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1.
Proc Natl Acad Sci U S A ; 118(44)2021 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-34706939

RESUMO

The quest for nonmagnetic Weyl semimetals with high tunability of phase has remained a demanding challenge. As the symmetry-breaking control parameter, the ferroelectric order can be steered to turn on/off the Weyl semimetals phase, adjust the band structures around the Fermi level, and enlarge/shrink the momentum separation of Weyl nodes which generate the Berry curvature as the emergent magnetic field. Here, we report the realization of a ferroelectric nonmagnetic Weyl semimetal based on indium-doped Pb1- x Sn x Te alloy in which the underlying inversion symmetry as well as mirror symmetry are broken with the strength of ferroelectricity adjustable via tuning the indium doping level and Sn/Pb ratio. The transverse thermoelectric effect (i.e., Nernst effect), both for out-of-plane and in-plane magnetic field geometry, is exploited as a Berry curvature-sensitive experimental probe to manifest the generation of Berry curvature via the redistribution of Weyl nodes under magnetic fields. The results demonstrate a clean, nonmagnetic Weyl semimetal coupled with highly tunable ferroelectric order, providing an ideal platform for manipulating the Weyl fermions in nonmagnetic systems.

3.
Lab Invest ; 101(1): 89-103, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32929177

RESUMO

Cardiovascular diseases are considered the leading cause of death worldwide. Myocardial ischaemia/reperfusion (I/R) injury is recognized as a critical risk factor for cardiovascular diseases. Although increasing advances have been made recently in understanding the mechanisms of I/R injury, they remain largely unknown. In this study, we found that the expression of circPAN3 (circular RNA PAN3) was decreased in a mouse model of myocardial I/R. Overexpression of circPAN3 significantly inhibited autophagy and alleviated cell apoptosis of cardiomyocytes, which was further verified in vivo by decreased autophagic vacuoles and reduced myocardial infarct sizes. Moreover, miR-421 (microRNA-421) was identified as a downstream target involved in circPAN3-mediated myocardial I/R injury. Additionally, miR-421 could negatively regulate Pink1 (phosphatase and tensin homologue-induced putative kinase 1) via a direct binding relationship. Furthermore, the mitigating effects of circPAN3 overexpression on myocardial I/R injury by suppressing autophagy and apoptosis were abolished by knockdown of Pink1. Our findings reveal a novel role for circPAN3 in modulating autophagy and apoptosis in myocardial I/R injury and the circPAN3-miR-421-Pink1 axis as a regulatory network, which might provide potential therapeutic targets for cardiovascular diseases.


Assuntos
Autofagia , MicroRNAs/metabolismo , Traumatismo por Reperfusão Miocárdica/metabolismo , Proteínas Quinases/metabolismo , Animais , Regulação para Baixo , Masculino , Camundongos Endogâmicos C57BL , RNA Circular/metabolismo
4.
Life Sci ; 257: 118015, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32629000

RESUMO

BACKGROUND: Cardiovascular disease (CVD) is the leading cause of mortality worldwide. Cardiac fibrosis is the scarring process occurs commonly with CVDs impairing the function and structure of heart. Herein, we investigated the role of circPAN3 in the pathogenesis of cardiac fibrosis. METHODS: A rat myocardial infarction (MI) model was constructed to evaluate the role of circPAN3. Expression of circPAN3 in MI was determined, and si-circPAN3 was applied to verify its profibrotic effects. With an in vitro model, cardiac fibroblasts were stimulated by transforming growth factor beta 1 (TGFß1). Immunofluorescent staining was employed to assess the fibrosis-related markers, as well as autophagy activity. CCK-8 and transwell assays were performed to determine cell proliferation and migration. Luciferase reporter assay and RNA pull-down were subjected to verify the interaction of circPAN3/miR-221. The enrichment of FoxO3 on the promoter region of ATG7 was detected using CHIP assay. RESULTS: Elevated circPAN3 was found in rat MI heart tissue, of which knockdown attenuated cardiac fibrosis after MI. In an in vitro model exposing with TGFß1, increasing cell proliferation and migration were observed, whereas these effects were abolished by circPAN3 knockdown, as well as autophagy activity. miR-221 was identified as a target to be involved in circPAN3-mediated cardiac fibrosis after MI. miR-221 negatively regulated FoxO3, thus causing the inhibition of ATG7 transcription. The regulatory network of circPAN3/miR-221/FoxO3/ATG7 in cardiac fibrosis was further determined in vivo. CONCLUSION: circPAN3 exhibited profibrotic effects during autophagy-mediated cardiac fibrosis via miR-221/FoxO3/ATG7 axis, which may serve as potential biomarkers for cardiac fibrosis therapeutics.


Assuntos
Infarto do Miocárdio/genética , Infarto do Miocárdio/metabolismo , RNA Circular/genética , Animais , Autofagia/genética , Autofagia/fisiologia , Proteína 7 Relacionada à Autofagia/metabolismo , Proliferação de Células/genética , Modelos Animais de Doenças , Fibroblastos/metabolismo , Fibrose/metabolismo , Proteína Forkhead Box O3/metabolismo , Masculino , MicroRNAs/genética , MicroRNAs/metabolismo , Miocárdio/metabolismo , RNA Circular/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/genética
5.
Huan Jing Ke Xue ; 40(9): 3973-3981, 2019 Sep 08.
Artigo em Chinês | MEDLINE | ID: mdl-31854859

RESUMO

Nitrous acid (HONO) is easily photolyzed with the production of·OH, which plays an important role in the formation of regional secondary pollution. In China, research of HONO observation is concentrated mainly in urban areas and is rarely reported in rural areas. In our study, a one-month HONO field observation was conducted at the Station of Rural Environment, Chinese Academy of Sciences (Dongbaituo Village, Wangdu County, Hebei Province) in November 2017 using the long path absorption photo meter (LOPAP). The concentration, variety characteristics, and budget of HONO was studied. During the observation period, HONO exhibited pronounced diurnal variation with low concentrations in the day and high concentration in the evening. The highest concentration at night was about 3.70×10-9, and the lowest concentration at noon was about 0.10×10-9, indicating the presence of a strong source of HONO in rural areas. The CO concentration increased significantly before and after heating, whereas the HONO concentration did not change significantly, indicating that heating combustion contributed less to HONO, Direct emission of motor vehicles at night contributed 23.20% and 31.20% to HONO in polluted and clean weather conditions, respectively, indicating the presence of strong sources of HONO in polluted weather conditions. The average formation rate of HONO at night from homogeneous reaction of·OH and NO could reach 0.40×10-9 h-1, which is 0.67 times higher than that of heterogeneous reaction of NO2 (0.24×10-9 h-1), indicating that the homogeneous reaction of·OH and NO is the main source of HONO at night. HONO has a strong unknown source in the daytime with an intensity reaching 1.37×10-9 h-1, which contributes about 50% to HONO.

6.
Aging Dis ; 10(2): 231-248, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31011475

RESUMO

Phenotypic transformation of vascular smooth muscle cells (VSMCs) contributes to vascular remodeling in hypertension. High mobility group box-1 (HMGB1) has been reported to be involved in several pathogenic processes including VSMC proliferation and migration. The present study was designed to determine the role of HMGB1 in VSMC phenotypic transformation in hypertension. First, we demonstrated that HMGB1 was elevated in a model of Ang II-induced VSMC phenotypic transformation, which showed down-regulation of contractile proteins and up-regulation of synthetic proteins. Knockdown of HMGB1 and losartan could block the phenotypic transformation. Next, we identified three potential miRNAs for upstream regulation of HMGB1 by bioinformatic analysis; only miR-181b-5p was significantly down-regulated in Ang II-treated cells. Co-treating the cells with miR-181b-5p mimics suppressed HMGB1 expression as well as the phenotypic transformation, migration, and proliferation. Furthermore, the luciferase reporter gene assay confirmed the direct interaction between miR-181b-5p and HMGB1. Finally, to extend these cell-based studies to clinical patients, we demonstrated that plasma miR-181b-5p levels were decreased, while Ang II and HMGB1 levels, as well as the intima-media thickness (IMT) were increased in hypertensive patients; these effects were reversed following the administration of angiotensin receptor blockers. Based on these observations, we conclude that the down-regulation of miR-181b-5p leads to the elevation of HMGB1 levels in hypertensive patients, which accounts, at least partially, for VSMCs phenotypic transformation and vascular remodeling. Our findings also highlight that the plasma levels of miR-181b-5p and HMGB1 may serve as novel biomarkers for vascular remodeling in the hypertensive patients.

7.
Nat Commun ; 10(1): 1028, 2019 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-30833678

RESUMO

Detecting the spectroscopic signatures of relativistic quasiparticles in emergent topological materials is crucial for searching their potential applications. Magnetometry is a powerful tool for fathoming electrons in solids, by which a clear method for discerning relativistic quasiparticles has not yet been established. Adopting the probes of magnetic torque and parallel magnetization for the archetype Weyl semimetal TaAs in strong magnetic field, we observed a quasi-linear field dependent effective transverse magnetization and a non-saturating parallel magnetization when the system enters the quantum limit. Distinct from the saturating magnetic responses for non-relativistic quasiparticles, the non-saturating signals of TaAs in strong field is consistent with our newly developed magnetization calculation for a Weyl fermion system in an arbitrary angle. Our results establish a high-field thermodynamic method for detecting the magnetic response of relativistic quasiparticles in topological materials.

8.
Nan Fang Yi Ke Da Xue Xue Bao ; 37(12): 1609-1614, 2017 Dec 20.
Artigo em Chinês | MEDLINE | ID: mdl-29292253

RESUMO

OBJECTIVE: To construct a cell model of 4.1R gene knockout in murine macrophage cell line RAW264.7 using CRISPR/Cas9 technique. METHODS: Three high?grade small?guide RNAs (sgRNAs) that could specifically identify 4.1R gene were synthesized and inserted into lentiCRISPRv2 plasmid. RAW264.7 cells were infected with sgRNA?Cas9 lentivirus from 293T cells transfected with the recombinant sgRNA?lentiCRISPRv2 plasmid, and the positive cells were screened using puromycin and the monoclonal cells were obtained. The expression of 4.1R protein in the monoclonal cells was measured by Western blotting, and the mutation site was confirmed by sequence analysis. Result A 4.1R gene knockout RAW264.7 cell line was obtained, which showed a 19?bp deletion mutation in the 4.1R gene sequence and obviously enhanced proliferation. CONCLUSION: We successfully constructed a 4.1R gene knockout macrophage cell line using CRISPR/Cas9 technique, which may facilitate further investigation of the function of 4.1R in macrophages.


Assuntos
Sistemas CRISPR-Cas , Técnicas de Inativação de Genes , Proteínas dos Microfilamentos/genética , RNA Guia/genética , Animais , Camundongos , Células RAW 264.7
9.
Nat Commun ; 7: 10735, 2016 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-26911701

RESUMO

Weyl semimetals provide the realization of Weyl fermions in solid-state physics. Among all the physical phenomena that are enabled by Weyl semimetals, the chiral anomaly is the most unusual one. Here, we report signatures of the chiral anomaly in the magneto-transport measurements on the first Weyl semimetal TaAs. We show negative magnetoresistance under parallel electric and magnetic fields, that is, unlike most metals whose resistivity increases under an external magnetic field, we observe that our high mobility TaAs samples become more conductive as a magnetic field is applied along the direction of the current for certain ranges of the field strength. We present systematically detailed data and careful analyses, which allow us to exclude other possible origins of the observed negative magnetoresistance. Our transport data, corroborated by photoemission measurements, first-principles calculations and theoretical analyses, collectively demonstrate signatures of the Weyl fermion chiral anomaly in the magneto-transport of TaAs.

10.
Int J Mol Sci ; 16(3): 4997-5013, 2015 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-25749476

RESUMO

MicroRNAs are small non-coding RNA molecules that are important regulators of gene expression at the post-transcriptional level. miRNAs impact the processes of cell proliferation, differentiation and apoptosis. Thus, the regulation of miRNA expression profiles associated with mastitis will be conducive for its control. In this study, Staphylococcus aureus (S. aureus) was administered to the mammary gland of Chinese Holstein cows to construct a bacteria-type mastitis model. Total RNA was isolated from bovine mammary gland tissue samples from the S. aureus-induced mastitis group and controls. miRNAs were analyzed using Solexa sequencing and bioinformatics processing for the experimental group and control group. Two miRNA libraries were constructed respectively. A total of 370 known bovine miRNAs and 341 novel mi RNAs were detected for the S. aureus and 358 known bovine miRNAs and 232 novel miRNAs for control groups. A total of 77 miRNAs in the S. aureus group showed significant differences compared to the control group. GO (Gene Ontology) analysis showed these target genes were involved in the regulation of cells, binding, etc., while KEGG (Kyoto Encyclopedia of Genes and Genomes) analysis showed that these genes were enriched in endocytosis, and olfactory transduction pathways involved in cancer. These results provide an experimental basis to reveal the cause and regulatory mechanism of mastitis and also suggest the potential of miRNAs to serve as biomarkers for the diagnosis of mastitis in dairy cows.


Assuntos
Perfilação da Expressão Gênica , Glândulas Mamárias Animais/metabolismo , MicroRNAs/metabolismo , Staphylococcus aureus/genética , Animais , Biomarcadores/metabolismo , Bovinos , DNA Bacteriano/química , DNA Bacteriano/metabolismo , Feminino , Biblioteca Gênica , Mastite Bovina/diagnóstico , Mastite Bovina/genética , Mastite Bovina/microbiologia , Modelos Biológicos , Reação em Cadeia da Polimerase em Tempo Real , Análise de Sequência de RNA , Staphylococcus aureus/isolamento & purificação
11.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 45(1): 34-8, 2014 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-24527578

RESUMO

OBJECTIVE: To determine the impact of Traditional Chinese Medicine on patients with chronic kidney disease (CKD). METHODS: A total of 225 CKD patients in an outpatient department were recruited for this study, among whom 170 received regular Western and Chinese medicine treatments (control group) and 55 received treatments guided by the theory of Traditional Chinese Medicine (experimental group). The effectiveness of the treatments was determined through a pre-post comparison. RESULTS: Significant pre-intervention differences in age (P < 0.01), stage of glomerular filtration rate (GFR) (P = 0.007) and urine protein (P < 0.01) were found between the two groups of patients. But age, gender and proteinuria were not significant predictors on clinical outcomes of the patients in the multivariate regression models. The experimental group had a greater level of decrease in blood urea nitrogen (P < 0.01) and serum creatine (P < 0. 01) than the control group. No significant differences between the groups were found in changes of uric acid (P = 0.475), urine protein (P = 0.058), urine red cells (P = 0.577), and urine white cells (P = 0.01). A greater level of increase in estimated glomerular filtration rate was found in the experimental group compared with the control (P < 0.001). The multivariate linear regression analysis identified group (B = 0.395, P < 0.001) and stage of GFR (B = 0.165, P = 0.008) as significant predictors on the outcomes of treatment. CONCLUSION: The treatment of CKD patients guided by the theory of Traditional Chinese Medicine can improve renal function through influencing glomerular filtration rate. The effect is more prominent than the regular treatment regime.


Assuntos
Medicina Tradicional Chinesa , Insuficiência Renal Crônica/terapia , Nitrogênio da Ureia Sanguínea , Taxa de Filtração Glomerular , Humanos , Proteinúria
12.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 43(1): 28-33, 2012 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-22455126

RESUMO

OBJECTIVE: Investigate the effects of compound Radix Notoginseng on renal interstitial fibrosis and kidney-targeting treatment. METHODS: 100 healthy Sprague-Dawley rats were randomly divided into 5 groups: Unilateral ureteral obstruction (UUO) group, sham-operation (SOR) group, Radix Notoginseng (RN) group, compound Radix Notoginseng (CRN) group and Losartan (ARB) group. After operation, RN, CRN and ARB groups were intragastric administrated with RN (3 mL/d), CRN (3 mL/d) and ARB [20 mg/(kg x d)] respectively. Each group randomly included 18 rats for statistical analysis. The histological changes of renal interstitial tissues were observed by HE, Masson and PAS staining. Total kidney collagen content was determined by measuring the amount of hydroxyproline. The mRNA of alpha-SMA, collagen I and fibronectin were reverse transcribed and quantified by real-time PCR. The expression of alpha-SMA protein was assessed by immunohistochemistry and Western blot analysis. RESULTS: In UUO model, the obstructed kidney showed typical features of renal tubulointerstitial fibrosis, such as severe tubular loss, dilation, atrophy, infiltration of inflammatory cells, interstitial matrix deposition (P < 0.05). Partial correlation assay showed that the expression of alpha-SMA was related to the renal tubular injury (r = 0.55; P < 0.05). Administration of RN, CRN and ARB improved tubulointerstitial damage and collagen matrix accumulation induced by UUO in different degree. The expression of the alpha-SMA at mRNA and protein levels were significantly increased in the UUO group (P < 0.05), which was also suppressed by treatment with RN, CRN and ARB in different degree. Moreover, more effective role in preventing fibrosis was observed in CRN group than when compared with that of RN group. CONCLUSION: RN and CRN can inhibit UUO-induced renal interstitial fibrosis in rats, and CRN treatment is more effective than RN in reducing interstitial fibrosis.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Rim/patologia , Nefrite Intersticial/prevenção & controle , Panax notoginseng/química , Fitoterapia , Actinas/genética , Actinas/metabolismo , Animais , Colágeno Tipo I/genética , Colágeno Tipo I/metabolismo , Fibronectinas/genética , Fibronectinas/metabolismo , Fibrose/etiologia , Fibrose/prevenção & controle , Losartan/uso terapêutico , Masculino , Nefrite Intersticial/etiologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Obstrução Ureteral/complicações
13.
Phytother Res ; 24(11): 1581-7, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21031612

RESUMO

Renal interstitial fibrosis is the major histopathological change seen in a variety of renal disorders and is closely related to renal dysfunction. Progressive interstitial fibrosis accompanied by the loss of renal tubules and interstitial capillaries typifies all progressive renal disease. Thrombospondin-1 (TSP-1) is a major angiogenic inhibitor. It is demonstrated that TSP-1 levels were correlated with the loss of glomerular and peritubular capillaries and TSP-1 could promote renal scarring by effects on the endothelium. It has been reported that ginsenoside Rg1 inhibited renal interstitial fibrosis in rats via suppressing the expression of TSP-1. The present study was designed to examine whether ginsenoside Rg1 could modulate the integrity of the microvasculature and hence affect the progression of renal fibrosis in a rat unilateral ureteral obstruction (UUO) model. In UUO control kidneys, associated with interstitial fibrosis, lower peritubular capillary densities were prominent. These changes were all improved by ginsenoside Rg1 treatment. Interestingly, ginsenoside Rg1 decreased the expression of TSP-1 and enhanced vascular endothelial growth factor (VEGF) expression. The results show for the first time that ginsenoside Rg1 can evidently inhibit renal interstitial fibrosis in rats with UUO. The mechanism might be related to suppression of the expression of TSP-1 and to repair of the peritubular capillary.


Assuntos
Ginsenosídeos/farmacologia , Nefrite Intersticial/tratamento farmacológico , Trombospondina 1/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Animais , Fibrose , Túbulos Renais/irrigação sanguínea , Túbulos Renais/patologia , Masculino , Nefrite Intersticial/patologia , Ratos , Ratos Sprague-Dawley , Obstrução Ureteral/patologia
14.
Soft Matter ; 4(6): 1230-1236, 2008 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-32907266

RESUMO

Lamellar and hexagonal-coil-cylinder self-assembled structures of ABA type triblock copolymers containing mesogen-jacketed liquid crystalline polymer (MJLCP) as the rod block, and polyisobutylene (PIB) as the coil middle block were discovered. PIB was synthesized by living cationic polymerization of isobutylene initiated by 1,4-bis(2-chloro-2-propyl)benzene (p-DCC), and then a small amount of styrene was introduced at the end of the PIB chains to form the difunctional PIB macroinitiator with -CH2CH(C6H5)Cl end groups for further atom transfer radical polymerization (ATRP). 2,5-Bis[(4-methoxyphenyl)oxycarbonyl]styrene (MPCS) was block-copolymerized from the difunctional PIB macroinitiators at 110 °C. The molecular characterization of the triblock copolymers was performed with 1H NMR, 13C NMR, gel permeation chromatography (GPC), and thermogravimetric analysis (TGA). Their phase structures and transitions were investigated by differential scanning calorimetry (DSC), small angle X-ray scattering (SAXS), and polarized optical microscopy experiments. It was demonstrated that the triblock copolymers formed lamellar structures at moderate rod fractions and hexagonal coil cylinders in the rod matrix at high rod fractions. The d-spacing of the microphase-separated structures was influenced by the liquid crystalline phase of rod-like PMPCS blocks.

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