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1.
Redox Biol ; 69: 103030, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38181705

RESUMO

Ferroptosis is a type of programmed cell death resulting from iron overload-dependent lipid peroxidation, and could be promoted by activating transcription factor 3 (ATF3). SIRT1 is an enzyme accounting for removing acetylated lysine residues from target proteins by consuming NAD+, but its role remains elusive in ferroptosis and activating ATF3. In this study, we found SIRT1 was activated during the process of RSL3-induced glioma cell ferroptosis. Moreover, the glioma cell death was aggravated by SIRT1 activator SRT2183, but suppressed by SIRT inhibitor EX527 or when SIRT1 was silenced with siRNA. These indicated SIRT1 sensitized glioma cells to ferroptosis. Furthermore, we found SIRT1 promoted RSL3-induced expressional upregulation and nuclear translocation of ATF3. Silence of ATF3 with siRNA attenuated RSL3-induced increases of ferrous iron and lipid peroxidation, downregulation of SLC7A11 and GPX4 and depletion of cysteine and GSH. Thus, SIRT1 promoted glioma cell ferroptosis by inducting ATF3 activation. Mechanistically, ATF3 activation was reinforced when RSL3-induced decline of NAD+ was aggravated by FK866 that could inhibit NAD + synthesis via salvage pathway, but suppressed when intracellular NAD+ was maintained at higher level by supplement of exogenous NAD+. Notably, the NAD + decline caused by RSL3 was enhanced when SIRT1 was further activated by SRT2183, but attenuated when SIRT1 activation was inhibited by EX527. These indicated SIRT1 promoted ATF3 activation via consumption of NAD+. Finally, we found RSL3 activated SIRT1 by inducing reactive oxygen species-dependent upregulation of AROS. Together, our study revealed SIRT1 activated by AROS sensitizes glioma cells to ferroptosis via activation of ATF3-dependent inhibition of SLC7A11 and GPX4.


Assuntos
Ferroptose , Glioma , Humanos , NAD , Fator 3 Ativador da Transcrição/genética , Linhagem Celular Tumoral , Sirtuína 1/genética , Glioma/genética , Glioma/metabolismo , RNA Interferente Pequeno
2.
Neurosurg Rev ; 47(1): 35, 2024 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-38183517

RESUMO

Clear cell meningiomas are a rare histological subtype of World Health Organization (WHO) grade II meningioma. Despite its relatively low frequency, clear cell meningioma has attracted considerable attention because of its unique pathological characteristics, clinical behavior, and challenging management considerations. The purpose of our systematic review is to provide clinicians with a better understanding of this rare disease. PubMed was searched for articles in the English language published from 1988 to 2023 June. The keywords were as follows: "clear cell meningioma," "clear cell" and "meningioma." We analyzed clinical manifestations, radiological manifestations, pathological features, comprehensive treatment strategies, and prognosis to determine the factors influencing recurrence-free survival (RFS). Recurrence-free survival curves of related factors were calculated by the Kaplan‒Meier method. The log-rank test and Cox univariate analysis were adopted to assess the intergroup differences and seek significant factors influencing prognosis and recurrence. Fifty-seven papers met the eligibility criteria, including 207 cases of clear cell meningioma (CCM), which were confirmed by postoperative pathology. The fifty-seven articles involved 84 (40.6%) males and 123 (59.4%) females. The average age at diagnosis was 27.9 years (range, 14 months to 84 years). Among the symptoms observed, headache, neurologic deficit, and hearing loss were the most commonly reported clinical manifestations. Most tumors (47.8%) were located in the skull base region. Most tumors showed significant enhancement, and homogeneous enhancement was more common. A total of 152 (74.1%) patients underwent gross total resection (GTR), and 53 (25.9%) patients underwent subtotal resection (STR). During the follow-up, the tumor recurred in 80 (39.4%) patients. The log-rank test and the Cox univariate analysis revealed that tumor resection range (GTR vs. STR) and adjuvant treatment (YES vs. NO) were significant predictors of recurrence-free survival (RFS). Clear cell meningioma is a rare type of meningioma with challenging diagnosis and therapy. The prognosis of this disease is different from that of regular meningiomas. Recurrence remains a possibility even after total tumor resection. We found that the surgical resection range and adjuvant treatment affected the recurrence period. This finding provides significant guidance for the treatment of clear cell meningioma.


Assuntos
Neoplasias Meníngeas , Meningioma , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Sistema Nervoso Central , Cefaleia , Neoplasias Meníngeas/cirurgia , Meningioma/cirurgia
3.
BMC Cancer ; 24(1): 110, 2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-38254159

RESUMO

BACKGROUNDS: Lymphoplasmacyte-rich meningioma(LPM) is a rare subtype of meningioma with a low degree of malignancy and an overall preferable prognosis. The purpose of this article is to increase the understanding of the disease, reduce misdiagnosis, and improve prognosis. METHODS: A search was conducted in the PubMed database for English articles published from 1993 to 2023. The keywords were "lymphoplasmacyte-rich (all fields) and meningioma (all fields) and English (lang)" and "lymphoplasmacyte-rich meningioma (title/abstract) and English (lang)".We further analyzed the clinical manifestations, imaging manifestations, pathological features, treatment strategies, and prognosis of LPM.The possible prognostic indicators were analyzed by the log-rank test and Pearson's chi-squared test. RESULTS: Fourteen reports with 95 LPM patients were included in this report, including 47 males and 48 females who were diagnosed between the ages of 9 and 79, with an average age of 45 years. The most common clinical manifestations are headache and limb movement disorders. In most cases, the tumor occurred on the convex portion of the brain. All tumors showed significant enhancement, with homogeneous enhancement being more common, and most patients showed peritumoral edema. Postoperative pathological EMA, LCA, and vimentin positivity were helpful for the final diagnosis of the patient. Log-rank tests showed a correlation between complete resection and better prognosis and recurrence. CONCLUSION: There is a lack of significant differences in the clinical symptoms and imaging manifestations of LPM compared to other diseases that need to be differentiated, and a clear diagnosis requires pathological examination. After standardized surgical treatment, the recurrence rate and mortality rate of LPM are both low. Complete surgical resection of tumors is associated with a better prognosis and lower recurrence rate.


Assuntos
Neoplasias Meníngeas , Meningioma , Feminino , Masculino , Humanos , Criança , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Meningioma/diagnóstico , Meningioma/epidemiologia , Prognóstico , Encéfalo , Bases de Dados Factuais , Neoplasias Meníngeas/diagnóstico , Neoplasias Meníngeas/epidemiologia
4.
Rev Sci Instrum ; 94(8)2023 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38065139

RESUMO

A new working principle for multimodal excitation of a resonant bidirectional rotary inertial impact piezoelectric motor with a self-clamping structure was developed based on previous research on piezoelectric motors. Unlike previous piezoelectric motors that relied on single harmonic waves for unidirectional rotation, in this motor, we can simply change the driving signal characteristics of the motor without changing the structure of the piezoelectric motor to excite multiple vibration modes, thereby achieving rotation in both directions. Compared with other bidirectional resonant motors, the structure and control signal are simpler. The finite element simulation software COMSOL5.5 was used to simulate the working mode of the motor, and the results were in good agreement with the final experiment. During the experiments, the optimal operating frequency of the motor prototype was 900 Hz. The maximum output speed of the motor prototype was 3.9 rad/s, the maximum output torque was 15 N mm, and the maximum resolution was 0.248° under the conditions of 240 Vp-p voltage, 900 Hz frequency, and 7.8 N mm preload torque.

5.
Front Pediatr ; 10: 870529, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35722472

RESUMO

Background: Asthma is a common chronic disease among children, especially preschoolers. Some evidence suggests that diet may play a role in asthma, but the current findings are contradictory. The objective of our study was to determine the association between dietary intake and asthma in preschool children aged 2-5 years. Methods: We selected preschool children aged 2-5 years with complete data on asthma diagnosis, diet, and body mass index (BMI) from the national health and nutrition examination survey (NHANES) database. In a selected population, children with self-reported asthma were included in the final sample. In children without self-reported asthma, we further used propensity score matching (PSM) to match age and sex for sampling, maintaining a ratio of 1:4 for cases. Lasso regression was used to identify dietary factors affecting asthma in preschoolers. Results: A total of 269 children with self-reported asthma and 1,076 children without self-reported asthma were included in our study. Univariate analysis showed that there were significant differences in ethnicity and dietary zinc intake between asthmatic children and children without asthma. After adjusting for all dietary and demographic variables, the results of logistic Lasso regression analysis showed that non-Hispanic black (ß = 0.65), vitamin B12 (ß = 0.14), and sodium (ß = 0.05) were positively associated with childhood asthma, while Vitamin K (ß = -0.04) was negatively associated with childhood asthma. Conclusion: In conclusion, our study confirms that non-Hispanic black and dietary sodium intake are associated with a higher risk of asthma in preschoolers. In addition, our study found that dietary vitamin B12 was positively associated with childhood asthma, while vitamin K was negatively associated with childhood asthma.

6.
Front Immunol ; 13: 894002, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35634320

RESUMO

Macrophages play an important role in clearing necrotic myocardial tissues, myocardial ischemia-reperfusion injury, and ventricular remodeling after myocardial infarction. M1 macrophages not only participate in the inflammatory response in myocardial tissues after infarction, which causes heart damage, but also exert a protective effect on the heart during ischemia. In contrast, M2 macrophages exhibit anti-inflammatory and tissue repair properties by inducing the production of high levels of anti-inflammatory cytokines and fibro-progenitor cells. Interleukin (IL)-38, a new member of the IL-1 family, has been reported to modulate the IL-36 signaling pathway by playing a role similar to that of the IL-36 receptor antagonist, which also affects the production and secretion of macrophage-related inflammatory factors that play an anti-inflammatory role. IL-38 can relieve myocardial ischemia-reperfusion injury by promoting the differentiation of M1 macrophages into M2 macrophages, inhibit the activation of NOD-like receptor thermal protein domain-associated protein 3 (NLRP3) inflammasome, and increase the secretion of anti-inflammatory cytokines, such as IL-10 and transforming growth factor-ß. The intact recombinant IL-38 can also bind to interleukin 1 receptor accessory protein-like 1 (IL-1RAPL1) to activate the c-jun N-terminal kinase/activator protein 1 (JNK/AP1) pathway and increase the production of IL-6. In addition, IL-38 regulates dendritic cell-induced cardiac regulatory T cells, thereby regulating macrophage polarization and improving ventricular remodeling after myocardial infarction. Accordingly, we speculated that IL-38 and macrophage regulation may be therapeutic targets for ameliorating myocardial ischemic injury and ventricular remodeling after myocardial infarction. However, the specific mechanism of the IL-38 action warrants further investigation.


Assuntos
Traumatismos Cardíacos , Infarto do Miocárdio , Traumatismo por Reperfusão Miocárdica , Anti-Inflamatórios/farmacologia , Citocinas/metabolismo , Traumatismos Cardíacos/metabolismo , Humanos , Interleucinas/metabolismo , Macrófagos/metabolismo , Infarto do Miocárdio/metabolismo , Traumatismo por Reperfusão Miocárdica/metabolismo , Remodelação Ventricular
7.
Oxid Med Cell Longev ; 2022: 1806513, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35602104

RESUMO

Background: Our previous studies have shown that interleukin- (IL-) 37 plays a protective role in patients and animal models with coronary artery disease. However, the role of IL-37 in patients with abdominal aortic aneurysm (AAA), another artery disease, is yet to be elucidated. Methods and Results: AAA tissues and plasma samples were obtained from patients with or without surgical intervention. Normal renal aortic tissues were collected from kidney transplant donors. Our findings established that in AAA, IL-37 was distributed in endothelial cells, macrophages, and vascular smooth muscle cells (VSMCs) and that it was chiefly concentrated in VSMCs. Furthermore, the expression was found to be downregulated compared with that in normal artery tissues. Immunofluorescence showed that, unlike normal arteries, IL-37 was translocated to the nucleus of VSMCs in AAA. Moreover, in patients with AAA, the expressions of IL-37, IL-6, and tumor necrosis factor- (TNF-) α were increased in the plasma in comparison with the healthy controls. Correlation analysis revealed that IL-37 was positively correlated with IL-6, TNF-α, age, aneurysm diameter, and blood pressure. Furthermore, human aortic vascular smooth muscle cells (HASMCs) were stimulated with angiotensin II (AngII) in vitro to simulate smooth muscle cell (SMC) damage in AAA. A decrease in IL-37 expression and an increase in receptor-interacting serine/threonine-protein kinase 3 (RIPK3) expression were observed in HASMCs stimulated with AngII. On this basis, inhibition of RIPK3 with GSK'872 significantly attenuated necroptosis. Moreover, the necroptosis rates were significantly lowered in HASMCs treated with recombinant IL-37, whereas the rates were enhanced when the cells were depleted of the interleukin. Immunoblotting results showed that both exogenous and endogenous IL-37 could affect the expressions of RIPK3, NLRP3, and IL-1ß. Also, the phosphorylation of RIPK3 and p65 was affected. Meanwhile, IL-37 promoted the transition of SMC from proliferative type to contractile type. Conclusions: The expression of IL-37 in VSMCs decreases in patients with AAA, whereas IL-37 supplementation suppresses RIPK3-mediated necroptosis and promotes the transition of VSMCs from proliferative to contractile type.


Assuntos
Aneurisma da Aorta Abdominal , Interleucina-1 , Miócitos de Músculo Liso , Necroptose , Angiotensina II/metabolismo , Angiotensina II/farmacologia , Aneurisma da Aorta Abdominal/patologia , Células Endoteliais/metabolismo , Humanos , Interleucina-1/metabolismo , Interleucina-6/metabolismo , Músculo Liso Vascular/citologia , Miócitos de Músculo Liso/citologia , Fator de Necrose Tumoral alfa/metabolismo
8.
Oxid Med Cell Longev ; 2021: 6454177, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34471467

RESUMO

As a chronic inflammatory disease, atherosclerosis is a leading cause of morbidity and mortality in most countries. Inflammation is responsible for plaque instability and the subsequent onset of acute coronary syndrome (ACS), which is one of the leading causes of hospitalization. Therefore, exploring the potential mechanism underlying ACS is of considerable concern, and searching for alternative therapeutic targets is very urgent. Interleukin-37 (IL-37) inhibits the production of proinflammatory chemokines and cytokines and acts as a natural inhibitor of innate and adaptive immunity. Interestingly, our previous study with murine models showed that IL-37 alleviated cardiac remodeling and myocardial ischemia/reperfusion injury. Of note, our clinical study revealed that IL-37 is elevated and plays a beneficial role in patients with ACS. Moreover, dendritic cells (DCs) orchestrate both immunity and tolerance, and tolerogenic DCs (tDCs) are characterized by more secretion of immunosuppressive cytokines. As expected, IL-37-treated DCs are tolerogenic. Hence, we speculate that IL-37- or IL-37-treated DCs is a novel therapeutic possibility for ACS, and the precise mechanism of IL-37 requires further study.


Assuntos
Síndrome Coronariana Aguda/tratamento farmacológico , Células Dendríticas/metabolismo , Interleucina-1/uso terapêutico , Animais , Humanos , Interleucina-1/farmacologia , Camundongos
9.
J Inflamm Res ; 14: 3465-3479, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34326655

RESUMO

PURPOSE: This study aims to clarify the specific mechanism by which GARP affects the atherosclerotic plaques in ApoE-/- mice and the effect of GARP-tDC on atherosclerosis. METHODS: The mice were randomly divided into three groups: the control group, the GARP-overexpressed group and the GARP-inhibited group. After 12 weeks, all the mice were euthanized, and the specimens were collected. In vitro, experiments were conducted to observe the effect of GARP on DC phenotype and the changes of the proportion of CD4+CD25+Foxp3+ Treg cells when GARP-tDCs were co-cultured with CD4+ T cells. Furthermore, adoptive transmission of GARP-tDCs was used to observe the effect on atherosclerotic plaque in mice. RESULTS: The GARP-overexpressed group enhanced the biological activity of Foxp3+ CD4+CD25+ Tregs and resulted in increased expression of LAP in T cells. In addition, the GARP-overexpressed group significantly suppressed the function of Th1 and Th17, and decreased the secretion of INF-γ and IL-17A. Thus, GARP had a protective effect on atherosclerosis. In vitro, we found that GARP-tDC had a tolerance-inducing phenotype, and GARP-tDC also had the ability to induce tolerance when co-cultured with CD4+ T cells. More importantly, adoptive transmission of GARP-tDCs reduced the size of atherosclerotic plaques. CONCLUSION: GARP and the GARP-tDC play protective roles in atherosclerosis. The protective effect of GARP on atherosclerosis is achieved by increasing CD4+CD25+Foxp3+ Treg cells and inhibiting the production of IFN-γ and IL-17A.

10.
Circ Rep ; 3(2): 86-94, 2021 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-33693294

RESUMO

Background: Atherosclerosis is an inflammatory disease involving activation of adaptive and innate immune responses to antigens, including oxidized low-density lipoprotein (oxLDL) and phosphorylcholine (PC). Dendritic cells (DCs), which are antigen-presenting cells that activate T cells, are present in atherosclerotic lesions and are activated in immune organs. However, the mechanism by which PC promotes atherosclerosis is unclear. Methods and Results: To evaluate whether PC promotes atherosclerosis via DCs, 2×105 DCs activated by PC-keyhole limpet hemocyanin (DCs+PC-KLH) were injected into ApoE-/- mice and the features of the plaques and the effects of the DCs on cellular and humoral immunity against PC-KLH were determined. Mice injected with DCs+PC-KLH had significantly larger atherosclerotic lesions than controls, with increased inflammation in the lesions and plaque instability. Furthermore, DCs+PC-KLH were characterized using flow cytometry after coculture of bone marrow-derived DCs and naïve T cells. DCs+PC-KLH showed an inflammatory phenotype, with increased CD86, CD40, and major histocompatibility complex Class II molecules (MHC-II), which promoted PC-specific T helper (Th) 1 and Th17 cell differentiation in vivo and in vitro. Moreover, 2 weeks after the administration of DCs+PC-KLH to mice, these mice produced PC- and oxLDL-specific IgG2a, compared with no production in the controls. Conclusions: These findings suggest that DCs presenting PC promote specific immunity to PC, increase lesion inflammation, and accelerate atherosclerosis, which may explain how PC promotes atherosclerosis.

11.
Medicine (Baltimore) ; 100(6): e24583, 2021 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-33578557

RESUMO

ABSTRACT: Lumbar disc prostheses have been used increasingly in recent years. The successful design of lumbar disc prostheses depends on accurate morphometric parameters. However, the morphologic dimensions of lumbar endplate area have not been investigated in Chinese population.A total of 1800 lumbar endplates were retrospectively accessed in 150 Chinese adults. Eighteen parameters of each lumbar segment were measured by three-dimensional computed tomography reconstructions from T12/L1 to L5/S1. These obtained parameters were compared between genders, bilateral sides, vertebral segments, and different populations.Endplate length and width increased in general, and there was a significant decrease for length/width ratio from T12 to S1 (P = .03). The average concavity depth of the lower lumbar endplate (2.09 ±â€Š0.93 mm) was usually larger than that of the upper lumbar endplate (1.61 ±â€Š0.74 mm) (P = .02). The percentage of the most concave point of the upper and lower lumbar endplate was 50.01 ±â€Š10.76% and 56.41 ±â€Š9.93%, respectively. Anterior, medium, or posterior intervertebral endplate height was severally 10.01 ±â€Š1.98 mm, 10.46 ±â€Š2.03 mm, and 6.41 ±â€Š1.74 mm, and increased among vertebral segments (P = .01).The intervertebral endplate angle significantly increased from T12-L1 to L5-S1 (P = .01). Parameters displayed significant difference between genders. The morphometric parameters of different populations also showed differences.In conclusion, there is a morphologic discrepancy in dimensions of lumbar endplate regarding genders, vertebral segments, and different populations. It is essential to design the lumbar disc prosthesis suited for Chinese patients specially, for which the morphometric parameters in our study can be utilized.


Assuntos
Disco Intervertebral , Vértebras Lombares/diagnóstico por imagem , Próteses e Implantes , Desenho de Prótese , Adulto , Feminino , Humanos , Imageamento Tridimensional , Masculino , Pessoa de Meia-Idade , Valores de Referência , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Adulto Jovem
12.
Rev Sci Instrum ; 92(1): 015003, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33514217

RESUMO

Resonant-type piezoelectric impact motors can improve the output capability effectively. A new construction of asymmetric inertial masses is proposed to synthesize approximate saw-tooth wave resonant vibration with matched anti-phase and in-phase modes. A prototype is designed, manufactured, and tested. With 40 Vp-p, 400 Hz exciting voltage for the anti-phase mode and 16 Vp-p, 800 Hz exciting voltage for the in-phase mode, the prototype provides a maximum no-load velocity of 17.2 mm/s and a maximum output power of 0.72 mW with 100 mN load. The velocity and output power of the prototype in the proposed resonant state are near three orders of magnitude higher than those in the traditional quasi-static state.

13.
Rev Sci Instrum ; 90(11): 115004, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31779451

RESUMO

A compact linear-rotary impact motor based on a single piezoelectric tube actuator is proposed. The motor can realize independent linear and rotary motions. With two independent electrodes, the piezoelectric actuator has an outer diameter of 6 mm, a thickness of 0.5 mm, and a length of 25 mm. The actuator produces a maximum axial displacement of 2.17 µm with a driving voltage of 720 Vp-p (peak-to-peak driving voltage), and it produces a maximum torsional angle of 599.98 µrad with a driving voltage of 720 Vp-p. The prototype motor can achieve the independent linear velocities of 6263.45 µm/s and -6331.58 µm/s in the positive and negative directions of motions under the saw-shaped driving voltage of 560 Vp-p at 8 kHz. The motor can realize the independent rotary velocities of 1.22 × 106µrad/s and -1.21 × 106µrad/s in the two motions under the saw-shaped driving voltage of 560 Vp-p at 9 kHz. The maximum output force of the motor is 0.45 N, and the maximum output torque is 0.80 mN m for linear and rotary motions, respectively.

14.
Front Neurosci ; 13: 859, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31481868

RESUMO

Chronic cerebral hypoperfusion (CCH) is a main cause of vascular dementia and is also an etiological factor of neurological diseases and mental disorders. However, few treatments are available for CCH, and new medications are needed. In the present study, we employed a rat model of CCH that was based on bilateral common carotid artery occlusion and investigated the therapeutic effects of resveratrol and its detailed mechanism of action. We evaluated neurological deficit scores and performed the Morris water maze test, hematoxylin and eosin staining, TUNEL staining, enzyme-linked immunosorbent assays, and Western blot. Resveratrol reduced neurological deficit scores in CCH rats and reduced pathological damage in the frontal cortex and hippocampus. Resveratrol activated autophagy and inhibited the expression of AKT/mechanistic target of rapamycin (mTOR) signaling pathway-related proteins. Treatment with a phosphoinositide-3 kinase inhibitor reversed the protective effect of resveratrol. These findings suggest that resveratrol improves cognitive function in a rat model of CCH and reduces oxidative stress-induced neuronal damage in the frontal cortex and hippocampus by activating autophagy and inhibiting neuronal apoptosis. These effects may be regulated by the AKT/mTOR signaling pathway.

15.
Life Sci ; 231: 116527, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31176783

RESUMO

AIMS: Extracellular vesicles (EVs) are vital for information exchange between donor and recipient cells. When cells are stressed (e.g., by oxygen glucose deprivation, OGD), the complex information carried by the EVs is altered by the donor cells. Here, we aimed to analyze the proteomic differences between EVs derived from OGD-damaged cells and EVs derived from undamaged cells to explore the potential mechanisms by which EVs aggravate ischemic stroke (IS). MAIN METHODS: EVs released by rat adrenal gland PC12 cells subjected to 0, 3, 6, or 12 h of OGD were isolated. The proteins from the EVs secreted by each of the OGD groups were profiled using liquid chromatography-tandem mass spectroscopy (LC-MS/MS). We predicted the functions, pathways, and interactions of the differentially expressed proteins using Gene Ontology (GO), KEGG pathways, and STRING. We used parallel reaction monitoring (PRM) to validate our results. KEY FINDINGS: We identified several differentially expressed proteins in the OGD groups as compared to the controls: 170 proteins in the 3 h OGD EVs, 44 proteins in the 6 h OGD EVs, and 77 proteins in the 12 h OGD EVs (fold-change ≥1.5; p ≤ 0.05). These proteins were associated with oxidative stress, carbohydrate metabolism, protein synthesis and degradation, and thrombosis. SIGNIFICANCE: We identified changes in protein expression in the EVs secreted by OGD-damaged cells, highlighting potential mechanisms by which EVs aggravate IS. Our results also suggested potential protein targets, which may be useful for the prevention and treatment of IS.


Assuntos
Vesículas Extracelulares/metabolismo , Vesículas Extracelulares/fisiologia , Acidente Vascular Cerebral/metabolismo , Animais , Isquemia Encefálica/metabolismo , Cromatografia Líquida/métodos , Glucose/metabolismo , Oxigênio/metabolismo , Células PC12 , Proteômica/métodos , Ratos , Acidente Vascular Cerebral/fisiopatologia , Espectrometria de Massas em Tandem/métodos
16.
Neurochem Res ; 44(8): 1807-1817, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31093905

RESUMO

Cerebral ischemic injury is a leading cause of human mortality and disability, seriously threatening human health in the world. Activin A (Act A), as a well-known neuroprotective factor, could alleviate ischemic brain injury mainly through Act A/Smads signaling. In our previous study, a noncanonical Act A/Smads signal loop with self-amplifying property was found, which strengthened the neuroprotective effect of Act A. However, this neuroprotective effect was limited due to the self-limiting behavior mediated by Smad anchor for receptor activation (SARA) protein. It was reported that microRNA-17-5p (miR-17-5p) could suppress the expression of SARA in esophageal squamous cell carcinoma. Thus we proposed that knockdown of miR-17-5p could strengthen the neuroprotective effect of Act A/Smads signal loop through SARA. To testify this hypothesis, oxygen-glucose deficiency (OGD) was introduced to highly differentiated rattus pheochromocytoma (PC12) cells. After the transfection of miR-17-5p mimic or inhibitor, the activity of Act A signal loop was quantified by the expression of phosphorylated Smad3. The results showed that suppression of miR-17-5p up-regulated the expression of SARA protein, which prolonged and strengthened the activity of Act A signaling through increased phosphorylation of downstream Smad3 and accumulation of Act A ligand. Further luciferase assay confirmed that SARA was a direct target gene of miR-17-5p. These practical discoveries will bring new insight on the endogenous neuroprotective effects of Act A signal loop by interfering a novel target: miR-17-5p.


Assuntos
Subunidades beta de Inibinas/metabolismo , MicroRNAs/genética , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Hipóxia Celular , Técnicas de Silenciamento de Genes , Glucose/deficiência , Isquemia/genética , Isquemia/metabolismo , Neuroproteção , Células PC12 , Ratos , Transdução de Sinais , Proteína Smad3/metabolismo , Regulação para Cima
17.
Sensors (Basel) ; 18(7)2018 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-29986524

RESUMO

This paper presents a novel impact rotary motor based on a piezoelectric tube actuator with helical interdigitated electrodes which has a compact structure and high resolution. The assembled prototype motor has a maximum diameter of 15 mm and a length of 65 mm and works under a saw-shaped driving voltage. The LuGre friction model is adopted to analyze the rotary motion process of the motor in the dynamic simulations. From the experimental tests, the first torsional resonant frequency of the piezoelectric tube is 59.289 kHz with a free boundary condition. A series of experiments about the stepping characteristics of different driving voltages, duty cycles, and working frequencies are carried out by a laser Doppler vibrometer based on a fabricated prototype motor. The experimental results show that the prototype rotary motor can produce a maximum torsional angle of about 0.03° using a driving voltage of 480 Vp-p (peak-to-peak driving voltage) with a duty ratio of 0% under a small friction force of about 0.1 N. The motor can produce a maximum average angle of about 2.55 rad/s and a stall torque of 0.4 mN∙m at 8 kHz using a driving voltage of 640 Vp-p with a duty ratio of 0% under a large friction force of about 3.6 N. The prototype can be driven in forward and backward motion and is working in stick-slip mode at low frequencies and slip-slip mode at high frequencies.

18.
Rev Sci Instrum ; 84(9): 096104, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24089879

RESUMO

We develop a novel approach to match harmonics and vibration modes based on the mechanism of multiple tuning fork structure (MTFS), through which it is promising to realize arbitrary periodical vibrations in the resonant state. A prototype three-layer MTFS with first three harmonics is presented to verify the feasibility of the proposed principle. The matching process and experimental results confirm the unique advantages of MTFS, as discussed in the theoretical analysis. Typical periodical motions, including sawtooth, square, half-wave rectified, and full-wave rectified waveforms, are achieved by the syntheses of resonant harmonics.

19.
Rev Sci Instrum ; 80(6): 065101, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19566220

RESUMO

Piezoelectric tubes with film electrodes on their outer and inner surfaces can be used to compose multitube actuators. The actuator of four piezoelectric tubes can substitute the traditional single-tube actuator with quartered electrodes which has been widely used in scanning probe microscopy and piezoelectric motors. In this article, the static deflection, static bending moment, resonant frequency, and dynamic deflection of the four-tube actuator are all studied in detail. The comparison between this actuator and the traditional single-tube actuator is also done and the results show that the four-tube actuator has better performances under certain conditions. The experiment results of a prototype actuator testified the validation of the analysis.

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