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1.
Macromol Rapid Commun ; : e2000021, 2020 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-32212226

RESUMO

Aqueous palladium-catalyzed direct arylation polymerization (DArP) of 2-bromothiophene derivatives 6-(2-(2-bromothiophen-3-yl)ethoxy)hexyl trimethylammonium bromide (T1) and 4-(2-(2-bromothien-3-yl)ethoxy)butylsulfonate (T2) is achieved. The supporting ligand, triphenylphosphine-3,3',3''-trisulfonic acid trisodium salt (m-TPPTs), facilitates DArP of both derivatives; however, its separation from the polymers by dialysis is difficult due to its strong aggregation in water and N,N-dimethylacetamide (DMAc). This is supported by dynamic light scattering, gel permeation chromatography (GPC), and single-crystal X-ray crystallography. Pyrimidine-Pd(OAc)2 is utilized in the DArP of T1 to afford PT1 without ligand contamination. Density functional theory calculations to determine the coordinating capability of the carboxylate/pivalic acid/water to palladium indicate the viability of implementing DArP in water. Finally, polyelectrolyte molecular-weight overestimation by GPC in water is attributed to the polyelectrolyte effect. Aggregation of the conjugated polyelectrolytes leads to a contracted hydrodynamic volume, and the molecular weight and dispersity assessed by GPC in DMAc significantly deviate from the actual values. An objective approach to evaluate the molecular weight for conjugated polyelectrolytes requires further development.

2.
Biomater Sci ; 8(2): 657-672, 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-31769455

RESUMO

Sericin has been exploited as a biomaterial due to its biocompatibility, biodegradability, and low-immunogenicity as an isolated polymer and support for cell adhesion. In the present study, human platelet-derived growth factor (PDGF-BB)-functionalized sericin hydrogels were generated using transgenic silkworms, where the as-spun silk incorporated engineered PDGF-BB (termed PDGFM) in the sericin layers of the cocoons. Sericin and PDGFM were simultaneously extracted from the silk fibroin cocoon fibers, and the soluble extract was then formed into a hydrogel via thermal exposure. The PDGFM sericin hydrogels exhibited increased ß-sheet content and a compressive modulus of 74.91 ± 2.9 kPa comparable to chemically crosslinked sericin hydrogels (1.68-55.53 kPa) and a porous microstructure, which contributed to cell adhesion and growth. A 13.1% of total extracted PDGFM from the initial silk fibers was incorporated and immobilized in the sericin hydrogels during material processing, and 1.33% of PDGFM was released over 30 days from the hydrogels in vitro. The remaining PDGFM achieved long-term storage/stability in the sericin hydrogels for more than 42 days at 37 °C. In addition, the PDGFM sericin hydrogels were not immunogenic, were biocompatible and bioactive in promoting the support of cell proliferation. When combined with BMP-9, the PDGFM sericin hydrogels provided synergy to support the osteoblastic differentiation of mesenchymal stem cells (hMSCs) in vitro and in vivo. This study demonstrates that genetically functionalized PDGFM sericin hydrogels can provide useful biomaterials to support cell and tissue outcomes, here with a focus on osteogenesis.

3.
J Pharm Biomed Anal ; 179: 112975, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-31735472

RESUMO

Ischemic stroke is the main cause of disability and mortality worldwide. 10-O-(N N-dimethylaminoethyl)-ginkgolide B methane-sulfonate (XQ-1 H) is a novel drug based on the remedial approach for ischemic stroke. Clopidogrel, a widely used anti-platelet drug, is often co-prescribed in the clinic. In this study, we established an UPLC-MS/MS spectrometry method for the determination of XQ-1H and investigated the pharmacokinetic effect of clopidogrel on XQ-1H in rats subjected to middle cerebral artery occlusion (MCAO). Meanwhile, the anti-apoptotic and neuroprotective effects of XQ-1H and its combination with clopidogrel were also studied. The results revealed that XQ-1H and its combination with clopidogrel abridged brain infarct volume, cerebral edema and alleviated neurological dysfunction caused by cerebral ischemic reperfusion injury. Further study demonstrated that XQ-1H combined with clopidogrel lessened TUNEL positive cells, up-regulated bcl-2 expression notably and down-regulated bax expression as compared to both XQ-1H and clopidogrel individually. In addition, a rapid, sensitive UPLC-MS/MS method was developed to quantify the concentration of XQ-1H in MCAO/R rats. Our pharmacokinetic results showed that clopidogrel significantly increased the exposure of XQ-1H, increased the peak plasma concentration (Cmax), area under the curve (AUC) and slowed elimination of XQ-1H in the co-administered group. Besides, for further exploring which CYP450 isoforms are involved in the XQ-1H metabolism, XQ-1H was incubated in human liver microsomes (HLMs) system with or without P450 isoform-selective inhibitors. Our results revealed that clopidogrel altered pharmacokinetics of XQ-1H potentially and subsequently enhanced the pharmacological effect of XQ-1H. Moreover, XQ-1H could be applied as an efficacious neuroprotective agent for ischemic stroke because of its considerable effect on averting neuronal apoptosis.

4.
ACS Appl Mater Interfaces ; 12(2): 3068-3079, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31869196

RESUMO

With growing interest in flexible and wearable devices, the demand for nature-inspired soft smart materials, especially intelligent hydrogels with multiple perceptions toward external strain and temperatures to mimic the human skin, is on the rise. However, simultaneous achievement of intelligent hydrogels with skin-compatible performances, including good transparency, appropriate mechanical properties, autonomous self-healing ability, multiple mechanical/thermoresponsiveness, and retaining flexibility at subzero temperatures, is still challenging and thus limits their application as skinlike devices. Here, conductive nanocomposite hydrogels (NC gels) were delicately designed and prepared via gelation of oligo(ethylene glycol) methacrylate (OEGMA)-based monomers in a glycerol-water cosolvent, where inorganic clay served as the physical cross-linker and provided conductive ions. The resultant NC gels exhibited good conductivity (∼3.32 × 10-4 S cm-1, akin to biological muscle tissue) and an autonomously self-healing capacity (healing efficiency reached 84.8%). Additionally, such NC gels displayed excellent flexibility and responded well to multiple strain/temperature external stimuli and subtle human motions in a wide temperature range (from -20 to 45 °C). These distinguished properties would endow such NC gels significant applications in fields of biosensors, human-machine interfaces, and soft robotics.

5.
J Am Chem Soc ; 141(45): 17995-17999, 2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31647653

RESUMO

Hydrogen is regarded as an attractive alternative energy carrier due to its high gravimetric energy density and only water production upon combustion. However, due to its low volumetric energy density, there are still some challenges in practical hydrogen storage and transportation. In the past decade, using chemical bonds of liquid organic molecules as hydrogen carriers to generate hydrogen in situ provided a feasible method to potentially solve this problem. Research efforts on liquid organic hydrogen carriers (LOHCs) seek practical carrier systems and advanced catalytic materials that have the potential to reduce costs, increase reaction rate, and provide a more efficient catalytic hydrogen generation/storage process. In this work, we used methanol as a hydrogen carrier to release hydrogen in situ with the single-site Pt1/CeO2 catalyst. Moreover, in this reaction, compared with traditional nanoparticle catalysts, the single site catalyst displays excellent hydrogen generation efficiency, 40 times higher than 2.5 nm Pt/CeO2 sample, and 800 times higher compared to 7.0 nm Pt/CeO2 sample. This in-depth study highlights the benefits of single-site catalysts and paves the way for further rational design of highly efficient catalysts for sustainable energy storage applications.

6.
Biomater Sci ; 7(11): 4536-4546, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31536077

RESUMO

Functional silk mats with improved cell proliferation activity are promising medical materials to accelerate damaged wound healing and tissue repair. In this study, novel functional silk mats were fabricated from human fibroblast growth factor (FGF)-containing cocoons generated by expressing human acid FGF1 and basic FGF2 in silkworms. First, functional silk mats containing FGF1 and FGF2 proteins alone or in combination were fabricated by physically cutting genetically engineered cocoons. Compared to those of normal silk mats, the physical properties of these functional silk mats such as silk fibre diameter, internal secondary structure, and mechanical properties were significantly changed. The expressed FGF1 and FGF2 proteins in these silk mats were efficiently and gradually released over 15 days. Moreover, these silk mats significantly promoted NIH/3T3 cell proliferation and growth by activating the extracellular signal-regulated kinase (ERK) pathway, and the silk mat containing FGF1 and FGF2 proteins showed higher cell proliferation. Importantly, this silk mat caused no obvious cytotoxicity or cell inflammation. These results suggest that these functional silk mats have potential medical applications.

7.
Life Sci ; 235: 116844, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31499069

RESUMO

AIMS: 10-O-(N,N-dimethylaminoethyl)-ginkgolide B methanesulfonate (XQ-1H), a new derivative of ginkgolide B, has drawn great attention for its potent bioactivities against ischemia-induced injury. The purpose of this study was to further investigate the effect of XQ-1H against acute ischemic stroke by inducing middle cerebral artery occlusion/reperfusion (MCAO/R) injuries in mice. MAIN METHODS: Treatment of XQ-1H (78 or 39 mg/kg, i.g., bid) 2 h after MCAO improved motor skills and ameliorated the severity of brain infarction and apoptosis seen in the mice by diminishing pathological changes and the activation of a pro-apoptotic protein Cleaved-Caspase-3, which in turn induced anti-apoptotic Bcl-xL. Through introducing Wnt/ß-catenin signaling inhibitor XAV-939, XQ-1H was proven to intensively promoted neurogenesis in the peri-infarct cortex, subventricular area (SVZ) and the dentate gyrus (DG) subgranular area (SGZ) in a Wnt signal dependent way by compromising the activation of GSK3ß, which in turn upregulated Wnt1, ß-catenin, Neuro D1 and Cyclin D1, most possibly through the activation of PI3K/Akt signaling via the upregulation of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF). KEY FINDINGS: We conclude that XQ-1H preserved the motor functions, limited apoptosis, and concomitantly promoted neurogenesis-related protein expression by Wnt signaling-dependently compromising GSK3ß/Caspase-3 activity and enhancing the expression of Wnt1/ß-catenin/Neuro D1/Cyclin D1 and Bcl-xL. SIGNIFICANCE: This research may benefit the development of stroke therapeutics targeting neurogenesis through Wnt upregulation by XQ-1H.


Assuntos
Apoptose/efeitos dos fármacos , Isquemia Encefálica/tratamento farmacológico , Ginkgolídeos/farmacologia , Ginkgolídeos/uso terapêutico , Lactonas/farmacologia , Lactonas/uso terapêutico , Neurogênese/efeitos dos fármacos , Via de Sinalização Wnt/efeitos dos fármacos , beta Catenina/metabolismo , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/patologia , Isquemia Encefálica/complicações , Isquemia Encefálica/patologia , Caspase 3/metabolismo , Ciclina D1/metabolismo , Glicogênio Sintase Quinase 3 beta/metabolismo , Compostos Heterocíclicos com 3 Anéis/farmacologia , Infarto da Artéria Cerebral Média , Masculino , Camundongos , Fator de Crescimento Neural/metabolismo , Recuperação de Função Fisiológica/efeitos dos fármacos , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/patologia , Regulação para Cima/efeitos dos fármacos , Proteína bcl-X/metabolismo
8.
J Stroke Cerebrovasc Dis ; 28(11): 104288, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31395423

RESUMO

PURPOSE: The present study was to observe the therapeutic efficiency of Clematichinenoside (AR) on cerebral ischemic injury in rats, especially on neurological and motor function recovery and to explore the underlying mechanism. METHODS: Following middle cerebral artery occlusion/reperfusion (MCAO/R) surgery, rats were treated orally with 32, 16, and 8 mg/kg AR respectively for 14 days during which cerebral injury was evaluated and proinflammatory factors tumor necrosis factor-α and interleukin-6 as well as neurotrophic factors brain-derived neurotrophic factor and Neurotrophin-3 levels were determined with ELISA kits. Immunohistochemical analysis on number of neurons and reactive astrocytes in the hippocampus was to demonstrate the effect of AR on neuronal survival. Motor, learning, and memory recovery were assessed by Morris water maze, passive avoidance experiment, and rotatory rod test. Neuroprotection and anti-inflammation-related Notch and nuclear factor-κB (NF-κB) signaling pathways were analyzed by PCR and Western blot techniques on mammalian achaete-scute homologs1, Notch-1, intracellular Notch receptor domain, Jagged-1, transcription factor hairy, enhancer of split1 (Hes1), as well as the nuclear import of NF-κB in hippocampus. RESULTS: AR administration reduced cerebral injury in rats exposed to MCAO/R and after treatment of AR for 14 days, proinflammatory reaction was inhibited, with neuronal survival rate raised and motor function recovery facilitated. PCR and WB analysis of Notch/NF-κB signaling pathway revealed the inhibitory effect of AR on pathway related components. CONCLUSIONS: AR is beneficial to recovery of neurological and motor function in rats after cerebral ischemic injury via inhibiting Notch/NF-κB pathway.


Assuntos
Anti-Inflamatórios/farmacologia , Comportamento Animal/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Infarto da Artéria Cerebral Média/tratamento farmacológico , Atividade Motora/efeitos dos fármacos , NF-kappa B/metabolismo , Fármacos Neuroprotetores/farmacologia , Receptor Notch1/metabolismo , Saponinas/farmacologia , Animais , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Hipocampo/metabolismo , Hipocampo/patologia , Hipocampo/fisiopatologia , Infarto da Artéria Cerebral Média/metabolismo , Infarto da Artéria Cerebral Média/fisiopatologia , Infarto da Artéria Cerebral Média/psicologia , Masculino , Memória/efeitos dos fármacos , Neurotrofina 3/metabolismo , Ratos Sprague-Dawley , Recuperação de Função Fisiológica , Transdução de Sinais
10.
J Biol Eng ; 13: 61, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31312254

RESUMO

Background: Silk glands are used by silkworms to spin silk fibers for making their cocoons. These have recently been regarded as bioreactor hosts for the cost-effective production of other valuable exogenous proteins and have drawn wide attention. Results: In this study, we established a transgenic silkworm strain which synthesizes the recombinant human lactoferrin (rhLF) in the silk gland and spins them into the cocoon by our previously constructed silk gland based bioreactor system. The yield of the rhLF with the highest expression level was estimated to be 12.07 mg/g cocoon shell weight produced by the transgenic silkworm strain 34. Utilizing a simple purification protocol, 9.24 mg of the rhLF with recovery of 76.55% and purity of 95.45% on average could be purified from 1 g of the cocoons. The purified rhLF was detected with a secondary structure similar with the commercially purchased human lactoferrin. Eight types of N-glycans which dominated by the GlcNAc (4) Man (3) (61.15%) and the GlcNAc (3) Man (3) (17.98%) were identified at the three typical N-glycosylation sites of the rhLF. Biological activities assays showed the significant evidence that the purified rhLF could relief the lipopolysaccharide (LPS)-induced cell inflammation in RAW264.7 cells and exhibit potent antibacterial bioactivities against the Escherichia coli (E. coli) and Bacillus subtilis. Conclusions: These results show that the middle silk gland of silkworm can be an efficient bioreactor for the mass production of rhLF and the potential application in anti-inflammation and antibacterial.

11.
Chin J Nat Med ; 17(5): 321-330, 2019 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-31171266

RESUMO

Traditional Chinese Medicine (TCM) is the treasure of Chinese Nation and gained the gradual acceptance of the international community. However, the methods and theories of TCM understanding of diseases are lack of appropriate modern scientific characterization systems. Moreover, traditional risk factors cannot promote to detection and prevent those patients with coronary artery disease (CAD) who have not developed acute myocardial infarction (MI) in time. To sum up, there is still no objective systematic evaluation system for the therapeutic mechanism of TCM in the prevention and cure of cardiovascular disease. Thus, new ideas and technologies are needed. The development of omics technology, especially metabolomics, can be used to predict the level of metabolites in vivo and diagnose the physiological state of the body in time to guide the corresponding intervention. In particular, metabolomics is also a very powerful tool to promote the modernization of TCM and the development of TCM in personalized medicine. This article summarized the application of metabolomics in the early diagnosis, the discovery of biomarkers and the treatment of TCM in CAD.


Assuntos
Doença das Coronárias/sangue , Doença das Coronárias/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Medicina Tradicional Chinesa , Metabolômica , Biomarcadores/sangue , Medicamentos de Ervas Chinesas/farmacologia , Humanos , Medicina Tradicional Chinesa/tendências , Metabolômica/instrumentação , Resultado do Tratamento
12.
Ann Vasc Surg ; 60: 476.e13-476.e17, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31075471

RESUMO

Behçet's disease is an autoimmune vasculitis, which mainly manifests as aneurysm when arteries are involved. Treatments including graft interposition or stent-graft implantation are best performed after active inflammation subsides, otherwise there will be complications such as anastomotic pseudoaneurysms and graft occlusion. We report the treatment of a suprarenal abdominal aortic pseudoaneurysm in a patient with Behçet's disease via multiple overlapping stent implantation combined with coil embolization which was performed in a subacute fashion because of impending rupture of the pseudoaneurysm. She was maintained on long-term immunosuppressive therapy and remained symptom free at 2-year follow-up.


Assuntos
Falso Aneurisma/terapia , Aneurisma da Aorta Abdominal/terapia , Ruptura Aórtica/prevenção & controle , Síndrome de Behçet/complicações , Embolização Terapêutica , Procedimentos Endovasculares/instrumentação , Stents , Adulto , Falso Aneurisma/diagnóstico por imagem , Falso Aneurisma/etiologia , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Aneurisma da Aorta Abdominal/etiologia , Ruptura Aórtica/diagnóstico por imagem , Ruptura Aórtica/etiologia , Síndrome de Behçet/diagnóstico , Síndrome de Behçet/tratamento farmacológico , Feminino , Humanos , Imunossupressores/uso terapêutico , Resultado do Tratamento
13.
Nano Lett ; 19(7): 4420-4426, 2019 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-31137933

RESUMO

Topological insulators (TIs) have emerged as some of the most efficient spin-to-charge convertors because of their correlated spin-momentum locking at helical Dirac surface states. While endeavors have been made to pursue large "charge-to-spin" conversions in novel TI materials using spin-torque-transfer geometries, the reciprocal process "spin-to-charge" conversion, characterized by the inverse Edelstein effect length (λIEE) in the prototypical TI material (Bi2Se3), remains moderate. Here, we demonstrate that, by incorporating a "second" spin-splitting band, namely, a Rashba interface formed by inserting a bismuth interlayer between the ferromagnet and the Bi2Se3 (i.e., ferromagnet/Bi/Bi2Se3 heterostructure), λIEE shows a pronounced increase (up to 280 pm) compared with that in pure TIs. We found that λIEE alters as a function of bismuth interlayer thickness, suggesting a new degree of freedom to manipulate λIEE by engineering the interplay of Rashba and Dirac surface states. Our finding launches a new route for designing TI- and Rashba-type quantum materials for next-generation spintronic applications.

14.
Zhongguo Zhong Yao Za Zhi ; 44(8): 1524-1530, 2019 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-31090314

RESUMO

In this study,the leaves of autumn-sown Angelica dahurica var. formosana from Sichuan province in different growth years was used to explore the fitting model of photosynthetic response curve and the different photosynthetic physiological characteristics between annual and biennial A. dahurica var. formosana from Sichuan province. The results showed that the fitting model of the optimum light response curve of the leaves of A. dahurica var. formosana from Sichuan province with different growth years was all rectangular hyperbolic correction model. The light saturation points were 1 600,1 700 µmol·m-2·s-1,the light compensation points were17. 98,52. 23 µmol·m-2·s-1 in the leaves of annual and biennial plant,respectively. The diurnal variation curves of net photosynthetic rate,transpiration rate and stomatal conductance in the leaves all acted as a single peak value wave. The daily mean values of net photosynthetic rate and transpiration rate in the leaves of biennial plant were significantly higher than that of annual plant. There was no significant difference in daily mean stomatal conductance. The net photosynthetic rate was significantly positively correlated with stomatal conductance in both of the different growth years. The net photosynthetic rate of annual and biennial A. dahurica var. formosana from Sichuan province had extremely significant and significantly negative correlation with the intercellular CO2 respectively. The transpiration rate of annual plant was positively correlated with the effective photosynthetic radiation intensity and air temperature,but had significantly negative correlation with the intercellular CO2 concentration. The transpiration rate of biennial plant had extremely positive correlation with the effective photosynthetic radiation intensity,and negatively correlated with the intercellular CO2 concentration. In conclusion,the photosynthetic efficiency of the leaves in biennial plant of A. dahurica var. formosana from Sichuan province was higher than that in annual plant,but the ability to utilize weak light was lower than that of annual plant. It should be planted in the sunny field.


Assuntos
Angelica/fisiologia , Fotossíntese , Folhas de Planta/fisiologia , Dióxido de Carbono , China , Transpiração Vegetal , Estações do Ano , Temperatura Ambiente
15.
Curr Pharm Des ; 25(10): 1105-1114, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31057104

RESUMO

RAS (H-ras, K-ras, and N-ras), as the second largest mutated gene driver in various human cancers, has long been a vital research target for cancer. Its function is to transform the extracellular environment into a cascade of intracellular signal transduction. RAS mutant protein regulates tumor cell proliferation, apoptosis, metabolism and angiogenesis through downstream MAPK, PI3K and other signaling pathways. In KRAS or other RAS-driven cancers, current treatments include direct inhibitors and upstream/downstream signaling pathway inhibitors. However, the research on these inhibitors has been largely restricted due to their escape inhibition and off-target toxicity. In this paper, we started with the role of normal and mutant RAS genes in cancer, elucidated the relevant RAS regulating pathways, and highlighted the important research advancements in RAS inhibitor research. We concluded that for the crosstalk between RAS pathways, the effect of single regulation may be limited, and the multi-target drug combined compensation mechanism is becoming a research hotspot.


Assuntos
Mutação , Neoplasias/genética , Proteínas ras/genética , Genes ras , Humanos , Neoplasias/tratamento farmacológico
16.
J Am Heart Assoc ; 8(8): e012011, 2019 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-30957675

RESUMO

Background The aim of this study was to assess the feasibility and safety of dynamic volumetric computed tomography angiography ( DV - CTA ) for endoleaks detected but not classified by conventional CTA in patients after endovascular aortic repair. Methods and Results From January 2016 to October 2017, 24 patients with endoleaks with aneurysm sac enlargement detected but not classified by conventional CTA were randomly assigned to the conventional CTA group and the DV - CTA group for further evaluation. The amount of contrast agent, radiation dosage, and changes in creatinine during the operation were compared between the 2 groups. Reintervention was performed according to the endoleak classification followed by the 6- and 12-month follow-up. The accuracy of classifying endoleaks by DV - CTA was comparable to that by digital subtraction angiography. Additionally, the total amount of contrast agent and the radiation dosage in the DV - CTA group during the operation were diminished by 14.0% ( P=0.007) and 12.1% ( P=0.004), respectively, compared with those in the conventional CTA group. No contrast-induced nephropathy was observed. All endoleaks were treated instantly after identification. No endoleaks were found in any of the patients during follow-up. Conclusions DV - CTA could replace digital subtraction angiography as an alternative method for the classification of endoleaks that cannot be differentiated by conventional CTA . Additionally, the amount of contrast agent and the total radiation dosage were substantially reduced, which improved safety among operators and patients.

18.
Mol Genet Genomics ; 294(4): 849-859, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30895377

RESUMO

The multigene expression system is highly attractive to co-express multiple genes or multi-subunit complex-based genes for their functional studies, and in gene therapy and visual tracking of expressed proteins. However, the current multiple gene co-expression strategies usually suffer from severe inefficiency and unbalanced expression of multiple genes. Here, we report on an improved 2A self-cleaving peptide (2A)-based multigene expression system (2A-MGES), by introducing an optimized Kozak region (Ck) and altering the gene arrangement, both of which contributed to the efficient expression of two fluorescent protein genes in silkworm. By co-expressing DsRed and EGFP genes in insect cells and silkworms, the potent Ck was first found to improve the translation efficiency of downstream genes, and the expression of the flanking genes of 2A were improved by altering the gene arrangement in 2A-MGES. Moreover, we showed that combining Ck and an optimized gene arrangement in 2A-MGES could synergistically improve the expression of genes in the cell. Further, these two flanking genes, regulated by modified 2A-MGES, were further co-expressed in the middle silk gland and secreted into the cocoon, and both achieved efficient expression in the transgenic silkworms and their cocoons. These results suggested that the modified Ck-2A-MGES will be a potent tool for multiple gene expression, for studies of their functions, and their applications in insect species.


Assuntos
Bombyx/metabolismo , Proteínas de Fluorescência Verde/genética , Proteínas Luminescentes/metabolismo , Peptídeos/genética , Animais , Animais Geneticamente Modificados , Bombyx/genética , Engenharia Genética/métodos , Proteínas de Fluorescência Verde/metabolismo , Proteínas de Insetos/genética , Proteínas Luminescentes/genética , Proteínas Recombinantes/metabolismo , Células Sf9
19.
J Neurol Sci ; 400: 72-82, 2019 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-30904689

RESUMO

There is increasing evidence indicating that autophagy may be a new target in the treatment of ischemic stroke. Moderate autophagy can clear damaged organelles, thereby protecting cells against various injuries. However, long-term excessive autophagy brings redundant degradation of cell contents, leading to cell death and eventually serious damage to tissues and organs. A number of different animal models of ischemic brain injury shows that autophagy is activated and involved in the regulation of neuronal death during ischemic brain injury. This article summarizes the role of autophagy, its underlying regulators and mechanisms in ischemic neuronal injury. We briefly introduce the relationship between apoptosis and autophagy and give a summary of research methods and modulators of autophagy.

20.
Heart Vessels ; 34(7): 1230-1239, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30671641

RESUMO

We established a rabbit iliac artery restenosis model to explore the impact of Telmisartan on the expression of Connexin43 (Cx43) and neointimal hyperplasia. Thirty New Zealand white rabbits were randomly divided into three groups: control group (n = 10), restenosis group (n = 10), and Telmisartan group (n = 10). The restenosis model was established by high-cholesterol diet combined with double-balloon injury of iliac arteries. In addition, Telmisartan at 5 mg/(kg day) was administered to the rabbits of Telmisartan group on the second day after the second balloon injury. All rabbits were killed at the end of the experiment followed by institution policy. Before sacrifice, blood samples were obtained to test serum angiotensinII (AngII). Iliac arteries were isolated for morphological analysis and determining the expression of Cx43 by HE staining, immunohistochemical analysis, reverse transcription-polymerase chain reaction (RT-PCR), and Western Blotting analysis. Then, the local AngII levels of arteries were measured by radioimmunoassay. As compared with controls, the expression of Cx43 mRNA (0.98 ± 0.08) vs. (1.27 ± 0.17), P < 0.01), and Cx43 protein [(0.75 ± 0.08) vs. (0.90 ± 0.08), P < 0.05] of restenosis group were increased, which were significantly higher than those of Telmisartan group [Cx43 mRNA: (1.27 ± 0.17) vs. (1.00 ± 0.20), P < 0.01; Cx43 protein: (0.90 ± 0.08) vs. (0.82 ± 0.05), P < 0.05]. Furthermore, The intima thickness [(266.12 ± 70.27) vs. (2.85 ± 0.19) µm, P < 0.01] and the local AngII [(115.6 ± 15.7) vs. (90.1 ± 7.7), P < 0.05] of restenosis group were raised when compared with controls. Telmisartan group exhibited thinner intima compared with restenosis group [(68.22 ± 24.37) vs. (266.12 ± 70.27), P < 0.01]. However, the local AngII levels between these two groups were approximate. In addition, the plasma concentration of AngII was not significantly different among three groups. In conclusion, Telmisartan can inhibit the expression of connexin43 and neointimal hyperplasia in iliac artery restenosis model.


Assuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Conexina 43/metabolismo , Artéria Ilíaca/lesões , Telmisartan/farmacologia , Animais , Cateterismo , Proliferação de Células/efeitos dos fármacos , Conexina 43/genética , Hiperplasia/prevenção & controle , Artéria Ilíaca/patologia , Masculino , Músculo Liso Vascular/metabolismo , Miócitos de Músculo Liso/citologia , Neointima/prevenção & controle , Coelhos
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