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1.
Chem Commun (Camb) ; 55(61): 8943-8946, 2019 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-31287468

RESUMO

An oxidative cyclization of ß,γ-unsaturated hydrazones for the divergent assembly of pyrazolones and pyrazolines under metal-free conditions is presented. This divergent synthetic strategy was achieved by controlling the reaction atmosphere. A number of pyrazolines were obtained via 5-exo-trig cyclization when the reaction was performed under N2. Whereas when the reaction was conducted under O2, diverse functionalized pyrazolones were achieved via oxidative cleavage of the C[double bond, length as m-dash]C double bond.

2.
Artigo em Inglês | MEDLINE | ID: mdl-31310159

RESUMO

The purpose of this study was to investigate the expression level of microRNA-4513 (miR-4513) in gastric cancer, and the underlying mechanisms of miR-4513 in regulating gastric cancer (GC) progression. Quantitative real time-polymerase chain reaction (qRT-PCR) was performed to measure the expression level of miR-4513 in GC cells. Transfection efficacy of synthetic miRNAs was examined by qRT-PCR. After synthetic miRNAs transfection, cell counting kit-8 assay and transwell invasion assay was conducted to measure biological changes in these groups. Key molecular expression level involved in epithelial-mesenchymal transition (EMT) was analyzed by western blot. Bioinformatic analysis and western blot were performed to investigate the connection between miR-4513 and lysine acetyltransferase 6B (KAT6B). qRT-PCR results showed miR-4513 expression level was upregulated in GC cell lines. Downregulate miR-4513 expression inhibited GC cell proliferation, invasion, and EMT. KAT6B was validated as a direct target of miR-4513. In addition, KAT6B expression level can be upregulated by miR-4513 inhibitor. Collectively, we showed miR-4513 involved in regulating the biological function of GC cells via KAT6B. In addition, miR-4513 may serve as a potential target for the molecular therapy of GC.

3.
Bull Environ Contam Toxicol ; 103(2): 323-329, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31230134

RESUMO

In order to investigate the influence of different lignin sources on humic substance formation during composting, this study selected two lignin sources, including wood sawdust and maize straw, to be co-composted with pig manure. Humic substances (HS) were characterized based on their fluorescence characteristics and complexing behaviors with heavy metals. The results showed that lignin sources, especially wood sawdust, were more conducive in promoting the formation of humic acids (HAs) than inorganic matter. The fluorescence excitation-emission matrix spectra also proved the positive effects of lignin on the formation of HAs during the humification process. The binding capacities of HAs isolated from mature composts for Cu and Cd followed the order of WS-90 > MS-90 > I-90, indicating that organic bulking agents are superior at increasing the complexing capacity of HAs. This finding suggests that the co-composting of pig manure with ligneous bulking agents is more advantageous at reducing the environmental risk of heavy metals.

4.
Sensors (Basel) ; 19(10)2019 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-31096714

RESUMO

: Urban road intersections play an important role in deciding the total travel time and the overall travel efficiency. In this paper, an innovative traffic grid model has been proposed, which evaluates and diagnoses the traffic status and the time delay at intersections across whole urban road networks. This method is grounded on a massive amount of floating car data sampled at a rate of 3 s, and it is composed of three major parts. (1) A grid model is built to transform intersections into discrete cells, and the floating car data are matched to the grids through a simple assignment process. (2) Based on the grid model, a set of key traffic parameters (e.g., the total time delay of all the directions of the intersection and the average speed of each direction) is derived. (3) Using these parameters, intersections are evaluated and the ones with the longest traffic delays are identified. The obtained intersections are further examined in terms of the traffic flow ratio and the green time ratio as well as the difference between these two variables. Using the central area of Beijing as the case study, the potential and feasibility of the proposed method are demonstrated and the unreasonable signal timing phases are detected. The developed method can be easily transferred to other cities, making it a useful and practical tool for traffic managers to evaluate and diagnose urban signal intersections as well as to design optimal measures for reducing traffic delay and increase operation efficiency at the intersections.

5.
Fish Shellfish Immunol ; 92: 11-20, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31132464

RESUMO

C-type lectin is a type of carbohydrate-binding protein and plays significant roles in innate immune response against pathogen infection. To date, thousands of C-type lectin had been identified in teleost. In the present study, we isolated a novel isoform of C-type lectin (OppCTL) from spotted knifejaw (Oplegnathus punctatus). The OppCTL encoded a typical Ca2+-dependent carbohydrate-binding protein, and was mainly expressed in liver in a tissue specific fashion. The expression of OppCTL was significantly up-regulated following Vibrio anguillarum infection in vivo, suggesting involvement in immune response. Hemagglutination analysis showed that the recombinant OppCTL (rOppCTL) could agglutinate erythrocyte from Mus musculus, Oplegnathus punctatus, Sebastes schlegelii and Paralichthys olivaceus. The rOppCTL could bind and agglutinate all tested bacteria. The rOppCTL possessed capacities of calcium-dependent agglutination to all tested bacteria. Sugar binding assay revealed that rOppCTL could also bind to the glycoconjugates of the bacterial surface, including lipopolysaccharide and peptidoglycan. Interestingly, Dual-luciferase analysis revealed that OppCTL could inhibit the activity of NF-κB in HEK-293T cells after OppCTL overexpression. Taken together, these results indicate that OppCTL has immune activity capable of defending invading pathogens and possesses potential immunoregulatory activity, enriching our understanding of the function of C-type lectin.

6.
Mol Ecol Resour ; 2019 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-31077549

RESUMO

The black rockfish (Sebastes schlegelii) is a teleost in which eggs are fertilized internally and retained in the maternal reproductive system, where they undergo development until live birth (viviparity). In the present study, we report a chromosome-level black rockfish genome assembly. High-throughput transcriptome analysis (RNA-seq and ATAC-seq) coupled with in situ hybridization (ISH) and immunofluorescence reveal several candidate genes for maternal preparation, sperm storage and release, and hatching. We propose that zona pellucida (ZP) proteins retain sperm at the oocyte envelope, while genes in two distinct astacin metalloproteinase subfamilies serve to release sperm from the ZP and free the embryo from chorion at prehatching stage. We present a model of black rockfish reproduction, and propose that the rockfish ovarian wall has a similar function to the uterus of mammals. Together, these genomic data reveal unprecedented insights into the evolution of an unusual teleost life history strategy, and provide a sound foundation for studying viviparity in nonmammalian vertebrates and an invaluable resource for rockfish ecological and evolutionary research.

7.
Wei Sheng Yan Jiu ; 48(2): 238-243, 2019 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-31133101

RESUMO

OBJECTIVE: To investigate the distribution and changes of blood copper, zinc, calcium, magnesium and iron in Chinese rural children aged 6 to 12 years in 2002 and 2012. METHODS: A total of 3420 blood samples were randomly selected from the China Nutrition and Health Survey 2002 and 2012. Metal concentrations in whole blood were determined by inductively coupled mass spectrometry(ICP-MS) after the dilution of 0. 5%(V/V) HNO_3 and 0. 05%(V/V) Triton-X-100. The changes between 2002 and 2012 of blood five elements concentration in children of 6-12 years in rural China were compared. RESULTS: The median of blood levels of copper, zinc, calcium, magnesium and iron in 2002 were 1. 02(95% CI 0. 79-1. 32), 4. 88(95% CI 3. 17-6. 77), 58. 59(95% CI 44. 97-74. 24), 41. 56(95% CI 33. 01-52. 28) and 423. 21(95% CI 338. 83-540. 69) mg/L, respectively. And in 2012, the median values were 1. 00(95% CI 0. 75-1. 31), 5. 12(95% CI 3. 17-7. 37), 63. 36(95% CI 41. 14-79. 16), 41. 78(95% CI 30. 89-52. 53) and 422. 06(95% CI 297. 83-522. 56) mg/L, respectively. There were significant differences in blood copper, zinc, calcium and iron levels in general, gender and age. There were also significant area differences in the distribution of copper, zinc, calcium, magnesium and iron, but the changes were opposite. CONCLUSION: In 2002 and 2012, there were differences in the blood distribution of Cu, Zn, Ca, Mg and Fe of children aged 6-12 in rural China in terms of general, gender, age and area.


Assuntos
Cálcio/sangue , Cobre/sangue , Ferro/sangue , Magnésio/sangue , Zinco/sangue , Criança , China , Feminino , Hemoglobinas/metabolismo , Humanos , Masculino , Espectrofotometria Atômica , Oligoelementos
8.
Proc Natl Acad Sci U S A ; 116(16): 7703-7711, 2019 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-30936308

RESUMO

Diamond is a wide-bandgap semiconductor possessing exceptional physical and chemical properties with the potential to miniaturize high-power electronics. Whereas boron-doped diamond (BDD) is a well-known p-type semiconductor, fabrication of practical diamond-based electronic devices awaits development of an effective n-type dopant with satisfactory electrical properties. Here we report the synthesis of n-type diamond, containing boron (B) and oxygen (O) complex defects. We obtain high carrier concentration (∼0.778 × 1021 cm-3) several orders of magnitude greater than previously obtained with sulfur or phosphorous, accompanied by high electrical conductivity. In high-pressure high-temperature (HPHT) boron-doped diamond single crystal we formed a boron-rich layer ∼1-1.5 µm thick in the {111} surface containing up to 1.4 atomic % B. We show that under certain HPHT conditions the boron dopants combine with oxygen defects to form B-O complexes that can be tuned by controlling the experimental parameters for diamond crystallization, thus giving rise to n-type conduction. First-principles calculations indicate that B3O and B4O complexes with low formation energies exhibit shallow donor levels, elucidating the mechanism of the n-type semiconducting behavior.

9.
J Mech Behav Biomed Mater ; 94: 288-297, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30933837

RESUMO

With their gradual and continuous properties, functionally graded polymers (FGP) have high potentials to reproduce the regional variation in microstructure/property of the natural intervertebral disc and, therefore, the functional anatomy and biomechanics of the soft tissue. This paper evaluates by finite element analysis the biomechanical response and stress distribution of a novel disc prosthesis using FGP. The kinetics of the FGP parameters is designed using experimental data issued from linear ethylene copolymers over a wide crystallinity range. The radial variation in crystallinity index within the disc prosthesis varies gradually and continuously following a special function in the aim to tailor and optimize the FGP parameters. The experimental data of a healthy human cervical spine segment are used to predict the optimal model of the FGP disc prosthesis loaded under different physiological loading conditions, i.e. rotation, lateral bending and flexion/extension. The results suggest that the FGP parameters can be tailored to control the stiffening, the non-linear behavior, the inelastic effects and the stress distribution in the aim to propose the optimal prosthesis model giving the great opportunity of patient-specific FGP prostheses via 3D printing technologies.

10.
J Mater Sci Mater Med ; 30(4): 46, 2019 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-30953223

RESUMO

Degeneration of the intervertebral disc (IVD) is a leading source of chronic low back pain or neck pain, and represents the main cause of long-term disability worldwide. In the aim to relieve pain, total disc replacement (TDR) is a valuable surgical treatment option, but the expected benefit strongly depends on the prosthesis itself. The present contribution is focused on the synthetic mimic of the native IVD in the aim to optimally restore its functional anatomy and biomechanics, and especially its time-dependency. Semi-crystalline polyethylene (PE) materials covering a wide spectrum of the crystallinity are used to propose new designs of TDR. The influence of the crystallinity on various features of the time-dependent mechanical response of the PE materials is reported over a large strain range by means of dynamic mechanical thermo-analysis and video-controlled tensile mechanical tests. The connection of the stiffness and the yield strength with the microstructure is reported in the aim to propose a model predicting the crystallinity dependency of the response variation with the frequency. New designs of TDR are proposed and implemented into an accurate computational model of a cervical spine segment in order to simulate the biomechanical response under physiological conditions. Predicted in-silico motions are found in excellent agreement with experimental data extracted from published in-vitro studies under compression and different neck movements, namely, rotation, flexion/extension and lateral bending. The simulation results are also criticized by analyzing the local stresses and the predicted biomechanical responses provided by the different prosthetic solutions in terms of time-dependency manifested by the hysteretic behavior under a cyclic movement and the frequency effect.


Assuntos
Fenômenos Biomecânicos/fisiologia , Substitutos Ósseos/química , Disco Intervertebral , Polietileno/química , Desenho de Prótese , Substituição Total de Disco , Alcenos/química , Cristalização , Testes de Dureza , Humanos , Disco Intervertebral/química , Disco Intervertebral/cirurgia , Vértebras Lombares , Teste de Materiais , Polietilenos/química , Polímeros/química , Amplitude de Movimento Articular/fisiologia , Estresse Mecânico , Fatores de Tempo , Substituição Total de Disco/instrumentação , Substituição Total de Disco/métodos , Suporte de Carga/fisiologia
11.
Fish Shellfish Immunol ; 89: 719-726, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30995543

RESUMO

Myeloid differentiation factor 88 (MyD88) links members of the toll-like receptor (TLR) and interleukin-1 receptor (IL-1R) superfamily to the downstream activation of NF-κB as a "bridge" molecular in response to exogenous pathogen, but the function in spotted knifejaw (Oplegnathus. punctatus), a commercial fish in China, is still unknown. We present a functional analysis of spotted knifejaw MyD88 (OppMyD88) with a typical death domain (DD) at the N-terminus and a conservative Toll/IL-1R (TIR) domain at the C-terminus and suggest that MyD88 is important for the activation of TLR-mediated NF-κB with the synergy between domains. Subcellular localization showed that OppMyD88 was distributed in the cytoplasm in a condensed form. Tissues expression profiling analysis showed that OppMyD88 ubiquitously expressed in all tested tissues with the highest expression in the liver, as determined by real-time PCR. The expression of OppMyD88 significantly upregulated in the liver, spleen, kidney and gills within 120 h post Vibrio anguillarum infection. Moreover, we further confirmed that over-expressed OppMyD88 could also induce apoptosis. These results indicate that OppMyD88 might possess important roles in defense against microbial infection and other biological processes in spotted knifejaw similar to those in mammals, which will deepen our understandings in innate immunity of spotted knifejaw.


Assuntos
Proteínas de Peixes/genética , Regulação da Expressão Gênica/imunologia , Imunidade Inata/genética , Fator 88 de Diferenciação Mieloide/genética , Perciformes/genética , Perciformes/imunologia , Transdução de Sinais/genética , Animais , Infecções Bacterianas/imunologia , Infecções Bacterianas/veterinária , Doenças dos Peixes/imunologia , Proteínas de Peixes/metabolismo , Perfilação da Expressão Gênica/veterinária , Fator 88 de Diferenciação Mieloide/metabolismo
12.
Ying Yong Sheng Tai Xue Bao ; 30(2): 661-667, 2019 Feb 20.
Artigo em Chinês | MEDLINE | ID: mdl-30915819

RESUMO

This study was conducted in 2017 from July 1st to August 31st at Xinglongshan musk deer farm in the Xinglongshan National Nature Reserve of Gansu Province, where we recorded behaviors and locations of 29 captive musk deer using the integrated methods of focal sampling and all occurrence recording. Based on the location selection patterns under artificial stress, we defined the animal's stress level and quantified individuals' boldness by combination with the occupation time ratio at each level. Then, the effects of gender, age-class, and other factors on boldness were analyzed along with musk secretion and reproduction success. The results showed that musk deer in better health (1.731±0.347) were significantly bolder than those in ill health (0.915±0.789). Female musk deer (1.901±0.391) were significantly bolder than the males (1.035±0.120). The boldness of sub-adults (1.450±0.463) was higher than those of the adults (1.093±0.321) and the old (1.430±0.189). No significant difference in boldness was observed among three age-classes under the same gender. Deer living in groups (1.397±0.179) were not significantly bolder than those living alone (0.853±0.326). More individuals in groups, less boldness. Furthermore, there was negative correlation between male's boldness and musk secretion. The litter size had positive relationship with boldness. The non-pregnant percentage was strongly correlated to the boldness, namely the bolder females had lower non-pregnant ratio. Our results provide reference for forecasting the musk secretion and reproduction success of captive musk deer, and provide new ideas for the study of boldness in captive animals.


Assuntos
Ácidos Graxos Monoinsaturados , Animais , Feminino , Masculino , Reprodução , Estações do Ano
13.
Res Microbiol ; 170(3): 147-155, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30817988

RESUMO

This study investigated the effects of 35 years of application of inorganic fertilizers containing nitrogen (N), phosphate (P), or potassium (K) alone or in combination on the abundance and composition of diazotrophic community in a black soil (Mollisol) in northeast China. The abundance and composition of diazotrophic community were analyzed using qPCR and Illumina MiSeq sequencing targeting nifH genes. Nitrogen fertilization decreased the abundance and Shannon diversity of nifH genes. The diazotrophic community was dominated by Alphaproteobacteria (Bradyrhizobium at the genus level), with relatively higher abundance in the N fertilization treatments than in the non-N fertilization treatments. All diazotrophic communities were clustered into two groups with and without N fertilization history, and the soil pH, total C, total N, and NO3--N significantly influenced the structure of the whole diazotrophic community. Moreover, random matrix theory analysis elucidated a clear difference in network structures between the N and non-N fertilization treatments, with N fertilization causing a less stable network structure. These results highlighted that it was N fertilizer, but not P and K fertilizers, contributed to great changes in the diazotrophic community in this black agricultural soil.


Assuntos
Biota/efeitos dos fármacos , Fixação de Nitrogênio/efeitos dos fármacos , Nitrogênio/metabolismo , Fosfatos/metabolismo , Potássio/metabolismo , Microbiologia do Solo , Agricultura/métodos , China , Fertilizantes , Sequenciamento de Nucleotídeos em Larga Escala , Oxirredutases/genética , Reação em Cadeia da Polimerase em Tempo Real
14.
EuroIntervention ; 14(18): e1854-e1860, 2019 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-30719978

RESUMO

AIMS: The aim of the study was to evaluate the feasibility, safety, and effectiveness of in situ diode laser fenestration of thoracic endovascular aortic repair (TEVAR) stent grafts to treat Stanford type A aortic dissection. METHODS AND RESULTS: Fifty-eight patients with acute or subacute Stanford type A aortic dissection treated with in situ diode laser fenestration during TEVAR under cerebral circulation protection with an extracorporeal bypass were reviewed retrospectively. Routine postoperative outcomes were recorded and assessed. Computed tomography angiography (CTA) was performed during the follow-up after 3, 6 and 12 months. Procedural success was achieved in 53 patients (91.4%). The average procedure time was 162±36 minutes. One patient died of pericardial tamponade during intervention, and one died of severe pneumonia after the intervention. Except for two minor strokes, no more fenestration-related complications occurred at 30 days and 12 months after the intervention. CTA imaging demonstrated 100% primary patency for the left subclavian artery and carotid arteries with favourable aortic remodelling after TEVAR during the follow-up. Two patients had a type Ia endoleak and one other a type II endoleak. CONCLUSIONS: In situ diode laser fenestration during TEVAR for type A aortic dissection was found to be feasible, safe, and effective, and may be beneficial as a less invasive approach.


Assuntos
Aneurisma Dissecante , Aneurisma da Aorta Torácica , Implante de Prótese Vascular , Procedimentos Endovasculares , Aortografia , Prótese Vascular , Humanos , Lasers Semicondutores , Estudos Retrospectivos , Stents , Resultado do Tratamento
15.
J Gene Med ; 21(4): e3070, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30659708

RESUMO

INTRODUCTION: Cardiac septal defects account for more than 50% of congenital heart defects. Ankyrin repeat domain 1 (ANKRD1) is an important transcription factor that is mutated in multiple cardiac diseases; however, a relationship between the ANKRD1 mutation and cardiac septal defects has not been described. METHODS: We examined genetic mutations in a large family with three cardiac septal defect patients. Whole exome sequencing, bioinformatics and conservation analysis were utilized to predict the pathogenicity of candidate mutations. Dual luciferase reporter assay and nuclear localization experiments were performed to evaluate the influence of target mutation. RESULTS: A heterozygous, missense variant of ANKRD1 (MIM* 609599): NM_014391: exon6: c.C560T:p.S187F was identified at a highly conserved region. Sanger sequencing in extended family members demonstrated an incomplete inheritance model. When co-activated with NKX2.5, ANKRD1 repressed ANF expression as assessed by a dual-luciferase reporter assay, and p.S187F mutation enhanced the repressive effect (0.318 ± 0.018 versus 0.564 ± 0.048, p < 0.01). A real-time polymerase chain reaction confirmed that p.S187F mutation of ANKRD1 decreased the expression of endogenous ANF (0.85 ± 0.05 versus 0.61 ± 0.04, p < 0.01). Furthermore, nuclear localization experiments demonstrated that the mutation significantly decreased the nuclear distribution of ANKRD1. CONCLUSIONS: The present study is the first to identify the p.S187F mutant of ANKRD1, which is associated with cardiac septal defects.

16.
Front Plant Sci ; 9: 1413, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30386351

RESUMO

Although the effect of elevated CO2 (eCO2) on soybean yield has been well documented, few studies have addressed seed quality, particularly at the fresh edible (R6) and mature stages (R8). Under the current global scenario of increasing CO2 levels, this potentially threatens the nutritional content and quality of food crops. Using four soybean cultivars, we assessed the effects of eCO2 on the concentrations of crude protein, crude oil, and isoflavones and analyzed the changes in free amino acids, fatty acids, and mineral elements in seeds. At R6, eCO2 had no influence on soybean seed protein and oil concentrations. At R8, eCO2 significantly decreased seed protein concentration but increased seed oil concentration; it also significantly decreased total free amino acid concentration. However, at the same stage, the proportion of oleic acid (18:1) among fatty acids increased in response to eCO2 in the cultivars of Zhongke-maodou 2 (ZK-2) and Zhongke-maodou 3 (ZK-3), and a similar trend was found for linoleic acid (18:2) in Zhongke-maodou 1 (ZK-1) and Hei-maodou (HD). Total isoflavone concentrations increased significantly at both the R6 and R8 stages in response to eCO2. Compared with ambient CO2, the concentrations of K, Ca, Mg, P, and S increased significantly under eCO2 at R6, while the Fe concentration decreased significantly. The response of Zn and Mn concentrations to eCO2 varied among cultivars. At R8 and under eCO2, Mg, S, and Ca concentrations increased significantly, while Zn and Fe concentrations decreased significantly. These findings suggest that eCO2 is likely to benefit from the accumulation of seed fat and isoflavone but not from that of protein. In this study, the response of seed mineral nutrients to eCO2 varied between cultivars.

17.
PLoS One ; 13(11): e0207916, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30481206

RESUMO

Traffic assignment and management objectives are considered as two significant parts in developing the emergency evacuation plan, which can directly influence the evacuation performance and efficiency. From the perspective of disaster response operators, the evacuation objective frequently is to minimize the total evacuation time to reduce losses, which may lead to an unreasonable and unfair phenomenon where people in highest risk areas may be forced to sacrifice their priorities of evacuation to improve the system evacuation efficiency. In this paper, considering both efficiency and social fairness in emergency evacuation, a weight function consisting of risk evaluation index as variable and the emphasis degree of managers on social fairness principle as coefficient was initially proposed and embedded in system optimal (SO) objective function. Combining the weight function and other constraints based on an extended cell transmission model (CTM), the linear program (LP) model was established to realize the simulation of dynamic traffic assignment in emergency evacuation. Employing this model, the impact of the management strategy of balancing both efficiency and social fairness on evacuation results was studied in the "Tianjin Explosions" case. In the end, the conclusion of "balancing social fairness is valuable during evacuation" was obtained.

18.
Stem Cell Res Ther ; 9(1): 285, 2018 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-30359296

RESUMO

BACKGROUND: Diabetic peripheral neurovascular diseases (DPNVs) are complex, lacking effective treatment. Autologous/allogeneic transplantation of adipose-derived stem cells (ADSCs) is a promising strategy for DPNVs. Nonetheless, the transplanted ADSCs demonstrate unsatisfying viability, migration, adhesion, and differentiation in vivo, which reduce the treatment efficiency. Netrin-1 secreted as an axon guidance molecule and served as an angiogenic factor, demonstrating its ability in enhancing cell proliferation, migration, adhesion, and neovascularization. METHODS: ADSCs acquired from adipose tissue were modified by Netrin-1 gene (NTN-1) using the adenovirus method (N-ADSCs) and proliferation, migration, adhesion, and apoptosis examined under high-glucose condition. The sciatic denervated mice (db/db) with type 2 diabetes mellitus (T2DM) were transplanted with N-ADSCs and treatment efficiency assessed based on the laser Doppler perfusion index, immunofluorescence, and histopathological assay. Also, the molecular mechanisms underlying Netrin-1-mediated proliferation, migration, adhesion, differentiation, proangiogenic capacity, and apoptosis of ADSCs were explored. RESULTS: N-ADSCs improved the proliferation, migration, and adhesion and inhibited the apoptosis of ADSCs in vitro in the condition of high glucose. The N-ADSCs group demonstrated an elevated laser Doppler perfusion index in the ADSCs and control groups. N-ADSCs analyzed by immunofluorescence and histopathological staining demonstrated the distribution of the cells in the injected limb muscles, indicating chronic ischemia; capillaries and endothelium were formed by differentiation of N-ADSCs. The N-ADSCs group showed a significantly high density of the microvessels than the ADSCs group. The upregulation of AKT/PI3K/eNOS/P-38/NF-κB signaling pathways and secretion of multiple growth factors might explain the positive effects of Netrin-1 on ADSCs. CONCLUSION: The overexpression of Netrin-1 in ADSCs improves proliferation, migration, and treatment effect in type 2 diabetic mice with sciatic denervation, which directs the clinical treatment of patients with DPNVs.

19.
Cell Physiol Biochem ; 50(1): 261-276, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30282072

RESUMO

BACKGROUND/AIMS: Treatment options for metastatic castrate-resistant prostate cancer (mCRPC) are limited and typically centered on paclitaxel-based chemotherapy. In this study, we aimed to evaluate whether miR-34a attenuates chemoresistance to paclitaxel by regulating target genes associated with drug resistance. METHODS: We used data from The Cancer Genome Atlas to compare miR-34a expression levels in prostate cancer (PC) tissues with normal prostate tissues. The effects of miR-34a inhibition and overexpression on PC proliferation were evaluated in vitro via Cell Counting Kit-8 (CCK-8) proliferation, colony formation, apoptosis, and cell-cycle assays. A luciferase reporter assay was employed to identify the interactions between miR-34a and specific target genes. To determine the effects of up-regulation of miR-34a on tumor growth and chemo-resistance in vivo, we injected PC cells overexpressing miR-34a into nude mice subcutaneously and evaluated the rate of tumor growth during paclitaxel treatment. We examined changes in the expression levels of miR-34a target genes JAG1 and Notch1 and their downstream genes via miR-34a transfection by quantitative reverse transcription PCR (qRT-PCR) and western blot assay. RESULTS: miR-34a served as an independent predictor of reduced patient survival. MiR-34a was down-regulated in PC-3PR cells compared with PC-3 cells. The CCK-8 assay showed that miR-34a overexpression resulted in increased sensitivity to paclitaxel while miR-34a down-regulation resulted in chemoresistance to paclitaxel in vitro. A study of gain and loss in a series of functional assays revealed that PC cells expressing miR-34a were chemosensitive. Furthermore, the overexpression of miR-34a increased the sensitivity of PC-3PR cells to chemotherapy in vivo. The luciferase reporter assay confirmed that JAG1 and Notch1 were directly targeted by miR-34a. Interestingly, western blot analysis and qRT-PCR confirmed that miR-34a inhibited the Notch1 signaling pathway. We found that miR-34a increased the chemosensitivity of PC-3PR cells by directly repressing the TCF1/ LEF1 axis. CONCLUSION: Our results showed that miR-34a is involved in the development of chemosensitivity to paclitaxel. By regulating the JAG1/Notch1 axis, miR-34a or its target genes JAG1 or Notch1 might serve as potential predictive biomarkers of response to paclitaxel-based chemotherapy and/or therapeutic targets that will help to overcome chemoresistance at the mCRPC stage.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Regulação para Baixo/efeitos dos fármacos , Proteína Jagged-1/metabolismo , MicroRNAs/metabolismo , Paclitaxel/farmacologia , Neoplasias da Próstata/patologia , Receptor Notch1/metabolismo , Regiões 3' não Traduzidas , Animais , Antagomirs/metabolismo , Antagomirs/uso terapêutico , Antineoplásicos Fitogênicos/uso terapêutico , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Fator 1-alfa Nuclear de Hepatócito/genética , Fator 1-alfa Nuclear de Hepatócito/metabolismo , Humanos , Proteína Jagged-1/genética , Estimativa de Kaplan-Meier , Masculino , Camundongos , Camundongos Nus , MicroRNAs/antagonistas & inibidores , MicroRNAs/genética , Paclitaxel/uso terapêutico , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/genética , Neoplasias da Próstata/mortalidade , Receptor Notch1/genética , Transdução de Sinais/efeitos dos fármacos
20.
Sci Rep ; 8(1): 14179, 2018 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-30242277

RESUMO

Soil erosion will cause a degradation in soil nitrogen supplying capacity (SNSC) and manure amendment is an effective way to restored eroded soils. Both labile fractions of soil organic N (SON) and N transformation enzymes are indicators for SNSC, but the effect of manure amendments on labile SON fractions and the relationship between labile SON fractions and enzyme activities remains unclear. In this study, five degrees of erosion were simulated in Mollisols (removal of 0, 5, 10, 20 and 30 cm of topsoil) to analyse the changes in labile SON fractions and nitrogen transformation enzyme activities after 8-year manure amendment. We found that soil total N (TN), labile SON fractions and enzyme activities all increased after manure amendments. The largest labile SON fraction was particle organic nitrogen (POM-N) and the second was light fraction organic nitrogen (LFOM-N), which accounted >60% for TN in total. Correlation analysis showed that both urease and protease activities were significantly correlated with POM-N, LFOM-N, microbial biomass N and dissolvable organic N, indicating that both urease and protease activities can be used to predict labile SON pools and enzyme activities worked similarly in indicating SNSC with labile SON fractions. Altogether, 8-year manure amendment could recover SNSC of lightly eroded Mollisols to natural levels, i.e. erosion depths at 5 cm and 10 cm; however, it is not able to recover SNSC in Mollisols suffering severe erosion.

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