressed rice roots. The tryptic signature peptides were chosen as surrogate analytes and winged peptides containing the isotope-labeled signature peptides were used as the internal standards. The signature peptides exhibited good linearity in the range of 0.6-60 and 0.3-30 nM, respectively. The limit of detection and limit of quantification were 4.5 and 14.5 µg/g for OsGSTF14, respectively, and 2.1 and 7.0 µg/g for OsGSTU6. The spiking recoveries rates at low, medium and high levels were in the range of 72.5-93.4%, with intra- and inter-day precisions of 5.5-9.1 and 4.2-10.2%, respectively. CONCLUSIONS: The assay successfully quantified the temporal and dose responses of OsGSTF14 and OsGSTU6 proteins in Cd-stressed rice roots, with good accuracy, precision and high-throughput. This assay will have significant application in developing quantification methods of other proteins in Cd-stressed rice, which may provide more insight into the mechanisms of Cd translocation and accumulation in rice.
RESUMO
PURPOSE: To compare the effectiveness and safety of individualized three-dimensional visualization technology (3DVT) on surgical planning and perioperative outcomes in laparoscopic partial nephrectomy (LPN) for renal cell carcinoma (RCC) with routine computed tomography (CT) examination in the treatment of renal tumor. METHODS: From May 2015 to March 2016, a total of 94 patients with cT1 RCC who underwent surgical treatment in our department were analyzed retrospectively. Among these patients, a total of 49 cases received LPN with operation plan based on 3DVT. Surgical plan was obtained by virtual operation and morphometry on 3D reconstruction model. The remaining 45 cases received surgical treatment with traditional CT examination. Patient demographic, surgical outcome, and postoperative parameters were compared between these two groups. RESULTS: No significant difference was found in blood loss volume, postoperative complication, selective clamping success rate, changes in postoperative renal function, and operative and ischemic time between the two groups. However, when handling complicated tumor with R.E.N.A.L score ≥8, operation time (126.7 ± 36.4 versus 154.8 ± 34.7, P = .018) and occurrence of postoperative urinary leak (0 versus 4, 0% versus 22.2%, P = .033) were diminished significantly in the 3DVT group. CONCLUSIONS: 3DVT provided precise information of anatomical structure in the operative area and reliable guidance for preoperative plan design. Our results indicated that 3DVT facilitated accurate visible image-guided tumor resection with ideal renal function preservation in LPN for renal tumor of high complexity.