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1.
Artigo em Inglês | MEDLINE | ID: mdl-32040291

RESUMO

Electrolytes in modern Li-ion batteries (LIBs) rely on additives of various structures to generate key interphasial chemistries needed for desired performances, although how these additives operate in battery environments remains little understood. Meanwhile, these traditional additives face increasing challenges from emerging battery chemistries, especially those based on high nickel cathode (Ni ≥ 50%) or the metallic lithium anode. In this work, we report a new additive structure with the highest unsaturation degree known so far, along with in-depth understanding of its breakdown mechanism on those aggressive electrode surfaces. Tripropargyl phosphate (TPP) containing three carbon-carbon triple bonds was found to form dense and protective interphases on both NMC532 cathode as well as graphitic and metallic lithium anodes, leading to significant improvements in performances of both LIBs and lithium metal batteries (LMBs). Comprehensive characterizations together with calculations reveal how the unsaturation functionalities of TPP interact with these electrode chemistries and establish interphases that inhibit gas generation, suppress lithium dendrite growth, prevent transition metal ion dissolution and deposition on the anode surface. The correlation established among the additive structure, interphasial chemistries and cell performance will doubtlessly guide us in designing the electrolytes with atomistic precision for future battery chemistries.

2.
Pathol Res Pract ; 216(2): 152795, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31879047

RESUMO

BACKGROUND: Dihydroartemisinin (DHA), a semisynthetic derivative of artemisinin, has a broad range of biological properties, including antitumor activity. However, the mechanisms by which DHA affects the tumorigenesis of gastric carcinoma (GC) are poorly understood. MATERIAL AND METHODS: The targets of DHA were identified by network pharmacology, and the association of CDK4 with clinicopathological characteristics and prognosis in patients with GC was analyzed by using TCGA data. CCK8, Transwell and flow cytometric analyses, as well as a tumor xenograft model, were used to assess the effects of DHA on the growth and migration of GC cells. qRT-PCR and Western blot analyses were used to determine the effects of DHA on the cyclin D1-CDK4-Rb signaling pathway. RESULTS: We identified 13 DHA targets and measured their expression of whichCDK4 expression levels were substantially higher in GC tissues than those in adjacent normal tissues, and high CDK4 expression acted as an independent prognostic factor of poor survival in patients with GC. DHA suppressed cell proliferation, migration and invasion in vitro and in vivo and induced G1 phase cell cycle arrest in a dose-dependent manner by regulating cyclin D1-CDK4-Rb signaling. CONCLUSIONS: DHA inhibits the tumorigenesis and invasion of GC by regulating cyclin D1-CDK4-Rb signaling and may provide therapeutic strategies for the treatment of GC.

4.
Oral Dis ; 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31715075

RESUMO

OBJECTIVES: Using next-generation sequencing (NGS) to determine whether aggressive periodontitis is associated with specific mitochondrial polymorphisms. MATERIALS AND METHODS: A total of 165 unrelated Han Chinese were enrolled in the study. We analyzed the mitochondrial DNA (mtDNA) in 97 patients with aggressive periodontitis and 68 healthy controls by NGS. The mitochondrial DNA was L-PCR-amplified and subsequently sequenced by an Illumina Genome Analyzer (NGS). Chi-square tests were used to assess the differences between the two groups. In cases of significant difference, multivariate logistic regression models were further used to analyze the association between mtDNA polymorphisms and aggressive periodontitis. RESULTS: Significant association was observed between aggressive periodontitis and eight mitochondrial polymorphisms: "8860G-10400C" (OR = 2.828, p = .002), "8701A" (OR = 2.308, p = .005), "12705C-10398A" (OR = 2.683, p = .002), "9540C" (OR = 3.838, p = .001) and "10873T-15043G" (OR = 4.375, p = .001). CONCLUSIONS: The pathogenesis of aggressive periodontitis is complicated, and its heredity is not well characterized. Our study was the first to use next-generation sequencing and found that 8860G-10400C, 8701A, 12705C-10398A, 9540C, and 10873T-15043G are associated with aggressive periodontitis in the Han Chinese population.

5.
Pathol Res Pract ; 215(11): 152677, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31591052

RESUMO

Sanguinarine (SAG), a benzophenanthridine alkaloid extracted from Sanguinaria canadensis, exerts antioxidant, anti-inflammatory and antiproliferative activities in a variety of malignancies. However, the underlying mechanisms by which SAG affects the tumorigenesis of gastric cancer (GC) are unclear. The common targets of SAG and GC were identified by network pharmacology, and the association of thymocyte selection-associated high mobility group box (TOX) with the clinicopathological characteristics and prognosis of patients with GC was analyzed by using datasets from The Cancer Genome Atlas (TCGA). 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assays, colony formation assays, flow cytometry analysis, and a xenograft tumor model were conducted to assess the effects of SAG on the growth of GC cells, and Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analysis were used to determine the effects of SAG on the TOX/DNA-PKcs/KU70/80 signaling pathway. We identified 9 collective targets of SAG and GC, of which TOX expression levels were dramatically downregulated in GC tissues compared with adjacent normal tissues, and a low expression of TOX served as an independent prognostic factor of poor survival in patients with GC. SAG suppressed cell viability, colony formation and in vivo tumorigenesis and induced cell apoptosis and cell cycle arrest. Furthermore, SAG increased the expression levels of TOX but decreased those of DNA-PKcs and KU70/80 in GC cells. Our findings indicate that SAG inhibits the tumorigenesis of GC cells by regulating TOX/DNA-PKcs/KU70/80 signaling and may provide therapeutic strategies for the treatment of GC.

7.
Parasit Vectors ; 12(1): 336, 2019 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-31287026

RESUMO

BACKGROUND: Clonorchiasis is caused by eating of raw or undercooked freshwater fish containing the larvae of Clonorchis sinensis; the Kato-Katz method is widely applied in diagnosis. The improvement of repeated Kato-Katz smears from multiple stool samples has been well illuminated in many helminths other than C. sinensis. METHODS: A cross-sectional investigation was implemented to capture the epidemiology and risk factors of clonorchiasis among middle school students in Qiyang county, China. Students with complete data of six Kato-Katz thick smears from two stool samples were included in this analysis. Data on the habits of eating raw freshwater fish were also collected and compared. RESULTS: Altogether, 397 students had complete information of six smears, out of which 394 reported the information on eating habits. According to the 'gold' standard by six smears, 77 students (19.4%) were detected with C. sinensis. However, only 45 (11.3%) were detected using a single smear, with an underestimation of 41.6% compared to the 'gold' standard. However, the geometric mean of eggs per gram of feces in detected cases was 126.4 in a single smear, overestimated by 105.2% compared to 61.6 by the 'gold' standard. The linear relationship between prevalence and infection intensity of detected cases based on different smears was significantly negative. The habits of eating raw freshwater fish in the false negative cases was similar to those in the detected cases, but these two groups had significantly higher levels for habits of eating raw freshwater fish than negative individuals. CONCLUSIONS: In low endemicity situations, underestimation of C. sinensis infection could not be avoided based on a limited number of Kato-Katz smears. Thus, repeated smears from at least two stool samples should be considered when an individual eats raw freshwater fish, drug efficacy is evaluated or elimination of C. sinensis is verified. Additionally, when logistics are insufficient for multiple samples to be taken for diagnosis for survey and surveillance in the areas or populations of low endemicity, prevalence accuracy needs to be corrected.


Assuntos
Clonorquíase/diagnóstico , Clonorchis sinensis/isolamento & purificação , Produtos Pesqueiros/parasitologia , Manejo de Espécimes/métodos , Animais , China/epidemiologia , Clonorquíase/epidemiologia , Clonorquíase/parasitologia , Estudos Transversais , Fezes/parasitologia , Comportamento Alimentar , Feminino , Peixes , Água Doce , Humanos , Masculino , Contagem de Ovos de Parasitas , Prevalência , Inquéritos e Questionários
8.
Quant Imaging Med Surg ; 9(4): 654-661, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31143656

RESUMO

Background: To assess the feasibility of dual-energy spectral computed tomography (DECT) for quantifying the liver iron content (LIC) with material decomposition (MD) technique in vitro. Methods: Liver-iron mixture samples (model A) and liver-iron-fat mixture samples (model B) were prepare and scanned by a single source DECT using GSI mode with successive tube currents of 200, 320, and 485 mA. A standard algorithm of 1.25 mm was used to reconstruct iron (fat) MD images and iron (water) MD images. The iron concentrations of all samples were measured and analyzed by Spearman's rank correlation and linear regression analysis. Results: Significant positive linear correlations were found between virtual iron content (VIC) and LIC in the absence of fat (model A) and in the presence of fat (model B) in the range of LIC 0 to 25 mg/mL. The lines of best fit to model A had slopes around 1.1 and an intercept around (-1.5) mg/mL for iron (water) MD images, and had slopes around 1.1 and an intercept around (-10) mg/mL for iron (fat) MD images. The lines of best fit to the model B had slopes around 1.5 and an intercept around (-15) mg/mL. At the same value of LIC (LIC >0), the VIC values of model A were always higher than those of model B. At the high value of LIC (12.5 mg/mL), the VIC values of model B were similar, but they differed greatly from those of model A. Conclusions: The fast-kilovolt-peak switching dual-energy CT imaging and MD techniques allow for quantification of iron content. Fat and the post-reconstruction algorithm of iron (fat) MD images, were confounding factors, and led to the underestimation and overestimation of LIC, respectively.

9.
J Cell Physiol ; 2019 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-30712321

RESUMO

Pancreatic cancer is a serious solid malignant tumor worldwide. Increasing evidence has pointed out that abnormal expressions of long noncoding RNAs are involved in various tumors. Meanwhile, LINC00052 is reported as a famous tumor regulator in several cancers. Nevertheless, the biological role of LINC00052 in pancreatic cancer progression is still unknown. Our study was to explore the specific mechanism of LINC00052 in pancreatic cancer. First, we observed that the LINC00052 was obviously downregulated in several pancreatic cancer cell lines. Overexpression of LINC00052 greatly repressed AsPC-1 and SW1990 cell proliferation, triggered the apoptosis and prevented cell cycle in the G1 phase. For another, AsPC-1 and SW1990 cell migration and invasion capacity were also obviously repressed by LINC00052 upregulation. Moreover, miR-330-3p was elevated in pancreatic cancer cells and can function as a target of LINC00052 confirmed by luciferase reporter and RNA Immunoprecipitation (RIP) experiments. Inhibition of miR-330-3p could depress pancreatic cancer progression while overexpressed miR-330-3p exhibited an opposite process. Finally, our data indicated that the LINC00052 also remarkably suppressed pancreatic tumor growth via modulating miR-330-3p in vivo. To conclude, our study revealed that the LINC00052 might provide a new perspective for pancreatic cancer therapy.

10.
Carbohydr Polym ; 208: 285-293, 2019 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-30658802

RESUMO

Levans and inulins are fructans with mainly ß-(2→6) and ß-(2→1) linkages, respectively. Levans are produced by many lactic acid bacteria, e.g. during sourdough fermentation. Levans have shown prebiotic properties and may also function as in situ-produced hydrocolloids. So far, levan contents have been measured by acid hydrolysis, which cannot distinguish levans from e.g. inulins. In order to develop a specific analysis for levan in food matrices, a Paenibacillus amylolyticus endolevanase was combined with exoinulinase for levan hydrolysis. A separate endoinulinase treatment was used to detect the possible presence of inulin. Interfering sugars were removed by a pre-wash with aqueous ethanol. Levan content was estimated from fructose and glucose released in the hydrolysis, with a correction made for the residual fructose and glucose-containing sugars. The method was validated using wheat model doughs spiked with commercial Erwinia levan, and tested by analyzing levan content in Leuconostoc mesenteroides DSM 20343-fermented fava bean doughs.


Assuntos
Frutanos/metabolismo , Lactobacillales/enzimologia , Lactobacillales/metabolismo , Fermentação/fisiologia , Glicosídeo Hidrolases/metabolismo , Inulina/metabolismo , Polissacarídeos/metabolismo , Triticum/enzimologia , Triticum/metabolismo , Vicia faba/enzimologia , Vicia faba/metabolismo
12.
World J Clin Cases ; 6(14): 854-861, 2018 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-30510955

RESUMO

Pretibial myxedema (PTM), an uncommon manifestation of Graves' disease (GD), is a local autoimmune reaction in the cutaneous tissue. The treatment of PTM is a clinical challenge. We herein report on a patient with PTM who achieved complete remission by multipoint subcutaneous injections of a long-acting glucocorticoid and topical glucocorticoid ointment application for a self-controlled study. A 53-year-old male presented with a history of GD for 3.5 years and a history of PTM for 1.5 years. Physical examination revealed slight exophthalmos, a diffusely enlarged thyroid gland, and PTM of both lower extremities. One milliliter of triamcinolone acetonide (40 mg) was mixed well with 9 mL of 2% lidocaine in a 10 mL syringe. Multipoint intralesional injections into the skin lesions of the right lower extremity were conducted with 0.5 mL of the premixed solution. A halometasone ointment was used once daily for PTM of the left lower extremity until the PTM had remitted completely. The patient's PTM achieved complete remission in both legs after an approximately 5-mo period of therpy that included triamcinolone injections once a week for 8 wk and then once a month for 2 mo for the right lower extremity and halometasone ointment application once daily for 8 wk and then once 3-5 d for 2 mo for the left lower extremity. The total dosage of triamcinolone acetonide for the right leg was 200 mg. Our experience with this patient suggests that multipoint subcutaneous injections of a long-acting glucocorticoid and topical glucocorticoid ointment application are safe, effective, and convenient treatments. However, the topical application of a glucocorticoid ointment is a more convenient treatment for patients with PTM.

13.
Appl Opt ; 57(32): 9589-9595, 2018 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-30461739

RESUMO

Carried on the deck of the satellite maritime tracking and control ship, Yuan Wang 6, we have conducted a long-term on-ship dynamic experiment for a star sensor in the South Pacific. Motion-blurred star images of the star sensor obtained under different dynamic conditions are processed by our previously proposed region confined restoration method method, after which the SNR of the motion-blurred star images and the identification rate of the star sensor have been improved remarkably. With the attitude-correlated frames approach, the random noise aroused by the motion of the ship is reduced further. As a result, considering the accuracy and star observation length of the ship-borne star sensor, we believe reported for the first time, a three-axis attitude accuracy of better than 5 arcseconds is obtained in our on-ship experiment.

14.
Biochem Biophys Res Commun ; 505(3): 657-663, 2018 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-30286956

RESUMO

Acute pancreatitis in pregnancy (APIP), which was thought to be a rare but severe disease, with a high perinatal mortality among maternal-fetuses. Our research aimed to study and assess thyroid injury in a rat model of APIP and its possible mechanisms. The APIP model was established by retrograde injection with sodium taurocholate. Sham-operated (SO) and APIP groups were performed at 3 time-points. Histological changes in the maternal thyroid and pancreas were assessed. The activities of serum amylase, lipase and levels of FT3, FT4, MDA, TNF-α and IL-1ß were detected in maternal rats, and the expression of MIF, ICAM-1 and CD68 in the maternal thyroids were determined. In this study, maternal thyroid injury as well as pancreas injury occurred in a time-dependent manner. The activities of serum amylase, lipase and levels of MDA, TNF-α and IL-1ß were markedly increased in acute pancreatitis rats, the levels of serum FT3 and FT4 were obviously decreased in APIP groups, and the expressions of MIF, ICAM-1 and CD68 were significantly increased in the thyroid of the APIP group. Ultrastructural thyroid injuries were observed in the APIP group. Our research suggests that thyroid injury is involved in the rat experimental model of APIP. The degree of thyroid dysfunction is associated with APIP, which may affect the prognosis of acute pancreatitis.


Assuntos
Modelos Animais de Doenças , Pancreatite/sangue , Complicações na Gravidez/sangue , Hormônios Tireóideos/sangue , Doença Aguda , Amilases/sangue , Animais , Citocinas/sangue , Feminino , Humanos , Microscopia Eletrônica de Transmissão , Pâncreas/metabolismo , Pâncreas/patologia , Pancreatite/induzido quimicamente , Gravidez , Ratos Sprague-Dawley , Ácido Taurocólico , Glândula Tireoide/metabolismo , Glândula Tireoide/patologia , Glândula Tireoide/ultraestrutura
15.
Sci Rep ; 8(1): 15393, 2018 10 18.
Artigo em Inglês | MEDLINE | ID: mdl-30337682

RESUMO

Pneumonia and sepsis are major risk factors for acute kidney injury (AKI). Patients with pneumonia and AKI are at increased risk for morbidity and mortality. Surfactant protein D (SP-D) expressed in lung and kidney plays important roles in innate immunity. However, little is known about the role of organ-specific SP-D in the sepsis. The current study uses wild type (WT), SP-D knockout (KO), and humanized SP-D transgenic (hTG, lung-specific SP-D expression) mice to study organ-specific role of SP-D in pneumonia-induced sepsis. Analyses demonstrated differential lung and kidney injury among three-type mice infected with Pseudomonas aeruginosa. After infection, KO mice showed higher injurious scores in both lung and kidney, and decreased renal function than WT and hTG mice. hTG mice exhibited comparable lung injury but more severe kidney injury compared to WT mice. Increased renal tubular apoptosis, NF-κB activation and proinflammatory cytokines in the kidney of KO mice were found when compared with WT and hTG mice. Furthermore, in vitro primary proximal tubular epithelial cells from KO mice showed more apoptosis with higher level of activated caspase-3 than those from WT mice after LPS treatment. Collectively, SP-D attenuates AKI in the sepsis by modulating renal apoptosis, inflammation and NF-κB signaling.


Assuntos
Lesão Renal Aguda/prevenção & controle , Lesão Pulmonar Aguda/prevenção & controle , Apoptose , Inflamação/prevenção & controle , NF-kappa B/metabolismo , Pneumonia/fisiopatologia , Proteína D Associada a Surfactante Pulmonar/fisiologia , Sepse/complicações , Lesão Renal Aguda/etiologia , Lesão Renal Aguda/metabolismo , Lesão Renal Aguda/patologia , Lesão Pulmonar Aguda/etiologia , Lesão Pulmonar Aguda/metabolismo , Lesão Pulmonar Aguda/patologia , Animais , Imunidade Inata/imunologia , Inflamação/etiologia , Inflamação/metabolismo , Inflamação/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , NF-kappa B/genética , Sepse/metabolismo , Sepse/patologia , Transdução de Sinais
16.
Int J Mol Med ; 42(5): 2750-2762, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30226562

RESUMO

GPR17 is a G (i)-coupled dual receptor, linked to P2Y and CysLT receptors stimulated by uracil nucleotides and cysteinyl leukotrienes, respectively. Recent evidence has demonstrated that GPR17 inhibition ameliorates the progression of cerebral ischemic injury by regulating neuronal death and microglial activation. The present study aimed to assess the detailed regulatory roles of this receptor in oxygen­glucose deprivation/recovery (OGD/R)­induced ischemia­like injury in vitro and explore the underlying mechanism. The results demonstrated that OGD/R induced ischemic neuronal injury and microglial activation, including enhanced phagocytosis and increased inflammatory cytokine release in neuron­glial mixed cultures of cortical cells. GPR17 upregulation during OGD/R was spatially and temporally correlated with neuronal injury and microglial activation. In addition, GPR17 knockdown inhibited OGD/R­induced responses in neuron­glial mixed cultures. GPR17 knockdown also attenuated cell injury induced by the agonist leukotriene D4 (LTD4) or uridine 5'­diphosphate (UDP) in neuron­glial mixed cultures. However, GPR17 knockdown did not affect OGD/R­induced ischemic neuronal injury in primary cultures of neurons. In primary astrocyte cultures, neither GPR17 nor OGD/R induced injury. By contrast, GPR17 knockdown ameliorated OGD/R­induced microglial activation, boosting phagocytosis and inflammatory cytokine release in primary microglia cultures. Finally, the results demonstrated that the conditioned medium of microglia pretreated with OGD/R induced neuronal death, and the neuronal injury was significantly inhibited by GPR17 knockdown. These findings suggested that GPR17 may mediate ischemia­like neuronal injury and microglial activation in vitro; however, the protective effects on ischemic neuronal injury might depend upon microglial activation. Whether GPR17 regulates neuronal injury mediated by oligodendrocyte linkage remains to be investigated.


Assuntos
Citocinas/imunologia , Microglia/patologia , Neurônios/patologia , Receptores Acoplados a Proteínas-G/imunologia , Traumatismo por Reperfusão/patologia , Animais , Astrócitos/imunologia , Astrócitos/metabolismo , Astrócitos/patologia , Isquemia Encefálica/genética , Isquemia Encefálica/imunologia , Isquemia Encefálica/patologia , Morte Celular , Células Cultivadas , Microglia/imunologia , Microglia/metabolismo , Neurônios/imunologia , Neurônios/metabolismo , Fagocitose , Interferência de RNA , Ratos Sprague-Dawley , Receptores Acoplados a Proteínas-G/genética , Traumatismo por Reperfusão/genética , Traumatismo por Reperfusão/imunologia , Regulação para Cima
17.
Biomed Environ Sci ; 31(8): 572-578, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30231961

RESUMO

OBJECTIVE: To validate the performance of Mycob. T Stainer and Scanner (MTSS) for detecting acid-fast bacilli (AFB). METHODS: A total of 3,816 sputum samples from 1,515 tuberculosis (TB) suspects were tested at the Anhui Provincial Chest Hospital and the Linyi People's Hospital from April-August, 2016. Each specimen was placed on two smear slides. One slide was stained by the ziehl-neelsen (ZN) method to be read by conventional microscopy (CM). The other slide was stained and scanned by MTSS. All specimens were decontaminated with 4% NaOH, and then inoculated into solid culture. The performance of MTSS was assessed. RESULTS: MTSS produced higher average positivity rate (27.96%) as compared with the CM (26.83%). The overall sensitivity and specificity of MTSS were 78.9% and 93.9%, respectively. The sensitivity and specificity of CM was 77.4% and 95.0%, respectively. CONCLUSION: MTSS exhibited a favorable performance in the detection of AFB. It may be an alternative to CM for screening TB.


Assuntos
Mycobacterium tuberculosis , Coloração e Rotulagem/métodos , Tuberculose Pulmonar/diagnóstico , China , Hospitais , Sensibilidade e Especificidade , Escarro/microbiologia
18.
Nanoscale ; 10(33): 15641-15653, 2018 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-30091442

RESUMO

Entwining-induced robust natural biosystems show superior mechanical performances over their counterparts. However, the role played by topological entwinement in the mechanical properties of artificial nanohelixes remains unknown. Here, the tensile characteristics of nano-entwined carbon nanocoil (ECNC) metamaterials are explored by atomistic simulations. The simulation results show that ECNCs exhibit heterogeneous pre-stress distribution along the spiral surfaces. The predicted stretching stress-strain responses correlate with the topological nano-entwining and dimensionality. Topological analysis reveals that the collective stretching of the bond and bond angle on the inner hexagon edge of the coils characterizes both early and final elastic extensions, whereas the intermediate elasticity is exclusively attributed to the inner-edged hexagon-angular deformation. The ECNCs impart pronounced tensile stiffnesses to the native structures, surprisingly with a maximum of over 13-fold higher stiffness for one triple-helix, beyond the scalability of mechanical springs in parallel, originating from the nano-entwining mechanism and increase in bulkiness. However, the reinforcement in strengths is restricted by the elastic strain limits that are degraded in ECNCs owing to the steric hindrance effect. All metastructures show superelongation-at-break due to a successive break-vs.-arrest process. Upon plastic deformation, the localized reduction in the radii of ECNCs leads to the formation of carbyne-based networks.

19.
Biomed Environ Sci ; 31(7): 499-506, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30145984

RESUMO

OBJECTIVE: To investigate the effects of YOD1 overexpression on the proliferation and migration of human oral keratinocytes (HOKs), and to clarify whether the mechanisms involve transforming growth factor-ß (TGF-ß) signaling. METHODS: HOKs were transfected with the plasmid pEGFP-N3-YOD1 containing YOD1. The mRNA levels of YOD1 and TGF-ß were determined by qPCR. The protein expressions of YOD1, TGF-ß, Smad2/3, Smad4, and phospho-Smad2/3 were determined by western blotting. Cell proliferation and migration were evaluated by Cell Counting Kit-8 assay and wound healing assay, respectively. RESULTS: The mRNA and protein levels of YOD1 were higher in HOKs transfected with YOD1. YOD1 overexpression significantly enhanced the migration of HOKs. The mRNA and protein levels of TGF-ß3 were increased by YOD1 overexpression. HOKs transfected with YOD1 exhibited increased phospho-Smad2/3 levels. CONCLUSION: YOD1 overexpression enhances cell migration by promoting TGF-ß3 signaling which may play an important role in lip and palate formation. YOD1 mutation may contribute to aberrant TGF-ß3 signaling associated with decreased cell migration resulting in NSCLP.


Assuntos
Movimento Celular/fisiologia , Endopeptidases/metabolismo , Queratinócitos/fisiologia , Tioléster Hidrolases/metabolismo , Fator de Crescimento Transformador beta3/metabolismo , Proliferação de Células , Células Cultivadas , Endopeptidases/genética , Humanos , Transdução de Sinais/fisiologia , Proteínas Smad/genética , Proteínas Smad/metabolismo , Tioléster Hidrolases/genética , Fator de Crescimento Transformador beta3/genética
20.
Am J Physiol Gastrointest Liver Physiol ; 315(5): G838-G847, 2018 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-30138574

RESUMO

This study was conducted to investigate the effect of 4-phenylbutyric acid (4-PBA) on vital organ injury following sodium taurocholate-induced acute pancreatitis (AP) in rats and the pertinent mechanism. The serum biochemical indicators and key inflammatory cytokines, histopathological damage and apoptosis of vital organs in rat AP, were evaluated in the presence or absence of 4-PBA. Moreover, mRNA and protein levels of endoplasmic reticulum stress (ERS) markers were assessed. 4-PBA significantly attenuated the structural and functional damage of vital organs, including serum pancreatic enzymes, hepatic enzymes, creatinine, and urea. The morphological changes and infiltration of neutrophils and macrophages were reduced as well. These effects were accompanied by decreased serum levels of proinflammatory TNF-α and IL-1ß. Furthermore, 4-PBA diminished the expression of ERS markers (glucose-regulated protein 78, CCAAT/enhancer-binding protein homologous protein, protein kinase R-like ER kinase, activated transcription factor 6, and type-1 inositol requiring enzyme) in vital organs of AP rats. 4-PBA also reduced AP-induced apoptosis in lung, liver, and kidney tissues as shown by TUNEL assay. The present study demonstrated that 4-PBA protected pancreas, lung, liver, and kidney from injury in rat AP by regulating ERS and mitigating inflammatory response to restrain cell death and further suggested that 4-PBA may have potential therapeutic implications in the disease. NEW & NOTEWORTHY In this study, we suggest that endoplasmic reticulum stress (ERS) is an important player in the development of acute pancreatitis-induced multiorgan injury, providing additional evidence for the proinflammatory role of ERS. Because 4-phenylbutyric acid has been suggested to inhibit ERS in many pathological conditions, it is possible that this effect can be involved in alleviating inflammatory response and cell death to ameliorate vital organ damage following acute pancreatitis induced by sodium taurocholate in rats.


Assuntos
Estresse do Retículo Endoplasmático/efeitos dos fármacos , Insuficiência de Múltiplos Órgãos/tratamento farmacológico , Pancreatite Necrosante Aguda/tratamento farmacológico , Fenilbutiratos/uso terapêutico , Animais , Apoptose , Interleucina-1beta/sangue , Masculino , Insuficiência de Múltiplos Órgãos/etiologia , Pancreatite Necrosante Aguda/complicações , Fenilbutiratos/farmacologia , Ratos , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfa/sangue
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