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1.
J Synchrotron Radiat ; 31(Pt 1): 55-64, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-37930257

RESUMO

X-ray photon correlation spectroscopy (XPCS) holds strong promise for observing atomic-scale dynamics in materials, both at equilibrium and during non-equilibrium transitions. Here an in situ XPCS study of the relaxor ferroelectric PbMg1/3Nb2/3O3 (PMN) is reported. A weak applied AC electric field generates strong response in the speckle of the diffuse scattering from the polar nanodomains, which is captured using the two-time correlation function. Correlated motions of the Bragg peak are also observed, which indicate dynamic tilting of the illuminated volume. This tilting quantitatively accounts for the observed two-time speckle correlations. The magnitude of the tilting would not be expected solely from the modest applied field, since PMN is an electrostrictive material with no linear strain response to the field. A model is developed based on non-uniform static charging of the illuminated surface spot by the incident micrometre-scale X-ray beam and the electrostrictive material response to the combination of static and dynamic fields. The model qualitatively explains the direction and magnitude of the observed tilting, and predicts that X-ray-induced piezoresponse could be an important factor in correctly interpreting results from XPCS and nanodiffraction studies of other insulating materials under applied AC field or varying X-ray illumination.

2.
Mediators Inflamm ; 2023: 6627393, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37159798

RESUMO

Background: The inflammatory response is an important part of the pathogenesis of acne vulgaris. Auriculotherapy has been shown to have a good therapeutic effect on this disease. The aim of this study was to explore the mechanism underlying the anti-inflammatory effect of auriculotherapy in the treatment of acne vulgaris. Methods: Propionibacterium acnes was injected subcutaneously into the ears of rats to establish an animal model of acne. The auriculotherapy intervention in rats consisted of auricular bloodletting therapy (ABT), auricular point sticking (APS), or a combination of both (ABPS). The anti-inflammatory effects of auriculotherapy were evaluated by measuring changes in ear thickness, local body surface microcirculation in the ear, and serum inflammatory factors in rats. The polarization of macrophages was analyzed by flow cytometry, and the expression of TLR2/NF-κB signaling pathway in the target tissues was analyzed using western blot. Results: ABT, APS, and ABPS all reduced the erythema of ear acne, decreased microcirculation in localized ear acne, and decreased serum levels of TNF-α and IL-1ß in rats. Meanwhile, the three interventions reduced M1-type macrophages and increased M2-type macrophages; only APS could reduce the expression of TLR2/NF-κB signaling pathway. Conclusion: ABT, APS, and ABPS can improve the inflammatory symptoms of acne and reduce inflammatory cytokines. APS may exert anti-inflammatory effects by altering macrophage polarization and decreasing TLR2/NF-κB expression.


Assuntos
Acne Vulgar , Auriculoterapia , Animais , Ratos , NF-kappa B , Receptor 2 Toll-Like , Acne Vulgar/terapia , Macrófagos , Anti-Inflamatórios/uso terapêutico
3.
Am Heart J ; 236: 49-58, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33621541

RESUMO

BACKGROUND: Current guidelines recommend administering dual antiplatelet therapy (DAPT) for 12 months to patients with acute coronary syndromes (ACS) and without contraindications after drug-eluting stent (DES) implantation. A recent study reported that 3 months of DAPT followed by ticagrelor monotherapy is effective and safe in ACS patients undergoing DES implantation compared with the standard duration of DAPT. However, it is unclear whether antiplatelet monotherapy with ticagrelor alone versus ticagrelor plus aspirin reduces the incidence of clinically relevant bleeding without increasing the risk of major adverse cardiovascular and cerebrovascular events (MACCEs) in ACS patients undergoing percutaneous coronary intervention (PCI) with DES implantation guided by either intravascular ultrasound (IVUS) or angiography who have completed a 1-month course of DAPT with aspirin plus ticagrelor. METHODS: The IVUS-ACS and ULTIMATE-DAPT is a prospective, multicenter, randomized, controlled trial designed to determine (1) whether IVUS-guided versus angiography-guided DES implantation in patients with ACS reduces the risk of target vessel failure (TVF) at 12 months and (2) whether ticagrelor alone versus ticagrelor plus aspirin reduces the risk of clinically relevant bleeding without increasing the risk of MACCE 1-12 months after the index PCI in ACS patients undergoing DES implantation guided by either IVUS or angiography. This study will enroll 3486 ACS patients eligible for DES implantation, as confirmed by angiographic studies. The patients who meet the inclusion criteria and none of the exclusion criteria will be randomly assigned in a 1:1 fashion to the IVUS- or angiography-guided group (first randomization). All enrolled patients will complete a 1-month course of DAPT with aspirin plus ticagrelor after the index PCI. Patients with no MACCEs or major bleeding (≥Bleeding Academic Research Consortium (BARC) 3b) within 30 days will be randomized in a 1:1 fashion to either the ticagrelor plus matching placebo (SAPT)group or ticagrelor plus aspirin (DAPT)group for an additional 11 months (second randomization). The primary endpoint of the IVUS-ACS trial is TVF at 12 months, including cardiac death, target vessel myocardial infarction (TVMI), or clinically driven target vessel revascularization (CD-TVR). The primary superiority endpoint of the ULTIMATE-DAPT trial is clinically relevant bleeding, defined as BARC Types 2, 3, or 5 bleeding, and the primary non-inferiority endpoint of the ULTIMATE-DAPT trial is MACCE, defined as cardiac death, myocardial infarction, ischemic stroke, CD-TVR, or definite stent thrombosis occurring 1-12 months in the second randomized population. CONCLUSION: The IVUS-ACS and ULTIMATE-DAPT trial is designed to test the efficacy and safety of 2 different antiplatelet strategies in ACS patients undergoing PCI with DES implantation guided by either IVUS or angiography. This study will provide novel insights into the optimal DAPT duration in ACS patients undergoing PCI and provide evidence on the clinical benefits of IVUS-guided PCI in ACS patients.


Assuntos
Síndrome Coronariana Aguda/terapia , Aspirina , Duração da Terapia , Hemorragia , Intervenção Coronária Percutânea , Complicações Pós-Operatórias/prevenção & controle , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Ticlopidina , Adulto , Aspirina/administração & dosagem , Aspirina/efeitos adversos , Angiografia Coronária/métodos , Stents Farmacológicos , Terapia Antiplaquetária Dupla/métodos , Feminino , Hemorragia/induzido quimicamente , Hemorragia/prevenção & controle , Humanos , Masculino , Estudos Multicêntricos como Assunto/métodos , Avaliação de Processos e Resultados em Cuidados de Saúde , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/instrumentação , Intervenção Coronária Percutânea/métodos , Inibidores da Agregação Plaquetária/administração & dosagem , Inibidores da Agregação Plaquetária/efeitos adversos , Complicações Pós-Operatórias/etiologia , Risco Ajustado/métodos , Cirurgia Assistida por Computador/métodos , Ticlopidina/administração & dosagem , Ticlopidina/efeitos adversos , Ultrassonografia de Intervenção/métodos
4.
Am Heart J ; 234: 101-110, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33465369

RESUMO

BACKGROUND: Double kissing (DK) crush approach for patients with coronary bifurcation lesions, particularly localized at distal left main or lesions with increased complexity, is associated with significant reduction in clinical events when compared with provisional stenting. Recently, randomized clinical trial has demonstrated the net clinical benefits by intravascular ultrasound (IVUS)-guided implantation of drug-eluting stent in all-comers. However, the improvement in clinical outcome after DK crush treatment guided by IVUS over angiography guidance for patients with complex bifurcation lesions have never been studied in a randomized fashion. TRIAL DESIGN: DKCRUSH VIII study is a prospective, multicenter, randomized controlled trial designed to assess superiority of IVUS-guided vs angiography-guided DK crush stenting in patients with complex bifurcation lesions according to DEFINITION criteria. A total of 556 patients with complex bifurcation lesions will be randomly (1:1 of ratio) assigned to IVUS-guided or angiography-guided DK crush stenting group. The primary end point is the rate of 12-month target vessel failure, including cardiac death, target vessel myocardial infarction, or clinically driven target vessel revascularization. The secondary end points consist of the individual component of primary end point, all-cause death, myocardial infarction, and in-stent restenosis. The safety end point is the incidence of definite or probable stent thrombosis. An angiographic follow-up will be performed for all patients at 13 months and clinical follow-up will be continued annually until 3 years after the index procedure. CONCLUSIONS: DKCRUSH VIII trial is the first study designed to evaluate the differences in efficacy and safety between IVUS-guided and angiography-guided DK crush stenting in patients with complex true bifurcation lesions. This study will also provide IVUS-derived criteria to define optimal DK crush stenting for bifurcation lesions at higher complexity.


Assuntos
Angiografia Coronária/métodos , Doença das Coronárias/terapia , Stents Farmacológicos , Intervenção Coronária Percutânea/métodos , Ultrassonografia de Intervenção/métodos , Causas de Morte , Doença das Coronárias/diagnóstico por imagem , Doença das Coronárias/mortalidade , Doença das Coronárias/patologia , Reestenose Coronária/etiologia , Trombose Coronária/etiologia , Stents Farmacológicos/efeitos adversos , Humanos , Infarto do Miocárdio/etiologia , Revascularização Miocárdica , Estudos Prospectivos
5.
Proc Natl Acad Sci U S A ; 115(29): E6680-E6689, 2018 07 17.
Artigo em Inglês | MEDLINE | ID: mdl-29970423

RESUMO

Technologically important properties of ferroic materials are determined by their intricate response to external stimuli. This response is driven by distortions of the crystal structure and/or by domain wall motion. Experimental separation of these two mechanisms is a challenging problem which has not been solved so far. Here, we apply X-ray photon correlation spectroscopy (XPCS) to extract the contribution of domain wall dynamics to the overall response. Furthermore, we show how to distinguish the dynamics related to the passing of domain walls through the periodic (Peierls) potential of the crystal lattice and through the random potential caused by lattice defects (pinning centers). The approach involves the statistical analysis of correlations between X-ray speckle patterns produced by the interference of coherent synchrotron X-rays scattered from different nanosize volumes of the crystal and identification of Poisson-type contribution to the statistics. We find such a contribution in the thermally driven response of the monoclinic phase of a ferroelectric PbZr0.55Ti0.45O3 crystal and calculate the number of domain wall jumps in the studied microvolume.

6.
Molecules ; 26(1)2021 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-33406776

RESUMO

Muehlenbeckia volcanica (Benth.) Endl. (M. volcanica), native to South America, is a traditional Peruvian medicinal plant that has multi-therapeutic properties; however, no phytochemicals have been identified from it yet. In this study, a five-step polarity-stepwise elution counter-current chromatography (CCC) was developed using methanol/water (1:5, v/v) as the stationary phase and different ratios of n-hexane, ethyl acetate, and n-butanol as mobile phases to separate the compounds from the 70% methanol extract of M. volcanica, by which six compounds with a wide range of polarities were separated in a single run of CCC and were identified as gallic acid, protocatechuic acid, 4,4'-dihydroxy-3,3'-imino-di-benzoic acid, rutin, quercitrin, and quercetin. Then, two compounds from the fractions of stepwise elution CCC were separated using conventional high-speed CCC, pH-zone-refining CCC, and preparative high-performance liquid chromatography, and identified as shikimic acid and miquelianin. These compounds are reported from M. volcanica for the first time. Notably, except for shikimic acid, all other compounds showed anti-diabetic potentials via antioxidant, antiglycation, and aldose reductase inhibition. The results suggest that the polarity-stepwise elution CCC can be used to efficiently separate or fractionate compounds with a wide range of polarities from natural products. Moreover, M. volcanica and its bioactive compounds are potent anti-diabetic agents.


Assuntos
Aldeído Redutase/antagonistas & inibidores , Antioxidantes/farmacologia , Produtos Finais de Glicação Avançada/antagonistas & inibidores , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/farmacologia , Polygonaceae/química , Cromatografia Líquida de Alta Pressão , Distribuição Contracorrente
7.
Nanotechnology ; 31(20): 205203, 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32018237

RESUMO

Previous studies have mainly focused on the resistive switching (RS) of amorphous or polycrystalline HfO2-RRAM. The RS of single crystalline HfO2 films has been rarely reported. Yttrium doped HfO2 (YDH) thin films were fabricated and successful Y incorporation into HfO2 was confirmed by x-ray photoemission spectroscopy. A pure cubic phase of YDH and an abrupt YDH/Si interface were obtained and verified by x-ray diffraction, Raman spectroscopy and transmission electron microscopy. A Pt/YDH/n++-Si heterostructure using Si as the bottom electrode was fabricated, which shows stable RS with an ON/OFF ratio of 100 and a reliable data retention (104 s). The electron transport mechanism was investigated in detail. It indicates that hopping conduction is dominating when the device is at a high resistance state, while space charge limited conduction acts as the dominant factor at a low resistance state. Such behavior, which is different from devices using TiN or Ti as electrodes, was attributed to the Y doping and specific YDH/Si interface. Our results demonstrate a proof of concept study to use highly doped Si as bottom electrodes along with single crystalline YDH as insulator layer for such RRAM applications as wireless sensors and synaptic simulation.

8.
J Mol Cell Cardiol ; 130: 170-183, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30998977

RESUMO

Hyperglycemia-induced apoptosis plays a critical role in the pathogenesis of diabetic cardiomyopathy (DCM). Our previous study demonstrated that ivabradine, a selective If current antagonist, significantly attenuated myocardial apoptosis in diabetic mice, but the underlying mechanisms remained unknown. This study investigated the underlying mechanisms by which ivabradine exerts anti-apoptotic effects in experimental DCM. Pretreatment with ivabradine, but not ZD7288 (an established If current blocker), profoundly inhibited high glucose-induced apoptosis via inactivation of nuclear factor (NF)-κB signaling in neonatal rat cardiomyocytes. The effect was abolished by transfection of an siRNA targeting protein phosphatase 2A catalytic subunit (PP2Ac). In streptozotocin-induced diabetic mice, ivabradine treatment significantly inhibited left ventricular hyperpolarization-activated cyclic nucleotide-gated channel 2 (HCN2) and HCN4 (major components of the If current), activated PP2Ac, and attenuated NF-κB signaling activation and apoptosis, in line with improved histological abnormalities, fibrosis, and cardiac dysfunction without affecting hyperglycemia. These effects were not observed in diabetic mice with virus-mediated knockdown of HCN2 or HCN4 after myocardial injection, but were alleviated by knockdown of PP2Acα. Molecular docking and phosphatase activity assay confirmed direct binding of ivabradine to, and activation of, PP2Ac. In conclusion, ivabradine may directly activate PP2Ac, leading to inhibition of NF-κB signaling activation, myocardial apoptosis, and fibrosis, and eventually improving cardiac function in experimental DCM. Taken together, the present findings suggest that ivabradine may be a promising drug for treatment of DCM.


Assuntos
Diabetes Mellitus Experimental/enzimologia , Cardiomiopatias Diabéticas/enzimologia , Ivabradina/farmacologia , Miócitos Cardíacos/enzimologia , Proteína Fosfatase 2/metabolismo , Transdução de Sinais/efeitos dos fármacos , Animais , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/patologia , Cardiomiopatias Diabéticas/tratamento farmacológico , Cardiomiopatias Diabéticas/patologia , Ativação Enzimática/efeitos dos fármacos , Masculino , Camundongos , Simulação de Acoplamento Molecular , Miócitos Cardíacos/patologia , NF-kappa B/metabolismo , Proteína Fosfatase 2/química , Ratos
9.
J Cell Physiol ; 233(12): 9786-9798, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30078216

RESUMO

BACKGROUND: Previous studies have suggested that exogenous hydrogen sulfide can alleviate the development of diabetic cardiomyopathy (DCM) by inhibiting oxidative stress, inflammation, and apoptosis. However, the underlying mechanism is not fully understood. Nuclear expression and function of the transcription factor Forkhead box protein O (FoxO1) have been associated with cardiovascular diseases, and thus, the importance of FoxO1 in DCM has gained increasing attention. This study was designed to investigate the interactions between hydrogen sulfide (H2 S) and nuclear FoxO1 in DCM. METHODS: Diabetes was induced in adult male C57BL/6J mice by intraperitoneal injection of streptozotocin and was treated with H2 S donor sodium hydrosulfide for 12 weeks. The H9C2 cardiomyoblast cell line and neonatal rat cardiomyocytes (NRCMs) were treated with the slow-releasing H2 S donor GYY4137 before high-glucose (HG) exposure with or without pretreatment with the Akt inhibitor MK-2206 2HCl. Changes in FoxO1 protein phosphorylation and subcellular localization were determined in H9C2 cells, NRCMs, and cardiac tissues from normal and diabetic mice. Cardiac structure and function in the diabetic mice were evaluated by echocardiography and histological analysis and compared with those in control animals. RESULTS: The echocardiographic and histopathological data indicated that exogenous H2 S improved cardiac function and attenuated cardiac hypertrophy and myocardial fibrosis in diabetic mice. H2 S also improved HG-induced oxidative stress and apoptosis in cardiac tissue and NRCMs. In addition, H2 S induced FoxO1 phosphorylation and nuclear exclusion in vitro and in vivo, and this function was not inhibited by MK-2206 2HCl. Alanine substitution mutation of three sites in FoxO1-enhanced FoxO1 transcriptional activity, and subsequent treatment with exogenous H2 S could not prevent HG-induced nuclear retention. CONCLUSIONS: Our data indicate that H2 S is a novel regulator of FoxO1 in cardiac cells and provide evidence supporting the potential of H2 S in inhibiting the progression of DCM.


Assuntos
Cardiomiopatias Diabéticas/tratamento farmacológico , Proteína Forkhead Box O1/genética , Sulfeto de Hidrogênio/administração & dosagem , Inflamação/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Cardiomiopatias Diabéticas/genética , Cardiomiopatias Diabéticas/fisiopatologia , Modelos Animais de Doenças , Coração/efeitos dos fármacos , Coração/fisiopatologia , Humanos , Inflamação/genética , Inflamação/fisiopatologia , Camundongos , Camundongos Endogâmicos NOD , Miócitos Cardíacos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Ratos , Transdução de Sinais
10.
BMC Cardiovasc Disord ; 18(1): 103, 2018 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-29793432

RESUMO

BACKGROUND: The relationship between platelet reactivity and long-term clinical outcomes remains controversial. The present prospective study was designed to explore the association between high platelet reactivity (HPR) on clopidogrel and long-term clinical outcomes following implantation of drug eluting stents (DES). METHODS: A total of 1769 consecutive patients assessed by Aggrestar (PL-11) were enrolled at our center from February 2011 to December 2017. The primary end point was major adverse cardiovascular and cerebrovascular events (MACCE), defined as definite or probable stent thrombosis, spontaneous myocardial infarction, all cause death, clinically driven target vessel revascularization (TVR), or ischemic stroke. Bleeding served as the safety endpoint. Propensity score matching (PSM) analysis was performed to adjust for baseline differences in the overall cohort. RESULTS: Finally, 409 patients (23.1%) were identified with HPR on clopidogrel. At a median follow-up of 4.1 years (interquartile range, 1.8 years), the occurrence of MACCE was significantly higher in HPR on clopidogrel group than normal platelet reactivity (NPR) on clopidogrel group (15.6% vs. 5.4%, p < 0.001). After PSM, 395 paired patients were matched, and the difference in MACCE between HPR (15.7%) versus NPR (9.4%) on clopidogrel groups remained significant (P < 0.001), mainly driven by increased all cause death (5.3% vs. 1.8%, p < 0.001), and clinically driven TVR (8.1% vs. 6.3%, p = 0.019) in the HPR group. The risk of bleeding between two groups was similar. CONCLUSIONS: This prospective study confirms the relationship between HPR on clopidogrel and long-term adverse cardiovascular events after coronary stenting.


Assuntos
Plaquetas/efeitos dos fármacos , Clopidogrel/uso terapêutico , Doença da Artéria Coronariana/cirurgia , Stents Farmacológicos , Intervenção Coronária Percutânea/instrumentação , Inibidores da Agregação Plaquetária/uso terapêutico , Idoso , Plaquetas/metabolismo , Clopidogrel/efeitos adversos , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/mortalidade , Feminino , Hemorragia/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/mortalidade , Inibidores da Agregação Plaquetária/efeitos adversos , Pontuação de Propensão , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
11.
Sensors (Basel) ; 18(4)2018 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-29570680

RESUMO

An In2O3/ITO thin film thermocouple was prepared via screen printing. Glass additives were added to improve the sintering process and to increase the density of the In2O3/ITO films. The surface and cross-sectional images indicate that both the grain size and densification of the ITO and In2O3 films increased with the increase in annealing time. The thermoelectric voltage of the In2O3/ITO thermocouple was 53.5 mV at 1270 °C at the hot junction. The average Seebeck coefficient of the thermocouple was calculated as 44.5 µV/°C. The drift rate of the In2O3/ITO thermocouple was 5.44 °C/h at a measuring time of 10 h at 1270 °C.

12.
Proc Natl Acad Sci U S A ; 111(5): 1754-9, 2014 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-24449912

RESUMO

PbZr(1-x)Ti(x)O3 (PZT) and Pb(Mg1/3Nb2/3)(1-x)Ti(x)O3 (PMN-xPT) are complex lead-oxide perovskites that display exceptional piezoelectric properties for pseudorhombohedral compositions near a tetragonal phase boundary. In PZT these compositions are ferroelectrics, but in PMN-xPT they are relaxors because the dielectric permittivity is frequency dependent and exhibits non-Arrhenius behavior. We show that the nanoscale structure unique to PMN-xPT and other lead-oxide perovskite relaxors is absent in PZT and correlates with a greater than 100% enhancement of the longitudinal piezoelectric coefficient in PMN-xPT relative to that in PZT. By comparing dielectric, structural, lattice dynamical, and piezoelectric measurements on PZT and PMN-xPT, two nearly identical compounds that represent weak and strong random electric field limits, we show that quenched (static) random fields establish the relaxor phase and identify the order parameter.

13.
Sensors (Basel) ; 16(1)2016 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-26771617

RESUMO

In this paper, we present a new approach to the fabrication of integrated silicon-based piezoelectric diaphragm-type biosensors by using sodium potassium niobate-silver niobate (0.82KNN-0.18AN) composite lead-free thin film as the piezoelectric layer. The piezoelectric diaphragms were designed and fabricated by micro-machining technology and chemical solution deposition. The fabricated device was very sensitive to the mass changes caused by various targets attached on the surface of diaphragm. The measured mass sensitivity value was about 931 Hz/µg. Its good performance shows that the piezoelectric diaphragm biosensor can be used as a cost-effective platform for nucleic acid testing.


Assuntos
Técnicas Biossensoriais/instrumentação , Metais/química , Microtecnologia/métodos , Eletrodos , Desenho de Equipamento , Propriedades de Superfície
14.
BMC Cardiovasc Disord ; 14: 150, 2014 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-25361902

RESUMO

BACKGROUND: Ivabradine (IVBD), a novel I(f)-channel inhibitor and specific heart rate-lowering agent, is known to have anti-oxidative activity that promotes endothelial function. However, the molecular mechanism through which IVBD acts on cardiac function has yet to be elucidated, especially in experimental diabetic animals. METHODS: For this reason, twenty diabetic mice were randomly assigned to IVBD-treated (10 mg/kg/day) and control (saline) groups. After a 3-month treatment, microarray assay was performed to identify differentia expressed genes, and cardiac function was measured by echocardiography, with subsequent immunohistochemistry analysis and western blotting. RESULTS: Our results showed that ivabradine treatment attenuated the expression and staining score of matrix metalloproteinase (MMP)-2, induced the dephosphorylation of caspase 3, BAX and MMP-2, and enhanced the phosphorylation of NF-κB. Ivabradine treatment led to a significant improvement in cardiac function. CONCLUSION: Ivabradine significantly improved cardiac function by attenuating apoptosis and inhibiting the expression and activity of MMP-2 in diabetic mice, which underscored the novel clinical implications of ivabradine for diabetic patients.


Assuntos
Apoptose/efeitos dos fármacos , Benzazepinas/farmacologia , Cardiotônicos/farmacologia , Diabetes Mellitus/tratamento farmacológico , Cardiomiopatias Diabéticas/prevenção & controle , Metaloproteinase 2 da Matriz/metabolismo , Miócitos Cardíacos/efeitos dos fármacos , Animais , Caspase 3/metabolismo , Células Cultivadas , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/genética , Cardiomiopatias Diabéticas/enzimologia , Cardiomiopatias Diabéticas/genética , Cardiomiopatias Diabéticas/patologia , Cardiomiopatias Diabéticas/fisiopatologia , Modelos Animais de Doenças , Regulação para Baixo , Ivabradina , Masculino , Metaloproteinase 2 da Matriz/genética , Camundongos , Miócitos Cardíacos/enzimologia , Miócitos Cardíacos/patologia , NF-kappa B/metabolismo , Fosforilação , Recuperação de Função Fisiológica , Transdução de Sinais/efeitos dos fármacos , Função Ventricular Esquerda/efeitos dos fármacos , Proteína X Associada a bcl-2/metabolismo
15.
Sci Rep ; 14(1): 7106, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38532061

RESUMO

In situ high-pressure/high-temperature Raman-scattering analyses on PbTiO 3 , 0.92PbTiO 3 - 0.08Bi(Zn 0.5 Ti 0.5 )O 3 and 0.83PbTiO 3 - 0.17Bi(Mg 0.5 Ti 0.5 )O 3 single crystals reveal an intensity transfer between the fine-structure components of the A 1 (TO) soft mode. The enhancement of the lowest-energy subpeak, which stems from intrinsic local non-tetragonal polar distortions, along with the suppression of the tetragonal A 1 (1TO) fundamental mode with increasing pressure and temperature indicates the key role of the local polarization fluctuations in transformation processes and emphasizes the significance of the order-disorder phenomena in both the pressure- and temperature-induced phase transitions of pure PbTiO 3 and its solid solutions with complex perovskites. Moreover, the temperature and pressure evolution of the fraction of the local non-tetragonal polar distortions is highly sensitive to the type of B-site substituent.

16.
Biochim Biophys Acta Mol Basis Dis ; 1870(2): 166979, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38065272

RESUMO

Heart failure (HF) with preserved ejection fraction (HFpEF) is now the most common form of HF and has been reported to be closely related to diabetes. Accumulating evidence suggests that HFpEF patients exhibit cardiac fibrosis. This study investigates whether direct targeted inhibition of the activation of cardiac fibroblasts (CFs), the main effector cells in cardiac fibrosis, improves diabetes-induced HFpEF and elucidates the underlying mechanisms. Twenty-week-old db/db mice exhibited HFpEF, as confirmed by echocardiography and hemodynamic measurements. Proteomics was performed on CFs isolated from the hearts of 20-week-old C57BL/6 and db/db mice. Bioinformatic prediction was used to identify target proteins. Experimental validation was performed in both high glucose (HG)-treated neonatal mouse CFs (NMCFs) and diabetic hearts. TAX1 binding protein 1 (TAX1BP1) was identified as the most significantly differentially expressed protein between 20-week-old C57BL/6 and db/db mice. TAX1BP1 mRNA and protein were markedly downregulated in CFs from diabetic hearts and HG-cultured NMCFs. Overexpression of TAX1BP1 profoundly inhibited HG/diabetes-induced NF-κB nuclear translocation and collagen synthesis in CFs, improved cardiac fibrosis, hypertrophy, inflammation and HFpEF in diabetic mice. Mechanistically, signal transducer and activator of transcription 3 (STAT3), which is phosphorylated and translocated from the cytoplasm into the nucleus under hyperglycemic conditions, bound to TAX1BP1 promoter and blocked TAX1BP1 transcriptional activity, consequently promoting NF-κB nuclear translocation and collagen synthesis in CFs, aggravating cardiac fibrosis, hypertrophy and inflammation, leading to HFpEF in db/db mice. Taken together, our findings demonstrate that targeting regulation of STAT3-TAX1BP1-NF-κB signaling in CFs may be a promising therapeutic approach for diabetes-induced HFpEF.


Assuntos
Cardiomiopatias , Diabetes Mellitus Experimental , Insuficiência Cardíaca , Animais , Humanos , Camundongos , Cardiomiopatias/metabolismo , Colágeno/metabolismo , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/metabolismo , Regulação para Baixo , Fibroblastos/metabolismo , Fibrose , Insuficiência Cardíaca/metabolismo , Hipertrofia/metabolismo , Inflamação/metabolismo , Camundongos Endogâmicos C57BL , Proteínas de Neoplasias/genética , NF-kappa B/metabolismo , Fator de Transcrição STAT3/metabolismo , Volume Sistólico
17.
Zhen Ci Yan Jiu ; 49(4): 367-375, 2024 Apr 25.
Artigo em Inglês, Zh | MEDLINE | ID: mdl-38649204

RESUMO

OBJECTIVES: To investigate the effect of electroacupuncture (EA) on Rho/Rho-associated coiled-coil-forming kinases (ROCK) signaling pathway of uterus tissue in rats with dysmenorrhea, so as to explore the underlying mechanism of EA treating primary dysmenorrhea (PD) and uterine smooth muscle spasm, and to observe whether there is a difference in the effect of meridian acupoints in Conception Vessel (CV) and Governer Vessel (GV). METHODS: Sixty female SD rats were randomly divided into saline, model, CV, GV, and non-acupoint groups, with 12 rats in each group. The dysmenorrhea model was established by subcutaneous injection of estradiol diphenhydrate combined with intraperitoneal injection of oxytocin (OT). EA (2 Hz) was applied to "Qihai" (CV6) and "Zhongji" (CV3) for CV group, "Mingmen" (GV4) and "Yaoshu" (GV2) for GV group, "non-acupoint 1" and "non-acupoint 3" on the left side for non-acupoint group, and manual acupuncture was applied to "Guanyuan" (CV4) for CV group, "Yaoyangguan" (GV3) for GV group, "non-acupoint 2" on the left side for non-acupoint group. The treatment was conducted for 20 min each time, once daily for 10 days. The writhing score was evaluated. The smooth myoelectric signals of rats' uterus in vivo were recorded by multi-channel physiological recorder. The uterine histopathological changes were observed by HE staining. The contents of prostaglandin F2α (PGF2α), OT and calcium ion (Ca2+) in uterine tissue of rats were detected by ELISA. The protein and mRNA expression levels of smooth muscle 22-α (SM22-α), RhoA and ROCKⅡ in uterine tissue were detected by Western blot and fluorescence quantitative PCR, respectively. RESULTS: Compared with the saline group, the writhing score of rats in the model group was increased (P<0.01), the amplitude voltage of uterine smooth muscle in vivo was elevated (P<0.01), the contents of PGF2α, OT and Ca2+, the protein and mRNA expression of SM22-α, RhoA and ROCK Ⅱ in uterine tissue were all increased (P<0.01). Compared with the model and the non-acupoint groups, the writhing scores of the CV and the GV groups were decreased (P<0.01, P<0.05), the amplitude voltage of uterine smooth muscle was decreased (P<0.01), the contents of PGF2α, OT and Ca2+ in uterine tissue were decreased (P<0.01, P<0.05), and the protein expression and mRNA expression of SM22-α, RhoA and ROCKⅡ in uterine tissue were decreased (P<0.01, P<0.05). HE staining showed extensive exfoliation of uterine intima with severe edema and increased glandular secretion in the model group, which was alleviated in the CV and GV groups. CONCLUSIONS: EA at acupoints of CV and GV can significantly reduce the writhing score, uterine smooth muscle amplitude voltage, pathological injury degree of uterus, and relieve spasm of uterine smooth muscle in dysmenorrhea rats, which may be related to its effect in regulating PGF2α and OT contents, inhibiting the Rho/ROCK signaling pathway, and reducing the SM22-α, RhoA, ROCKⅡ protein and mRNA expression, and Ca2+ content in uterine tissue.


Assuntos
Pontos de Acupuntura , Dismenorreia , Eletroacupuntura , Ratos Sprague-Dawley , Transdução de Sinais , Útero , Quinases Associadas a rho , Animais , Feminino , Dismenorreia/terapia , Dismenorreia/metabolismo , Dismenorreia/genética , Quinases Associadas a rho/metabolismo , Quinases Associadas a rho/genética , Ratos , Humanos , Útero/metabolismo , Músculo Liso/metabolismo , Espasmo/terapia , Espasmo/genética , Espasmo/metabolismo , Espasmo/fisiopatologia
18.
JACC Cardiovasc Interv ; 17(13): 1519-1528, 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38842991

RESUMO

BACKGROUND: Drug-coated balloon (DCB) angioplasty seems a safe and effective option for specific de novo coronary lesions. However, the beneficial effect of intravascular ultrasound (IVUS)-guided DCB angioplasty in de novo lesions remains uncertain. OBJECTIVES: This study aimed to assess the benefits of IVUS guidance over angiography guidance during DCB angioplasty in de novo coronary lesions. METHODS: A total of 260 patients with high bleeding risk who had a de novo coronary lesion (reference vessel diameter 2.0-4.0 mm, and lesion length ≤15 mm) were randomly assigned to either an IVUS-guided or an angioplasty-guided DCB angioplasty group. The primary endpoint was in-segment late lumen loss (LLL) at 7 months after procedure. The secondary endpoint was target vessel failure at 6 months. RESULTS: A total of 2 patients in the angiography-guided group and 7 patients in the IVUS-guided group underwent bailout stent implantation (P = 0.172). The primary endpoint of 7-month LLL was 0.03 ± 0.52 mm with angiography guidance vs -0.10 ± 0.34 mm with IVUS guidance (mean difference 0.14 mm; 95% CI: 0.02-0.26; P = 0.025). IVUS guidance was also associated with a larger 7-month minimal lumen diameter (2.06 ± 0.62 mm vs 1.75 ± 0.63 mm; P < 0.001) and a smaller diameter stenosis (28.15% ± 13.88% vs 35.83% ± 17.69%; P = 0.001) compared with angiography guidance. Five target vessel failures occurred at 6 months, with 4 (3.1%) in the angiography-guided group and 1 (0.8%) in the IVUS-guided group (P = 0.370). CONCLUSIONS: This study demonstrated that IVUS-guided DCB angioplasty is associated with a lower LLL in patients with a de novo coronary lesion compared with angiography guidance. (Intravascular Ultrasound Versus Angiography Guided Drug-Coated Balloon [ULTIMATE-III]; NCT04255043).


Assuntos
Angioplastia Coronária com Balão , Cateteres Cardíacos , Fármacos Cardiovasculares , Materiais Revestidos Biocompatíveis , Angiografia Coronária , Doença da Artéria Coronariana , Valor Preditivo dos Testes , Ultrassonografia de Intervenção , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Angioplastia Coronária com Balão/instrumentação , Angioplastia Coronária com Balão/efeitos adversos , Resultado do Tratamento , Fatores de Tempo , Doença da Artéria Coronariana/terapia , Doença da Artéria Coronariana/diagnóstico por imagem , Fármacos Cardiovasculares/administração & dosagem , Fármacos Cardiovasculares/efeitos adversos , Estudos Prospectivos , Fatores de Risco , China
19.
Nat Commun ; 15(1): 6735, 2024 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-39112446

RESUMO

Improvements in the polarization of environmentally-friendly perovskite ferroelectrics have proved to be a challenging task in order to replace the toxic Pb-based counterparts. In contrast to common methods by complex chemical composition designs, we have formed Mn-inlaid antiphase boundaries in Mn-doped (K,Na)NbO3 thin films using pulsed laser deposition method. Here, we observed that mono- or bi-atomic layer of Mn has been identified to inlay along the antiphase boundaries to balance the charges originated from the deficiency of alkali ions and to induce the strain in the KNN films. Thus, rectangular saturated polarization-electric field hysteresis loops have been achieved, with a significantly improved twice remanent polarization of 114 µC/cm2 with an applied electric field of 606 kV/cm, which can be comparable to that of the typical Pb-based thin films. Moreover, we directly see the Mn occupation at the A-site of KNN perovskite structure using atomic-scale microstructure and composition analysis. The Mn-inlaid antiphase boundary can further enrich the understanding of perovskite crystal structure and give more possibilities for the design and optimization of perovskite materials.

20.
Zhongguo Zhong Xi Yi Jie He Za Zhi ; 33(9): 1252-5, 2013 Sep.
Artigo em Zh | MEDLINE | ID: mdl-24273984

RESUMO

OBJECTIVE: To observe whether Xuefu Zhuyu Decoction (XZD) could induce the differentiation of mesenchymal stem cells (MSCs) into cardiac myoid cells, thus seeking for safe and effective inducers. METHODS: The serum pharmacological method was used to induce. XZD containing serum was prepared. MSCs were isolated and cultured. The serum cytotoxicity was detected by MTT. The third generation of favorably grown cells was selected in this experiment. Cells were divided into three groups, i.e., the vehicle control group, the XZD containing serum induced group, and the 5-azacytidine induced group. Expressions of Desmin and alpha-actin were detected by immunocytochemical staining method. RESULTS: Before induction protein expressions of Desmin and alpha-actin were negative, and few was weakly positive. There was no statistical difference in the weak positive expression rate among the 3 groups (P > 0.05). After induction protein expressions of Desmin and alpha-actin were negative, and few was weakly positive in the vehicle control group. Protein expressions of Desmin and alpha-actin were positive in the XZC containing serum induced group and the 5-azacytidine induced group. There was statistical difference in the positive expression rate when compared with the vehicle control group (P > 0.05). CONCLUSIONS: XZD played a role in in vitro inducing differentiation MSCs to cardiac myoid cells. It might participate in expressions of Desmin and alpha-actin.


Assuntos
Actinas/metabolismo , Células da Medula Óssea/efeitos dos fármacos , Desmina/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Animais , Células da Medula Óssea/citologia , Células da Medula Óssea/metabolismo , Células Cultivadas , Masculino , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Ratos , Ratos Wistar , Soro
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