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1.
J Am Chem Soc ; 145(42): 23152-23159, 2023 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-37844139

RESUMO

In biological or abiotic systems, rhythms occur, owing to the coupling between positive and negative feedback loops in a reaction network. Using the Semenov-Whitesides oscillatory network for thioester hydrolysis as a prototype, we experimentally and theoretically analyzed the role of fast and slow inhibitors in oscillatory reaction networks. In the presence of positive feedback, a single fast inhibitor generates a time delay, resulting in two saddle-node bifurcations and bistability in a continuously stirred tank reactor. A slow inhibitor produces a node-focus bifurcation, resulting in damped oscillations. With both fast and slow inhibitors present, the node-focus bifurcation repeatedly modulates the saddle-node bifurcations, producing stable periodic oscillations. These fast and slow inhibitions result in a pair of time delays between steeply ascending and descending dynamics, which originate from the positive and negative feedbacks, respectively. This pattern can be identified in many chemical relaxation oscillators and oscillatory models, e.g., the bromate-sulfite pH oscillatory system, the Belousov-Zhabotinsky reaction, the trypsin oscillatory system, and the Boissonade-De Kepper model. This study provides a novel understanding of chemical and biochemical rhythms and suggests an approach to designing such behavior.

2.
Neuropathol Appl Neurobiol ; 49(1): e12860, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36331758

RESUMO

AIMS: Accumulation and propagation of pathological α-synuclein (α-Syn) are the major contributing factors to the pathogenesis of Parkinson's disease (PD). Therapy to halt the spreading of α-Syn pathology needs to be established. METHODS: After phage display and affinity maturation, human-derived anti-α-Syn autoantibodies were selected and applied to biochemical, cellular and animal models of PD. RESULTS: The novel naturally occurring anti-α-Syn autoantibodies (α-Syn-nAbs), P21 and P22, selectively bind α-Syn preformed fibrils (PFFs), recognise Lewy bodies (LBs) and Lewy neurites (LNs) in human PD brains, block α-Syn fibrillization and inhibit the seeding of α-Syn PFFs. Moreover, systematic administration of P21 and P22 attenuates α-Syn pathology, degeneration of the nigrostriatal pathway and motor deficits in mice injected with α-Syn PFFs. CONCLUSIONS: P21 and P22 attenuate α-synuclein pathology and are promising candidates for PD treatment.


Assuntos
Doença de Parkinson , Sinucleinopatias , Camundongos , Humanos , Animais , Doença de Parkinson/patologia , alfa-Sinucleína/metabolismo , Autoanticorpos/metabolismo , Encéfalo/patologia , Modelos Animais de Doenças
3.
Chemphyschem ; 24(12): e202300336, 2023 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-37323101

RESUMO

The front cover artwork is provided by Prof. Gao's group. The image shows the motion patterns transition of the active gel group under the step light intensity, which describes the mechanism of a new collective emergence structure. Read the full text of the Research Article at 10.1002/cphc.202300054.


Assuntos
Luz , Movimento (Física)
4.
Chemphyschem ; 24(12): e202300054, 2023 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-36988019

RESUMO

Abrupt (i. e. step) environmental changes, such as natural disasters or the intervention of predators, can alter the internal dynamics of groups with active units, leading to the rapid destruction and/or restructuring of the group, with the emergence of new collective structures that endow the system with adaptability. Few studies, to date, have considered the influence of abrupt environmental changes on emergent behavior. Here, we use a model of active matter, the Belousov-Zhabotinsky (BZ) self-oscillating gel, to study the mechanism of formation and transition between modes of collective locomotion caused by changes of illumination intensity in arrays of interacting photosensitive active units. New forms of collective motion can be generated by step changes of illumination intensity. These transformations arise from the phase resetting and wave-signal regeneration induced by the abrupt parameter variation, while gradual change results in different evolution of collective motion. Our results not only suggest a novel mechanism for emergence, but also imply that new collective behaviors could be accessible via discontinuous parameter changes.


Assuntos
Luz , Géis/química , Movimento (Física)
5.
BMC Endocr Disord ; 23(1): 191, 2023 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-37684683

RESUMO

OBJECTIVES: The purpose of this study was to investigate the correlation between triglyceride-glucose (TyG) index and cervical vascular function parameters in the general population without cerebrovascular disease. MATERIALS AND METHODS: This was a cross-sectional study that recruited a total of 1996 participants without cerebrovascular disease. TyG index was calculated based on fasting triglycerides and glucose. All patients were divided into two groups based on the median TyG index: the high TyG group and the low TyG group. The differences in basic clinical characteristics and neck vascular function parameters between the two groups of participants were compared, and then the correlation between TyG index and neck vascular function parameters was investigated. RESULTS: Participants with a high TyG index had lower systolic, diastolic, and mean flow velocities in the basilar, vertebral, and internal carotid arteries compared with those with a low TyG index. Participants with a high TyG index had higher pulsatility index in the left vertebral artery and right internal carotid artery, but this difference was not observed in the basilar artery. In addition, TyG index was significantly negatively correlated with systolic, diastolic, and mean flow velocities in the basilar, vertebral, and internal carotid arteries, and the correlation remained after adjusting for confounding factors. CONCLUSION: In the general population, there was a well-defined correlation between TyG index and cervical vascular function parameters, and increased TyG index was independently associated with reduced cervical vascular blood flow velocity.


Assuntos
Glucose , Pacientes Ambulatoriais , Humanos , Estudos de Coortes , Estudos Transversais , Triglicerídeos
6.
BMC Med Educ ; 23(1): 882, 2023 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-37978370

RESUMO

"Clinical basic inspection technology" is one of the essential courses in the medical laboratory profession. Combining the characteristics of the discipline itself, the research and practice of the BOPPPS model based on the OBE concept in clinical basic laboratory experiment teaching are discussed, and the reform of in teaching objectives, teaching contents, and teaching design path is implemented. The "student-centered" teaching process is divided into six stages: before, during, and after class, and the teaching process is continuously improved to achieve the desired teaching effect. Results of the experiment teaching show that the model has improved students' active participation and developed their clinical thinking skills, and more than 95% of students are satisfied with this teaching model.


Assuntos
Medicina , Estudantes , Humanos , Pensamento , Competência Clínica , Laboratórios
7.
JAMA ; 329(8): 640-650, 2023 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-36757755

RESUMO

Importance: Previous studies suggested a benefit of argatroban plus alteplase (recombinant tissue-type plasminogen activator) in patients with acute ischemic stroke (AIS). However, robust evidence in trials with large sample sizes is lacking. Objective: To assess the efficacy of argatroban plus alteplase for AIS. Design, Setting, and Participants: This multicenter, open-label, blinded end point randomized clinical trial including 808 patients with AIS was conducted at 50 hospitals in China with enrollment from January 18, 2019, through October 30, 2021, and final follow-up on January 24, 2022. Interventions: Eligible patients were randomly assigned within 4.5 hours of symptom onset to the argatroban plus alteplase group (n = 402), which received intravenous argatroban (100 µg/kg bolus over 3-5 minutes followed by an infusion of 1.0 µg/kg per minute for 48 hours) within 1 hour after alteplase (0.9 mg/kg; maximum dose, 90 mg; 10% administered as 1-minute bolus, remaining infused over 1 hour), or alteplase alone group (n = 415), which received intravenous alteplase alone. Both groups received guideline-based treatments. Main Outcomes and Measures: The primary end point was excellent functional outcome, defined as a modified Rankin Scale score (range, 0 [no symptoms] to 6 [death]) of 0 to 1 at 90 days. All end points had blinded assessment and were analyzed on a full analysis set. Results: Among 817 eligible patients with AIS who were randomized (median [IQR] age, 65 [57-71] years; 238 [29.1%] women; median [IQR] National Institutes of Health Stroke Scale score, 9 [7-12]), 760 (93.0%) completed the trial. At 90 days, 210 of 329 participants (63.8%) in the argatroban plus alteplase group vs 238 of 367 (64.9%) in the alteplase alone group had an excellent functional outcome (risk difference, -1.0% [95% CI, -8.1% to 6.1%]; risk ratio, 0.98 [95% CI, 0.88-1.10]; P = .78). The percentages of participants with symptomatic intracranial hemorrhage, parenchymal hematoma type 2, and major systemic bleeding were 2.1% (8/383), 2.3% (9/383), and 0.3% (1/383), respectively, in the argatroban plus alteplase group and 1.8% (7/397), 2.5% (10/397), and 0.5% (2/397), respectively, in the alteplase alone group. Conclusions and Relevance: Among patients with acute ischemic stroke, treatment with argatroban plus intravenous alteplase compared with alteplase alone did not result in a significantly greater likelihood of excellent functional outcome at 90 days. Trial Registration: ClinicalTrials.gov Identifier: NCT03740958.


Assuntos
Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Feminino , Idoso , Masculino , Ativador de Plasminogênio Tecidual , Fibrinolíticos/uso terapêutico , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/induzido quimicamente , AVC Isquêmico/tratamento farmacológico , Isquemia Encefálica/tratamento farmacológico , Resultado do Tratamento
8.
J Sci Food Agric ; 103(6): 3139-3145, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36694937

RESUMO

BACKGROUND: The characteristics of corn kernels are strongly connected with the content of three statuses of water: bound water, immobilized water, and free water. Monitoring different water contents is very important to optimize the drying process, improve corn quality, and reduce energy consumption. The feasibility of nondestructive detection of water status and its distribution in corn kernels during the hot-air drying process using multispectral imaging was investigated. RESULTS: The chemometric methods used to develop prediction models were back propagation neural network, least-squares support vector machine, and partial least squares. The back propagation neural network achieved the best prediction performance for total and free water contents, with correlation coefficient of prediction (Rp ) of 0.9717 and 0.9782 respectively, root-mean-square error of prediction (RMSEP) of 4.48% and 2.54% respectively, and ratio of prediction to deviation (RPD) of 4.87 and 4.29 respectively. And partial least squares was better for the prediction of immobilized and bound water contents, with Rp of 0.9612 and 0.9798 respectively, RMSEP of 0.57% and 0.06% respectively, and RPD of 4.78 and 4.42 respectively. CONCLUSION: It could be concluded that multispectral imaging combined with chemometric methods would be a promising technique for rapid and nondestructive detection of water status and its distribution in corn kernels. © 2023 Society of Chemical Industry.


Assuntos
Água , Zea mays , Zea mays/química , Redes Neurais de Computação , Análise dos Mínimos Quadrados , Máquina de Vetores de Suporte
9.
Small ; 18(11): e2107544, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35038225

RESUMO

Chronic wound infection is one of the critical complications of diabetes and is difficult to cure. Although great efforts have been made, the development of special dressings that serve as therapeutic strategies to effectively promote wound healing in diabetic individuals remains a major challenge. In this study, a shape-programmable hierarchical fibrous membrane composite system is developed for synergistic modulation of the inflammatory microenvironment to treat chronically infected wounds. The system comprises a functional layer and a shape-programmable backing layer. A temperature-responsive shape-memory mechanism achieves biaxial mechanically active contractions of diabetic wounds in a programmable manner. To summarize, the membrane system combines antimicrobial activity, controlled drug release according to the need of wound healing, mechanical modulation with shape-programmable, robust adhesion, and on-demand debonding to biological tissue to rationally guide chronic wound management. A synergistic combination of antibacterial fiber network and released drugs shows broad-spectrum antibacterial activity. In vitro and in vivo evaluations indicate the dressing efficiency in promoting and supporting wound healing. The insights from this study demonstrate the effectiveness of a hierarchical composite membrane system with shape-programmability as a potential treatment in the care of diabetic wounds.


Assuntos
Diabetes Mellitus , Cicatrização , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Bandagens , Liberação Controlada de Fármacos , Humanos
10.
Int J Clin Pract ; 2022: 2235994, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36212053

RESUMO

Objective: To investigate the correlation of obesity and overweight with cardiac ultrasound parameters and future cardiovascular risk among healthy populations. Methods: Basic clinical characteristics as well as cardiac ultrasound parameters were collected from healthy people. Firstly, all participants were divided into three groups: normal, overweight, and obese. Then the differences in cardiac ultrasound parameters between the three groups were calculated. Subsequently, those aged 35-60 years were screened to determine their cardiovascular risk according to the SCORE system. Finally, the correlation between cardiac ultrasound indices and cardiovascular risk was calculated. Results: A total of 1328 healthy participants were included, of whom 504 were normal, 580 were overweight and 244 were obese. Obesity and overweight significantly increased the aorta, left atrium, right atrium, right ventricle, the end-diastolic diameter of the left ventricle, main pulmonary artery, right ventricular outflow tract, interventricular septum, left ventricular posterior wall, and triglycerides and decreased E/A values and high-density lipoprotein-cholesterol. Ejection fraction, fractional shortening, low-density lipoprotein-cholesterol, and total cholesterol did not change between the three groups. A total of 781 participants were screened for SCORE scores. Obesity and being overweight significantly increased the incidence of future cardiovascular events, and lower E/A values were also associated with cardiovascular risk. All cardiac parameters were strongly associated with cardiovascular risk. Conclusion: Our research demonstrates that obesity and overweight can damage heart shape and function and raise the risk of future cardiovascular events in people that are healthy. Cardiovascular risk and cardiac structural and functional impairments are significantly positively correlated.


Assuntos
Doenças Cardiovasculares , Sobrepeso , Índice de Massa Corporal , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/etiologia , HDL-Colesterol , LDL-Colesterol , Fatores de Risco de Doenças Cardíacas , Humanos , Obesidade/complicações , Sobrepeso/complicações , Fatores de Risco , Triglicerídeos
11.
JAMA ; 328(7): 627-636, 2022 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-35972485

RESUMO

Importance: Preclinical and clinical studies have suggested a neuroprotective effect of remote ischemic conditioning (RIC), which involves repeated occlusion/release cycles on bilateral upper limb arteries; however, robust evidence in patients with ischemic stroke is lacking. Objective: To assess the efficacy of RIC for acute moderate ischemic stroke. Design, Setting, and Participants: This multicenter, open-label, blinded-end point, randomized clinical trial including 1893 patients with acute moderate ischemic stroke was conducted at 55 hospitals in China from December 26, 2018, through January 19, 2021, and the date of final follow-up was April 19, 2021. Interventions: Eligible patients were randomly assigned within 48 hours after symptom onset to receive treatment with RIC (using a pneumatic electronic device and consisting of 5 cycles of cuff inflation for 5 minutes and deflation for 5 minutes to the bilateral upper limbs to 200 mm Hg) for 10 to 14 days as an adjunct to guideline-based treatment (n = 922) or guideline-based treatment alone (n = 971). Main Outcomes and Measures: The primary end point was excellent functional outcome at 90 days, defined as a modified Rankin Scale score of 0 to 1. All end points had blinded assessment and were analyzed on a full analysis set. Results: Among 1893 eligible patients with acute moderate ischemic stroke who were randomized (mean [SD] age, 65 [10.3] years; 606 women [34.1%]), 1776 (93.8%) completed the trial. The number with excellent functional outcome at 90 days was 582 (67.4%) in the RIC group and 566 (62.0%) in the control group (risk difference, 5.4% [95% CI, 1.0%-9.9%]; odds ratio, 1.27 [95% CI, 1.05-1.54]; P = .02). The proportion of patients with any adverse events was 6.8% (59/863) in the RIC group and 5.6% (51/913) in the control group. Conclusions and Relevance: Among adults with acute moderate ischemic stroke, treatment with remote ischemic conditioning compared with usual care significantly increased the likelihood of excellent neurologic function at 90 days. However, these findings require replication in another trial before concluding efficacy for this intervention. Trial Registration: ClinicalTrials.gov Identifier: NCT03740971.


Assuntos
Pós-Condicionamento Isquêmico , AVC Isquêmico , Idoso , China , Feminino , Humanos , Pós-Condicionamento Isquêmico/métodos , AVC Isquêmico/complicações , AVC Isquêmico/terapia , Masculino , Pessoa de Meia-Idade , Doenças do Sistema Nervoso/etiologia , Doenças do Sistema Nervoso/prevenção & controle , Doenças do Sistema Nervoso/terapia , Recuperação de Função Fisiológica , Resultado do Tratamento , Extremidade Superior/irrigação sanguínea
12.
Anal Chem ; 93(39): 13161-13168, 2021 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-34499839

RESUMO

Carbon nanotube (CNT)-modified electrodes are used to obtain new measurements of vesicle content via amperometry. We have investigated the interaction between CNTs and isolated adrenal chromaffin vesicles (as a model) by vesicle impact electrochemical cytometry. Our data show that the presence of CNTs not only significantly increased the vesicular catecholamine number from 2,250,000 ± 112,766 molecules on a bare electrode to 3,880,000 ± 686,573 molecules on CNT/carbon fiber electrodes but also caused an enhancement in the maximum intensity of the current, which implies the existence of strong interactions between vesicle biolayers and CNTs and an altered electroporation process. We suggest that CNTs might perturb and destabilize the membrane structure of intracellular vesicles and cause the aggregation or fusion of vesicles into new vesicles with larger size and higher content. Our findings are consistent with previous computational and experimental results and support the hypothesis that CNTs as a mediator can rearrange the phospholipid bilayer membrane and trigger homotypic fusion of intracellular vesicles.


Assuntos
Nanotubos de Carbono
13.
Pharmacol Res ; 166: 105527, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33667689

RESUMO

The invasion and metastasis of tumor cells are the hallmarks of malignant diseases and the greatest obstacle to overcome. Heparanase-mediated degradation of heparan sulfate (HS) is the critical process for tumor angiogenesis and metastasis, therefore, heparanase become an attractive target for cancer research. Herein, we reported a native fucosylated glycosaminoglycan (nHG) extracted from sea cucumber Holothuria fuscopunctata and a depolymerized nHG (dHG) and its contained oligosaccharides (hs17, hs14, hs11, hs8 and hs5), acting as heparanase inhibitors. nHG and its derivatives have the ability to bind with heparanase directly, leading to significant inhibition of heparanase activity. Moreover, their apparent binding affinity to heparanase was comparable to their inhibitory effect, which was elevated along with the increase of chain length, similar to the effect of heparins. In addition, oligosaccharides inhibited the migration and invasion of 4T1 mammary carcinoma cells and human umbilical vein endothelial cells (HUVECs) and also suppressed tube formation in Matrigel matrix and angiogenesis in the chick chorioallantoic membrane (CAM) assay. In the metastatic mouse model, oligosaccharides exhibited practical antimetastatic effects on 4T1 mammary carcinoma cells. According to the reported anticoagulant activity and the low bleeding tendency of dHG and its oligosaccharides, the use of the oligosaccharides may lead to better effects on tumor patients with thrombosis tendency.


Assuntos
Antineoplásicos/uso terapêutico , Glucuronidase/antagonistas & inibidores , Glicosaminoglicanos/uso terapêutico , Neoplasias Mamárias Experimentais/patologia , Metástase Neoplásica/prevenção & controle , Neovascularização Patológica/tratamento farmacológico , Animais , Antineoplásicos/química , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Feminino , Glicosaminoglicanos/química , Células Endoteliais da Veia Umbilical Humana , Humanos , Neoplasias Mamárias Experimentais/tratamento farmacológico , Camundongos , Simulação de Acoplamento Molecular , Metástase Neoplásica/patologia , Neovascularização Patológica/patologia , Oligossacarídeos/química , Oligossacarídeos/uso terapêutico , Pepinos-do-Mar/química
14.
Water Sci Technol ; 83(8): 2001-2011, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33905368

RESUMO

Rapid removal of radioactive strontium from nuclear wastewater is of great significance for environmental safety and human health. This work reports the effective adsorption of strontium ion in a stable dual-group metal-organic framework, Zr6(OH)14(BDC-(COOH)2)4(SO4)0.75 (Zr-BDC-COOH-SO4), which contains strontium-chelating groups (-COOH and SO4) and a strongly ionizable group (-COOH). Zr-BDC-COOH-SO4 exhibits very rapid adsorption kinetics (<5 min) and a maximum adsorption capacity of 67.5 mg g-1. The adsorption behaviors can be well fitted to the pseudo-second-order model and the Langmuir isotherm model. Further investigations indicate that the adsorption of Sr2+ onto Zr-BDC-COOH-SO4 would not be obviously affected by solution pH and adsorption temperature. The feasible regeneration of the adsorbent was also demonstrated using a simple elution method. Mechanism investigation suggests that free -COOH contributes to the rapid adsorption based on electrostatic interaction, while the introduction of -SO4 significantly enhanced the adsorption capacity. Thus, these results suggest that Zr-BDC-COOH-SO4 is a potential candidate for Sr2+ removal. They also introduce dual groups as an effective strategy for designing high-efficiency adsorbents.


Assuntos
Estruturas Metalorgânicas , Poluentes Químicos da Água , Adsorção , Humanos , Concentração de Íons de Hidrogênio , Cinética , Estrôncio , Sulfatos , Poluentes Químicos da Água/análise
15.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 52(4): 679-685, 2021 Jul.
Artigo em Zh | MEDLINE | ID: mdl-34323049

RESUMO

OBJECTIVE: To establish a method for simultaneous determination of 12 kinds of perfluorinated compounds (PFCs) in human urine based on ultra performance liquid chromatography tandem quadrupole linear ion trap mass spectrometry (UPLC-QTtrap-MS). METHODS: After pH adjustment with 2% formic acid, the urine samples were loaded on a WAX solid phase extraction (SPE) cartridge for extraction, purification and concentration. The eluates were collected, concentrated to dryness under nitrogen, and reconstituted with 10 mmol/L ammonium acetate aqueous solution-methanol ( V water∶ V methanol = 70∶30) before injection. UPLC was performed on a C 18 cartridge, and methanol and 10 mmol/L ammonium acetate aqueous solution was used as mobile phases with gradient elution. QTtrap-MS was operated in multiple reaction monitoring (MRM) mode, and the internal standard calibration curves were applied for quantitative analysis. RESULTS: Good linearity was obtained in the linear range, with the method detection limits and method quantification limits being 0.032 ng/L-6.5 ng/L and 0.10 ng/L-21 ng/L, respectively, for the 12 kinds of PFCs. The spiked recoveries of the 12 kinds of PFCs were 91.5%-114%, with the intra-day precision and the inter-day precision being 0.57%-16.0% and 1.88%-20.1%, respectively. The established method was applied to the determination of 12 kinds of PFCs in the urine samples of primary school students collected in one area. Nine kinds of PFCs were detected in the urine samples in this area. Among the PFCs detected, perfluorobutanesulfonic acid (PFBS) and perfluorooctanoic acid (PFOA) were the main PFCs found in the student urine samples. CONCLUSION: The method established in this study could be used to simultaneously examine 12 kinds of PFCs in urine. The method combined SPE with isotope internal standard correction and achieved good sensitivity and accuracy.


Assuntos
Extração em Fase Sólida , Espectrometria de Massas em Tandem , Cromatografia Líquida de Alta Pressão , Cromatografia Líquida , Humanos
16.
Angew Chem Int Ed Engl ; 60(14): 7593-7596, 2021 03 29.
Artigo em Inglês | MEDLINE | ID: mdl-33340209

RESUMO

Recent work has shown that chemical release during the fundamental cellular process of exocytosis in model cell lines is not all-or-none. We tested this theory for vesicular release from single pancreatic beta cells. The vesicles in these cells release insulin, but also serotonin, which is detectible with amperometric methods. Traditionally, it is assumed that exocytosis in beta cells is all-or-none. Here, we use a multidisciplinary approach involving nanoscale amperometric chemical methods to explore the chemical nature of insulin exocytosis. We amperometrically quantified the number of serotonin molecules stored inside of individual nanoscale vesicles (39 317±1611) in the cell cytoplasm before exocytosis and the number of serotonin molecules released from single cells (13 310±1127) for each stimulated exocytosis event. Thus, beta cells release only one-third of their granule content, clearly supporting partial release in this system. We discuss these observations in the context of type-2 diabetes.


Assuntos
Exocitose/fisiologia , Células Secretoras de Insulina/metabolismo , Insulina/análise , Serotonina/química , Animais , Glicemia/metabolismo , Citoplasma/metabolismo , Citoplasma/ultraestrutura , Diabetes Mellitus Tipo 2/metabolismo , Técnicas Eletroquímicas , Humanos , Camundongos
17.
Biochem Cell Biol ; 98(3): 378-385, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32160475

RESUMO

Myocardial ischemia-reperfusion injury (MIRI) is the leading cause of the poor prognosis for patients undergoing clinical cardiac surgery. Micro-RNAs are involved in MIRI; however, the effect of miR-760 on MIRI and the molecular mechanisms behind it have not yet been described. For our in-vivo experiments, 20 rats were randomly distributed between 2 groups (n = 10): the sham-treatment group and the ischemia-reperfusion (I/R) group. For our in-vitro experiments, H9C2 cells were subjected to hypoxia for 6 h, and then reoxygenated to establish an hypoxia-reoxygenation (H/R) model. High expression levels of of miR-760 were observed in the rats subjected to MIRI and the H9C2 cells subjected to H/R. Further, the levels of lactate dehydrogenase (LDH) and malonaldehyde (MDA) were increased, and the size of the myocardial infarct was notably greater in the rats subjected to MIRI, suggesting that miR-760 worsens the effects of MIRI. The inhibitory effects from NaHS on apoptosis were enhanced, as were the expression levels of cleaved caspase 3 and cleaved PARP in H9C2 cells exposed to H/R, and with low-expression levels of miR-760. TargetScan and dual luciferase reporter assays further confirmed the targeted relationship between dual-specificity protein phosphatase (DUSP1) and miR-760. Additionally, miR-760 overexpression and H/R treatment of H9C2 cells inhibited the expression of DUSP1, which further promoted apoptosis. Furthermore, DUSP1 enhanced the anti-apoptotic effects of NaHS in rats subjected to MIRI. Taken together, these findings suggest that miR-760 inhibits the protective effect of NaHS against MIRI.


Assuntos
Fosfatase 1 de Especificidade Dupla/metabolismo , MicroRNAs/metabolismo , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão/metabolismo , Sulfetos/farmacologia , Animais , Apoptose , Hipóxia Celular , Sobrevivência Celular/efeitos dos fármacos , Regulação da Expressão Gênica , L-Lactato Desidrogenase/metabolismo , Masculino , Malondialdeído/metabolismo , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Miócitos Cardíacos/efeitos dos fármacos , Ratos , Ratos Wistar , Traumatismo por Reperfusão/tratamento farmacológico , Regulação para Cima
18.
Oncologist ; 25(12): e1909-e1920, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33000490

RESUMO

LESSONS LEARNED: This is the first trial to explore the neoadjuvant therapy of pyrotinib in HER2-positive operable and locally advanced breast cancer, in combination with epirubicin plus cyclophosphamide followed by docetaxel plus trastuzumab. Results primarily showed that pyrotinib in combination with epirubicin plus cyclophosphamide followed by docetaxel plus trastuzumab was effective and safe in HER2-positive operable and locally advanced breast cancer. A subsequent randomized controlled trial is still warranted to confirm these results. BACKGROUND: The efficacy and safety of neoadjuvant therapy of pyrotinib, a new irreversible tyrosine kinase inhibitor (TKI), was first estimated in patients with HER2-positive breast cancer in this phase II study, in combination with trastuzumab and chemotherapy. METHODS: Between February 19, 2019, and November 20, 2019, 20 female Chinese patients with stage I-III HER2-positive breast cancer were assigned to receive eight cycles of neoadjuvant pyrotinib (P) in combination with four cycles of epirubicin (E) and cyclophosphamide (C) followed by four cycles of docetaxel (T) and trastuzumab (H), once every 3 weeks, referred to as P + EC-TH. RESULTS: A total of 19 patients completed the therapy and final surgery. The total pathological complete response (tpCR) rate was 73.7% (95% confidence interval [CI], 48.8-90.9), and no recurrence or metastasis occurred during the short-term follow-up period. The objective response rate (ORR) was 100% (95% CI, 82.4-100). The most common adverse events (AEs) were diarrhea and leukopenia in 18 of 20 patients (90%), but no grade 5 AEs were reported. CONCLUSION: This study showed that in HER2-positive operable or locally advanced breast cancer, the tpCR rate of P + EC-TH neoadjuvant therapy was about twice as high as that of EC-TH neoadjuvant therapy reported in other trials, with tolerable side effects.


Assuntos
Neoplasias da Mama , Terapia Neoadjuvante , Acrilamidas , Aminoquinolinas , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Ciclofosfamida/uso terapêutico , Feminino , Humanos , Recidiva Local de Neoplasia/tratamento farmacológico , Receptor ErbB-2/uso terapêutico , Trastuzumab/uso terapêutico , Resultado do Tratamento
19.
J Phys Chem A ; 124(18): 3530-3534, 2020 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-32298110

RESUMO

In a self-oscillating gel, unidirectional chemical waves generated by the Belousov-Zhabotinsky reaction can drive locomotion, which results from the difference between the push and pull forces in the wavefront and waveback, respectively. In a narrow tube, such a gel is subject not only to the asymmetric force engendered by the propagation of the chemical waves but also to additional forces originating from the capillary effect in the polymer skeleton. The ends of a self-oscillating gel in a tube are squeezed unequally during unidirectional motion, causing new waves of higher frequency and ultimately giving rise to reversal of the direction of chemical wave propagation. This peculiar phenomenon of a self-oscillating gel in a narrow glass tube results in a nonmonotonic evolution of the gel locomotion velocity.

20.
Proc Natl Acad Sci U S A ; 114(33): 8704-8709, 2017 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-28760961

RESUMO

Periodic to-and-fro migration is a sophisticated mode of locomotion found in many forms of active matter in nature. Providing a general description of periodic migration is challenging, because many details of animal migration remain a mystery. We study periodic migration in a simpler system using a mechanistic model of a photosensitive, active material in which a stimulus-responsive polymer gel is propelled by chemical waves under the regulation of an illumination gradient sensed by the gel, which plays a role analogous to the environment in periodic animal migration. The reciprocating gel migration results from autonomous transitions between retrograde and direct wave locomotion modes arising from the gradient distribution of the illumination intensity. The local dynamics of the chemical waves modulates the asymmetry between push and pull forces to achieve repeated reorientation of the direction of locomotion. Materials that display similar intelligent, self-adaptive locomotion might be tailored for such functions as drug delivery or self-cleaning systems.

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