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1.
Front Pharmacol ; 13: 1000316, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36160452

RESUMO

Atherosclerosis is the primary cause of cardiovascular diseases, such as myocardial infarction and stroke, which account for the highest death toll worldwide. Macrophage is the major contributor to atherosclerosis progression, and therefore, macrophage-associated pathological process is considered an extremely important target for the diagnosis and treatment of atherosclerosis. However, the existing clinical strategies still have many bottlenecks and challenges in atherosclerosis's early detection and management. Nanomedicine, using various nanoparticles/nanocarriers for medical purposes, can effectively load therapeutic agents, significantly improve their stability and accurately deliver them to the atherosclerotic plaques. In this review, we summarized the latest progress of the macrophage-targeted nanomedicine in the diagnosis and treatment of atherosclerosis, and their potential applications and clinical benefits are also discussed.

2.
Anal Bioanal Chem ; 412(26): 7187-7194, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32767015

RESUMO

Calcium ion (Ca2+) is an indispensable second messenger in living organisms. The impaired Ca2+ handling can induce many diseases. In this paper, we developed a simple and effective method to encapsulate a coumarin-based Ca2+ probe ((E)-2-hydroxy-N'-((7-hydroxy-2-oxo-2H-chromen-8-yl)methylene)-2-phenylacetohydrazide, CPM) into nanoparticles (NPs), and CPM NPs with blue fluorescence were obtained, whose maximum excitation and maximum emission wavelengths were characterized at 365 nm and 450 nm, respectively. The CPM NPs show significant fluorescence enhancement toward Ca2+ over other metal ions, with a limit of determination (LOD) of 0.04 µM. To optimize the optical property of the NPs, CPM and curcumin, which were introduced as the Förster resonance energy transfer (FRET) donor and acceptor, respectively, were co-encapsulated, and bright green CPM@Cur NPs with large stokes shift and narrow emission band width were constructed. Due to their low cytotoxicity and excellent stability, CPM NPs and CPM@Cur NPs were further successfully used to discriminate the primary aortic smooth muscle cells isolated from mice with abnormal Ca2+ homeostasis from their littermate controls. It is worth noting that CPM@Cur NPs exhibit stronger fluorescence signal and diminished background interference, which make them have great potential in the Ca2+ monitoring during biological processes. This strategy opens a new way to synthesize NPs with high brightness and has a potential application prospect in composite sensing and intracellular imaging. CPM@Cur NPs are developed and applied in biological sensing and intracellular Ca2+ imaging, as well as discriminating the cells with abnormal calcium homeostasis.


Assuntos
Cálcio/metabolismo , Corantes Fluorescentes/química , Animais , Transferência Ressonante de Energia de Fluorescência , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Nanopartículas/química
3.
ACS Biomater Sci Eng ; 6(3): 1727-1734, 2020 03 09.
Artigo em Inglês | MEDLINE | ID: mdl-33455364

RESUMO

Mitochondria are critical organelles in eukaryotes that efficiently generate adenosine 5'-triphosphate (ATP) for various biological activities, and any defect in the process of ATP synthesis may lead to mitochondrial dysfunction and directly link to a variety of medical disorders. Monitoring the ATP variations in cells is key for innovative early diagnosis of mitochondrial diseases. Herein, multifunctional single-layered graphene quantum dots (s-GQDs) with bright green emission were constructed, which exhibit strong binding affinity for ATP and good mitochondria targeting ability. Using the proposed s-GQDs, we successfully discriminated the primary smooth muscle cells isolated from the transgenic mouse (heterozygote sarco/endoplasmic reticulum Ca2+ ATPase (SERCA) 2 C674S knock-in mouse) with mitochondrial disorders or their littermate controls, indicating s-GQDs as promising probes for the study of cell metabolism and mitochondrial malfunction-related diseases, and targeting endoplasmic reticulum stress is an effective way to modulate metabolic pathways relevant to SERCA 2 inactivity mitochondrial dysfunction.


Assuntos
Grafite , Doenças Mitocondriais , Pontos Quânticos , Animais , Cálcio/metabolismo , Camundongos , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/metabolismo
4.
RSC Adv ; 9(37): 21134-21138, 2019 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-35521328

RESUMO

The molecular mechanism of cancer cell death caused by silver nanoparticles (AgNPs) of different sizes is investigated. Compared with the larger nanoparticles, 13 nm AgNPs significantly inhibit the migration and invasiveness of lung adenocarcinoma A549 cells, induce elevated reactive oxygen species and lead to NF-κB directed cellular apoptosis.

5.
Diab Vasc Dis Res ; 15(4): 322-335, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29762054

RESUMO

Sarco(endo)plasmic reticulum calcium adenosine triphosphatase is responsible for transporting cytosolic calcium into the sarcoplasmic reticulum and endoplasmic reticulum to maintain calcium homeostasis. Sarco(endo)plasmic reticulum calcium adenosine triphosphatase is the dominant isoform expressed in cardiac tissue, which is regulated by endogenous protein inhibitors, post-translational modifications, hormones as well as microRNAs. Dysfunction of sarco(endo)plasmic reticulum calcium adenosine triphosphatase is associated with heart failure, which makes sarco(endo)plasmic reticulum calcium adenosine triphosphatase a promising target for heart failure therapy. This review summarizes current approaches to ameliorate sarco(endo)plasmic reticulum calcium adenosine triphosphatase function and focuses on phospholamban, an endogenous inhibitor of sarco(endo)plasmic reticulum calcium adenosine triphosphatase, pharmacological tools and gene therapies.


Assuntos
Proteínas de Ligação ao Cálcio/metabolismo , Inibidores Enzimáticos/uso terapêutico , Terapia Genética/métodos , Insuficiência Cardíaca/terapia , Miócitos Cardíacos/efeitos dos fármacos , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/antagonistas & inibidores , Animais , Sinalização do Cálcio/efeitos dos fármacos , Proteínas de Ligação ao Cálcio/genética , Inibidores Enzimáticos/efeitos adversos , Regulação Neoplásica da Expressão Gênica , Insuficiência Cardíaca/enzimologia , Insuficiência Cardíaca/genética , Insuficiência Cardíaca/fisiopatologia , Humanos , Isoenzimas , Terapia de Alvo Molecular , Contração Miocárdica/efeitos dos fármacos , Miócitos Cardíacos/enzimologia , Miócitos Cardíacos/patologia , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/genética , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/metabolismo
6.
Am J Physiol Cell Physiol ; 299(3): C643-53, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20573996

RESUMO

Hyperglycemia is an indication of poor outcome for heart attack patients, even for nondiabetic patients with stress-induced hyperglycemia. Previous studies showed that inhibition of aldose reductase, the first and rate-limiting enzyme of the polyol pathway, attenuated contractile dysfunction in diabetic animals, but the mechanism is unclear. We therefore wanted to find out whether the polyol pathway also contributes to acute hyperglycemia-induced cardiac contractile dysfunction, and determine the mechanism involved. Rat hearts were isolated and retrogradely perfused with Krebs buffer containing either normal or high concentrations of glucose for 2 h. Short exposure to high-glucose medium led to contractile dysfunction as indicated by decreased -dP/dt(max), as well as elevation in left ventricular end-diastolic pressure. Cardiomyocytes incubated in high-glucose medium showed abnormal Ca2+ signaling, most likely because of decreased activity of sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) inactivated by oxidative stress. Inhibition of aldose reductase or sorbitol dehydrogenase, the second enzyme in the polyol pathway, ameliorated contractile dysfunction, attenuated oxidative stress, and normalized Ca2+ signaling and SERCA activity caused by high glucose, indicating that the polyol pathway is the major contributor to acute hyperglycemia-induced oxidative stress leading to the inactivation of SERCA and contractile dysfunction.


Assuntos
Aldeído Redutase/fisiologia , Coração/fisiopatologia , Hiperglicemia/metabolismo , Estresse Oxidativo , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/metabolismo , Transdução de Sinais , Doença Aguda , Animais , Sinalização do Cálcio , Glucose/farmacologia , Glutationa/metabolismo , Hiperglicemia/fisiopatologia , Técnicas In Vitro , Ácido Láctico/metabolismo , Masculino , Contração Miocárdica , Miocárdio/metabolismo , Oxirredução , Perfusão , Ácido Peroxinitroso/metabolismo , Ácido Pirúvico/metabolismo , Ratos , Ratos Sprague-Dawley , Superóxidos/metabolismo , Tirosina/metabolismo
7.
J Mol Cell Cardiol ; 49(1): 58-69, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20025885

RESUMO

A number of studies have shown that the polyol pathway, consisting of aldose reductase (AR) and sorbitol dehydrogenase (SDH), contributes to ischemia-reperfusion (I/R)-induced myocardial infarction due to depletion of ATP. In this report we show that the polyol pathway in I/R heart also contributes to the impairment of sacro/endoplasmic reticulum Ca(2+)-ATPase (SERCA) and ryanodine receptor (RyR), two key players in Ca(2+) signaling that regulate cardiac contraction. Rat hearts were isolated and retrogradely perfused with either Krebs' buffer containing 1 microM AR inhibitor, zopolrestat, or 200 nM SDH inhibitor, CP-170,711, and challenged by 30 min of regional ischemia and 45 min of reperfusion. We found that post-ischemic contractile function of the isolated perfused hearts was improved by pharmacological inhibition of the polyol pathway. I/R-induced contractile dysfunction is most likely due to impairment in Ca(2+) signaling and the activities of SERCA and RyR. All these abnormalities were significantly ameliorated by treatment with ARI or SDI. We showed that the polyol pathway activities increase the level of peroxynitrite, which enhances the tyrosine nitration of SERCA and irreversibly modifies it to form SERCAC674-SO(3)H. This leads to reduced level of S-glutathiolated SERCA, contributing to its inactivation. The polyol pathway activities also deplete the level of GSH, leading to decreased active RyR, the S-glutathiolated RyR. Thus, in I/R heart, inhibition of polyol pathway improved the function of SERCA and RyR by protecting them from irreversible oxidation.


Assuntos
Coração/fisiopatologia , Canal de Liberação de Cálcio do Receptor de Rianodina/metabolismo , Aldeído Redutase/antagonistas & inibidores , Aldeído Redutase/metabolismo , Animais , Benzotiazóis , L-Iditol 2-Desidrogenase/metabolismo , Masculino , Contração Miocárdica , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/fisiopatologia , Isquemia Miocárdica/metabolismo , Isquemia Miocárdica/fisiopatologia , Reperfusão Miocárdica , Oxirredução , Ftalazinas , Polímeros , Proteínas/metabolismo , Ratos , Ratos Sprague-Dawley
8.
Neurosci Lett ; 373(2): 99-104, 2005 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-15567561

RESUMO

To explore the ionic mechanisms of memory deficits induced by cholinergic lesion, whole-cell patch clamp recording techniques in combination with single-cell RT-PCR were used to characterize delayed rectifier potassium currents (IK) in acutely isolated hippocampal pyramidal neurons of scopolamine-induced cognitive impairment rats. Scopolamine could induce deficits in spatial memory of rats. The peak amplitude and current density of IK measured in hippocampal pyramidal neurons were increased from 1.2+/-0.6 nA and 38+/-19 pA/pF of the control group (n=12) to 1.8+/-0.5 nA and 62+/-24 pA/pF (n=48, P<0.01) of the scopolamine-treated group. The steady-state activation curve of IK was shifted about 8 mV (P<0.01) in the direction of hyperpolarization in scopolamine-treated rats. The mRNA level of Kv2.1 was increased (P<0.01) in the scopolamine-treated group, but there was no significant change of Kv1.5 mRNA level. The present study demonstrated for the first time that IK was enhanced significantly in hippocampal pyramidal neurons of scopolamine-induced cognitive impairment rats. The increase of Kv2.1 mRNA expression in hippocampal pyramidal cells might be responsible for the enhancement of IK and could be the ionic basis of the memory deficits induced by scopolamine.


Assuntos
Potenciais de Ação/fisiologia , Memória/fisiologia , Antagonistas Muscarínicos/farmacologia , Neurônios/metabolismo , Canais de Potássio de Abertura Dependente da Tensão da Membrana/fisiologia , Escopolamina/farmacologia , Potenciais de Ação/efeitos dos fármacos , Animais , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Canal de Potássio Kv1.5 , Masculino , Memória/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Técnicas de Cultura de Órgãos , Técnicas de Patch-Clamp , Potássio/metabolismo , RNA Mensageiro/análise , Ratos , Ratos Wistar , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Canais de Potássio Shab
9.
Neurosci Lett ; 332(1): 21-4, 2002 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-12377375

RESUMO

To investigate the effect of chronic global cerebral ischemia on gene expression of Na(+)/Ca(2+) exchanger isoforms NCX1, NCX2 and NCX3 in rat brain. Chronic global cerebral ischemia was induced by bilateral common carotid artery ligation (BCAL) in rats for 1 week, 2 weeks and 4 weeks, respectively. Morris water maze was applied to demonstrate the credibility of BCAL models. After BCAL for 4 weeks, there was learning and memory deficiency that the latency and distance of BCAL group were longer than those of sham group from the second trial to tenth trial in hidden platform trials. Reverse transcription-polymerase chain reaction was used to assess the gene expression of Na(+)/Ca(2+) exchanger isoforms at mRNA level in cerebral cortex and hippocampus. For NCX1, its expression was decreased by 35%, 54% and 27% of rats with BCAL for 1 week, 2 weeks and 4 weeks, respectively; For NCX2, its expression was decreased by 41%, 29% and 12% of rats with BCAL for 1 week, 2 weeks and 4 weeks, respectively; For NCX3, its expression was decreased by 29%, 27% and 12% of rats with BCAL for 1 week, 2 weeks and 4 weeks, respectively. However, in hippocampus, the expressions of NCX1 and NCX3 did not change significantly in different BCAL groups. NCX2 was increased by 60% in BCAL for 1 week only, but did not change significantly in BCAL for 2 weeks or 4 weeks. The study indicated that brain ischemia regulated gene expression levels of Na(+)/Ca(2+) exchanger isoforms especially in cerebral cortex.


Assuntos
Isquemia Encefálica/metabolismo , Regulação da Expressão Gênica/fisiologia , Proteínas de Membrana Transportadoras , Trocador de Sódio e Cálcio/biossíntese , Animais , Córtex Cerebral/metabolismo , Doença Crônica , Hipocampo/metabolismo , Masculino , Isoformas de Proteínas/biossíntese , Ratos , Ratos Wistar
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