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1.
Nature ; 629(8011): 348-354, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38658760

RESUMO

Natural diamonds were (and are) formed (thousands of million years ago) in the upper mantle of Earth in metallic melts at temperatures of 900-1,400 °C and at pressures of 5-6 GPa (refs. 1,2). Diamond is thermodynamically stable under high-pressure and high-temperature conditions as per the phase diagram of carbon3. Scientists at General Electric invented and used a high-pressure and high-temperature apparatus in 1955 to synthesize diamonds by using molten iron sulfide at about 7 GPa and 1,600 °C (refs. 4-6). There is an existing model that diamond can be grown using liquid metals only at both high pressure and high temperature7. Here we describe the growth of diamond crystals and polycrystalline diamond films with no seed particles using liquid metal but at 1 atm pressure and at 1,025 °C, breaking this pattern. Diamond grew in the subsurface of liquid metal composed of gallium, iron, nickel and silicon, by catalytic activation of methane and diffusion of carbon atoms into and within the subsurface regions. We found that the supersaturation of carbon in the liquid metal subsurface leads to the nucleation and growth of diamonds, with Si playing an important part in stabilizing tetravalently bonded carbon clusters that play a part in nucleation. Growth of (metastable) diamond in liquid metal at moderate temperature and 1 atm pressure opens many possibilities for further basic science studies and for the scaling of this type of growth.

2.
Nature ; 606(7912): 88-93, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35650356

RESUMO

Large-area single-crystal monolayers of two-dimensional (2D) materials such as graphene1-3, hexagonal boron nitride (hBN)4-6 and transition metal dichalcogenides7,8 have been grown. hBN is considered to be the 'ideal' dielectric for 2D-materials-based field-effect transistors (FETs), offering the potential for extending Moore's law9,10. Although hBN thicker than a monolayer is more desirable as substrate for 2D semiconductors11,12, highly uniform and single-crystal multilayer hBN growth has yet to be demonstrated. Here we report the epitaxial growth of wafer-scale single-crystal trilayer hBN by a chemical vapour deposition (CVD) method. Uniformly aligned hBN islands are found to grow on single-crystal Ni (111) at early stage and finally to coalesce into a single-crystal film. Cross-sectional transmission electron microscopy (TEM) results show that a Ni23B6 interlayer is formed (during cooling) between the single-crystal hBN film and Ni substrate by boron dissolution in Ni. There are epitaxial relationships between hBN and Ni23B6 and between Ni23B6 and Ni. We also find that the hBN film acts as a protective layer that remains intact during catalytic evolution of hydrogen, suggesting continuous single-crystal hBN. This hBN transferred onto the SiO2 (300 nm)/Si wafer acts as a dielectric layer to reduce electron doping from the SiO2 substrate in MoS2 FETs. Our results demonstrate high-quality single-crystal  multilayered hBN over large areas, which should open up new pathways for making it a ubiquitous substrate for 2D semiconductors.

3.
Nature ; 596(7873): 519-524, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34433942

RESUMO

Chemical vapour deposition of carbon-containing precursors on metal substrates is currently the most promising route for the scalable synthesis of large-area, high-quality graphene films1. However, there are usually some imperfections present in the resulting films: grain boundaries, regions with additional layers (adlayers), and wrinkles or folds, all of which can degrade the performance of graphene in various applications2-7. There have been numerous studies on ways to eliminate grain boundaries8,9 and adlayers10-12, but graphene folds have been less investigated. Here we explore the wrinkling/folding process for graphene films grown from an ethylene precursor on single-crystal Cu-Ni(111) foils. We identify a critical growth temperature (1,030 kelvin) above which folds will naturally form during the subsequent cooling process. Specifically, the compressive stress that builds up owing to thermal contraction during cooling is released by the abrupt onset of step bunching in the foil at about 1,030 kelvin, triggering the formation of graphene folds perpendicular to the step edge direction. By restricting the initial growth temperature to between 1,000 kelvin and 1,030 kelvin, we can produce large areas of single-crystal monolayer graphene films that are high-quality and fold-free. The resulting films show highly uniform transport properties: field-effect transistors prepared from these films exhibit average room-temperature carrier mobilities of around (7.0 ± 1.0) × 103 centimetres squared per volt per second for both holes and electrons. The process is also scalable, permitting simultaneous growth of graphene of the same quality on multiple foils stacked in parallel. After electrochemical transfer of the graphene films from the foils, the foils themselves can be reused essentially indefinitely for further graphene growth.

4.
Mol Cell Biochem ; 2024 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-39223351

RESUMO

Diabetes is a well-known risk factor for atherosclerosis (AS), but the underlying molecular mechanism remains unknown. The dysregulated immune response is an important reason. High glucose is proven to induce foam cell formation under lipidemia situations in clinical patients. Exploring the potential regulatory programs of accelerated foam cell formation stimulated by high glucose is meaningful. Macrophage-derived foam cells were induced in vitro, and high-throughput sequencing was performed. Coexpression gene modules were constructed using weighted gene co-expression network analysis (WGCNA). Highly related modules were identified. Hub genes were identified by multiple integrative strategies. The potential roles of selected genes were further validated in bulk-RNA and scRNA datasets of human plaques. By transfection of the siRNA, the role of the screened gene during foam cell formation was further explored. Two modules were found to be both positively related to high glucose and ox-LDL. Further enrichment analyses confirmed the association between the brown module and AS. The high correlation between the brown module and macrophages was identified and 4 hub genes (Aldoa, Creg1, Lgmn, and Pkm) were screened. Further validation in external bulk-RNA and scRNA revealed the potential diagnostic and therapeutic value of selected genes. In addition, the survival analysis confirmed the prognostic value of Aldoa while knocking down Aldoa expression alleviated the foam cell formation in vitro. We systematically investigated the synergetic effects of high glucose and ox-LDL during macrophage-derived foam cell formation and identified that ALDOA might be an important diagnostic, prognostic, and therapeutic target in these patients.

5.
Molecules ; 29(16)2024 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-39202960

RESUMO

The widespread use of per- and polyfluoroalkyl substances (PFASs) with different physico-chemical properties poses a great threat to the environment and human health. Simultaneous detection of different classes of PFASs is a difficult task, especially for rapid analysis of polluted water samples in environmental forensic cases. In this study, a simple sample preparation ultrahigh-performance liquid chromatography coupled with quadrupole Orbitrap high-resolution mass spectrometry was established for the detection of PFASs in a wide range of water matrices. By optimizing the conditions of pretreatment and the parameters of the instrument, the developed method provided good linearity of calibration standards (R2 > 0.99), and demonstrated excellent MLOQ (0.008-1.2 µg/L), with spiked recoveries ranging from 57.7% to 151% for 47 targets in surface water samples, and from 45.7 to 165% for 46 targets in ground and waste water samples, respectively. This method required an injection volume of 3 µL and an analysis time of only 18 min per sample. The validation method was successfully applied to the analysis of 20 environmental water samples, in which 15 target substances with different concentrations were detected, with total concentrations of 0.082 to 262.455 µg/L. The method is simple and exclusive, and can rapidly confirm the occurrence of PFASs in different water samples, providing a convenient and fast high-throughput analysis, which is especially suitable for the application in the environmental forensic investigation of PFASs pollution.


Assuntos
Fluorocarbonos , Poluentes Químicos da Água , Poluentes Químicos da Água/análise , Fluorocarbonos/análise , Fluorocarbonos/química , Cromatografia Líquida de Alta Pressão/métodos , Monitoramento Ambiental/métodos , Humanos , Espectrometria de Massas/métodos
6.
Biol Cell ; 114(5): 127-137, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35235701

RESUMO

BACKGROUND INFORMATION: Endothelial progenitor cells (EPCs) can exert angiogenic effects by a paracrine mechanism, where exosomes work as an important mediator. Recent studies reported functional expression of toll-like receptor (TLR) 4 on human EPCs and dose-dependent effects of lipopolysaccharide (LPS) on EPC angiogenic properties. To study the effects of TLR4/LPS signaling on EPC-derived exosomes (Exo) and clarify the mechanism, we investigated the role of LPS on exosomes secretion from human EPCs and tested their anti-oxidation/senescence functions. We employed the inhibitors of the plasma membrane Ca2+ -ATPase (PMCA), endoplasmic reticulum Ca2+ -ATPase (ERCA), PLC-IP3 pathway and store-operated calcium entry to assess the effects of LPS on EPC intracellular calcium signalings which critical for exosome secretion. RESULTS: LPS induced the release of Exo in a TLR4-dependent manner in vitro, which effect can be partly abrogated by an membrane-permeable IP 3 R antagonist, 2-aminoethyl diphenylborinate (2-APB), but not PLC inhibitor, U-73122. The LPS can significantly delay the fallback of [Ca2+ ]i after isolating the cellular PMCA activity, and disturb PMCA 1/4 expression. The distribution of elevated intracellular calcium seemed coincident with the development of the multivesicular bodies (MVBs). furthermore, the anti-oxidation/senescence properties of LPS-induced Exo were validated by the senescence-associated ß-galactosidase activity assay and reactive oxygen species (ROS) related H2 DCF-DA assay. CONCLUSIONS: The mechanism of PMCA downregulation and IP3 R-dependent ER Ca2+ release may contribute to the pro-exosomal effects of LPS on EPCs. SIGNIFICANCE: This study provides new insights into the potential role of LPS/TLR4 pathway in regulating EPC-derived exosomes, which may help to develop some feasible approach to manipulate the Exo secretion and promote the clinical application of EPCs therapy in future.


Assuntos
Células Progenitoras Endoteliais , Exossomos , Adenosina Trifosfatases/metabolismo , Cálcio/metabolismo , Células Progenitoras Endoteliais/metabolismo , Exossomos/metabolismo , Humanos , Lipopolissacarídeos/metabolismo , Lipopolissacarídeos/farmacologia , Receptor 4 Toll-Like/metabolismo
7.
Ecotoxicol Environ Saf ; 262: 115172, 2023 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-37354564

RESUMO

Waterlogging has been shown to have a significant inhibitory effect on plant growth. However, the response mechanisms of the soil environment of sugar beet seedlings under waterlogging conditions still need to be fully understood. This study aimed to investigate the effects of waterlogging treatments on the content of effective nutrients and the microbial communities in the rhizosphere and non-rhizosphere using high-throughput sequencing. We set up waterlogging and non-waterlogging treatments, sampled sugar beet seedlings after 10 days of waterlogging, determined the effective soil nutrients in the rhizosphere and non-rhizosphere of the plants, and analyzed the differences in microbial diversity at ten days of waterlogging. The results showed that waterlogging significantly affected available potassium (AK) content. The Ak content of waterlogged soil was significantly higher than that of non-waterlogged soil. Waterlogging caused no significant difference in available nitrogen (AN) content and pH. Moreover, the plant growth-promoting bacteria Pseudomonas was significantly enriched in sugar beet waterlogged rhizospheres compared with the non-waterlogged ones. Similarly, the harmful fungi Gibellulopsis and Alternaria were enriched in sugar beet non-waterlogged rhizosphere. The network analysis revealed that waterlogging built a less complex root-microbial network than non-waterlogging. These findings implied that sugar beets subjected to waterlogging stress were enriched with beneficial microorganisms in the rhizosphere, potentially alleviating the stress.

8.
Circulation ; 144(9): 712-727, 2021 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-34102853

RESUMO

BACKGROUND: Metabolic remodeling precedes most alterations during cardiac hypertrophic growth under hemodynamic stress. The elevation of glucose utilization has been recognized as a hallmark of metabolic remodeling. However, its role in cardiac hypertrophic growth and heart failure in response to pressure overload remains to be fully illustrated. Here, we aimed to dissect the role of cardiac PKM1 (pyruvate kinase muscle isozyme 1) in glucose metabolic regulation and cardiac response under pressure overload. METHODS: Cardiac-specific deletion of PKM1 was achieved by crossing the floxed PKM1 mouse model with the cardiomyocyte-specific Cre transgenic mouse. PKM1 transgenic mice were generated under the control of tetracycline response elements, and cardiac-specific overexpression of PKM1 was induced by doxycycline administration in adult mice. Pressure overload was triggered by transverse aortic constriction. Primary neonatal rat ventricular myocytes were used to dissect molecular mechanisms. Moreover, metabolomics and nuclear magnetic resonance spectroscopy analyses were conducted to determine cardiac metabolic flux in response to pressure overload. RESULTS: We found that PKM1 expression is reduced in failing human and mouse hearts. It is important to note that cardiomyocyte-specific deletion of PKM1 exacerbates cardiac dysfunction and fibrosis in response to pressure overload. Inducible overexpression of PKM1 in cardiomyocytes protects the heart against transverse aortic constriction-induced cardiomyopathy and heart failure. At the mechanistic level, PKM1 is required for the augmentation of glycolytic flux, mitochondrial respiration, and ATP production under pressure overload. Furthermore, deficiency of PKM1 causes a defect in cardiomyocyte growth and a decrease in pyruvate dehydrogenase complex activity at both in vitro and in vivo levels. CONCLUSIONS: These findings suggest that PKM1 plays an essential role in maintaining a homeostatic response in the heart under hemodynamic stress.


Assuntos
Proteínas de Transporte/genética , Suscetibilidade a Doenças , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/metabolismo , Proteínas de Membrana/genética , Miócitos Cardíacos/metabolismo , Hormônios Tireóideos/genética , Remodelação Ventricular/genética , Animais , Biomarcadores , Proteínas de Transporte/metabolismo , Respiração Celular , Modelos Animais de Doenças , Progressão da Doença , Ativação Enzimática , Expressão Gênica , Glucose/metabolismo , Glicólise , Insuficiência Cardíaca/fisiopatologia , Testes de Função Cardíaca , Humanos , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Knockout , Mitocôndrias/genética , Mitocôndrias/metabolismo , Modelos Biológicos , Hormônios Tireóideos/metabolismo , Proteínas de Ligação a Hormônio da Tireoide
9.
Mol Med ; 28(1): 94, 2022 08 12.
Artigo em Inglês | MEDLINE | ID: mdl-35962329

RESUMO

BACKGROUND: The proliferation ability and autophagy level of pulmonary artery endothelial cells (PAECs) play an important role in promoting the development of pulmonary artery hypertension (PAH), and there is still no effective treatment for PAH. Farnesyl diphosphate synthase (FDPS) is a key enzyme in the mevalonate pathway. The intermediate metabolites of this pathway are closely related to the activity of autophagy-associated small G proteins, including Ras-related C3 botulinum toxin substrate 1 (Rac1). Studies have shown that the mevalonate pathway affects the activation levels of different small G proteins, autophagy signaling pathways, vascular endothelial function, and so on. However, the exact relationship between them is still unclear in PAH. METHOD: In vitro, western blotting and mRFP-GFP-LC3 puncta formation assays were used to observe the expression of FDPS and the level of autophagy in PAECs treated with monocrotaline pyrrole (MCTP). In addition, cell proliferation and migration assays were used to assess the effect of FDPS on endothelial function, and Rac1 activity assays were used to evaluate the effect of Rac1 activation on PAEC autophagy via the PI3K/AKT/mTOR signaling pathway. In vivo, the right heart catheterization method, hematoxylin and eosin (H&E) staining and western blotting were used to determine the effect of FDPS on PAEC autophagy and monocrotaline (MCT)-induced PAH. RESULTS: We show that the expression of FDPS is increased in the PAH module in vitro and in vivo, concomitant with the induction of autophagy and the activation of Rac1. Our data demonstrate that inhibition of FDPS ameliorates endothelial function and decreases MCT-induced autophagy levels. Mechanistically, we found that FDPS promotes autophagy, Rac1 activity and endothelial disfunction through the PI3K/AKT/mTOR signaling pathway. CONCLUSION: Our study suggests that FDPS contributes to active small G protein-induced autophagy during MCT-induced PAH, which may serve as a potential therapeutic target against PAH.


Assuntos
Hipertensão Pulmonar , Proteínas Monoméricas de Ligação ao GTP , Hipertensão Arterial Pulmonar , Animais , Autofagia , Proliferação de Células , Células Endoteliais/metabolismo , Geraniltranstransferase/metabolismo , Geraniltranstransferase/farmacologia , Hipertensão Pulmonar/tratamento farmacológico , Hipertensão Pulmonar/metabolismo , Ácido Mevalônico/farmacologia , Ácido Mevalônico/uso terapêutico , Monocrotalina/efeitos adversos , Proteínas Monoméricas de Ligação ao GTP/metabolismo , Proteínas Monoméricas de Ligação ao GTP/farmacologia , Proteínas Monoméricas de Ligação ao GTP/uso terapêutico , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Artéria Pulmonar , Ratos , Ratos Sprague-Dawley , Serina-Treonina Quinases TOR/metabolismo
10.
Int J Mol Sci ; 23(2)2022 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-35054932

RESUMO

The rapid growth of obesity worldwide has made it a major health problem, while the dramatic increase in the prevalence of obesity has had a significant impact on the magnitude of chronic kidney disease (CKD), especially in developing countries. A vast amount of researchers have reported a strong relationship between obesity and chronic kidney disease, and obesity can serve as an independent risk factor for kidney disease. The histological changes of kidneys in obesity-induced renal injury include glomerular or tubular hypertrophy, focal segmental glomerulosclerosis or bulbous sclerosis. Furthermore, inflammation, renal hemodynamic changes, insulin resistance and lipid metabolism disorders are all involved in the development and progression of obesity-induced nephropathy. However, there is no targeted treatment for obesity-related kidney disease. In this review, RAS inhibitors, SGLT2 inhibitors and melatonin would be presented to treat obesity-induced kidney injury. Furthermore, we concluded that melatonin can protect the kidney damage caused by obesity by inhibiting inflammation and oxidative stress, revealing its therapeutic potential.


Assuntos
Biomarcadores , Suscetibilidade a Doenças , Desenvolvimento de Medicamentos , Nefropatias/etiologia , Obesidade/complicações , Animais , Citocinas/metabolismo , Gerenciamento Clínico , Humanos , Mediadores da Inflamação , Resistência à Insulina , Nefropatias/tratamento farmacológico , Nefropatias/metabolismo , Glomérulos Renais/metabolismo , Glomérulos Renais/patologia , Túbulos Renais , Terapia de Alvo Molecular/métodos , Estresse Oxidativo , Sistema Renina-Angiotensina
11.
Angew Chem Int Ed Engl ; 61(15): e202117815, 2022 04 04.
Artigo em Inglês | MEDLINE | ID: mdl-35107863

RESUMO

Graphene has demonstrated broad applications due to its prominent properties. Its molecular structure makes graphene achiral. Here, we propose a direct way to prepare chiral graphene by transferring chiral structural conformation from chiral conjugated amino acids onto graphene basal plane through π-π interaction followed by thermal fusion. Using atomic resolution transmission electron microscopy, we estimated an areal coverage of the molecular imprints (chiral regions) up to 64 % on the basal plane of graphene (grown by chemical vapor deposition). The high concentration of molecular imprints in their single layer points to a close packing of the deposited amino acid molecules prior to "thermal fusion". Such "molecular chirality-encoded graphene" was tested as an electrode in electrochemical enantioselective recognition. The chirality-encoded graphene might find use for other chirality-related studies and the encoding procedure might be extended to other two-dimensional materials.


Assuntos
Grafite , Aminoácidos/química , Conformação Molecular , Estrutura Molecular , Estereoisomerismo
12.
Cardiovasc Drugs Ther ; 35(1): 153-166, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32770521

RESUMO

PURPOSE: To evaluate the potential association between the lowering of low-density lipoprotein cholesterol (LDL-C) with contemporary lipid-lowering medicines and cognitive function. METHODS: Randomized controlled trials (RCTs) in databases including PubMed, Embase, and the Web of Science and all databases in the Cochrane Library and ClinicalTrials.gov were collected from inception to January 1, 2020. The cognitive function of patients receiving proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, statins and ezetimibe was evaluated using meta-analysis. RESULTS: A total of 2910 studies were obtained from databases and other sources. Thirty-three studies were selected by screening, including 11 studies on alirocumab, 9 studies on evolocumab, 11 studies on statins and 2 studies on ezetimibe. In our study, a total of 128,691 patients with no cognitive impairment were divided into an intervention group (66,330 patients) and a control group (62,361 patients). The data were subjected to a random-effects model or a fixed-effects model for meta-analysis. The contemporary lipid-lowering medicines significantly reduced LDL-C in terms of both percentage (WMD: -45.06%, 95% CI -50.12% to -40.00%, P < 0.001) and absolute value (WMD: -64.01 mg/dL, 95% CI -72.25 to -55.78, P < 0.001). Compared with the control group, patients receiving treatment with contemporary lipid-lowering medicines did not show a significant difference in the rate of neurocognitive disorder (RR: 1.02, 95% CI 0.90 to 1.16, I2 = 0.0%, p = 0.696). Subgroup analysis was performed according to the intervention and LDL-C stratification. The result of this subgroup analysis was consistent with the main findings. Regarding global cognitive performance, no difference in major cognition was found among the pooled data (SMD: 0.02, 95% CI -0.01 to 0.04, P = 0.002), except for psychomotor speed (SMD: 0.09, 95% CI 0.02 to 0.16, P = 0.0024). CONCLUSIONS: Contemporary lipid-lowering medicines were not associated with cognitive impairment in RCTs. A low LDL-C level did not influence the incidence of cognitive disorder or global cognitive performance.


Assuntos
Anticolesterolemiantes/efeitos adversos , LDL-Colesterol/efeitos dos fármacos , Cognição/efeitos dos fármacos , LDL-Colesterol/sangue , Ezetimiba/efeitos adversos , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Inibidores de PCSK9/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto
13.
Int J Mol Sci ; 22(2)2021 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-33477525

RESUMO

Adult humans and mice possess significant classical brown adipose tissues (BAT) and, upon cold-induction, acquire brown-like adipocytes in certain depots of white adipose tissues (WAT), known as beige adipose tissues or WAT browning/beiging. Activating thermogenic classical BAT or WAT beiging to generate heat limits diet-induced obesity or type-2 diabetes in mice. Adiponectin is a beneficial adipokine resisting diabetes, and causing "healthy obese" by increasing WAT expansion to limit lipotoxicity in other metabolic tissues during high-fat feeding. However, the role of its receptors, especially adiponectin receptor 1 (AdipoR1), on cold-induced thermogenesis in vivo in BAT and in WAT beiging is still elusive. Here, we established a cold-induction procedure in transgenic mice over-expressing AdipoR1 and applied a live 3-D [18F] fluorodeoxyglucose-PET/CT (18F-FDG PET/CT) scanning to measure BAT activity by determining glucose uptake in cold-acclimated transgenic mice. Results showed that cold-acclimated mice over-expressing AdipoR1 had diminished cold-induced glucose uptake, enlarged adipocyte size in BAT and in browned WAT, and reduced surface BAT/body temperature in vivo. Furthermore, decreased gene expression, related to thermogenic Ucp1, BAT-specific markers, BAT-enriched mitochondrial markers, lipolysis and fatty acid oxidation, and increased expression of whitening genes in BAT or in browned subcutaneous inguinal WAT of AdipoR1 mice are congruent with results of PET/CT scanning and surface body temperature in vivo. Moreover, differentiated brown-like beige adipocytes isolated from pre-adipocytes in subcutaneous WAT of transgenic AdipoR1 mice also had similar effects of lowered expression of thermogenic Ucp1, BAT selective markers, and BAT mitochondrial markers. Therefore, this study combines in vitro and in vivo results with live 3-D scanning and reveals one of the many facets of the adiponectin receptors in regulating energy homeostasis, especially in the involvement of cold-induced thermogenesis.


Assuntos
Tecido Adiposo Bege/metabolismo , Tecido Adiposo Marrom/metabolismo , Receptores de Adiponectina/genética , Termogênese/genética , Proteína Desacopladora 1/genética , Adipócitos Bege/metabolismo , Tecido Adiposo Bege/diagnóstico por imagem , Tecido Adiposo Marrom/diagnóstico por imagem , Tecido Adiposo Branco/diagnóstico por imagem , Tecido Adiposo Branco/metabolismo , Animais , Metabolismo Energético/genética , Regulação da Expressão Gênica no Desenvolvimento/genética , Camundongos , Camundongos Transgênicos/genética , Camundongos Transgênicos/metabolismo , Mitocôndrias/genética , Obesidade/genética , Obesidade/metabolismo , Obesidade/patologia , Tomografia por Emissão de Pósitrons
14.
Biochem Biophys Res Commun ; 528(3): 574-579, 2020 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-32505355

RESUMO

Myocardial ischemia/reperfusion (MI/R) injury, a complicated pathophysiological process, is regulated by lots of signaling pathways. Here in our present study, we identified TANK-binding kinase 1 (TBK1), an IKK-related serine/threonine kinase, as a protective regulator in MI/R injury. Our results indicated that TBK1 was decreased in MI/R injury in mice. However, after overexpressing TBK1 through an intramyocardial injection of TBK1 adenovirus, TBK1 overexpression improved cardiac function detected by echocardiography, decreased infarct size detected by Evans Blue and TTC staining, reduced cardiomyocyte apoptosis measured by TUNEL staining and alleviated disruption of mitochondria and cardiac muscle fibers detected by TEM in response to MI/R injury. Consistently, TBK1 overexpression ameliorated mitochondrial oxygen consumption rate (OCR) in neonatal rat cardiomyocytes (NRCMs) in response to hypoxia/reoxygenation (H/R) injury. Mechanistically, TBK1 overexpression upregulated Bcl-2 (an anti-apoptotic protein) but downregulated Bax (a pro-apoptotic protein) in vivo and in vitro. Collectively, our findings uncovered a pivotal function of TBK1 in MI/R injury through regulating the levels of apoptotic proteins for the first time, which might represent a promising target in treating MI/R patients in the future.


Assuntos
Traumatismo por Reperfusão Miocárdica/enzimologia , Proteínas Serina-Treonina Quinases/metabolismo , Animais , Apoptose/genética , Apoptose/fisiologia , Células Cultivadas , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Traumatismo por Reperfusão Miocárdica/patologia , Traumatismo por Reperfusão Miocárdica/terapia , Miócitos Cardíacos , Consumo de Oxigênio , Proteínas Serina-Treonina Quinases/genética , Ratos , Ratos Sprague-Dawley , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Transdução de Sinais , Regulação para Cima
15.
Opt Express ; 28(20): 28819-28830, 2020 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-33114792

RESUMO

We present a reference-free method to determine electrical parameters of thin conducting films by steady state transmission-mode terahertz time-domain spectroscopy (THz-TDS). We demonstrate that the frequency-dependent AC conductivity of graphene can be acquired by comparing the directly transmitted THz pulse with a transient internal reflection within the substrate which avoids the need for a standard reference scan. The DC sheet conductivity, scattering time, carrier density, mobility, and Fermi velocity of graphene are retrieved subsequently by fitting the AC conductivity with the Drude model. This reference-free method was investigated with two complementary THz setups: one commercial fibre-coupled THz spectrometer with fast scanning rate (0.2-1.5 THz) and one air-plasma based ultra-broadband THz spectrometer for greatly extended frequency range (2-10 THz). Certain propagation correction terms for more accurate retrieval of electrical parameters are discussed.

16.
Mol Cell Biochem ; 465(1-2): 103-114, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31858380

RESUMO

MicroRNA-125b (miR-125b) reduces myocardial infarct area and restrains myocardial ischemia reperfusion injury (I/R). In this study, we aimed to investigate the effect of bone marrow mesenchymal stem cell (BMSC)-derived exosomes carrying miR-125b on I/R rats. The myocardial I/R model in rats was constructed by ligation of the left anterior descending coronary artery (LAD). Rats were randomly divided into I/R and Sham group. Lv-cel-miR-67 (control) or Lv-miR-125b was transfected into BMSCs. Exosomes were extracted from transfected BMSCs, and separately named BMSC-Exo-67, BMSC-Exo-125b, and BMSC-Exo. MTT assay and flow cytometry were used to detect the viability and apoptosis of I/R myocardium cells, respectively. The expression of cell apoptosis proteins and the levels of inflammatory factors were examined by Western blot and ELISA assay, respectively. The target relationship between miR-125b and SIRT7 was predicted by using StarBase3.0, and was confirmed by using dual-luciferase reporter gene assay. qRT-PCR, immunohistochemistry staining, and Western blot were used to evaluate the expression of SIRT7 in myocardium tissues in I/R rats. BMSC-derived exosomes were successfully isolated and identified by TEM and positive expression of CD9 and CD63. The expression of miR-125b was down-regulated in I/R myocardium tissues and cells. BMSC-Exo-125b significantly up-regulated miR-125b in I/R myocardium cells. The intervention of BMSC-Exo-125b significantly increased the cell viability, decreased the apoptotic ratio, down-regulated Bax and caspase-3, up-regulated Bcl-2, and decreased the levels of IL-1ß, IL-6, and TNF-α in I/R myocardium cells. SIRT7 was a target of miR-125b, and BMSC-Exo-125b significantly down-regulated SIRT7 in myocardium cells. In addition, the injection of BMSC-Exo-125b alleviated the pathological damages and down-regulated SIRT7 in myocardium tissues of I/R rats. BMSC-derived exosomes carrying miR-125b protected against myocardial I/R by targeting SIRT7.


Assuntos
Células da Medula Óssea/metabolismo , Exossomos , Células-Tronco Mesenquimais/metabolismo , MicroRNAs , Traumatismo por Reperfusão Miocárdica , Sirtuínas , Animais , Apoptose/genética , Células da Medula Óssea/patologia , Citocinas/genética , Citocinas/metabolismo , Exossomos/genética , Exossomos/metabolismo , Exossomos/patologia , Exossomos/transplante , Masculino , Células-Tronco Mesenquimais/patologia , MicroRNAs/genética , MicroRNAs/metabolismo , Traumatismo por Reperfusão Miocárdica/genética , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/patologia , Traumatismo por Reperfusão Miocárdica/terapia , Ratos , Ratos Sprague-Dawley , Sirtuínas/genética , Sirtuínas/metabolismo
17.
J Cardiovasc Pharmacol ; 75(6): 584-595, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32205566

RESUMO

Vascular remodeling is one of the most critical complications caused by hypertension. Previous studies have demonstrated that rosuvastatin has anti-inflammatory, antioxidant, and antiplatelet effects and therefore can be used to treat cardiovascular disease. In this study, we explored the beneficial effects of rosuvastatin in reversing aortic remodeling in spontaneously hypertensive rats. After treating with different doses of rosuvastatin, its antilipid, antiapoptosis, and anti-inflammatory effects were determined. We also examined whether rosuvastatin can improve the structure and function of the aorta. We found that rosuvastatin treatment of spontaneously hypertensive rats for 2 months at 2 different doses can effectively reduce the media thickness of the aorta compared with the control group. Similarly, rosuvastatin improved the vascular relaxation function of the aortic rings at a high level of acetylcholine in vitro. Mechanistically, it was found that rosuvastatin increased the expression of endothelial nitric oxide synthase and plasma nitrite/nitrate levels. Besides, rosuvastatin suppressed the apoptosis and inflammation and upregulated the expression of gap-junction complex connexin 43 both in media and endothelium. Finally, rosuvastatin inhibited the AT1R/PKCα/HSP70 signaling transduction pathway. In summary, these findings demonstrated that rosuvastatin could improve the vascular structure and function mainly by increasing endothelial nitric oxide synthase expression and preventing apoptosis and inflammation. This study provided evidence that rosuvastatin has beneficial effects in reversing the remodeling of the aorta due to hypertension.


Assuntos
Anti-Inflamatórios/farmacologia , Aorta/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Endotélio Vascular/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Rosuvastatina Cálcica/farmacologia , Remodelação Vascular/efeitos dos fármacos , Vasodilatação/efeitos dos fármacos , Vasodilatadores/farmacologia , Animais , Aorta/metabolismo , Aorta/patologia , Aorta/fisiopatologia , Conexina 43/metabolismo , Modelos Animais de Doenças , Endotélio Vascular/metabolismo , Endotélio Vascular/patologia , Endotélio Vascular/fisiopatologia , Hipertensão/metabolismo , Hipertensão/patologia , Hipertensão/fisiopatologia , Mediadores da Inflamação/metabolismo , Masculino , Óxido Nítrico Sintase Tipo III/metabolismo , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Transdução de Sinais/efeitos dos fármacos
18.
J Cell Physiol ; 234(10): 17999-18016, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30847932

RESUMO

Theaflavin 3,3'-digallate (TF3), is reported to protect cardiomyocytes from lipotoxicity and reperfusion injury. However, the role of TF3 in the protection of high-glucose injury is still poorly understood. This study investigated the protective effects of TF3 on gap junctions and autophagy in neonatal cardiomyocytes (NRCMs). NRCMs preincubated with high glucose were coincubated with TF3. The expression of connexins and autophagy-related proteins was determined. The functioning of gap-junctional intercellular communication (GJIC) was measured by a dye transfer assay. Adenosine monophosphate-activated protein kinase (AMPK) activity was determined by western blot. Moreover, AMPK was activated with aminoimidazole-4-carboxamide-1-ß-d-ribofuranoside (AICAR) or inhibited by AMPKα small interfering RNA (siRNA) to explore the role of AMPK in the modulation of connexin 43 (Cx43) and autophagy. Meanwhile, autophagy was activated or blocked to observe the change in Cx43 expression. It was found that the protein expression of Cx43 and autophagy-related proteins was increased in a TF3 dose- and time-dependent manner under high glucose. TF3 also recovered the reduced GJIC function induced by high glucose concentrations. TF3 activated phosphorylated AMPK in a time-dependent way. AMPKα siRNA abrogated the protection of TF3, while AICAR showed similar results compared to the TF3 treatment. Meanwhile, autophagy activation caused decreased Cx43, while cotreatment with baf A1 enhanced Cx43 expression further compared with the TF3 treatment alone under high glucose. We concluded that TF3 partly reversed the inhibition of Cx43 expression and autophagy induced by high glucose in NRCMs, partly by restoring AMPK activity. Inhibition of autophagy might be protective by preserving Cx43 expression in NRCMs stimulated by high glucose.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Autofagia/efeitos dos fármacos , Biflavonoides/farmacologia , Catequina/análogos & derivados , Conexina 43/metabolismo , Glucose/toxicidade , Miócitos Cardíacos/efeitos dos fármacos , Proteínas Quinases Ativadas por AMP/genética , Animais , Animais Recém-Nascidos , Cardiotoxicidade , Catequina/farmacologia , Células Cultivadas , Conexina 43/genética , Ativação Enzimática , Junções Comunicantes/efeitos dos fármacos , Junções Comunicantes/metabolismo , Junções Comunicantes/patologia , Miócitos Cardíacos/enzimologia , Miócitos Cardíacos/patologia , Ratos Sprague-Dawley , Transdução de Sinais
19.
Cell Mol Biol (Noisy-le-grand) ; 65(4): 101-106, 2019 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-31078159

RESUMO

Endothelial progenitor cells (EPCs) improve neovascularization and endothelium regeneration. Transplantation with EPCs is a therapeutic strategy for the treatment of ischemic diseases. However, the transplanted EPCs are susceptible to adverse environments such as hypoxia, inflammation and oxidative stress. Oxidative stress-induced apoptosis of transplanted EPCs greatly reduces their therapeutic efficacy. Lipopolysaccharide (LPS) is a highly immunogenic antigen. Recent findings suggest that low dose of LPS pretreatment has protective effect against apoptosis. In this study, the role of LPS in apoptosis of EPCs was investigated. Pretreatment with 1µg/ml LPS prevented oxidative stress-induced EPCs apoptosis and ROS generation, which effects were abolished by TAK-242, a specific TLR4 antagonist. Further investigation of the mechanisms demonstrated that the activation was mediated by TLR4, and that PI3K/Akt/ NF-κB p65 signaling pathway may play a critical role in the process.


Assuntos
Apoptose/efeitos dos fármacos , Células Progenitoras Endoteliais/patologia , Lipopolissacarídeos/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptor 4 Toll-Like/metabolismo , Fator de Transcrição RelA/metabolismo , Células Progenitoras Endoteliais/efeitos dos fármacos , Humanos , Fosforilação/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proteína X Associada a bcl-2/metabolismo
20.
Can J Physiol Pharmacol ; 97(10): 945-951, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31397599

RESUMO

The aim of our work was to test whether thymosin beta 4 protected endothelial progenitor cells against apoptosis induced by advanced glycation endproducts and investigate the underlying mechanism. Treatment with thymosin beta 4 or transfection with microRNA-34a inhibitor enhanced cell viability, reduced apoptosis, abated oxidative stress, and attenuated mitochondrial dysfunction in endothelial progenitor cells exposed to advanced glycation endproducts. Incubation with advanced glycation endproducts led to increased levels of microRNA-34a, which was attenuated by treatment with thymosin beta 4. Transfection with microRNA-34a reversed the beneficial effect of thymosin beta 4 against injuries induced by advanced glycation endproducts. The microRNA-34a could directly bind to the 3'UTRs of the mRNA of B-cell lymphoma 2, and thymosin beta 4 treatment upregulated B-cell lymphoma 2 expression in endothelial progenitor cells exposed to advanced glycation endproducts. More importantly, knockdown of B-cell lymphoma 2 abolished the protection of thymosin beta 4 and microRNA-34a inhibitor against advanced glycation endproducts. In conclusion, inhibition of microRNA-34a mediated protection of thymosin beta 4 in endothelial progenitor cells against advanced glycation endproducts by targeting B-cell lymphoma 2, which was helpful for understanding the therapeutic potential of thymosin beta 4 for diabetic patients.


Assuntos
Células Progenitoras Endoteliais/patologia , Produtos Finais de Glicação Avançada/metabolismo , MicroRNAs/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/genética , Timosina/farmacologia , Apoptose/genética , Células Cultivadas , Células Progenitoras Endoteliais/metabolismo , Perfilação da Expressão Gênica , Técnicas de Silenciamento de Genes , Voluntários Saudáveis , Humanos , Leucócitos Mononucleares , MicroRNAs/antagonistas & inibidores , Análise de Sequência com Séries de Oligonucleotídeos , Cultura Primária de Células , RNA Interferente Pequeno/metabolismo , Regulação para Cima
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