Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 150
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Sensors (Basel) ; 20(3)2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-31973228

RESUMO

Joint structures, such as riveting, hinges, and flanges, are widely used in complex mechanical systems. A small unexpected change of a joint can lead to complicated wave-scattering in its connected waveguides. The conversion between wave modes can be used to quantify the variation of the connection status of joints. This gives rise to the challenge of exciting and sensing only one specific wave mode in practice. In this paper, transmitted wave amplitudes of a flange joint are first calculated by the wave finite element method (WFEM) to study the quantitative relationship between the local stiffness changes of the damaged site and the wave-mode conversion. Wave-mode piezoelectric transducers are subsequently designed for torsional, longitudinal, and flexural waves in cylindrical waveguides. The idea is to use the distribution and interconnection of the piezoelectric materials to cancel the charge contributed from the non-targeting waves. We conducted numerical simulations to demonstrate the selective coupling features of the designed wave transducers and found difference of several orders of magnitude in voltages between targeting wave mode and other wave modes. Four selected wave transducers were then extended to monitor the connection status of the flange. The wave-scattering features in the simulation and WFEM were verified to be in good agreement.

2.
Interv Neuroradiol ; 26(1): 90-98, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31451026

RESUMO

OBJECTIVE: The purpose of the study was to investigate the treatments and outcomes of patients with traumatic carotid-cavernous sinus fistula (TCCF). METHODS: All patients diagnosed with TCCF at our institution from January 2013 to December 2018 and meeting the inclusion/exclusion criteria were included in the study. RESULTS: A total of 24 patients were included in this study. Of them, 21 (87.5%) were treated with detachable balloon embolization, 1 (4%) with coil embolization, 1 (4%) with balloon-assisted coil embolization, and 1 (4%) with balloon-assisted coil and glue embolization. Among the 21 patients treated with detachable balloon embolization, 10 underwent double-balloon technique embolization including double-detachable balloon embolization (n = 6) and balloon-assisted detachable balloon embolization (n = 4). The fistulas in 17 patients (17/21, 81%) were successfully occluded after the first attempt of detachable balloon embolization, while those in the remaining 4 patients were occluded after a second surgery due to TCCF recurrence or pseudoaneurysm development. Preservation of the internal carotid artery (ICA) was observed in 19 cases after the first treatment by detachable balloon embolization (19/21, 90.4%). ICA was occluded in the remaining two patients, as revealed by a complete angiographic evaluation of the circle of Willis. All patients achieved complete resolution of ocular and orbital manifestations as well as pulsatile bruit, except for three patients whose oculomotorius and/or abducens remained paralyzed during the follow-up period. CONCLUSION: Although several endovascular treatment options are available for TCCF, the detachable balloon embolization is still the preferred method of TCCF, as evidenced in our study. Furthermore, double balloon technique, an improvement upon the conventional detachable balloon embolization, is extremely safe and can effectively treat patients with refractory TCCF.

3.
ACS Appl Mater Interfaces ; 12(3): 3773-3783, 2020 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-31880427

RESUMO

Although Sb doping is regarded as the most effective method to regulate the carrier concentration within the optimum range for ZrNiSn-based half-Heusler (HH) alloys, the resulting thermal conductivity remains high. Hence, the aim of this study was to investigate the effect of "diagonal-rule" doping; that is, the Zr site was displaced by Ta, which can simultaneously enhance the electrical conductivity and reduce the lattice thermal conductivity. The solid-solubility limit of Ta in the ZrNiSn matrix was determined to be x = 0.04. The highest ZT, 0.72, was achieved at 923 K for Zr0.98Ta0.02NiSn. In addition, ZTavg increased by 10.2% for Zr0.98Ta0.02NiSn compared with that for ZrNiSn0.99Sb0.01 at 873 K, which was mainly attributed to the reduced lattice thermal conductivity of Zr0.98Ta0.02NiSn. These results suggest that Ta doping is more effective than Sb doping in ZrNiSn-based HH alloys. In addition, the microhardness of Zr1-xTaxNiSn was substantially improved with increasing Ta content and was also much higher than that of other traditional thermoelectric materials.

4.
J Pharm Biomed Anal ; 180: 113046, 2020 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-31874311

RESUMO

Murraya paniculata (L.) is a traditional Chinese medicine (TCM) wildly grown in southeast China, and used for abortion in folk. Murrayone, a coumarin-containing compound extracted from M. paniculata, is the most bioactive substance in this species and is being developed as a novel cancer metastasis chemopreventive agent based on its unique pharmacological properties. In the present study, a novel rapid and sensitive method for quantitative analysis of murrayone in rat plasma and for determining its pharmacokinetics in rats was developed and validated using UPLC/MS/MS. Plasma samples were subjected to protein precipitation and then directly analyzed by UPLC/MS/MS. Both murrayone and coumarin as an internal standard (I.S.) were carried on a C18 column with a gradient mobile phase consisting of acetonitrile and water at a flow rate of 0.3 mL/min. Several gradient elution procedures were evaluated to achieve effective chromatography resolution and a sensitive response to murrayone and the I.S.. Mass spectrometry was carried out using a triple-quadrupole system via positive electrospray ionization and multiple reaction monitoring (MRM). Good linearity (r 2 = 0.9987) was achieved over a linear range of 4.0-1600 ng/mL with a lower limit of quantitation (LLOQ) of 4.0 ng/mL for murrayone. The inter- and intraday accuracy and precision ranged from 90.0 to 99.7% and 1.1 to 12.3% at four quality control concentrations, respectively. The average absolute recoveries of murrayone and the I.S. were determined to be 85.9-92.4% and 86.5-90.7%, respectively, at 10.0, 80.0, and 800 ng/mL. Murrayone was stable under a variety of storage and processing conditions that may be routinely encountered in laboratories based on all the stability tests. This newly developed method was successfully applied to the pharmacokinetic study of murrayone in rats for the first time, and the current assay methodology could provide important insights into potential therapeutics and facilitate further pharmacodynamic explorations of murrayone.

5.
Artigo em Inglês | MEDLINE | ID: mdl-31745702

RESUMO

OBJECTIVE: To assess the use of the cell cycle progression (CCP) score versus actual risk stratification practice in making treatment decisions for prostate cancer patients with locally adverse pathology after radical prostatectomy (RP). PATIENTS AND METHODS: Men with adverse pathologic features, pT3 or positive surgical margins who underwent RP in 2010-2014 at Renji hospital were retrospectively analyzed. The primary outcome was biochemical recurrence (BCR) after RP. RNA was quantified from paraffin-embedded RP specimens. The CCP score was calculated as average expression of 31 CCP genes, normalized to 15 housekeeper genes. The prognostic utility of the CCP score was assessed using Kaplan-Meier analysis and multivariable Cox proportional hazards model. RESULTS: Among the 100 men identified, 5-year BCR-free survival for the low- (< 0), intermediate- (0-1) and high- (> 1) CCP score groups was 89.3%, 38.8%, and 12.9%, respectively. In multivariable models adjusting for clinical and pathological variables with the cancer of the prostate risk assessment post-surgical (CAPRA-S) score, both continuous CCP score [hazard ratio (HR) 1.373 per unit score, 95% confidence interval (CI) 1.006-1.874; p = 0.046) and the categorized CCP score (p < 0.001)were independent predictors of BCR. CONCLUSIONS: The present study provides insights into the role the CCP score plays in risk stratification of this cohort and in determining candidacy for deferred secondary treatment. From our perspective, the CCP score allows better stratification and can help identifying patients at lower risk of disease recurrence who could benefit from a wait-and-see policy.

6.
Sci Rep ; 9(1): 12972, 2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31506464

RESUMO

Microbial metabolisms of arsenic, iron, sulfur, nitrogen and organic matter play important roles in arsenic mobilization in aquifer. In this study, microbial community composition and functional potentials in a high arsenic groundwater were investigated using integrated techniques of RNA- and DNA-based 16S rRNA gene sequencing, metagenomic sequencing and functional gene arrays. 16S rRNA gene sequencing showed the sample was dominated by members of Proteobacteria (62.3-75.2%), such as genera of Simplicispira (5.7-6.7%), Pseudomonas (3.3-5.7%), Ferribacterium (1.6-4.4%), Solimonas (1.8-3.2%), Geobacter (0.8-2.2%) and Sediminibacterium (0.6-2.4%). Functional potential analyses indicated that organics degradation, assimilatory sulfate reduction, As-resistant pathway, iron reduction, ammonification, nitrogen fixation, denitrification and dissimilatory nitrate reduction to ammonia were prevalent. The composition and function of microbial community and reconstructed genome bins suggest that high level of arsenite in the groundwater may be attributed to arsenate release from iron oxides reductive dissolution by the iron-reducing bacteria, and subsequent arsenate reduction by ammonia-producing bacteria featuring ars operon. This study highlights the relationship between biogeochemical cycling of arsenic and nitrogen in groundwater, which potentially occur in other aquifers with high levels of ammonia and arsenic.

7.
Opt Express ; 27(17): 24194-24206, 2019 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-31510313

RESUMO

A unique freestanding nickel (Ni) metallic mesh-based electromagnetic interference shielding film has been fabricated though the direct-writing technique and a subsequent selective metal electrodeposited process. The structured freestanding Ni mesh film demonstrates a series of advantages, including ultrathin thickness (2.5-6.0 µm) and ultralight weight (0.23 mg cm-2), extraordinary optoelectronic performance (sheet resistance about 0.24-0.7 Ω sq-1 with transparency of 92%-93%), high figure of merit (18000) and outstanding flexibility as it can withstand folding, rolling and crumpling into various shapes while keeping the conductivity constant. Furthermore, by using this high-performance Ni mesh, an ultrathin, lightweight, freestanding and transparent electromagnetic interference shielding (EMI) film with extraordinary optoelectronic properties (shielding effectiveness about 40 dB with transparency of 92%) is demonstrated in X-band, with no performance attenuation observed even in bending state. This freestanding metallic mesh-structured electrode can be further explored or applied in various potential applications, such as conformal microwave antennas, transparent EMI windows, and wearable electronics.

8.
Oncol Rep ; 42(6): 2279-2292, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31545501

RESUMO

The minichromosome maintenance (MCM) gene family plays an essential role in DNA replication and cell cycle progression. However, MCM gene expression has not been well­studied in lung adenocarcinoma (LUAD). In the present study, the expression, prognostic value and functions of MCMs in LUAD were investigated using several databases and bioinformatic tools, including Oncomine, GEPIA, cBioPortal, CancerSEA and Kaplan­Meier plotter. It was demonstrated that the mRNA expression of MCM2, MCM4 and MCM10 were significantly increased in patients with LUAD. High mRNA expression of MCM2­5, MCM8 and MCM10 were associated with poor overall survival and progression­free survival. High MCM4 expression was associated with adverse post­progression survival. In addition, the Human Protein Atlas database showed that MCM protein expression was consistent with the mRNA expression. These results demonstrate that MCM2, MCM4 and MCM10 are potential prognostic markers and therapeutic targets for LUAD.

9.
Biochem Biophys Res Commun ; 517(1): 111-117, 2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31303273

RESUMO

Doxorubicin (DOX) is a potent anti-neoplastic agent with cumulative cardiotoxicity. DOX-induced cardiotoxicity has been shown to depend on the different dosing times. However, the basis for determining the dosing time to minimize DOX-induced cardiotoxicity and the underlying mechanisms remain incompletely understood. Here we first showed that SIRT3, the major mitochondrial deacetylase, is negatively correlated to DOX-induced cardiotoxicity through the regulation of ATP production, mitochondrial membrane potential (MMP) level and ROS level in human pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). Then, we used in vivo experiments to demonstrate that DOX significantly reduced the SIRT3 expression and the SIRT3 activity as reflected by the increased AcK68MnSOD/MnSOD ratio in rats after six weeks of treatment. Notably, the activity of SIRT3 had an obvious diurnal rhythm pattern in the myocardium of healthy rats. More importantly, an obvious lower AcK68MnSOD/MnSOD ratio was observed in rat hearts with DOX administrated at Zeitgeber time (ZT) 9 (ZT 0 was the time lights were turned on) than ZT1, which represent the peak and trough of SIRT3 activity. Moreover, DOX ZT9 reduced the body weight loss, extended the survival period, improved the heart function and alleviated the myocardial lesions compared to DOX ZT1. Mechanistic investigations demonstrated that DOX ZT1 significantly reduced ATP production, oxygen consumption rate (OCR) at various respiration states, MMP level and MnSOD activity and enhanced the H2O2 level compared with CON ZT1, whereas there was no significant effect for DOX ZT9 compared with CON ZT9. Taken together, dosing at the peak time of SIRT3 activity reduced DOX-induced cardiotoxicity, which may be related to the increased endogenous tolerance against the mitochondrial dysfunction and oxidative stress caused by DOX.

10.
ACS Appl Mater Interfaces ; 11(27): 24047-24056, 2019 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-31192577

RESUMO

Flexible transparent electrochemical supercapacitors are critical components for the rapid development of fully flexible transparent electronics; however, typical flexible transparent supercapacitor electrodes store limited energy due to the requirements of transparency. Self-standing core-shell structure metal oxide mesh electrodes with metal oxide as active "shell" and metallic mesh as current collector "core" are efficient for simultaneously achieving high capacity, flexibility, and transparency. In this work, we perform a morphology-controlled electrodeposition of MnO2 on a self-standing flexible transparent metallic Ni mesh electrode to achieve a high-capacity flexible transparent supercapacitor electrode. Under optimized conditions, the MnO2 nanosheet-composed flowerlike multiscale microstructure was constructed. The open, loose, and porous MnO2 multiscale microstructure "shell" and high electrical conductivity of self-standing metallic mesh "core" synergistically enable efficient ionic and electronic transport and meanwhile retain high structural stability. The metal oxide mesh electrode yields an outstanding areal capacitance of 1.15 F/cm2 at an optical transmittance of 69.4% and excellent cycling stability. The symmetric solid-state supercapacitor device exhibits a high areal capacitance value (78.46 mF/cm2), superior cycling life, as well as high optical transmittance and mechanical flexibility, superior to the most reported flexible transparent supercapacitors. This work provides a comprehensive understanding on how to achieve high-capacity flexible transparent supercapacitor electrodes and solid-state devices.

11.
Cancer Cell Int ; 19: 162, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31210753

RESUMO

Background: AT-rich interactive domain-containing protein 1A (ARID1A) is a subunit of the mammary SWI/SNF chromatin remodeling complex and a tumor suppressor protein. The loss of ARID1A been observed in several types of human cancers and associated with poor patient prognosis. Previously, we have reported that ARID1A protein was rapidly ubiquitinated and destructed in gastric cancer cells during DNA damage response. However, the ubiquitin e3 ligase that mediated this process remains unclear. Materials and methods: The interaction between ARID1A and ß-TRCP was verified by co-immunoprecipitation (Co-IP) assay. The degron site of ARID1A protein was analyzed by bioinformatics assay. Short hairpin RNAs (shRNAs) were used to knockdown (KD) gene expression. Results: Here we show that DNA damage promotes ARID1A ubiquitination and subsequent destruction via the ubiquitin E3 ligase complex SCFß-TRCP. ß-TRCP recognizes ARID1A through a canonical degron site (DSGXXS) after its phosphorylation in response to DNA damage. Notably, genetic inactivation of the Ataxia Telangiectasia Mutated (ATM) kinase impaired DNA damage-induced ARID1A destruction. Conclusions: Our studies provide a novel molecular mechanism for the negative regulation of ARID1A by ß-TRCP and ATM in DNA damaged gastric cancer cells.

12.
Aging (Albany NY) ; 11(10): 3080-3093, 2019 05 22.
Artigo em Inglês | MEDLINE | ID: mdl-31118311

RESUMO

Gibberellin, a plant growth regulator, is widely used to increase the shelf life and quality of fruits and vegetables. In this study, human semen samples were exposed to different concentrations of gibberellin, which reduced spermatozoa motility in vitro. Gibberellin exposure also increased levels of reactive oxygen species and the protein levels of apoptosis markers in human sperm. Gibberellin inhibited the activity of Na+/K+-adenosine triphosphatase (ATPase) and Ca2+-ATPase, which maintain the stability of ions inside and outside the membranes of spermatozoa. Moreover, gibberellin exposure suppressed adenosine triphosphate production and reduced the protein levels of adenosine triphosphate synthases, which may have induced the protein expression of adenosine 5'-monophosphate-activated protein kinase (AMPK) and its phosphorylated form. These results suggest that gibberellin reduces human sperm motility in vitro by increasing reactive oxygen species levels and reducing ATPase activity, which may upregulate AMPK and consequently reduce the fertilization potential of spermatozoa.

13.
Cancer Lett ; 455: 36-47, 2019 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-31004700

RESUMO

Oxidative phosphorylation (OXPHOS) in cancer has attracted a considerable attention in the past decades, and accumulated evidence has suggested that it plays an important role in tumor proliferation, metastasis and drug resistance. However, the mechanisms involved in these effects are still ambiguous to date. In this study, we found that LYR motif containing 2 (LYRM2), a novel molecule, is up-regulated in colorectal cancer and promotes tumor growth both in vivo and in vitro. Furthermore, we discovered that LYRM2 locates in the mitochondria, directly interacts with complex I and increases its activity, thus promoting OXPHOS in colorectal cancer cells. More importantly, we identified a new Akt-S58phos-LYRM2-Complex I axis, which is responsible for the LYRM2-induced tumor growth and the activation of OXPHOS in colorectal cancer. Our finding illustrates the role of LYRM2 in regulating tumor metabolism and provides a new potential target for colorectal cancer treatment.

14.
BMC Genomics ; 20(1): 159, 2019 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-30813896

RESUMO

BACKGROUND: Maize is one of the primary crops of genetic manipulation, which provides an excellent means of promoting stress resistance and increasing yield. However, the differences in induction and regeneration capacity of embryonic callus (EC) among various genotypes result in genotypic dependence in genetic transformation. RESULTS: In this study, embryonic calli of two maize inbred lines with strong redifferentiation capacity and two lines with weak redifferentiation capability were separately subjected to transcriptome sequencing analysis during the early redifferentiation stages (stage I, 1-3 d; stage II, 4-6 d; stage III, 7-9 d) along with their corresponding controls. A total of ~ 654.72 million cDNA clean reads were yielded, and 62.64%~ 69.21% clean reads were mapped to the reference genome for each library. In comparison with the control, the numbers of differentially expressed genes (DEGs) for the four inbred lines identified in the three stages ranged from 1694 to 7193. By analyzing the common and specific DEGs of the four materials, we found that there were 321 upregulated genes and 386 downregulated genes identified in the high-regeneration lines (141 and DH40), whereas 611 upregulated genes and 500 downregulated genes were specifically expressed in the low-regeneration lines (ZYDH381-1 and DH3732). Analysis of the DEG expression patterns indicated a sharp change at stage I in both the high- and low-regeneration lines, which suggested that stage I constitutes a crucial period for EC regeneration. Notably, the specific common DEGs of 141 and DH40 were mainly associated with photosynthesis, porphyrin and chlorophyll metabolism, ribosomes, and plant hormone signal transduction. In contrast, the DEGs in ZYDH381-1 and DH3732 were mainly related to taurine and hypotaurine metabolism, nitrogen metabolism, fatty acid elongation, starch and sucrose metabolism, phenylpropanoid biosynthesis, and plant circadian rhythm. More importantly, WOX genes, which have an ancestral role in embryo development in seed plants and promote the regeneration of transformed calli, were specifically upregulated in the two high-regeneration lines. CONCLUSIONS: Our research contributes to the elucidation of molecular regulation during early redifferentiation in the maize embryonic callus.


Assuntos
Zea mays/genética , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Fenótipo , Reação em Cadeia da Polimerase em Tempo Real , Regeneração/genética , Análise de Sequência de RNA , Zea mays/embriologia , Zea mays/metabolismo , Zea mays/fisiologia
15.
Mol Cancer ; 18(1): 56, 2019 03 30.
Artigo em Inglês | MEDLINE | ID: mdl-30925885

RESUMO

CircRNAs, as new members of long noncoding RNAs, have been the focus of recent investigation. CircRNAs feature a closed continuous loop structure without 5'-3' polarity or a poly A tail. Many studies have reported the potential application of circRNAs in the clinic as new biomarkers and therapeutic targets in different diseases, especially for cancer. Additionally, the exosomes are important vehicles in cell-to-cell communication. And exo-circRNAs are circRNAs in exosomes which can be detected to provide additional evidence for conventional diagnostic methods and can be applied to suppress the malignant progress in cancer. In this review, we describe the biogenesis, characteristics, and functions of circRNAs and exosomes. Specifically, we present a comprehensive update of the promising role of exo-circRNAs in anticancer therapy.


Assuntos
Exossomos/genética , Regulação da Expressão Gênica , Neoplasias/genética , Neoplasias/terapia , RNA Longo não Codificante/genética , RNA Neoplásico/genética , RNA/genética , Animais , Comunicação Celular , Humanos
16.
Cancer Manag Res ; 11: 1541-1549, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30863164

RESUMO

Trametes robiniophila Murr also known as Huaier, one of the traditional Chinese medicines, has been shown an effective adjuvant of cancer therapy. Accumulating evidence suggests that the anti-cancer effects of Huaier can be briefly divided into two aspects: the direct effects on tumor cells and the indirect effects on immune cells. In vitro and in vivo experiment showed Huaier directly inhibited tumor cell proliferation, induced tumor cell death, prevented metastasis and interfered with angiogenesis via various signaling pathways. The immunomodulatory effect of Huaier is associated with enhancement of the number and function of CD4+ T cells and NK cells, regulation of the polarization and function of macrophages, and elevated secretion of immune stimulatory cytokines. In this review, the anti-cancer effects and combined treatments of Huaier with other anti-cancer therapies, and the underlying mechanisms are summarized and discussed.

17.
Sheng Li Xue Bao ; 71(1): 163-172, 2019 Feb 25.
Artigo em Chinês | MEDLINE | ID: mdl-30778515

RESUMO

The analysis of the relationship between personality and depression can facilitate the development of subclinical preventive measures and clinical treatment schemes. Moreover, the personality is associated with a variety of mental diseases, and there is substantial comorbidity between depression and some other mental diseases. So, to reveal pathological relationships between personality and depression is helpful to understand the etiology of the comorbidity between depression and multiple mental disorders. In this review, we first summarize the empirical researches on the relationship between personality and depression from the aspects of behavior and neural mechanisms, and then discuss the hypothetical model to explain the relationship between personality and depression. In a word, high neuroticism, low extroversion and conscientiousness, and other related traits (rumination, self-criticism, dependency, etc.) have a moderate to strong correlation with depression. Among them, neuroticism is the most concerned. To a certain extent, it can predict the onset of depression and affect the duration and treatment outcome of depression. Other traits, such as positive emotionality/ extroversion and effortful control/responsibility, can moderate the relationship between negative emotionality/neuroticism and depression. And after the onset of depression, the neuroticism may change, but the extroversion does not seem to change.


Assuntos
Depressão , Personalidade , Comorbidade , Humanos
18.
Planta ; 249(5): 1319-1336, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30627889

RESUMO

MAIN CONCLUSION: Futile cycling between free sugars and hexose phosphates occurring under phosphate deficiency could be involved in the maintenance of a threshold level of free cellular phosphate to preserve respiratory metabolism. We studied the metabolic response of potato cell cultures growing in Pi sufficient (2.5 mM, +Pi) or deficient (125 µM, -Pi) conditions. Under Pi deficiency, cellular growth was severely affected, however -Pi cells were able to maintain a low but steady level of free Pi. We surveyed the activities of 33 primary metabolic enzymes during the course of a 12 days Pi deficiency period. Our results show that many of these enzymes had higher specific activity in -Pi cells. Among these, we found typical markers of Pi deficiency such as phosphoenolpyruvate phosphatase and phosphoenolpyruvate carboxylase as well as enzymes involved in the biosynthesis of organic acids. Intriguingly, several ATP-consuming enzymes such as hexokinase (HK) and phosphofructokinase also displayed increased activity in -Pi condition. For HK, this was associated with an increase in the steady state of a specific HK polypeptide. Quantification of glycolytic intermediates showed a pronounced decrease in phosphate esters under Pi deficiency. Adenylate levels also decreased in -Pi cells, but the Adenylate Energy Charge was not affected by the treatment. To investigate the significance of HK induction under low Pi, [U-14C]-glucose tracer studies were conducted. We found in vivo evidence of futile cycling between pools of hexose phosphates and free sugars under Pi deficiency. Our study suggests that the futile cycling between hexose phosphates and free sugars which is active under +Pi conditions is sustained under Pi deficiency. The possibility that this process represents a metabolic adaptation to Pi deficiency is discussed with respect to Pi homeostasis in Pi-deficient conditions.


Assuntos
Hexosefosfatos/metabolismo , Fosfatos/deficiência , Solanum tuberosum/metabolismo , Açúcares/metabolismo , Técnicas de Cultura de Células , Hexoquinase/metabolismo , Solanum tuberosum/citologia
19.
Radiat Res ; 191(1): 107-121, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30430918

RESUMO

The development of effective biomarkers for detecting the magnitude of radiation exposure and resiliency of host response is crucial to identifying appropriate treatment strategies after radiation exposure. We hypothesized that the gastrointestinal resident bacteria would demonstrate predictable, dose-dependent changes after radiation exposure across two large animal models of acute radiation syndrome. Here, Göttingen minipigs (GMP) (n = 50) and rhesus macaques (n = 48) were exposed to five dose levels (resulting in mortality rates of 33-100% and 25-68.7%, respectively). Fecal samples taken prior to and after irradiation (day 0 for GMP; day 0, 3 and 14 for macaques) were used for 16S rRNA gene sequence amplicon high-throughput sequencing. Baseline gut microbiota profiles were dissimilar between GMP and macaques, however, radiation appeared to have similar effect at the phylum level, resulting in Bacteroidetes decrease and Firmicutes increase in both models. The abundance of the main Bacteroidetes genus ( Bacteroides for GMP, Prevotella for macaques) was profoundly decreased by irradiation. Intracellular symbionts [Elusimicrobia in GMP, Treponema (Spirochaetes) in macaques] consistently increased after irradiation, suggesting their use as potential biomarkers of intestinal injury, and potential negative effect on health. Prevotella, Lactobacillus, Clostridium XIVa, Oscillibacter and Elusimicrobium/ Treponema abundances were found to be very significantly correlated with radiation intensity. Furthermore, Prevotella, Enterorhabdus and Ruminococcus and Enterorhabdus maintenance was strongly associated with survival in GMP, while Prevotella, Oscillibacter and Treponema were strongly associated with survival and Streptococcus with death in macaques. Overall, we found that a wide range of gut bacterial genera known to be abundant in the human gut microbiota are excellent biomarkers of radiation intensity and resilience in animal models, and that detrimental effects can be monitored, and potentially prevented, by targeting selected genera.


Assuntos
Síndrome Aguda da Radiação/mortalidade , Microbioma Gastrointestinal , Modelos Animais , Doses de Radiação , Síndrome Aguda da Radiação/etiologia , Animais , Biomarcadores/metabolismo , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Macaca mulatta , RNA Ribossômico 16S/genética , Reprodutibilidade dos Testes , Suínos , Porco Miniatura
20.
Curr Cancer Drug Targets ; 19(4): 312-320, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-29984658

RESUMO

OBJECTIVE: To improve solubility and to reduce aggregation, ZnPcC4 was conjugated to a third-generation poly-amidoamine dendrimer with amino end group (G3-PAMAM-NH2), which acts as a novel photodynamic therapy (PDT) drug carrier system. METHODS: The phthalocyanines were synthesized by construction reaction. The nano drug was obtained from the conjugation of ZnPcC4 to G3-PAMAM-NH2, using EDC and NHS as coupling agents. The ZnPcC4@G3-PAMAM-NH2 conjugation was characterized by UV-Vis and MS. The 1O2 quantum yield of ZnPcC4@G3-PAMAM-NH2 in water was measured by the chemiluminescence method. The in vitro PDT responses of the studied photosensitizers were studied in hepatocellular carcinoma cell line HepG2 by MTT assay. RESULTS: At ZnPcC4/G3-PAMAM-NH2 raw ratio of 100/1, the ZnPcC4 conjugate had improved solubility and reduced aggregation tendency in aqueous solution. At this optimum molar ratio, ZnPcC4- G3-PAMAM-NH2 inhibited HepG2 cells, with a half-maximal inhibitory concentration of 1.67 µg/mL upon infrared light exposure. The controls, including dark conditions, or media as well as G3-PAMAM-NH2 exposure, exhibited no inhibitory response. CONCLUSION: The conjugation of phthalocyanine photosensitizer ZnPcC4 to poly-amidoamine dendrimer G3-PAMAM-NH2 improved the PDT outcomes, in which the optimized binding ratio of ZnPcC4 to G3-PAMAM-NH2 was 6:1.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA