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1.
J Biol Chem ; 2020 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-32213599

RESUMO

Site-specific recombinases, such as Cre, are a widely used tool for genetic lineage tracing in the fields of developmental biology, neural science, stem cell biology, and regenerative medicine. However, unspecific cell labeling by some genetic Cre tools remains a technical limitation of this recombination system, which has resulted in data misinterpretation and led to many controversies in the scientific community. In the past decade, to enhance the specificity and precision of genetic targeting, researchers have used two or more orthogonal recombinases simultaneously for labeling cell lineages. Here, we review the history of cell tracing strategies and then elaborate on the working principle and application of a recently developed dual genetic lineage tracing approach for cell fate studies. We place an emphasis on discussing the technical strengths and caveats of different methods, with the goal to develop more specific and efficient tracing technologies for cell fate mapping. Our review also provides several examples for how to use different types of DNA recombinase-mediated lineage tracing strategies to improve the resolution of the cell fate mapping in order to probe and explore cell fate-related biological phenomena in the life sciences.

2.
J Radiat Res ; 2020 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-32123912

RESUMO

The deep inspiration breath-hold (DIBH) technique has been utilized to reduce the cardiac dose in left-sided breast cancer (BC) patients undergoing radiotherapy. Further investigation of the parameters for selecting which patients will benefit most from DIBH is essential. We performed dosimetric comparisons for 21 patients with left-sided BC who had both computed tomography (CT)-based free-breathing (FB) and DIBH plans. The doses to the heart and left anterior descending artery (LAD) and any reduction due to the DIBH technique were analysed. Based on CTFB plans, dosimetric analysis revealed that the irradiation doses to the heart and LAD were significantly correlated with the target volume, the ipsilateral lung volume (ILV) and the total lung volume (TLV). When patients had an ILV ≥ 950 cm3 or a TLV ≥ 2200 cm3, the irradiation doses to the heart and LAD were significantly decreased. Furthermore, the reduction in the mean heart dose (MHD) was correlated to the difference in lung volume between FB and DIBH. The difference in ILV between DIBH and FB of 1.8 indicated that the patients obtained more benefit from the DIBH technique. The data suggest that lung volume (ILV and TLV) measured on a CT-simulation scan and the difference between FB and DIBH could be utilized to help select patients for DIBH.

3.
Mol Genet Genomic Med ; : e1188, 2020 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-32107880

RESUMO

BACKGROUND: The ECE1 gene polymorphisms have been studied as a candidate gene in essential hypertension, but no consensus has been reached. To systematically explore their possible association, a case-control study was conducted. METHODS: This study included 398 hypertensive subjects and 596 healthy volunteers as control subjects in the Northern Han Chinese. A total of 10 tag SNPs of ECE1 gene were genotyped successfully by TaqMan assay. RESULTS: A total of 10 SNPs (rs212544, rs2076280, rs115071, rs2076283, rs9426748, rs11590928, rs212515, rs2236847, rs2282715, and rs2774028) were identified as the tag SNPs for ECE1 gene. Although no positive connection has been found in general population, several SNPs have been found to be related to EH risk in gender-stratified subgroup analysis. In males, rs115071 T allele influenced EH risk in a protective manner, with dominant model (TT+TC vs. CC: p = .032, OR = 0.655, 95% CI = 0.445-0.965), additive model (TT vs. TC vs. CC: p = .019, OR = 0.616, 95% CI = 0.411-0.924), as well as allele comparison (T vs. C: p = .045, OR = 0.702, 95% CI = 0.496-0.992). While, in females, rs212544 AA genotype would increase the onset risk of EH (recessive model: AA vs. GA+GG, p = .024, OR = 1.847, 95% CI = 1.086-3.142). In the three haplotype blocks identified, rs2076283-rs2236847 C-T haplotype was associated with a decreased risk of EH (OR = 0.558, p = .046). CONCLUSION: The current case-control study suggested that several SNPs and related haplotypes on ECE1 gene might be associated with the susceptibility of EH in certain gender subgroups in the Northern Han Chinese population.

4.
Molecules ; 25(2)2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31952105

RESUMO

Casticin was obtained from natural plants, and it has been shown to exert biological functions; however, no report concerns the induction of DNA damage and repair in human lung cancer cells. The objective of this study was to investigate the effects and molecular mechanism of casticin on DNA damage and repair in human lung cancer A549 cells. Cell viability was determined by flow cytometric assay. The DNA damage was evaluated by 4',6-diamidino-2-phenylindole (DAPI) staining and electrophoresis which included comet assay and DNA gel electrophoresis. The protein levels associated with DNA damage and repair were analyzed by western blotting. The expression and translocation of p-H2A.X were observed by confocal laser microscopy. Casticin reduced total viable cell number and induced DNA condensation, fragmentation, and damage in A549 cells. Furthermore, casticin increased p-ATM at 6 h and increased p-ATR and BRCA1 at 6-24 h treatment but decreased p-ATM at 24-48 h, as well as decreased p-ATR and BRCA1 at 48 h. Furthermore, casticin decreased p-p53 at 6-24 h but increased at 48 h. Casticin increased p-H2A.X and MDC1 at 6-48 h treatment. In addition, casticin increased PARP (cleavage) at 6, 24, and 48 h treatment, DNA-PKcs and MGMT at 48 h in A549 cells. Casticin induced the expressions and nuclear translocation of p-H2AX in A549 cells by confocal laser microscopy. Casticin reduced cell number through DNA damage and condensation in human lung cancer A549 cells.

5.
EMBO J ; 39(4): e102675, 2020 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-31943281

RESUMO

Site-specific recombinase-mediated genetic technology, such as inducible Cre-loxP recombination (CreER), is widely used for in vivo genetic manipulation with temporal control. The Cre-loxP technology improves our understanding on the in vivo function of specific genes in organ development, tissue regeneration, and disease progression. However, inducible CreER often remains inefficient in gene deletion. In order to improve the efficiency of gene manipulation, we generated a self-cleaved inducible CreER (sCreER) that switches inducible CreER into a constitutively active Cre by itself. We generated endocardial driver Npr3-sCreER and fibroblast driver Col1a2-sCreER, and compared them with conventional Npr3-CreER and Col1a2-CreER, respectively. For easy-to-recombine alleles such as R26-tdTomato, there was no significant difference in recombination efficiency between sCreER and the conventional CreER. However, for alleles that were relatively inert for recombination such as R26-Confetti, R26-LZLT, R26-GFP, or VEGFR2flox/flox alleles, sCreER showed a significantly higher efficiency in recombination compared with conventional CreER in endocardial cells or fibroblasts. Compared with conventional CreER, sCreER significantly enhances the efficiency of recombination to induce gene expression or gene deletion, allowing temporal yet effective in vivo genomic modification for studying gene function in specific cell lineages.

6.
J Biol Chem ; 295(3): 690-700, 2020 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-31771978

RESUMO

Genetic lineage tracing is widely used to study organ development and tissue regeneration. Multicolor reporters are a powerful platform for simultaneously tracking discrete cell populations. Here, combining Dre-rox and Cre-loxP systems, we generated a new dual-recombinase reporter system, called Rosa26 traffic light reporter (R26-TLR), to monitor red, green, and yellow fluorescence. Using this new reporter system with the three distinct fluorescent reporters combined on one allele, we found that the readouts of the two recombinases Cre and Dre simultaneously reflect Cre+Dre-, Cre-Dre+, and Cre+Dre+ cell lineages. As proof of principle, we show specific labeling in three distinct progenitor/stem cell populations, including club cells, AT2 cells, and bronchoalveolar stem cells, in Sftpc-DreER;Scgb1a1-CreER;R26-TLR mice. By using this new dual-recombinase reporter system, we simultaneously traced the cell fate of these three distinct cell populations during lung repair and regeneration, providing a more comprehensive picture of stem cell function in distal airway repair and regeneration. We propose that this new reporter system will advance developmental and regenerative research by facilitating a more sophisticated genetic approach to studying in vivo cell fate plasticity.

7.
Methods Mol Biol ; 2067: 189-201, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31701454

RESUMO

The ability of individual cells to synchronize activity is a basic feature of efficient and appropriate tissue function. Central to this is the physicochemical binding between cells through multiprotein complexes that functionally mediate adhesion. Importantly, the direct connection of physical properties and intercellular signaling is of great importance to certain pathologies including diabetes. Atomic force microscopy (AFM) single-cell force spectroscopy (SCFS) is a high-resolution technique that provides a statistically reliable measurement of the minute forces involved in cell tethering and membrane dynamics. Detection of altered nanoscale forces underlying the loss of adhesion in early tubular injury is pivotal for the development of novel therapeutic strategies for diabetic nephropathy. Here we describe the step-by-step use of an integrated AFM-SCFS system designed to measure functional force-displacement in separating renal tubular epithelial cells. Parameters such as unbinding forces, detachment energy, and distance to complete separation can be obtained from force-displacement (F-d) curves and are critical in assessing how physical changes of cellular adhesion contribute to cell contact, coupling, and communication in the diabetic kidney.

8.
Cell Stem Cell ; 26(1): 81-96.e4, 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31883835

RESUMO

Rapid regeneration of smooth muscle after vascular injury is essential for maintaining arterial function. The existence and putative roles of resident vascular stem cells (VSCs) in artery repair are controversial, and vessel regeneration is thought to be mediated by proliferative expansion of pre-existing smooth muscle cells (SMCs). Here, we performed cell fate mapping and single-cell RNA sequencing to identify Sca1+ VSCs in the adventitial layer of artery walls. After severe injury, Sca1+ VSCs migrate into the medial layer and generate de novo SMCs, which subsequently expand more efficiently compared with pre-existing smooth muscle. Genetic lineage tracing using dual recombinases distinguished a Sca1+PDGFRa+ VSC subpopulation that generates SMCs, and genetic ablation of Sca1+ VSCs or specific knockout of Yap1 in Sca1+ VSCs significantly impaired artery repair. These findings provide genetic evidence of a bona fide Sca1+ VSC population that produces SMCs and delineates their critical role in vessel repair.

9.
J Hazard Mater ; 382: 120970, 2020 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-31465945

RESUMO

A series of Fe-V-Ti oxide catalysts were prepared by a co-precipitation method, among which the Fe0.1V0.1TiOx catalyst showed the optimal NH3-SCR performance and excellent SO2 resistance. Fe0.1V0.1TiOx achieved > 90% NOx conversion at 225-450 °C under a GHSV of 200,000 h-1. When introducing SO2 and H2O to the SCR reaction for 24 h, the NOx conversion maintained a level above 93% at 250 °C. The Raman and Mössbauer spectra showed that FeVO4 and Fe2O3 coexisted on the surface of TiO2. In Fe-V-Ti catalysts, the charge interaction between Fe2O3 and FeVO4 as well as the electronic inductive effect between Fe and V species resulted in the improvement of SCR activity and N2 selectivity at high temperatures. The NH3-SCR process on the Fe0.1V0.1TiOx catalyst mainly followed the Eley-Rideal (E-R) reaction mechanism with gaseous NO reacting with adsorbed NH3 adsorbed species.

10.
J Therm Biol ; 86: 102430, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31789226

RESUMO

Control of the therapeutic temperature is essential in performing magnetic fluid hyperthermia. Thus, reliable predictions of the power dissipation are required to determine the correct dosage of magnetic particles to be injected into the cancerous tissue prior to treatment. To meet this requirement, the present study evaluates the power dissipation requirement for two magnetic hyperthermia problems reported in the literature. There is a significant challenge for solving the bio-heat transfer model for concentric bi-layered solid spheres. Consequently, the present study employs a hybrid technique based on Laplace transformation and a modified discretization scheme to solve the considered hyperthermia problems. Analytical solutions are provided to demonstrate the validity of the proposed approach. The unreliability of the results presented in the literature is then demonstrated using the proposed numerical scheme. In general, the results presented in this study show that the power dissipation required to maintain an effective temperature range in the tumor domain is related to the rate of temperature rise, the tumor size, the blood perfusion rate, and the tissue properties. In particular, the power dissipation should be increased for the cooling effect of blood perfusion or a smaller tumor volume.

11.
Comput Assist Surg (Abingdon) ; 24(sup2): 34-42, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31502481

RESUMO

A metal implant was placed in an acrylic phantom to enable quantitative analysis of the metal artifact reduction techniques used in computed tomography (CT) scanners from three manufacturers. Two titanium rods were placed in a groove in a cylindrical phantom made by acrylic, after which the groove was filled with water. The phantom was scanned using three CT scanners (Toshiba, GE, Siemens) under the abdomen CT setting. CT number accuracy, contrast-to-noise ratio, area of the metal rods in the images, and fraction of affected pixel area of water were measured using ImageJ. Different iterative reconstruction, dual energy, and metal artifact reduction techniques were compared within three vendors. The highest contrast-to-noise ratio of three scanners were 85.7 ± 8.4 (Toshiba), 85.9 ± 11.7 (GE), and 55.0 ± 14.8 (Siemens); and the most correct results of metal area were 157.1 ± 1.4 mm2 (Toshiba), 155.0 ± 1.0 (GE), and 170.6 ± 5.3 (Siemens). The fraction of affected pixel area obtained using single-energy metal artifact reduction of Toshiba scanner was 2.2% ± 0.7%, which is more favorable than 4.1% ± 0.7% obtained using metal artifact reduction software of GE scanner (p = 0.002). Among all quantitative results, the estimations with fraction of affected pixel areas matched the effect of metal artifact reduction in the actual images. Therefore, the single-energy metal artifact reduction technique of Toshiba scanner had a desirable effect. The metal artifact reduction software of GE scanner effectively reduced the effect of metal artifacts; however, it underestimated the size of the metal rods. The monoenergetic and dual energy composition techniques of Siemens scanner could not effectively reduce metal artifacts.

12.
Front Aging Neurosci ; 11: 226, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31555120

RESUMO

Objective: This study was aimed to explore the effects of dietary nutrients on cognitive function among the middle-aged and elderly populations. Methods: A prospective cohort study of 1,385 middle-aged and elderly people was conducted from January 2014 to December 2017. Dietary nutrients were assessed according to the food frequency questionnaire (FFQ) and China Food Composition Database (CFCD). Montreal cognitive assessment (MoCA) was used to evaluate the participants' global cognitive function. Six other neuropsychological measures [auditory verbal learning test-immediate recall (AVLT-IR), auditory verbal learning test-short recall (AVLT-SR), auditory verbal learning test-long recall (AVLT-LR), logical memory test (LMT), digit span forward (DST-F), and digit span backward (DST-B)] were used to assess the verbal memory domain and the attention domain by principal component analysis (PCA). Multiple linear regressions were conducted to explore associations between nutrients and cognition. Sensitivity analyses were performed to confirm the results. Results: Dietary riboflavin was protective for global cognitive function (ß = 1.31, 95% CI: 0.26, 2.35) and the verbal memory domain (ß = 0.37, 95% CI: 0.02, 0.71). Unsaturated fatty acid (USFA) played a protective role in global cognitive function (ß = 1.15, 95% CI: 0.16, 2.14). The protective effects of riboflavin and USFA on cognitive function were consistent and reliable when different confounders were adjusted during sensitivity analyses. During the follow-up, neuropsychological measure scores revealed a reduced decline in the high-riboflavin group (d-MoCA, P = 0.025; d-AVLT-IR, P = 0.001; d-DST-B, P = 0.004; and d-composite score, P = 0.004) and the high-USFA group (d-AVLT-IR, P = 0.007; d-LMT, P = 0.032; d-DST-B, P = 0.002; and d-composite score, P = 0.008). Conclusion: Higher intake of riboflavin and USFA can improve multi-dimensional cognitive functioning in middle-aged and elderly people. These findings were consistent in different models of sensitivity analyses.

13.
Environ Sci Technol ; 53(18): 10855-10862, 2019 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-31418541

RESUMO

Adsorption is an efficient method for atmospheric NOx abatement under ambient conditions; however, traditional adsorbents suffer from limited adsorption capacity and byproduct formation. Developing a low-cost material with high capacity for atmospheric NO2 elimination remains a challenge. Here, we synthesized a nanodispersed Mn3O4/γ-Al2O3 (Mn/Al) material that exhibits excellent ability to remove NO2. The 10 wt % Mn/Al sample showed the highest removal capacity, with 247.6 mgNO2/gMn/Al, which is superior to that of activated carbon (42.6 mgNO2/g). There were no byproducts produced when Mn/Al was tested with ppb-level NO2. The NO2 abatement mechanism with Mn/Al is different from physisorption or chemisorption. NO2 removal is mainly a catalytic process in air, during which surface hydroxyls and lattice oxygen are involved in the oxidation of NO2 to nitrate. In contrast, a chemical reaction between Mn3+ and NO2 is dominant in N2, where Mn3+ is converted into Mn4+ and NO2 is reduced to nitrite. Washing with deionized water is an effective and convenient method for the regeneration of saturated Mn/Al, and an 86% adsorption capacity was recovered after one washing. The results suggest that this low-cost Mn/Al material with easy preparation and regeneration is a promising candidate material for atmospheric NO2 elimination.


Assuntos
Nitratos , Adsorção , Catálise , Oxirredução , Temperatura Ambiente
14.
Toxicol Appl Pharmacol ; 382: 114734, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31470033

RESUMO

Curcumin (Cur), a natural product, has been shown to have anti-tumor activities in many human cancer cells. Gefitinib (Gef) is a clinical drug for cancer patients. However, there is no available information to show whether Gef/Cur nanoparticles (NPs) increased cell apoptosis and anti-tumor effects on xenograft mice model in vivo. In this study, γ-polyglutamic acid-coated nanoparticles loaded with Gef and Cur (γ-PGA-Gef/Cur NPs) were developed and its physicochemical properties and antitumor effects were investigated in vitro and in vivo. The γ-PGA-Gef/Cur NPs showed 548.5 ±â€¯93.7 nm in diameter and -40.3 ±â€¯3.87 mV on surface charge. The loading efficiencies of Gef and Cur were 89.5 and 100%, respectively. γ-PGA-Gef/Cur NPs could be internalized into SAS cells and significantly decreased total cell viability of SAS cells. Western blotting results indicated that both free Gef/Cur and γ-PGA-Gef/Cur NPs induced apoptotic cell death via caspase- and mitochondria-dependent pathways. In vivo studies indicated that treatments of PLGA NPs, free Gef/Cur, and γ-PGA-Gef/Cur NPs did not significantly affect appearances and bodyweights of mice. But the γ-PGA-Gef/Cur NPs significantly suppressed tumor size when comparing to free Gef/Cur-treated group. The nanoparticles developed in this study may be used as a potential therapy for oral cancer.

15.
Genet Test Mol Biomarkers ; 23(7): 435-441, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31294628

RESUMO

Aims: To discover possible relationships between CXCL12 single nucleotide polymorphisms (SNPs) and type 2 diabetes mellitus (T2DM) and its risk factors. Methods: The present sib-pair study was conducted in a rural community of Beijing, China. SNPs rs2297630, rs1746048, and rs1801157 located within or nearby the CXCL12 gene were genotyped using the allele-specific polymerase chain reaction method. Haseman-Elston regression was used to investigate linkages between these SNPs and T2DM. A generalized estimating equation logistic regression model was used to discover associations between the SNPs, T2DM, and its risk factors. Results: A total of 3171 participants were recruited, comprising 2277 sib pairs. After Bonferroni correction (α = 0.016), rs2297630 was found to be significantly linked to (p = 0.003) and associated with T2DM (AA vs. GG/GA: OR = 2.26, 95% CI: 1.31-3.88, p = 0.003). There were interactions between rs2297630 and dyslipidemia (p < 0.001) and between rs1746048 and hypertension (p = 0.011). Compared to dyslipidemia-free subjects with rs2297630 GG/GA genotypes, dyslipidemia patients with rs2297630 AA had a higher risk of T2DM (OR = 4.15, 95% CI: 2.24-7.67, p < 0.001). Compared to hypertension-free subjects with rs1746048 CC genotypes, hypertension-free subjects with rs1746048 CT/TT had a decreased risk of T2DM (OR = 0.77, 95% CI: 0.60-0.99, p = 0.045). Conclusions: A novel linkage and association was found between rs2297630 and T2DM. Moreover, novel interactions were found between rs2297630 and dyslipidemia as well as rs1746048 and hypertension. These findings will help identify individuals at higher risk of developing T2DM.


Assuntos
Quimiocina CXCL12/genética , Diabetes Mellitus Tipo 2/genética , China , Dislipidemias/genética , Feminino , Interação Gene-Ambiente , Estudos de Associação Genética , Humanos , Estilo de Vida , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Fatores de Risco
16.
Medicine (Baltimore) ; 98(29): e16303, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31335676

RESUMO

To investigate the incidence, outcomes, and risk factors of postoperative acute respiratory distress syndrome (ARDS) in patients undergoing surgical repair for acute type A aortic dissection.This retrospective study involved 270 patients who underwent surgical repair for acute type A aortic dissection between January 2009 and December 2015. Data on clinical characteristics and outcomes were collected. Patients who immediately died after surgery and with preoperative myocardial dysfunction were excluded. The included patients were divided into the ARDS (ARDS patients who met the Berlin definition) and non-ARDS groups. Primary outcome was postoperative ARDS, according to the 2012 Berlin definition for ARDS and was reviewed by 2 qualified physicians with expertise in critical care and cardiac surgery. Outcomes of interest were the incidence and severity of risk factors for ARDS in this population, and perioperative outcomes and survival rates were compared with patients with or without ARDS.A total of 233 adult patients were enrolled into this study; of these, 37 patients (15.9%) had ARDS. Three, 20, and 14 patients had mild, moderate, and severe ARDS, respectively, according to the Berlin definition, with no significant difference in age, sex, and underlying disease. The ARDS group had lower mean oxygenation index (OI) than the non-ARDS group in the first 3 days post-surgery and demonstrated an improvement in lung function after the fourth day. Postoperative complication risks were higher in the ARDS group than in the non-ARDS group. However, no significant difference was observed in in-hospital mortality between the 2 groups (10.8% vs 5.6%, P = .268). Additionally, there was also no significant difference in the 3-year mortality rate between the 2 groups (P of log-rank test = .274). Postoperative hemoglobin level (odds ratio [OR]: 0.78; 95% confidence interval [CI]: 0.62-0.99) and perioperative blood transfusion volume (OR: 1.07; 95% CI: 1.03-1.12) were associated with ARDS risk.Postoperative ARDS after type A aortic dissection repair surgery was associated with risks of postoperative complications but not with risk of in-hospital mortality or 3-year mortality. A higher perioperative blood transfusion volume and a lower postoperative hemoglobin level may be risk factors for ARDS.


Assuntos
Aneurisma Dissecante/cirurgia , Aneurisma Aórtico/diagnóstico , Transfusão de Sangue , Hemoglobinas/análise , Complicações Pós-Operatórias , Procedimentos Cirúrgicos Vasculares/efeitos adversos , Adulto , Idoso , Aneurisma Dissecante/diagnóstico , Aneurisma Aórtico/complicações , Gasometria/métodos , Transfusão de Sangue/métodos , Transfusão de Sangue/estatística & dados numéricos , Cuidados Críticos , Análise Fatorial , Feminino , Mortalidade Hospitalar , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/sangue , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/mortalidade , Síndrome do Desconforto Respiratório do Adulto/sangue , Síndrome do Desconforto Respiratório do Adulto/etiologia , Síndrome do Desconforto Respiratório do Adulto/mortalidade , Testes de Função Respiratória/métodos , Medição de Risco/métodos , Fatores de Risco , Taxa de Sobrevida , Procedimentos Cirúrgicos Vasculares/métodos
17.
Circ Res ; 125(3): 343-355, 2019 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-31185811

RESUMO

RATIONALE: The developing heart is composed of cardiomyocytes and noncardiomyocytes since the early stage. It is generally believed that noncardiomyocytes including the cardiac progenitors contribute to new cardiomyocytes of the looping heart. However, it remains unclear what the cellular dynamics of nonmyocyte to cardiomyocyte conversion are and when the lineage segregation occurs during development. It also remains unknown whether nonmyocyte to cardiomyocyte conversion contributes to neonatal heart regeneration. OBJECTIVE: We quantify the lineage conversion of noncardiomyocytes to cardiomyocytes in the embryonic and neonatal hearts and determine when the 2 cell lineages segregate during heart development. Moreover, we directly test if nonmyocyte to cardiomyocyte conversion contributes to neonatal heart regeneration. METHODS AND RESULTS: We generated a dual genetic lineage tracing strategy in which cardiomyocytes and noncardiomyocytes of the developing heart could be simultaneously labeled by 2 orthogonal recombination systems. Genetic fate mapping showed that nonmyocyte to cardiomyocyte conversion peaks at E8.0 (embryonic day) to E8.5 and gradually declines at E9.5 and E10.5. Noncardiomyocytes do not generate any cardiomyocyte at and beyond E11.5 to E12.5. In the neonatal heart, noncardiomyocytes also do not contribute to any new cardiomyocyte in homeostasis or after injury. CONCLUSIONS: Noncardiomyocytes contribute to new cardiomyocytes of the developing heart at early embryonic stage before E11.5. The noncardiomyocyte and cardiomyocyte lineage segregation occurs between E10.5 and E11.5, which is maintained afterward even during neonatal heart regeneration.

18.
Int J Nanomedicine ; 14: 4007-4016, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31213812

RESUMO

Background: This study exploited sheath-core-structured lidocaine/human EGF (hEGF)-loaded anti-adhesive poly[(d,l)-lactide-co-glycolide] (PLGA) nanofibrous films for surgical wounds via a co-axial electrospinning technique. Materials and methods: After spinning, the properties of the co-axially spun membranes were characterized by scanning electron microscopy, laser-scanning confocal microscopy, Fourier Transform Infrared spectrometry, water contact angle measurements, and tensile tests. Furthermore, a HPLC analysis and an ELISA evaluated the in vitro and in vivo release curves of lidocaine and hEGF from the films. Results: PLGA anti-adhesion nanofibers eluted high levels of lidocaine and hEGF for over 32 and 27 days, respectively, in vitro. The in vivo evaluation of post-surgery recovery in a rat model demonstrated that no adhesion was noticed in tissues at 2 weeks after surgery illustrating the anti-adhesive performance of the sheath-core-structured nanofibers. Nanofibrous films effectively released lidocaine and hEGF for >2 weeks in vivo. In addition, rats implanted with the lidocaine/hEGF nanofibrous membranes exhibited greater activities than the control demonstrating the pain relief efficacy of the films. Conclusion: The empirical outcomes suggested that the anti-adhesive nanofibrous films with extended release of lidocaine and hEGF offer post-operative pain relief and wound healing.


Assuntos
Adesivos/uso terapêutico , Fator de Crescimento Epidérmico/uso terapêutico , Nanofibras/química , Dor/tratamento farmacológico , Ferida Cirúrgica/tratamento farmacológico , Cicatrização/efeitos dos fármacos , Adesivos/farmacologia , Anestésicos Locais/farmacologia , Animais , Sobrevivência Celular/efeitos dos fármacos , Liberação Controlada de Fármacos , Fator de Crescimento Epidérmico/farmacologia , Humanos , Lidocaína/farmacologia , Lidocaína/uso terapêutico , Masculino , Nanofibras/ultraestrutura , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Ratos Wistar , Espectroscopia de Infravermelho com Transformada de Fourier , Ferida Cirúrgica/patologia
19.
Medicine (Baltimore) ; 98(20): e15453, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31096441

RESUMO

Preoperative renal dysfunction is associated with mortality in patients who undergo coronary artery bypass graft and valve surgery. However, the role of preoperative renal dysfunction in type A aortic dissection (TAAD) remains unclear. This study aimed to evaluate the impact of preoperative renal dysfunction on the outcome of surgical intervention in patients with TAAD.We retrospectively studied the outcomes of 159 patients with TAAD who were treated at a tertiary referral hospital between 2005 and 2010. The demographics and surgical details of patients were analyzed according to their renal function. Risk factors for outcomes were analyzed using multivariable logistic regression. Thirty-two of the patients (20.1%) had preoperative serum creatinine of 1.5 mg/dL or more. The multivariable logistic regression model revealed independent risk factors of in-hospital mortality to be renal dysfunction (odds ratio [OR], 3.79; 95% confidence interval [CI], 1.64-8.77), preoperative shock (OR, 8.75; 95% CI, 2.83-27.02), and bypass time (OR, 1.008; 95% CI, 1.003-1.013). In addition, patients with renal dysfunction exhibited a lower 90-day survival rate than did patients without the condition (P of log-rank test = .005).Preoperative renal dysfunction may have a critical role in the surgical outcomes of patients with TAAD. Additional large-scale investigations are warranted.


Assuntos
Aneurisma Dissecante/cirurgia , Nefropatias/diagnóstico , Nefropatias/fisiopatologia , Rim/fisiopatologia , Adulto , Idoso , Aneurisma Dissecante/mortalidade , Aneurisma Dissecante/fisiopatologia , Ponte de Artéria Coronária/mortalidade , Creatinina/sangue , Feminino , Mortalidade Hospitalar , Humanos , Nefropatias/mortalidade , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Período Pré-Operatório , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Resultado do Tratamento
20.
Nat Genet ; 51(4): 766, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30846878

RESUMO

In the version of this article initially published, the following grant numbers and recipients were missing from the Acknowledgements: XDB19000000 to H.J. and B.Z.; 81430066 and 31621003 to H.J.; 2017YFA0505500 to H.J.; and 15XD1504000 to H.J. The errors have been corrected in the HTML and PDF versions of the article.

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