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1.
Nature ; 603(7902): 631-636, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35322249

RESUMO

Metastable phases-kinetically favoured structures-are ubiquitous in nature1,2. Rather than forming thermodynamically stable ground-state structures, crystals grown from high-energy precursors often initially adopt metastable structures depending on the initial conditions, such as temperature, pressure or crystal size1,3,4. As the crystals grow further, they typically undergo a series of transformations from metastable phases to lower-energy and ultimately energetically stable phases1,3,4. Metastable phases sometimes exhibit superior physicochemical properties and, hence, the discovery and synthesis of new metastable phases are promising avenues for innovations in materials science1,5. However, the search for metastable materials has mainly been heuristic, performed on the basis of experiences, intuition or even speculative predictions, namely 'rules of thumb'. This limitation necessitates the advent of a new paradigm to discover new metastable phases based on rational design. Such a design rule is embodied in the discovery of a metastable hexagonal close-packed (hcp) palladium hydride (PdHx) synthesized in a liquid cell transmission electron microscope. The metastable hcp structure is stabilized through a unique interplay between the precursor concentrations in the solution: a sufficient supply of hydrogen (H) favours the hcp structure on the subnanometre scale, and an insufficient supply of Pd inhibits further growth and subsequent transition towards the thermodynamically stable face-centred cubic structure. These findings provide thermodynamic insights into metastability engineering strategies that can be deployed to discover new metastable phases.

2.
Small ; 20(23): e2308815, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38161254

RESUMO

Non-neural extracellular matrix (ECM) has limited application in humanized physiological neural modeling due to insufficient brain-specificity and safety concerns. Although brain-derived ECM contains enriched neural components, certain essential components are partially lost during the decellularization process, necessitating augmentation. Here, it is demonstrated that the laminin-augmented porcine brain-decellularized ECM (P-BdECM) is xenogeneic factor-depleted as well as favorable for the regulation of human neurons, astrocytes, and microglia. P-BdECM composition is comparable to human BdECM regarding brain-specificity through the matrisome and gene ontology-biological process analysis. As augmenting strategy, laminin 111 supplement promotes neural function by synergic effect with laminin 521 in P-BdECM. Annexin A1(ANXA1) and Peroxiredoxin(PRDX) in P-BdECM stabilized microglial and astrocytic behavior under normal while promoting active neuroinflammation in response to neuropathological factors. Further, supplementation of the brain-specific molecule to non-neural matrix also ameliorated glial cell inflammation as in P-BdECM. In conclusion, P-BdECM-augmentation strategy can be used to recapitulate humanized pathophysiological cerebral environments for neurological study.


Assuntos
Encéfalo , Diferenciação Celular , Matriz Extracelular , Laminina , Humanos , Matriz Extracelular/metabolismo , Matriz Extracelular/química , Laminina/química , Encéfalo/metabolismo , Animais , Neurônios/metabolismo , Doenças Neuroinflamatórias/metabolismo , Suínos , Astrócitos/metabolismo , Microglia/metabolismo , Inflamação/patologia
3.
Proc Natl Acad Sci U S A ; 118(36)2021 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-34475212

RESUMO

Toll-like receptor 4 (Tlr) interactor with leucine-rich repeats (Tril) functions as a Tlr coreceptor to mediate innate immunity in adults. In Xenopus embryos, Tril triggers degradation of the transforming growth factor ß (Tgf-ß) family inhibitor, Smad7. This enhances bone morphogenetic protein (Bmp) signaling to enable ventral mesoderm to commit to a blood fate. Here, we show that Tril simultaneously dampens Nodal signaling by catalytically activating the ubiquitin ligase NEDD4 Like (Nedd4l). Nedd4l then targets Nodal receptors for degradation. How Tril signals are transduced in a nonimmune context is unknown. We identify the ubiquitin ligase Pellino2 as a protein that binds to the cytoplasmic tail of Tril and subsequently forms a complex with Nedd4l and another E3 ligase, TNF-receptor associated factor 6 (Traf6). Pellino2 and Traf6 are essential for catalytic activation of Nedd4l, both in Xenopus and in mammalian cells. Traf6 ubiquitinates Nedd4l, which is then recruited to membrane compartments where activation occurs. Collectively, our findings reveal that Tril initiates a noncanonical Tlr-like signaling cascade to activate Nedd4l, thereby coordinately regulating the Bmp and Nodal arms of the Tgf-ß superfamily during vertebrate development.


Assuntos
Peptídeos e Proteínas de Sinalização Intercelular/fisiologia , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Proteínas de Membrana/fisiologia , Ubiquitina-Proteína Ligases Nedd4/metabolismo , Proteína Nodal/metabolismo , Proteínas Nucleares/metabolismo , Transdução de Sinais/fisiologia , Animais , Desenvolvimento Embrionário , Células HEK293 , Células HeLa , Humanos , Ubiquitina-Proteína Ligases Nedd4/genética , Fosforilação , Xenopus
4.
Proc Natl Acad Sci U S A ; 118(16)2021 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-33853949

RESUMO

Fibroblast growth factor 23 (FGF23), a hormone generally derived from bone, is important in phosphate and vitamin D homeostasis. In acute kidney injury (AKI) patients, high-circulating FGF23 levels are associated with disease progression and mortality. However, the organ and cell type of FGF23 production in AKI and the molecular mechanism of its excessive production are still unidentified. For insight, we investigated folic acid (FA)-induced AKI in mice. Interestingly, simultaneous with FGF23, orphan nuclear receptor ERR-γ expression is increased in the liver of FA-treated mice, and ectopic overexpression of ERR-γ was sufficient to induce hepatic FGF23 production. In patients and in mice, AKI is accompanied by up-regulated systemic IL-6, which was previously identified as an upstream regulator of ERR-γ expression in the liver. Administration of IL-6 neutralizing antibody to FA-treated mice or of recombinant IL-6 to healthy mice confirms IL-6 as an upstream regulator of hepatic ERR-γ-mediated FGF23 production. A significant (P < 0.001) interconnection between high IL-6 and FGF23 levels as a predictor of AKI in patients that underwent cardiac surgery was also found, suggesting the clinical relevance of the finding. Finally, liver-specific depletion of ERR-γ or treatment with an inverse ERR-γ agonist decreased hepatic FGF23 expression and plasma FGF23 levels in mice with FA-induced AKI. Thus, inverse agonist of ERR-γ may represent a therapeutic strategy to reduce adverse plasma FGF23 levels in AKI.


Assuntos
Injúria Renal Aguda/fisiopatologia , Fator de Crescimento de Fibroblastos 23/metabolismo , Receptores de Estrogênio/metabolismo , Injúria Renal Aguda/metabolismo , Animais , Modelos Animais de Doenças , Fator de Crescimento de Fibroblastos 23/genética , Ácido Fólico/efeitos adversos , Ácido Fólico/farmacologia , Interleucina-6/metabolismo , Rim/metabolismo , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Receptores Nucleares Órfãos/metabolismo , Receptores de Estrogênio/genética , Ativação Transcricional
5.
Dev Dyn ; 252(6): 761-769, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36825302

RESUMO

BACKGROUND: The Bone morphogenetic protein 4 (BMP4) precursor protein is cleaved at two sites to generate an active ligand and inactive prodomain. The ligand and prodomain form a noncovalent complex following the first cleavage, but dissociate after the second cleavage. Transient formation of this complex is essential to generate a stable ligand. Fibrillins (FBNs) bind to the prodomains of BMPs, and can regulate the activity of some ligands. Whether FBNs regulate BMP4 activity is unknown. RESULTS: Mice heterozygous for a null allele of Bmp4 showed incompletely penetrant kidney defects and females showed increased mortality between postnatal day 6 and 8. Removal of one copy of Fbn1 did not rescue or enhance kidney defects or lethality. The lungs of Fbn1+/- females had enlarged airspaces that were unchanged in Bmp4+/- ;Fbn1+/- mice. Additionally, removal of one or both alleles of Fbn1 had no effect on steady state levels of BMP4 ligand or on BMP activity in postnatal lungs. CONCLUSIONS: These findings do not support the hypothesis that FBN1 plays a role in promoting BMP4 ligand stability or signaling, nor do they support the alternative hypothesis that FBN1 sequesters BMP4 in a latent form, as is the case for other BMP family members.


Assuntos
Proteínas Morfogenéticas Ósseas , Rim , Feminino , Camundongos , Animais , Proteína Morfogenética Óssea 4/genética , Proteína Morfogenética Óssea 4/metabolismo , Ligantes , Proteínas Morfogenéticas Ósseas/metabolismo , Alelos , Rim/metabolismo , Proteína Morfogenética Óssea 7 , Proteína Morfogenética Óssea 2
6.
Small ; 19(21): e2300250, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36828790

RESUMO

Bioelectrodes have been developed to efficiently mediate electrical signals of biological systems as stimulators and recording devices. Recently, conductive hydrogels have garnered great attention as emerging materials for bioelectrode applications because they can permit intimate/conformal contact with living tissues and tissue-like softness. However, administration and control over the in vivo lifetime of bioelectrodes remain challenges. Here, injectable conductive hydrogels (ICHs) with tunable degradability as implantable bioelectrodes are developed. ICHs were constructed via thiol-ene reactions using poly(ethylene glycol)-tetrathiol and thiol-functionalized reduced graphene oxide with either hydrolyzable poly(ethylene glycol)-diacrylate or stable poly(ethylene glycol)-dimaleimide, the resultant hydrogels of which are degradable and nondegradable, respectively. The ICH electrodes had conductivities of 21-22 mS cm-1 and Young's moduli of 15-17 kPa, and showed excellent cell and tissue compatibility. The hydrolyzable conductive hydrogels disappeared 3 days after in vivo administration, while the stable conductive hydrogels maintained their shapes for up to 7 days. Our proof-of-concept studies reveal that electromyography signals with significantly improved sensitivity from rats could be obtained from the injected ICH electrodes compared to skin electrodes and injected nonconductive hydrogel electrodes. The ICHs, offering convenience in use, controllable degradation and excellent signal transmission, will have great potential to develop various bioelectronics devices.


Assuntos
Hidrogéis , Polietilenoglicóis , Ratos , Animais , Próteses e Implantes , Condutividade Elétrica
7.
Small ; 19(16): e2206238, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36617520

RESUMO

SiOx is a promising next-generation anode material for lithium-ion batteries. However, its commercial adoption faces challenges such as low electrical conductivity, large volume expansion during cycling, and low initial Coulombic efficiency. Herein, to overcome these limitations, an eco-friendly in situ methodology for synthesizing carbon-containing mesoporous SiOx nanoparticles wrapped in another carbon layers is developed. The chemical reactions of vinyl-terminated silanes are designed to be confined inside the cationic surfactant-derived emulsion droplets. The polyvinylpyrrolidone-based chemical functionalization of organically modified SiO2 nanoparticles leads to excellent dispersion stability and allows for intact hybridization with graphene oxide sheets. The formation of a chemically reinforced heterointerface enables the spontaneous generation of mesopores inside the thermally reduced SiOx nanoparticles. The resulting mesoporous SiOx -based nanocomposite anodes exhibit superior cycling stability (≈100% after 500 cycles at 0.5 A g-1 ) and rate capability (554 mAh g-1 at 2 A g-1 ), elucidating characteristic synergetic effects in mesoporous SiOx -based nanocomposite anodes. The practical commercialization potential with a significant enhancement in initial Coulombic efficiency through a chemical prelithiation reaction is also presented. The full cell employing the prelithiated anode demonstrated more than 2 times higher Coulombic efficiency and discharge capacity compared to the full cell with a pristine anode.

8.
Mol Syst Biol ; 18(3): e10785, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35315586

RESUMO

Living materials combine a material scaffold, that is often porous, with engineered cells that perform sensing, computing, and biosynthetic tasks. Designing such systems is difficult because little is known regarding signaling transport parameters in the material. Here, the development of a porous microplate is presented. Hydrogel barriers between wells have a porosity of 60% and a tortuosity factor of 1.6, allowing molecular diffusion between wells. The permeability of dyes, antibiotics, inducers, and quorum signals between wells were characterized. A "sentinel" strain was constructed by introducing orthogonal sensors into the genome of Escherichia coli MG1655 for IPTG, anhydrotetracycline, L-arabinose, and four quorum signals. The strain's response to inducer diffusion through the wells was quantified up to 14 mm, and quorum and antibacterial signaling were measured over 16 h. Signaling distance is dictated by hydrogel adsorption, quantified using a linear finite element model that yields adsorption coefficients from 0 to 0.1 mol m-3 . Parameters derived herein will aid the design of living materials for pathogen remediation, computation, and self-organizing biofilms.


Assuntos
Escherichia coli , Percepção de Quorum , Escherichia coli/genética , Hidrogéis , Porosidade , Transdução de Sinais
9.
Proc Natl Acad Sci U S A ; 117(23): 12991-12999, 2020 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-32439710

RESUMO

Malignant melanoma has one of the highest mortality rates of any cancer because of its aggressive nature and high metastatic potential. Clinical staging of the disease at the time of diagnosis is very important for the prognosis and outcome of melanoma treatment. In this study, we designed and synthesized the 18F-labeled pyridine-based benzamide derivatives N-(2-(dimethylamino)ethyl)-5-[18F]fluoropicolinamide ([18F]DMPY2) and N-(2-(dimethylamino)ethyl)-6-[18F]fluoronicotinamide ([18F]DMPY3) to detect primary and metastatic melanoma at an early stage and evaluated their performance in this task. [18F]DMPY2 and [18F]DMPY3 were synthesized by direct radiofluorination of the bromo precursor, and radiochemical yields were ∼15-20%. Cell uptakes of [18F]DMPY2 and [18F]DMPY3 were >103-fold and 18-fold higher, respectively, in B16F10 (mouse melanoma) cells than in negative control cells. Biodistribution studies revealed strong tumor uptake and retention of [18F]DMPY2 (24.8% injected dose per gram of tissue [ID/g] at 60 min) and [18F]DMPY3 (11.7%ID/g at 60 min) in B16F10 xenografts. MicroPET imaging of both agents demonstrated strong tumoral uptake/retention and rapid washout, resulting in excellent tumor-to-background contrast in B16F10 xenografts. In particular, [18F]DMPY2 clearly visualized almost all metastatic lesions in lung and lymph nodes, with excellent image quality. [18F]DMPY2 demonstrated a significantly higher tumor-to-liver ratio than [18F]fluorodeoxyglucose ([18F]FDG) and the previously reported benzamide tracers N-[2-(diethylamino)-ethyl]-5-[18F]fluoropicolinamide ([18F]P3BZA) and N-[2-(diethylamino)-ethyl]-4-[18F]fluorobenzamide ([18F]FBZA) in B16F10-bearing or SK-MEL-3 (human melanoma)-bearing mice. In conclusion, [18F]DMPY2 might have strong potential for the diagnosis of early stage primary and metastatic melanoma using positron emission tomography (PET).


Assuntos
Melanoma/diagnóstico por imagem , Imagem Molecular/métodos , Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos/administração & dosagem , Neoplasias Cutâneas/diagnóstico por imagem , Animais , Linhagem Celular Tumoral , Radioisótopos de Flúor/administração & dosagem , Humanos , Camundongos , Ácidos Picolínicos/administração & dosagem , Compostos Radiofarmacêuticos/química , Ensaios Antitumorais Modelo de Xenoenxerto
10.
Vet Radiol Ultrasound ; 64(1): 113-122, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36444910

RESUMO

In this retrospective, analytical study, we developed a deep learning-based diagnostic model that can be applied to canine stifle joint diseases and compared its accuracy with that achieved by veterinarians to verify its potential as a reliable diagnostic method. A total of 2382 radiographs of the canine stifle joint from cooperative animal hospitals were included in a dataset. Stifle joint regions were extracted from the original images using the faster region-based convolutional neural network (R-CNN) model, and the object detection accuracy was evaluated. Four radiographic findings: patellar deviation, drawer sign, osteophyte formation, and joint effusion, were observed in the stifle joint and used to train a residual network (ResNet) classification model. Implant and growth plate groups were analyzed to compare the classification accuracy against the total dataset. All deep learning-based classification models achieved target accuracies exceeding 80%, which is comparable to or slightly less than those achieved by veterinarians. However, in the case of drawer signs, further research is necessary to improve the low sensitivity of the model. When the implant group was excluded, the classification accuracy significantly improved, indicating that the implant acted as a distraction. These results indicate that deep learning-based diagnoses can be expected to become useful diagnostic models in veterinary medicine.


Assuntos
Aprendizado Profundo , Doenças do Cão , Artropatias , Cães , Animais , Joelho de Quadrúpedes/diagnóstico por imagem , Estudos Retrospectivos , Artropatias/diagnóstico por imagem , Artropatias/veterinária , Redes Neurais de Computação , Doenças do Cão/diagnóstico por imagem
11.
Sensors (Basel) ; 21(9)2021 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-33946700

RESUMO

As COVID-19 solidifies its presence in everyday life, the interest in mental health is growing, resulting in the necessity of sentiment analysis. A smart mirror is suitable for encouraging mental comfort due to its approachability and scalability as an in-home AI device. From the aspect of natural language processing (NLP), sentiment analysis for Korean lacks an emotion dataset regarding everyday conversation. Its significant differences from English in terms of language structure make implementation challenging. The proposed smart mirror LUX provides Korean text sentiment analysis with the deep learning model, which examines GRU, LSTM, CNN, Bi-LSTM, and Bi-GRU networks. There are four emotional labels: anger, sadness, neutral, and happiness. For each emotion, there are three possible interactive responses: reciting wise sayings, playing music, and sympathizing. The implemented smart mirror also includes more-typical functions, such as a wake-up prompt, a weather reporting function, a calendar, a news reporting function, and a clock.


Assuntos
COVID-19 , Emoções , Humanos , Idioma , Processamento de Linguagem Natural , SARS-CoV-2
12.
Sensors (Basel) ; 21(24)2021 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-34960454

RESUMO

With the inclusion of tactile Internet (TI) in the industrial sector, we are at the doorstep of the tactile Industrial Internet of Things (IIoT). This provides the ability for the human operator to control and manipulate remote industrial environments in real-time. The TI use cases in IIoT demand a communication network, including ultra-low latency, ultra-high reliability, availability, and security. Additionally, the lack of the tactile IIoT testbed has made it more severe to investigate and improve the quality of services (QoS) for tactile IIoT applications. In this work, we propose a virtual testbed called IoTactileSim, that offers implementation, investigation, and management for QoS provisioning in tactile IIoT services. IoTactileSim utilizes a network emulator Mininet and robotic simulator CoppeliaSim to perform real-time haptic teleoperations in virtual and physical environments. It provides the real-time monitoring of the implemented technology parametric values, network impairments (delay, packet loss), and data flow between operator (master domain) and teleoperator (slave domain). Finally, we investigate the results of two tactile IIoT environments to prove the potential of the proposed IoTactileSim testbed.


Assuntos
Internet das Coisas , Humanos , Indústrias , Reprodutibilidade dos Testes , Tecnologia , Tato
13.
Molecules ; 26(20)2021 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-34684684

RESUMO

Memory deterioration in Alzheimer's disease (AD) is thought to be underpinned by aberrant amyloid ß (Aß) accumulation, which contributes to synaptic plasticity impairment. Avenanthramide-C (Avn-C), a polyphenol compound found predominantly in oats, has a range of biological properties. Herein, we performed methanolic extraction of the Avns-rich fraction (Fr. 2) from germinated oats using column chromatography, and examined the effects of Avn-C on synaptic correlates of memory in a mouse model of AD. Avn-C was identified in Fr. 2 based on 1H-NMR analysis. Electrophysiological recordings were performed to examine the effects of Avn-C on the hippocampal long-term potentiation (LTP) in a Tg2576 mouse model of AD. Avn-C from germinated oats restored impaired LTP in Tg2576 mouse hippocampal slices. Furthermore, Avn-C-facilitated LTP was associated with changes in the protein levels of phospho-glycogen synthase kinase-3ß (p-GSK3ß-S9) and cleaved caspase 3, which are involved in Aß-induced synaptic impairment. Our findings suggest that the Avn-C extract from germinated oats may be beneficial for AD-related synaptic plasticity impairment and memory decline.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Hipocampo/efeitos dos fármacos , Potenciação de Longa Duração/efeitos dos fármacos , ortoaminobenzoatos/farmacologia , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Animais , Avena/química , Modelos Animais de Doenças , Glicogênio Sintase Quinase 3 beta/metabolismo , Hipocampo/metabolismo , Potenciação de Longa Duração/fisiologia , Masculino , Camundongos , Camundongos Transgênicos , Plasticidade Neuronal , Extratos Vegetais/farmacologia
14.
J Anesth ; 35(1): 86-92, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33221959

RESUMO

PURPOSE: Many studies have been published on the beneficial effects of oral carbohydrate solutions (OCS) administered prior to surgery. However, the risk of pulmonary aspiration cannot be excluded in all patients undergoing anesthesia. But, there are few studies on the safety of OCS at lung aspiration. METHODS: Experiments were conducted with mice (Nine- to ten-week-old male BALB/c mice weighted 23-26 g). Lung aspiration was performed by intratracheal administration of OCS and its major constituents, fructose and maltodextrin. Bronchoalveolar lavage fluid (BALF) was collected 3 and 24 h after lung aspiration. The level of Tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and macrophage inflammatory protein-2 (MIP-2) were measured in BALF. The total white blood cell, neutrophil counts, wet to dry ratio and histological examination were performed in BALF and lung tissue, respectively, at 24 h after aspiration. RESULTS: The OCS increased the level of TNF-α, IL-6 and MIP-2 at 3 h and the neutrophil count at 24 h in BALFs, compared to a phosphate-buffered saline (PBS) group. The increase in IL-6 level induced by OCS was maintained for 24 h. The OCS also increased the number of white blood cells and the percentage of neutrophils in BALFs. Compared to fructose, maltodextrin significantly increased the production of MIP-2 in BALFs. OCS and maltodextrin also increased neutrophil recruitment in lung tissue. CONCLUSION: Aspiration of OCS may cause inflammation of the lungs. The preoperative use of OCS may require caution under specific clinical conditions, such as patients at risk of lung aspiration.


Assuntos
Pulmão , Fator de Necrose Tumoral alfa , Animais , Líquido da Lavagem Broncoalveolar , Carboidratos , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Neutrófilos
15.
Biochem Biophys Res Commun ; 530(2): 389-395, 2020 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-32532423

RESUMO

Recent studies have revealed that protein arginine methyltransferases (PRMTs) are responsible for diverse neurodegenerative diseases. However, their pathophysiological role in dopaminergic neuronal death in Parkinson's disease (PD) has not been evaluated. In this study, we demonstrated that 1-Methyl-4-phenylpyridinium iodide (MPP+), rotenone and paraquat, which cause dopaminergic neuronal cell death, increased PRMT1 expression in dopaminergic cell line. Dopaminergic neuronal cell death was increased by PRMT1 overexpression. MPP+-induced cell death was attenuated by PRMT1 knockdown. Poly (ADP-ribose) polymerase-1 (PARP1) expression and activity, poly-ADP-ribosylation (PARylation), were elevated by MPP+. Moreover, we found that PRMT1 positively regulates nuclear translocation of apoptosis-inducing factor (AIF). Elevated PRMT1 expression was observed in the substantia nigra pars compacta of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-injected mice. Furthermore, MPTP-induced dopaminergic neuronal death was reduced in PRMT1 haploinsufficient (prmt1+/-) mice. These data suggest that PRMT1 is implicated in PARP1/AIF-mediated dopaminergic neuronal cell death, which might be involved in the pathology of PD. Therefore, our results propose PRMT1 as a new target to develop a potential treatment of PD.


Assuntos
Neurônios Dopaminérgicos/patologia , Doença de Parkinson/patologia , Proteína-Arginina N-Metiltransferases/metabolismo , Animais , Morte Celular , Modelos Animais de Doenças , Neurônios Dopaminérgicos/metabolismo , Humanos , Masculino , Camundongos , Doença de Parkinson/metabolismo , Proteína-Arginina N-Metiltransferases/análise
16.
Rheumatology (Oxford) ; 59(8): 2124-2134, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32087015

RESUMO

OBJECTIVE: This study was designed to investigate the role of mucosal-associated invariant T (MAIT) cells in gouty arthritis (GA) and their effects on osteoclastogenesis. METHODS: Patients with GA (n = 61), subjects with hyperuricaemia (n = 11) and healthy controls (n = 30) were enrolled in this study. MAIT cells, cytokines, CD69, programmed death-1 (PD-1) and lymphocyte-activation gene 3 (LAG-3) levels were measured by flow cytometry. In vitro osteoclastogenesis experiments were performed using peripheral blood mononuclear cells in the presence of M-CSF and RANK ligand. RESULTS: Circulating MAIT cell levels were significantly reduced in GA patients. However, their capacities for IFN-γ, IL-17 and TNF-α production were preserved. Expression levels of CD69, PD-1 and LAG-3 in MAIT cells were found to be elevated in GA patients. In particular, CD69 expression in circulating MAIT cells was increased by stimulation with MSU crystals, suggesting that deposition of MSU crystals might contribute to MAIT cell activation. Interestingly, MAIT cells were found to be accumulated in synovial fluid and infiltrated into gouty tophus tissues within joints. Furthermore, activated MAIT cells secreted pro-resorptive cytokines (i.e. IL-6, IL-17 and TNF-α) and facilitated osteoclastogenesis. CONCLUSION: This study demonstrates that circulating MAIT cells are activated and numerically deficient in GA patients. In addition, MAIT cells have the potential to migrate to inflamed tissues and induce osteoclastogenesis. These findings provide an important role of MAIT cells in the pathogenesis of inflammation and bone destruction in GA patients.


Assuntos
Artrite Gotosa/metabolismo , Hiperuricemia/metabolismo , Células T Invariantes Associadas à Mucosa/metabolismo , Osteogênese/fisiologia , Adulto , Idoso , Movimento Celular/fisiologia , Citocinas/metabolismo , Feminino , Citometria de Fluxo , Humanos , Leucócitos Mononucleares/metabolismo , Masculino , Pessoa de Meia-Idade
17.
Plant Physiol ; 180(4): 1912-1929, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31171578

RESUMO

Until they become photoautotrophic juvenile plants, seedlings depend upon the reserves stored in seed tissues. These reserves must be mobilized and metabolized, and their breakdown products must be distributed to the different organs of the growing seedling. Here, we investigated the mobilization of soybean (Glycine max) seed reserves during seedling growth by initially constructing a genome-scale stoichiometric model for this important crop plant and then adapting the model to reflect metabolism in the cotyledons and hypocotyl/root axis (HRA). A detailed analysis of seedling growth and alterations in biomass composition was performed over 4 d of postgerminative growth and used to constrain the stoichiometric model. Flux balance analysis revealed marked differences in metabolism between the two organs, together with shifts in primary metabolism occurring during different periods postgermination. In particular, from 48 h onward, cotyledons were characterized by the oxidation of fatty acids to supply carbon for the tricarboxylic acid cycle as well as production of sucrose and glutamate for export to the HRA, while the HRA was characterized by the use of a range of imported amino acids in protein synthesis and catabolic processes. Overall, the use of flux balance modeling provided new insight into well-characterized metabolic processes in an important crop plant due to their analysis within the context of a metabolic network and reinforces the relevance of the application of this technique to the analysis of complex plant metabolic systems.


Assuntos
Glycine max/metabolismo , Plântula/metabolismo , Carbono/metabolismo , Cotilédone/genética , Cotilédone/metabolismo , Regulação da Expressão Gênica de Plantas , Ácido Glutâmico/metabolismo , Hipocótilo/genética , Hipocótilo/metabolismo , Plântula/genética , Glycine max/genética , Sacarose/metabolismo
18.
Cancer Cell Int ; 19: 171, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31297035

RESUMO

BACKGROUND: Caveolin-1 (Cav-1) plays an important role in the development of various human cancers. We investigated the relationship between Cav-1 expression and non-small cell lung cancer (NSCLC) progression in the context of brain metastasis (BM). METHODS: Cav-1 expression was investigated in a series of 102 BM samples and 49 paired primary NSCLC samples, as well as 162 unpaired primary NSCLC samples with (63 cases) or without (99 cases) metastasis to distant organs. Human lung cancer cell lines were used for in vitro functional analysis. RESULTS: High Cav-1 expression in tumor cells was observed in 52% (38/73) of squamous cell carcinomas (SQCs) and 33% (45/138) of non-SQCs. In SQC, high Cav-1 expression was increased after BM in both paired and unpaired samples of lung primary tumors and BM (53% vs. 84% in paired samples, P = 0.034; 52% vs. 78% in unpaired samples, P = 0.020). Although the difference in median overall survival in patients NSCLC was not statistically significant, high Cav-1 expression in tumor cells (P = 0.005, hazard ratio 1.715, 95% confidence index 1.175-2.502) was independent prognostic factors of overall survival on multivariate Cox regression analyses, in addition to the presence of BM and non-SQC type. In vitro assays revealed that Cav-1 knockdown inhibited the invasion and migration of lung cancer cells. Genetic modulation of Cav-1 was consistently associated with SNAIL up- and down-regulation. These findings were supported by increased SNAIL and Cav-1 expression in BM samples of SQC. CONCLUSIONS: Cav-1 plays an important role in the BM of NSCLC, especially in SQC. The mechanism may be linked to SNAIL regulation.

19.
Nat Mater ; 16(4): 454-460, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-27918566

RESUMO

The short charging times and high power capabilities associated with capacitive energy storage make this approach an attractive alternative to batteries. One limitation of electrochemical capacitors is their low energy density and for this reason, there is widespread interest in pseudocapacitive materials that use Faradaic reactions to store charge. One candidate pseudocapacitive material is orthorhombic MoO3 (α-MoO3), a layered compound with a high theoretical capacity for lithium (279 mA h g-1 or 1,005 C g-1). Here, we report on the properties of reduced α-MoO3-x(R-MoO3-x) and compare it with fully oxidized α-MoO3 (F-MoO3). The introduction of oxygen vacancies leads to a larger interlayer spacing that promotes faster charge storage kinetics and enables the α-MoO3 structure to be retained during the insertion and removal of Li ions. The higher specific capacity of the R-MoO3-x is attributed to the reversible formation of a significant amount of Mo4+ following lithiation. This study underscores the potential importance of incorporating oxygen vacancies into transition metal oxides as a strategy for increasing the charge storage kinetics of redox-active materials.

20.
Biometals ; 31(6): 1115, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30225625

RESUMO

Due to a technical error, the copyright line of the above mentioned article was incorrect. The original publication has been corrected.

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