Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.256
Filtrar
1.
Nat Struct Mol Biol ; 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31570874

RESUMO

Cotranslational protein targeting is a conserved process for membrane protein biogenesis. In Escherichia coli, the essential ATPase SecA was found to cotranslationally target a subset of nascent membrane proteins to the SecYEG translocase at the plasma membrane. The molecular mechanism of this pathway remains unclear. Here we use biochemical and cryoelectron microscopy analyses to show that the amino-terminal amphipathic helix of SecA and the ribosomal protein uL23 form a composite binding site for the transmembrane domain (TMD) on the nascent protein. This binding mode further enables recognition of charged residues flanking the nascent TMD and thus explains the specificity of SecA recognition. Finally, we show that membrane-embedded SecYEG promotes handover of the translating ribosome from SecA to the translocase via a concerted mechanism. Our work provides a molecular description of the SecA-mediated cotranslational targeting pathway and demonstrates an unprecedented role of the ribosome in shielding nascent TMDs.

2.
Biomed Chromatogr ; : e4701, 2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31596954

RESUMO

Patrinia villosa (Thunb.) Juss. (PVJ) is described as pungent, bitter and slightly cold in Chinese medicine, and is associated with the large intestine, stomach and liver meridians. The preliminary experiments of our research team proved that PVJ total flavonoids have excellent inhibitory effects on liver cancer cells. And, the present experiment use the UPLC-Q-TOF-MS technology and serum pharmacochemistry methods to analyze the chemical components in vitro and in vivo of PVJ anti-liver tumors. The results show that a total of 14 chemical components are identified in the total flavonoids extract of PVJ, and it is mainly composed of flavonoids, flavonones, flavonols and phenolic acids. At the same time, 7 prototypical components and 7 metabolic components are detected in the drug-containing plasma. Hydrocaffeate and scutellarein are the phase I metabolites of caffeic acid and scutellarin, respectively. Sulfated apigenin, sulfated luteolin, sulfated kaempferol, and methylated kaempferol are the II phase metabolites of apigenin, luteolin, kaempferol, respectively. The experiment provides a reference for the research and development of anti-tumor drug candidates, and provides a basis for revealing the bioactive components of PVJ and anti-tumor mechanism.

3.
Mar Pollut Bull ; 145: 278-286, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31590788

RESUMO

Microplastics have emerged as new pollutants in oceans. Nevertheless, information of the long-term variations in the composition of plastic-associated microbial communities in coastal waters remains limited. This study applied high-throughput sequencing to investigate the successional stages of microbial communities attached to polypropylene and polyvinyl chloride microplastics exposed for one year in the coastal seawater of China. The composition of plastisphere microbial communities varied remarkably across geographical locations and exposure times. The dominant bacteria in the plastisphere were affiliated with the Alphaproteobacteria class, particularly Rhodobacteraceae, followed by the Gammaproteobacteria class. Scanning electron microscopy analysis revealed that the microplastics showed signs of degradation. Microbial communities showed adaptations to plastisphere including more diverse microbial community and greater "xenobiotics biodegradation and metabolism" in metabolic pathway analysis. The findings elucidate the long-term changes in the community composition of microorganisms that colonize microplastics and expand the understanding of plastisphere microbial communities present in the marine environment.

4.
Mol Plant ; 2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-31622682

RESUMO

Wheat stripe rust, due to infection by Puccinia striiformis f. sp. tritici (Pst), is a devastating disease that is causing significant global grain yield losses. Yr36, which encodes the Wheat Kinase START1 (WKS1), is an effective high-temperature adult-plant resistance gene and confers resistance to a broad spectrum of Pst races. We previously showed that WKS1 phosphorylates the thylakoid ascorbate peroxidase (tAPX) protein and reduces its ability to detoxify peroxides, which may contribute to the accumulation of reactive oxygen species (ROS). WKS1-mediated Pst resistance is accompanied by leaf chlorosis in the Pst-infected regions, but the underlying mechanisms remain still elusive. Here, we show that WKS1 interacts with and phosphorylates PsbO, an extrinsic member of photosystem II (PSII), to reduce photosynthesis and regulate leaf chlorosis in conferring Pst resistance. A point mutation in PsbO-A1 or reductions in its transcript levels by RNA interference resulted in chlorosis and reduced Pst sporulation. Biochemical analyses revealed that WKS1 phosphorylates PsbO at two conserved amino acids involved in its physical interactions with PSII and reduces the binding affinity of PsbO to PSII. Phosphorylated PsbO dissociated from the PSII protein complex, and underwent fast degradation by cysteine and aspartic proteases. Taken together, these results demonstrate that perturbations of wheat PsbO by point mutation or its phosphorylation by WKS1 reduce photosynthesis rate and delays the growth of Pst pathogen before the induction of ROS.

5.
Curr Microbiol ; 2019 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-31646352

RESUMO

Using antagonistic bacterium is an effective method to control plant disease by fungal pathogens. An aerobic bacterium designated SJ-25, capable of suppressing Fusarium graminearum, Exserohilum turcicum, Pythium aphanidermatum, and Cochliobolus sativus, was isolated from farmland soil. The phylogenetic analysis revealed that strain SJ-25 belongs to the species of Sphingobacterium psychroaquaticum. The genome of strain SJ-25 consists of a 4,396,535-bp chromosome with a G+C content of 41.7 mol%; including 3696 CDS, 64 tRNA genes and six rRNA operons. Genomic analysis revealed that its genome contains multiple genes responsible for biosynthesis of siderophore, methyl 4-hydroxybenzoate, chitinase, giving strain SJ-25 the antagonistic ability on fungi pathogen. Strain SJ-25 harbors sets genes responsible for production of 2, 3-butanediol and salicylic acid, which could elicit the induced systemic resistance of the host plant. This genome sequence could be used as a basis material for further exploration of antagonistic mechanisms on fungi, widening our understanding of the ecological role of the genus Sphingobacterium in farmland ecosystem.

6.
Food Funct ; 2019 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-31647087

RESUMO

Some studies have reported that vinegar ingestion at mealtime attenuates postprandial glycemia in healthy adults and individuals with type 2 diabetes. Emerging data suggest that chronic vinegar ingestion impacts fat metabolism and reduces adiposity, although no study has yet corroborated the events of vinegar supplementation metabolically through a metabolomics approach. To examine the impact of daily vinegar ingestion on glucose homeostasis, adiposity, and the metabolome, an 8-week, randomized controlled trial design was implemented utilizing two parallel treatment arms: daily red wine vinegar ingestion and a control treatment. Participants were 45 healthy adults at increased risk for metabolic complications as determined by high waist circumferences. Measurements and blood samples were collected pre- and post-intervention. Central adiposity and visceral fat were assessed by waist circumference and dual-energy X-ray absorptiometry, respectively. Plasma metabolites were analyzed using gas chromatography-mass spectrometry (MS) and liquid chromatography-MS/MS. Analysis showed significant reductions in fasting glucose (p = 0.003) and insulin (p < 0.001). Insulin resistance was reduced 8.3% in the red wine vinegar group and increased 9.7% in the control group (p < 0.001). No significant between-group differences in body mass index, body weight, waist circumference, or visceral fat were observed. Significant differences were observed in amino valerate and indole-3-acetic acid (p < 0.05), with high magnitudes of fold change (>2) between groups. Metabolic pathway analysis revealed significant alterations in tryptophan metabolism. Although daily red wine vinegar ingestion for 8 weeks induced significant improvements in glucose homeostasis, our results indicate that daily red wine vinegar ingestion for 8 weeks is not associated with reductions in adiposity. This is the first study to investigate the effects of daily red wine vinegar supplementation using a metabolomics approach. Our results provide strong rationales for larger prospective studies to further clarify associations among obesity, chronic diseases, and functional foods such as vinegar using metabolomics.

8.
J Immunol Res ; 2019: 3979352, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31583256

RESUMO

Methicillin-resistant Staphylococcus aureus (MRSA) is the major pathogen responsible for community and hospital bacterial infections. Sublancin, a glucosylated antimicrobial peptide isolated from Bacillus subtilis 168, possesses antibacterial infective effects. In this study, we investigated the role and anti-infection mechanism of sublancin in a mouse model of MRSA-induced sublethal infection. Sublancin could modulate innate immunity by inducing the production of IL-1ß, IL-6, TNF-α, and nitric oxide, enhancing phagocytosis and MRSA-killing activity in both RAW264.7 cells and mouse peritoneal macrophages. The enhanced macrophage function by the peptide in vitro correlated with stronger protective activity in vivo in the MRSA-invasive sublethal infection model. Macrophage activation by sublancin was found to be partly dependent on TLR4 and the NF-κB and MAPK signaling pathways. Moreover, oral administration of sublancin increased the frequencies of CD4+ and CD8+ T cells in mesenteric lymph nodes. The protective activity of sublancin was associated with in vivo augmenting phagocytic activity of peritoneal macrophages and partly improving T cell-mediated immunity. Macrophages thus represent a potentially pivotal and novel target for future development of innate defense regulator therapeutics against S. aureus infection.

9.
Medicine (Baltimore) ; 98(41): e17425, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31593095

RESUMO

To evaluate whether the adult patients with acquired pure red cell aplasia (PRCA) could benefit more from cyclosporine A (CsA) combined with corticosteroids (CS) than CsA or CS alone.Seventy-three patients were evaluated in 2 institutions (6 patients lost to follow-up).The induction therapy included CsA (n = 21), CS (n = 21), or CsA combined with CS (n = 31), and remission was achieved in 16/21 (76.2%), 10/21 (47.6%), and 21/31 (71.0%) patients, respectively. Higher complete remission (CR) rate was achieved in CsA combined with CS group than in CS group (61.3% vs 19.0%, P = .003). Patients achieved CR faster in CsA combined with CS group than in CS group or CsA group (median time, 1 month vs 2 month vs 3 month, P = .010). By multivariate analysis, CsA combined with CS therapy and primary PRCA were the influence factors for CR rate. Twenty-seven patients relapsed due to discontinuation or tapering therapy, and 19 patients regained response by increasing the dose of original regimens or changing to other immunosuppressive therapy. Complete remission to induction therapy was a correlative factor for death (P = .035).CsA combined with CS produced faster and higher CR rate in treating adult patients with PRCA than did CsA or CS alone.


Assuntos
Corticosteroides/administração & dosagem , Ciclosporina/administração & dosagem , Imunossupressores/administração & dosagem , Quimioterapia de Indução/métodos , Aplasia Pura de Série Vermelha/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
10.
Med Sci Monit ; 25: 7709-7714, 2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-31608899

RESUMO

BACKGROUND The network pharmacological approach was used to identity the anti-colorectal cancer (CRC) targets of formononetin (FN) and the molecular mechanisms of FN against CRC. MATERIAL AND METHODS A tool of the DisGeNET database was used for collection of CRC-based targets. Other tools of SuperPred, herbal ingredients target (HIT), and SwissTargetPrediction databases were applied in prediction of pharmacological targets of FN against cancer. A protein-protein interaction (PPI) network of FN against CRC was obtained by using a STRING database. All top biological functional processes and signaling pathways of FN against CRC were identified by using Database for Annotation, Visualization and Integrated Discovery (DAVID) software and Omicshare cloud platform. RESULTS The most key anti-CRC targets of FN were identified as tumor protein p53 (TP53), cytochrome P450 3A4 (CYP3A4), ATP binding cassette subfamily G member 2 (ABCG2), tumor necrosis factor (TNF), epidermal growth factor receptor (EGFR), Erb-B2 receptor tyrosine kinase 2 (ERBB2), and cytochrome P450 1A1 (CYP1A1). In further assays, the treatment of CRC by FN was mainly involved in biological functional processes of reactive oxygen species metabolic process, positive regulation of transcription, DNA-templated, positive regulation of nucleic acid-templated transcription, and positive regulation of RNA metabolic process. anti-CRC by FN of signaling pathways were associated with amyotrophic lateral sclerosis (ALS), allograft rejection, cytokine-cytokine receptor interaction, asthma, mitogen-activated protein kinase (MAPK) signaling pathways, and others. CONCLUSIONS The anti-CRC molecular mechanisms of FN are implicated in suppression of cellular proliferation and regulation of cancer-related metabolic pathways. Interestingly, 8 optimal biological targets may be used as potential molecular markers for predicting and treating CRC.

11.
Nat Chem Biol ; 2019 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-31659317

RESUMO

PARP1 inhibitors (PARPi) are known to kill tumor cells via two mechanisms (PARP1 catalytic inhibition and PARP1 trapping). The relative contribution of these two pathways in mediating the cytotoxicity of PARPi, however, is not well understood. Here we designed a series of small molecule PARP degraders. Treatment with one such compound iRucaparib-AP6 results in highly efficient and specific PARP1 degradation. iRucaparib-AP6 blocks the enzymatic activity of PARP1 in vitro, and PARP1-mediated poly-ADP-ribosylation signaling in intact cells. This strategy mimics PARP1 genetic depletion, which enables the pharmacological decoupling of PARP1 inhibition from PARP1 trapping. Finally, by depleting PARP1, iRucaparib-AP6 protects muscle cells and primary cardiomyocytes from DNA-damage-induced energy crisis and cell death. In summary, these compounds represent 'non-trapping' PARP1 degraders that block both the catalytic activity and scaffolding effects of PARP1, providing an ideal approach for the amelioration of the various pathological conditions caused by PARP1 hyperactivation.

12.
World J Gastroenterol ; 25(39): 6025-6040, 2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31660038

RESUMO

BACKGROUND: Allicin (2-propene-1-sulfinothioic acid S-2-propenyl ester, diallyl thiosulfinate) extracted from garlic, has proven activity against Helicobacter pylori (H. Pylori) infection. In recent years, clinical trials have explored its utility as an add-on therapy with variable outcomes reported. AIM: To perform a systemic review of allicin as an add-on treatment for H. Pylori infection and assess its efficacy in randomized controlled trials (RCTs). METHODS: Electronic databases including MEDLINE, EMBASE, the Web of Science, the Cochrane Database, the China National Knowledge Infrastructure Database, Chinese VIP Information Databases, Chinese Medical Databases, and the Wan-Fang Database were searched for keywords including "allicin", "Helicobacter pylori", "randomized clinical trials", and their synonyms. A meta-analysis was performed using the fixed-effects model for low heterogeneity and the random-effects model for high heterogeneity with sensitivity analysis. Bias was evaluated using Egger's tests. Trial sequential analysis (TSA) was used to evaluate information size and treatment benefits. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) was used to assess the level of quality, and studies were classed as "high quality", "moderate quality", "low quality", and "very low quality". RESULTS: A total of eight RCTs consisting of 867 participants (435 from the allicin group and 432 from the control group) were included. Eradication rate in the allicin group (93.33%, 406/435) was significantly higher than that of the control group (83.56%, 361/432) [I 2 = 0%, odds ratio (OR) = 2.75, 95% confidence interval (CI): 1.74-4.35, P < 0.001]. The healing rate of ulcers following H. pylori therapy in the allicin group (86.17%, 349/405) was significantly higher than that of the control group (75.87%, 305/402) [I 2 = 0%, OR = 2.05, 95%CI: 1.39-3.03, P < 0.001]. The total remission rate of peptic ulcers across all allicin groups was 97.16%, which was significantly higher than that of controls [96.05% (389/405) vs 86.55% (360/402), I 2 = 0, OR = 3.04, 95%CI: 1.51-6.12, P = 0.015]. No significant differences in side effects were observed. TSA suggested that the trials were of sufficient standard to draw reliable conclusions. The quality of outcomes including eradication rates and side effects was graded as "very low" due to downgrades for "risk of bias" and "indirectness". Other outcomes such as ulcer healing rates and total ulcer remission rates were graded as "low" due to downgrades for "risk of bias". CONCLUSION: Allicin as an add-on therapy improves H. pylori eradication, healing of ulcers, and remission of symptoms. These results are suggested to be treated with caution due to limited quality.

13.
EBioMedicine ; 2019 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-31631041

RESUMO

BACKGROUND: Histological assessment of resected margins has some drawbacks. We therefore aimed to identify a panel of metabolic markers for evaluating the surgical margins of oral squamous cell carcinoma during surgery. METHODS: A total of 28 case of OSCC samples were enrolled in the study. Gas chromatography-mass spectrometry based untargeted metabolic analysis was employed to acquire the metabolic perturbation of the distance-related surgical margins in the development group. The acquired MS data were then subjected to univariate and multivariate analysis by MetaboAnalyst. Ultra-high performance liquid chromatography-tandem mass spectrometerbased targeted metabolomics for quantitative analysis of the validation group was performed to verify the results of the development group. Another 60 OSCC patients with dysplastic surgical margins were used to further validate the results of the development group by immunohistochemical examination of key enzyme expression, and correlate them with clinicopathological parameters and clinical outcomes. FINDINGS: We finally identified 4 amino acids as negative margin markers, and 6 amino acids as dysplastic margin markers. IHC analysis showed that asparagine synthetase positive expression in dysplastic surgical margins and its higher expression was correlated with tumor recurrence and local relapse-free survival. INTERPRETATIONS: We developed a panel of metabolic molecular markers to supplement the evaluation of negative and dysplastic margins. FUND: This study was supported by Nanjing Municipal Key Medical Laboratory Constructional Project Funding (Since 2012); Center of Nanjing Clinical Medicine Tumor (Since 2014). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

14.
Br J Radiol ; : 20181055, 2019 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-31596129

RESUMO

OBJECTIVE: We proposed to determine whether the performance of inexperienced radiologists in determining extramural vascular invasion (EMVI) in rectal cancer on MRI can be promoted by means of targeted training. METHODS: 230 rectal cancer patients who underwent pre-operative chemoradiotherapy were included. Pre-therapy and post-therapy MR images and pathology EMVI evaluation were available for cases. 230 cases were randomly divided into 150 training cases and 80 testing cases, including 40 testing case A and 40 testing case B. Four radiologists were included for MRI EMVI evaluation, who were divided into targeted training group and non-targeted training group. The two groups evaluated testing case A at baseline, 3 month and 6 month, evaluated testing case B at 6 month. The main outcome was agreement with expert-reference for pre-therapy and post-therapy evaluation, the other outcome was accuracy with pathology for post-therapy evaluation. RESULTS: After 6 months of training, targeted training group showed statistically higher agreement with expert-reference than non-targeted training group for both pre-therapy and post-therapy MRI EMVI evaluation of testing case A and testing case B, all p < 0.05. Targeted training group also showed significantly higher accuracy with pathology than non-targeted training group for post-therapy evaluation of testing case A and testing case B after 6 months of training, all p < 0.05. CONCLUSION: The diagnostic performance for MRI EMVI evaluation could be promoted by targeted training for inexperienced radiologist. ADVANCES IN KNOWLEDGE: This study provided the first evidence that after 6 month targeted training, inexperienced radiologists demonstrated improved diagnostic performance, with a 20% increase in agreement with expert-reference for both pre-therapy and post-therapy MRI EMVI evaluation and also a 20% increase in or accuracy with pathology for post-therapy evaluation, while inexperienced radiologists could not gain obvious improvement in MRI EMVI evaluation through the same period of regular clinical practice. It indicated that targeted training may be necessary for helping inexperienced radiologist to acquire adequate experience for the MRI EMVI evaluation of rectal cancer, especially for radiologist who works in a medical unit where MRI EMVI diagnosis is uncommon.

15.
Zhongguo Zhong Yao Za Zhi ; 44(15): 3239-3245, 2019 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-31602878

RESUMO

The present study was conducted to explores the effects of short-term addition of 17ß-E2 on the growth,gonad development and internal quality of overwintering Whitmania pigra. Before overwintering,0. 0,1. 0,10. 0,25. 0,50. 0,100. 0 µg·L~(-1) of 17ß-E2 were added to the aquaculture water for 6 weeks and then hibernated for 60 days. The changes of growth performance,gonad index,morphological structure of spermary( ovary),endogenous steroid hormones level and internal quality were measured. The results showed that the body weight,weight gain rate,specific growth rate,female gonad index,oocyte development and endogenous estrogen level of the leech increased first and then decreased with the increase of the concentration of exogenous 17ß-E2,which were higher than those of the control group. The body weight,weight gain rate and specific growth rate of the leech at the concentration of 25 µg·L~(-1)17ß-E2 were significantly higher than those of the other groups( P<0. 05),oocyte development and endogenous estrogen levels were significantly higher than those of other groups at the concentration of 50 µg·L~(-1)( P<0. 05). When the concentration of exogenous 17ß-E2 was higher than 50 µg·L~(-1),the levels of male gonad index,spermatocyte development,endogenous androgen and progesterone were significantly inhibited( P< 0. 05). There was no significant difference in endogenous corticosteroid levels among the groups. In conclusion,short-term addition of exogenous 17ß-E2 of 10-25 µg·L~(-1) could promote the growth of overwintering leeches,oocyte development and antithrombin activity without inhibiting the development of male gonads.


Assuntos
Estradiol/farmacologia , Gônadas/crescimento & desenvolvimento , Sanguessugas/efeitos dos fármacos , Sanguessugas/crescimento & desenvolvimento , Androgênios/análise , Animais , Estrogênios/análise , Feminino , Gônadas/efeitos dos fármacos , Hibernação , Masculino , Progesterona/análise
16.
Front Immunol ; 10: 2241, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31611873

RESUMO

The recognition of ω-3 polyunsaturated acids (PUFAs) as essential fatty acids to normal growth and health was realized more than 80 years ago. However, the awareness of the long-term nutritional intake of ω-3 PUFAs in lowering the risk of a variety of chronic human diseases has grown exponentially only since the 1980s (1, 2). Despite the overwhelming epidemiological evidence, many attempts of using fish-oil supplementation to intervene human diseases have generated conflicting and often ambiguous outcomes; null or weak supporting conclusions were sometimes derived in the subsequent META analysis. Different dosages, as well as the sources of fish-oil, may have contributed to the conflicting outcomes of intervention carried out at different clinics. However, over the past decade, mounting evidence generated from genetic mouse models and clinical studies has shed new light on the functions and the underlying mechanisms of ω-3 PUFAs and their metabolites in the prevention and treatment of rheumatoid arthritis, systemic lupus erythematosus (SLE), multiple sclerosis, and type 1 diabetes. In this review, we have summarized the current understanding of the effects as well as the underlying mechanisms of ω-3 PUFAs on autoimmune diseases.

17.
Mol Ther ; 2019 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-31636038

RESUMO

Inflammation is associated with retinal diseases. Our recent data demonstrate that immunoproteasome catalytic subunit ß2i contributes to angiotensin II (Ang II)-induced retinopathy in mice. Here, we investigated the role of another catalytic subunit ß5i in regulating retinopathy and its underlying mechanisms. We induced a murine model of retinopathy by infusing Ang II (3,000 ng/kg/min) for 3 weeks into wild-type (WT) mice, ß5i-knockout (KO) mice, or WT mice injected with either adenovirus-expressing ß5i (Ad-ß5i) or angiotensin II type 1 receptor (AT1R)-associated protein (Ad-ATRAP), which inhibits AT1R. The ß5i expression and chymotrypsin-like activity were most significantly elevated in Ang II-infused retinas and serum from patients with hypertensive retinopathy. Moreover, Ang II infusion-induced retinopathy was markedly attenuated in ß5i-KO mice but aggravated in Ad-ß5i-injected mice. Accordingly, ß5i KO markedly restored Ang II-induced downregulation of ATRAP and activation of AT1R downstream mediators, which was further enhanced in Ad-ß5i-injected mice. Interestingly, overexpression of ATRAP significantly abrogated Ang II-induced retinopathy in Ad-ß5i-injected mice. This study found that ß5i promoted Ang II-induced retinopathy by promoting ATRAP degradation and activation of AT1R-mediated signals.

18.
Theranostics ; 9(20): 5937-5955, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31534530

RESUMO

Prolonged occlusion of multiple microvessels causes microvascular injury. G protein-coupled receptor 124 (GPR124) has been reported to be required for maintaining central nervous system (CNS) angiogenesis and blood-brain barrier integrity. However, the molecular mechanisms by which GPR124 regulates pericytes during ischemia have remained elusive. Methods: A microsphere embolism-induced ischemia model was used to evaluate the expression of GPR124 following microsphere embolism. Immunocytochemistry and stochastic optical reconstruction microscopy imaging were used to assess the expression and distribution of GPR124 in human brain vascular pericytes (HBVPs) and after the treatment with 3-morpholino-sydnonimine (SIN-1) or oxygen-glucose deprivation (OGD). The effect of GPR124 knockdown or overexpression on HBVP migration was analyzed in vitro using wound healing assays and a microfluidic device. GPR124 loss-of-function studies were performed in HBVPs and HEK293 cells using CRISPR-Cas9-mediated gene deletion. Time-lapse imaging was used to assess dynamic changes in the formation of filopodia in an individual cell. Finally, to explore the functional domains required for GPR124 activity, deletion mutants were constructed for each of the N-terminal domains. Results: GPR124 expression was increased in pericytes following microsphere embolism. Morphological analysis showed localization of GPR124 to focal adhesions where GPR124 bound directly to the actin binding protein vinculin and upregulated Cdc42. SIN-1 or OGD treatment redistributed GPR124 to the leading edges of HBVPs where GPR124 signaling was required for pericyte filopodia formation and directional migration. Partial deletion of GPR124 domains decreased SIN-1-induced filopodia formation and cell migration. Conclusion: Taken together, our results provide the first evidence for a role of GPR124 in pericyte migration under ischemic conditions and suggest that GPR124 was essential for Cdc42 activation and filopodia formation.

19.
Appl Opt ; 58(18): 4884-4891, 2019 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-31503804

RESUMO

The azimuth multi-channel synthetic aperture ladar (SAL), which arranges multiple telescopes along the flight direction of the platform, transmits signals through a single telescope and receives echoes by multiple telescopes simultaneously to obtain data. The aperture synthesis technology, which has the ability to achieve high resolution through multiple small telescopes, is applied to the multi-channel SAL system to realize the reconstruction of the complete azimuth Doppler spectrum in a short observation time. However, there are gaps inevitably between telescopes, which degrade the results of aperture synthesis. In this work, the effect of gaps on the instantaneous Doppler spectrum of each channel and the influence on the result of the azimuth impulse compression after aperture synthesis are analyzed. In addition, an estimation method of gaps based on the phase errors between channels is proposed to reduce the influence. The estimation accuracy of the proposed method is analyzed, and the effectiveness of the method is verified with simulations. The estimated gaps are used to compensate for the phase discontinuity of the azimuth signal after aperture synthesis caused by gaps. The method improves the result of aperture synthesis and reduces the side-lobe of the azimuth impulse compression after aperture synthesis.

20.
Artigo em Inglês | MEDLINE | ID: mdl-31550437

RESUMO

PURPOSE: The purpose of the present study was to investigate the differences in postoperative thrombosis and flap failure between internal jugular vein (IJV) system anastomosis and external jugular vein (EJV) system anastomosis in free flaps for the reconstruction of head and neck defects. MATERIALS AND METHODS: We searched PubMed, Web of Science, EMBASE, Chinese BioMedical Literature Database, and other databases until March 2019 for studies that had reported data for anastomosis for the 2 different venous systems in the microvascular free-flap reconstruction of head and neck defects. We assessed thrombosis and flap failure in patients undergoing anastomosis of the IJV system and patients undergoing anastomosis of the EJV system. RESULTS: Nine studies with a total of 2051 patients with venous anastomosis were included in the present meta-analysis. IJV system anastomosis showed a significantly lower incidence of venous thrombosis than did the EJV system (relative risk [RR], 0.55; 95% confidence interval [CI], 0.37 to 0.82). Eight studies were included in the analysis of the flap failure rate, which showed a lower failure rate for the IJV system anastomosis than for the EJV system (RR, 0.59; 95% CI, 0.35 to 1.00). CONCLUSIONS: The incidence of thrombosis and flap failure after venous anastomosis in the IJV system was lower than that in the EJV system. The results from the present study have shown that the IJV system should be the first choice for venous anastomosis in the reconstruction of free flaps.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA