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1.
J Environ Sci (China) ; 124: 379-396, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36182147

RESUMO

Wastewater containing an azo dye Orange G (OG) causes massive environmental pollution, thus it is critical to develop a highly effective, environmental-friendly, and reusable catalyst in peroxymonosulfate (PMS) activation for OG degradation. In this work, we successfully applied a magnetic MnFe2O4/α-MnO2 hybrid fabricated by a simple hydrothermal method for OG removal in water. The characteristics of the hybrid were investigated by X-ray diffraction, scanning electron microscopy, energy-dispersive X-ray spectroscopy, Fourier transform infrared spectroscopy, Brunauer-Emmett-Teller method, vibrating sample magnetometry, electron paramagnetic resonance, thermogravimetric analysis, and X-ray photoelectron spectroscopy. The effects of operational parameters (i.e., catalytic system, catalytic dose, solution pH, and temperature) were investigated. The results exhibited that 96.8% of OG degradation was obtained with MnFe2O4/α-MnO2(1:9)/PMS system in 30 min regardless of solution pH changes. Furthermore, the possible reaction mechanism of the coupling system was proposed, and the degradation intermediates of OG were identified by mass spectroscopy. The radical quenching experiments and EPR tests demonstrated that SO4•̶, O2•̶, and 1O2 were the primary reactive oxygen species responsible for the OG degradation. The hybrid also displayed unusual stability with less than 30% loss in the OG removal after four sequential cycles. Overall, magnetic MnFe2O4/α-MnO2 hybrid could be used as a high potential activator of PMS to remove orange G and maybe other dyes from wastewater.


Assuntos
Compostos de Manganês , Águas Residuárias , Compostos Azo/química , Corantes , Fenômenos Magnéticos , Compostos de Manganês/química , Óxidos , Peróxidos/química , Espécies Reativas de Oxigênio , Água
2.
Artigo em Inglês | MEDLINE | ID: mdl-33482339

RESUMO

DL-methionine (DL-Met) and its analogue DL-2-hydroxy-4-(methylthio) butanoic acid (DL-methionine hydroxyl analogue or DL-MHA) have been used as nutritional supplements in the diets of farmed raised animals. Knowledge of the intestinal transport mechanisms involved in these products is important for developing dietary strategies. This review provides updated information of the expression, function, and transport kinetics in the intestine of known Met-linked transporters along with putative MHA-linked transporters. As a neutral amino acid (AA), the transport of DL-Met is facilitated by multiple apical sodium-dependent/-independent high-/low-affinity transporters such as ASCT2, B0AT1 and rBAT/b0,+AT. The basolateral transport largely relies on the rate-limiting uniporter LAT4, while the presence of the basolateral antiporter y+LAT1 is probably necessary for exchanging intracellular cationic AAs and Met in the blood. In contrast, the intestinal transport kinetics of DL-MHA have been scarcely studied. DL-MHA transport is generally accepted to be mediated simply by the proton-dependent monocarboxylate transporter MCT1. However, in-depth mechanistic studies have indicated that DL-MHA transport is also achieved through apical sodium monocarboxylate transporters (SMCTs). In any case, reliance on either a proton or sodium gradient would thus require energy input for both Met and MHA transport. This expanding knowledge of the specific transporters involved now allows us to assess the effect of dietary ingredients on the expression and function of these transporters. Potentially, the resulting information could be furthered with selective breeding to reduce overall feed costs.


Assuntos
Fenômenos Fisiológicos da Nutrição Animal , Suplementos Nutricionais , Mucosa Intestinal/metabolismo , Proteínas de Membrana Transportadoras/metabolismo , Metionina/administração & dosagem , Ração Animal/análise , Animais , Metionina/análogos & derivados , Metionina/farmacocinética
3.
Nanotechnology ; 31(34): 345401, 2020 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-32365336

RESUMO

In this work, a feasible one-pot approach to synthesize manganese oxide/graphene composites, the so-called plasma-enhanced electrochemical exfoliation process (PE3P), has been developed. Herein, a composite of graphene decorated with manganese oxide nanoparticles was prepared via PE3P from a KMnO4 solution and graphite electrode under a voltage of 70 V in an ambient environment. By controlling the initial KMnO4 concentration, we obtained distinct MnO2/graphene samples. The prepared samples were characterized by scanning electron microscopy, transmission electron microscopy, x-ray diffraction, x-ray photoelectron spectroscopy, and Raman spectroscopy. The electrochemical measurements of the MnO2/graphene composites revealed that the specific capacitance of the samples is approximately 320 F g-1 at a scan rate of 10 mV s-1, which is comparably very high for manganese oxide/carbon-based supercapacitor electrode materials. Considering the simple, low-cost, one-step and environmentally friendly preparation, our approach has the potential to be used for the fabrication of MnO2/graphene composites as the electrode materials of supercapacitors.

4.
Artigo em Inglês | MEDLINE | ID: mdl-32712085

RESUMO

The aim of this study was to identify the unknown transport mechanism of the extensively used monocarboxylate methionine feed supplement DL-methionine hydroxy analogue (DL-MHA) in rainbow trout intestine. Transport across the pyloric caeca (PC), midgut (MG), and hindgut (HG) regions were kinetically studied in Na+- and H+-dependent manners. Gene expression of monocarboxylate (MCTs) and sodium monocarboxylate transporters (SMCTs) were assessed. Results demonstrated that DL-MHA transport from 0.2-20 mM was Na+-dependent and obeyed Michaelis-Menten kinetics with low affinity in PC & MG in apical/basal pH of 7.7/7.7. Changes in apical/basal pH (6.0/6.0, 6.0/7.7, and 7.7/8.7) had insignificant effects on kinetics. In contrast, HG flux kinetics were only obtained in pH 7.7/8.7 or in the presence of lactate with medium affinity. Additionally, DL-MHA transport from 0-150 µM demonstrated the presence of a Na+-dependent high-affinity transporter in PC & MG. Conclusively, two distinct carrier-mediated DL-MHA transport mechanisms along the trout gut were found: 1) in PC & MG: apical transport was regulated by Na+-requiring systems that possibly contained low- and high-affinity transporters, and basolateral transport was primarily achieved through a H+-independent transporter; 2) in HG: uptake was apically mediated by a Na+-dependent transporter with medium affinity, and basolateral exit was largely controlled by an H+-dependent transporter. Finally, two major methionine feed supplements, DL-MHA and DL-methionine (DL-Met) were compared to understand the differences in their bioefficacy. Flux rates of DL-MHA were only about 42.2-66.0% in PC and MG compared to DL-Met, suggesting intestinal transport of DL-MHA was lower than DL-Met.


Assuntos
Perfilação da Expressão Gênica , Mucosa Intestinal/metabolismo , Intestinos/efeitos dos fármacos , Intestinos/fisiologia , Metionina/análogos & derivados , Metionina/farmacologia , Oncorhynchus mykiss/fisiologia , Ração Animal/análise , Animais , Transporte Biológico , Suplementos Nutricionais , Concentração de Íons de Hidrogênio , Cinética , Metionina/química , Transportadores de Ácidos Monocarboxílicos , Prótons , Sódio/química , Sódio/metabolismo
5.
J Appl Toxicol ; 36(12): 1551-1557, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27734548

RESUMO

ATP-binding cassette (ABC) proteins are efflux transporters and some of them are involved in xenobiotic detoxification. The involvement of four zebrafish ABC transporters in cadmium, zinc and mercury detoxification was characterized in a metal hypersensitive mutant of Escherichia coli. The E. coli tolC mutant expressing ABCB3 or ABCB7 transporters exhibited higher survival ratios and lower metal accumulation under a metal exposure condition than the controls. For instance, in the presence of 8 and 10 µM of HgCl2 , the survival ratios of bacteria expressing ABCB3 were four and six-times higher than the control whereas the mercury concentrations were 2.5 and 2-times lower than in the control. This work provides new data on the function of zebrafish ABCB3 and ABCB7 transporters and highlights their significance in metal detoxification. Copyright © 2016 John Wiley & Sons, Ltd.


Assuntos
Transportadores de Cassetes de Ligação de ATP/genética , Metais Pesados/toxicidade , Poluentes Químicos da Água/toxicidade , Proteínas de Peixe-Zebra/genética , Peixe-Zebra/genética , Animais , Relação Dose-Resposta a Droga , Escherichia coli/genética , Expressão Gênica/efeitos dos fármacos , Metais Pesados/metabolismo , Viabilidade Microbiana/efeitos dos fármacos , Mutação , Poluentes Químicos da Água/metabolismo
6.
RSC Adv ; 14(21): 14506-14513, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38708110

RESUMO

HIV-1 (human immunodeficiency virus-1) has been causing severe pandemics by attacking the immune system of its host. Left untreated, it can lead to AIDS (acquired immunodeficiency syndrome), where death is inevitable due to opportunistic diseases. Therefore, discovering new antiviral drugs against HIV-1 is crucial. This study aimed to explore a novel machine learning approach to classify compounds that inhibit HIV-1 integrase and screen the dataset of repurposing compounds. The present study had two main stages: selecting the best type of fingerprint or molecular descriptor using the Wilcoxon signed-rank test and building a computational model based on machine learning. In the first stage, we calculated 16 different types of fingerprint or molecular descriptors from the dataset and used each of them as input features for 10 machine-learning models, which were evaluated through cross-validation. Then, a meta-analysis was performed with the Wilcoxon signed-rank test to select the optimal fingerprint or molecular descriptor types. In the second stage, we constructed a model based on the optimal fingerprint or molecular descriptor type. This data followed the machine learning procedure, including data preprocessing, outlier handling, normalization, feature selection, model selection, external validation, and model optimization. In the end, an XGBoost model and RDK7 fingerprint were identified as the most suitable. The model achieved promising results, with an average precision of 0.928 ± 0.027 and an F1-score of 0.848 ± 0.041 in cross-validation. The model achieved an average precision of 0.921 and an F1-score of 0.889 in external validation. Molecular docking was performed and validated by redocking for docking power and retrospective control for screening power, with the AUC metrics being 0.876 and the threshold being identified at -9.71 kcal mol-1. Finally, 44 compounds from DrugBank repurposing data were selected from the QSAR model, then three candidates were identified as potential compounds from molecular docking, and PSI-697 was detected as the most promising molecule, with in vitro experiment being not performed (docking score: -17.14 kcal mol-1, HIV integrase inhibitory probability: 69.81%).

7.
Front Chem ; 12: 1382319, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38690013

RESUMO

Introduction: 3D pharmacophore models describe the ligand's chemical interactions in their bioactive conformation. They offer a simple but sophisticated approach to decipher the chemically encoded ligand information, making them a valuable tool in drug design. Methods: Our research summarized the key studies for applying 3D pharmacophore models in virtual screening for 6,944 compounds of APJ receptor agonists. Recent advances in clustering algorithms and ensemble methods have enabled classical pharmacophore modeling to evolve into more flexible and knowledge-driven techniques. Butina clustering categorizes molecules based on their structural similarity (indicated by the Tanimoto coefficient) to create a structurally diverse training dataset. The learning method combines various individual pharmacophore models into a set of pharmacophore models for pharmacophore space optimization in virtual screening. Results: This approach was evaluated on Apelin datasets and afforded good screening performance, as proven by Receiver Operating Characteristic (AUC score of 0.994 ± 0.007), enrichment factor of (EF1% of 50.07 ± 0.211), Güner-Henry score of 0.956 ± 0.015, and F-measure of 0.911 ± 0.031. Discussion: Although one of the high-scoring models achieved statistically superior results in each dataset (AUC of 0.82; an EF1% of 19.466; GH of 0.131 and F1-score of 0.071), the ensemble learning method including voting and stacking method balanced the shortcomings of each model and passed with close performance measures.

8.
ACS Omega ; 9(18): 20056-20065, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38737018

RESUMO

Graphene quantum dots have been widely studied owing to their unique optical, electrical, and optoelectrical properties for various applications in solar devices. Here, we investigate the optoelectronic properties of hexagonal and nitrogen-doped graphene quantum dots using the first-principles method. We find that doping nitrogen atoms to hexagonal graphene quantum dots results in a significant red shift toward the visible light range as compared to that of the pristine graphene quantum dots, and the doped nitrogen atoms also induce a clear signature of anisotropy of the frontier orbitals induced by the electron correlation between the doped nitrogen atoms and their adjacent carbon atoms. Moreover, time-dependent density functional theory calculations with the M06-2X functional and 6-311++G(d,p) basis set reproduce well the experimental absorption spectra reported recently. These results provide us with a novel approach for more systematic investigations on next-generation solar devices with assembled quantum dots to improve their light selectivity as well as efficiency.

9.
ACS Omega ; 8(48): 45414-45427, 2023 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-38075749

RESUMO

Lithium-ion batteries lay the foundation for satisfying the fast-growing demand of portable electronics and electric vehicles. However, due to the complexity of material syntheses, high fabrication temperature condition, and toxic gas emission, high volume manufacturing of lithium-ion batteries is still challenging. Here, we propose a modified coprecipitation method to synthesize Li1.0Ni0.6Mn0.2Co0.2O2 (NMC622-MCP) as a cathode material in a simple, cost-effective, and environmentally friendly approach. We demonstrate that the proposed method can be operated in a lower temperature environment, with respect to the requirement of conventional synthesis methods. Furthermore, only CO2 gas is emitted during synthesis. We also employed first-principles simulations to evaluate the crystallinity of the synthesized materials via X-ray diffractometer patterns. During charge/discharge processes, the obtained cathode materials induce outstanding electrochemical performance with a maximum specific capacity of up to 206.9 mAh g-1 at 0.05 C and a retention capacity of 83.22% after 100 cycles. Thus, the simple, cost-effective, environmentally friendly, and highly electrochemical performance of the newly acquired material envisages the modified coprecipitation method as a promising tool to manufacture cathode materials for lithium-ion batteries.

10.
Front Immunol ; 13: 968395, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36059451

RESUMO

Chimeric antigen receptor (CAR)-T therapy has demonstrated remarkable outcomes for B cell malignancies, however, its application for T cell lymphoma, particularly cutaneous T cell lymphoma (CTCL), has been limited. Barriers to effective CAR-T cell therapy in treating CTCL include T cell aplasia in autologous transplants, CAR-T product contamination with leukemic T cells, CAR-T fratricide (when the target antigen is present on normal T cells), and tumor heterogeneity. To address these critical challenges, innovative CAR engineering by targeting multiple antigens to strike a balance between efficacy and safety of the therapy is necessary. In this review, we discuss the current obstacles to CAR-T cell therapy and highlight potential targets in treating CTCL. Looking forward, we propose strategies to develop more powerful dual CARs that are advancing towards the clinic in CTCL therapy.


Assuntos
Linfoma Cutâneo de Células T , Receptores de Antígenos Quiméricos , Neoplasias Cutâneas , Humanos , Imunoterapia Adotiva/efeitos adversos , Linfoma Cutâneo de Células T/terapia , Receptores de Antígenos Quiméricos/genética , Neoplasias Cutâneas/terapia , Linfócitos T
11.
Dev Reprod ; 25(4): 313-319, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35141457

RESUMO

Hub cells comprise a niche for germline stem cells and cyst stem cells in the Drosophila testis. Hub cells arise from common somatic gonadal precursors in embryos, but the mechanism of their specification is still poorly understood. Here we find that RNA binding proteins Lin28 and Imp mediate transcript stability of Bowl, a known hub specification factor; Bowl transcripts were reduced in the testis of Lin28 and Imp mutants, and also when RNA-mediated interference against Lin28 or Imp was expressed in hub cells. In tissue culture Luciferase assays involving the Bowl 3'UTR, stability of Luc reporter transcripts depended on the Bowl 3'UTR and required Lin28 and Imp. Our findings suggest that proper Bowl function during hub cell specification requires Lin28 and Imp in the testis hub cells.

12.
Pathol Res Pract ; 216(4): 152898, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32089414

RESUMO

KRAS, NRAS, and BRAF are potential tumor-driven genes that are involved in the RAS/RAF/MAPK signaling pathway. RAS/RAF mutations importantly contribute to colorectal tumorigenesis since they remain the activated status of downstream pathways without regulation of the upstream EGFR signal. However, it has not been unclear how epigenetic alterations involved in colorectal tumorigenesis mediated by KRAS, NRAS, or BRAF mutations. Therefore, in this study, we investigated the frequency and distribution of KRAS/NRAS/BRAF mutations in Vietnamese colorectal cancer (CRC) and explored the relationship between genetic and epigenetic abnormalities in 156 tumors of CRC. Somatic mutations of KRAS (exon 2, codon 12/13; exon 3, codon 61), NRAS (exon 2, codon 12/13; exon 3, codon 61), and BRAF (exon 15, codon 600) was determined by Cobas® KRAS Mutation Test, Therascreen NRAS Pyro Kit and Cobas® 4800 BRAF V600 Mutation Test, respectively. Methylation status of BRCA1, MLH1, MGMT, p16, RASSF1A, and APC was detected by methylation-specific PCR. Distribution of each abnormality in clinicopathological features was also analyzed. Results showed the mutation rates of KRAS, NRAS, and BRAF were 41.0 %, 9.6 %, 8.3 % respectively, while the methylation rates of BRCA1, MLH1, MGMT, p16, RASSF1A, and APC were 16.7 %, 16.7 %, 32.7 %, 30.1 %, 30.1 %, and 37.2 % respectively. The distribution of KRAS mutation was mutually exclusive against that of NRAS (p < 0.001) and BRAF (p < 0.001) mutations in CRC. RAS/RAF mutations were more common in adenocarcinoma subtype (p = 0.020), whereas RASSF1A methylation was more frequent in mucinous adenocarcinoma subtype (p = 0.007). In addition, the frequency of having KRAS mutations was significantly higher in MGMT (p = 0.035) or RASSF1A (p = 0.043) methylated cases than in those without methylation. BRAF mutations were positively associated with MLH1 hypermethylation (p = 0.028) but were inversely associated with APC hypermethylation (p = 0.032). Overall, our results show specific interactions of genetic and epigenetic alterations and suggest the presence of independent oncogenic pathways in tumorigenesis of CRC.


Assuntos
Adenocarcinoma/genética , Neoplasias Colorretais/genética , Metilação de DNA/genética , GTP Fosfo-Hidrolases/genética , Proteínas de Membrana/genética , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Adenocarcinoma/patologia , Adulto , Idoso , Povo Asiático/genética , Neoplasias Colorretais/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação
13.
Dalton Trans ; 49(20): 6718-6729, 2020 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-32369071

RESUMO

We report the synthesis of manganese-doped nickel cobalt oxide (Mn-doped NiCo2O4) nanoparticles (NPs) by an efficient hydrothermal and subsequent calcination route. The material exhibits a homogeneous distribution of the Mn dopant and a battery-type behavior when tested as a supercapacitor electrode material. Mn-doped NiCo2O4 NPs show an excellent specific capacity of 417 C g-1 at a scan rate of 10 mV s-1 and 204.3 C g-1 at a current density of 1 A g-1 in a standard three-electrode configuration, ca. 152-466% higher than that of pristine NiCo2O4 or MnCo2O4. In addition, Mn-doped NiCo2O4 NPs showed an excellent capacitance retention of 99% after 1000 charge-discharge cycles at a current density of 2 A g-1. The symmetric solid-state supercapacitor device assembled using this material delivered an energy density of 0.87 µW h cm-2 at a power density of 25 µW h cm-2 and 0.39 µW h cm-2 at a high power density of 500 µW h cm-2. The cost-effective synthesis and high electrochemical performance suggest that Mn-doped NiCo2O4 is a promising material for supercapacitors.

14.
Zootaxa ; 4571(3): zootaxa.4571.3.8, 2019 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-31715808

RESUMO

First record of Indolestes cyaneus (Selys, 1862) from Vietnam with providing illustrations of its detailed structures, as well as notes on the coloration of the populations from Taiwan, Nepal and India.


Assuntos
Odonatos , Animais , Índia , Nepal , Taiwan , Vietnã
15.
Physiol Rep ; 7(21): e14274, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31705630

RESUMO

Methionine (Met) is an important building block and metabolite for protein biosynthesis. However, the mechanism behind its absorption in the fish gut has not been elucidated. Here, we describe the fundamental properties of Met transport along trout gut at µmol/L and mmol/L concentration. Both electrogenic and unidirectional DL-[14 C]Met flux were employed to characterize Met transporters in Ussing chambers. Exploiting the differences in gene expression between diploid (2N) and triploid (3N) and intestinal segment as tools, allowed the association between gene and methionine transport. Specifically, three intestinal segments including pyloric caeca (PC), midgut (MG), and hindgut (HG) were assessed. Results at 0-150 µmol/L concentration demonstrated that the DL-Met was most likely transported by apical transporter ASCT2 (SLC1A5) and recycled by basolateral transporter y+ LAT1 (SLC7A7) due to five lines of observation: (1) lack of Na+ -independent kinetics, (2) low expression of B0 AT2-like gene, (3) Na+ -dependent, high-affinity (Km , µmol/L ranges) kinetics in DL-[14 C]Met flux, (4) association mRNA expression with the high-affinity kinetics and (5) electrogenic currents induced by Met. Results at 0.2-20 mmol/L concentration suggested that the DL-Met transport is likely transported by B0 AT1-like (SLC6A19-like) based on gene expression, Na+ -dependence and low-affinity kinetics (Km , mmol/L ranges). Similarly, genomic and gene expression analysis suggest that the basolateral exit of methionine was primarily through LAT4-like transporter (SLC43A2-like). Conclusively, DL-Met uptake in trout gut was most likely governed by Na+ -dependent apical transporters ASCT2 and B0 AT1-like and released through basolateral LAT4-like, with some recycling through y+ LAT1. A comparatively simpler model than that previously described in mammals.


Assuntos
Sistema ASC de Transporte de Aminoácidos/metabolismo , Sistema y+L de Transporte de Aminoácidos/metabolismo , Proteínas de Peixes/metabolismo , Mucosa Intestinal/metabolismo , Metionina/metabolismo , Oncorhynchus mykiss/metabolismo , Animais , Transporte Biológico , Radioisótopos de Carbono/administração & dosagem , Expressão Gênica , Genômica , Cinética
16.
Aging (Albany NY) ; 11(3): 855-873, 2019 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-30713156

RESUMO

Age-related decline in stem cell function is observed in many tissues from invertebrates to humans. While cell intrinsic alterations impair stem cells, aging of the stem cell niche also significantly contributes to the loss of tissue homeostasis associated with reduced regenerative capacity. Hub cells, which constitute the stem cell niche in the Drosophila testis, exhibit age-associated decline in number and activities, yet underlying mechanisms are not fully understood. Here we show that Lin28, a highly conserved RNA binding protein, is expressed in hub cells and its expression dramatically declines in old testis. lin28 mutant testes exhibit hub cell loss and defective hub architecture, recapitulating the normal aging process. Importantly, maintained expression of Lin28 prolongs hub integrity and function in aged testes, suggesting that Lin28 decline is a driver of hub cell aging. Mechanistically, the level of unpaired (upd), a stem cell self-renewal factor, is reduced in lin28 mutant testis and Lin28 protein directly binds and stabilizes upd transcripts, in a let-7 independent manner. Altogether, our results suggest that Lin28 acts to protect upd transcripts in hub cells, and reduction of Lin28 in old testis leads to decreased upd levels, hub cell aging and loss of the stem cell niche.


Assuntos
Envelhecimento/metabolismo , Proteínas de Drosophila/metabolismo , Drosophila/metabolismo , Proteínas de Ligação a RNA/metabolismo , Nicho de Células-Tronco , Testículo/metabolismo , Animais , Drosophila/genética , Proteínas de Drosophila/genética , Masculino , Proteínas de Ligação a RNA/genética , Fatores de Transcrição STAT/metabolismo , Testículo/citologia , Fatores de Transcrição/metabolismo
17.
Pathol Res Pract ; 215(5): 885-892, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30723053

RESUMO

Genetic and epigenetic alterations importantly contribute to the pathogenesis of lung cancer. In the study, we measured the frequency and distribution of molecular abnormalities of EGFR as well as the aberrant promoter methylations of BRCA1, MGMT, MLH1, and RASSF1A in Vietnamese lung adenocarcinomas. We investigated the association between genetic and epigenetic alteration, and between each abnormality with clinicopathologic parameters. Somatic EGFR mutation that was found in 49/139 (35.3%) lung adenocarcinomas showed a significant association with young age, female gender, and non-smokers. EGFR overexpression was identified in 82 tumors (59.0%) and statistical relationships with EGFR or BRCA1 methylation but not EGFR mutation. In addition, EGFR, BRCA1, MGMT, MLH1, and RASSF1A methylations were found in 33 (23.7%), 41 (29.5%), 46 (33.1%), 28 (20.1%), and 41 (29.5%) cases of a total of 139 lung adenocarcinomas, respectively. The RASSF1A methylation was found to be linked to the smoking habit. Methylations in MGMT and RASSF1A were also found to correlate with metastasis status. Furthermore, the distribution of EGFR mutation and that of BRCA1, MGMT or RASSF1A methylation were significantly exclusive in lung adenocarcinomas. The main finding of our study demonstrate that epigenetic abnormalities might play a critical role for the lung tumorigenesis in patients with smoking history and metastasis, and partly affect the predictive value of EGFR mutations through blocking expression due to promoter EGFR hypermethylation. Mutually exclusive distribution of genetic and epigenetic alterations reflects differently biological characteristics in the etiology of lung adenocarcinomas.


Assuntos
Adenocarcinoma de Pulmão/genética , Metilação de DNA/genética , Epigênese Genética/genética , Neoplasias Pulmonares/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Povo Asiático/genética , Proteína BRCA1/genética , Biomarcadores Tumorais/genética , Metilases de Modificação do DNA/genética , Enzimas Reparadoras do DNA/genética , Receptores ErbB/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Regiões Promotoras Genéticas/genética , Proteínas Supressoras de Tumor/genética
18.
J Cereb Blood Flow Metab ; 28(6): 1212-21, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18334994

RESUMO

Current thrombolytic therapy for acute ischemic stroke with tissue-type plasminogen activator (tPA) has clear global benefits. Nevertheless, evidences argue that in addition to its prohemorrhagic effect, tPA might enhance excitotoxic necrosis. In the brain parenchyma, tPA, by binding to and then cleaving the amino-terminal domain (ATD) of the NR1 subunit of N-methyl-D-aspartate (NMDA) glutamate receptors, increases calcium influx to toxic levels. We show here that tPA binds the ATD of the NR1 subunit by a two-sites system (K(D)=24 nmol/L). Although tenecteplase (TNK) and reteplase also display two-sites binding profiles, the catalytically inactive mutant TNKS478A displays a one-site binding profile and desmoteplase (DSPA), a kringle 2 (K2) domain-free plasminogen activator derived from vampire bat, does not interact with NR1. Moreover, we show that in contrast to tPA, DSPA does not promote excitotoxicity. These findings, together with three-dimensional (3D) modeling, show that a critical step for interaction of tPA with NR1 is the binding of its K2 domain, followed by the binding of its catalytic domain, which in turn cleaves the NR1 subunit at its ATD, leading to a subsequent potentiation of NMDA-induced calcium influx and neurotoxicity. This could help design safer new generation thrombolytic agents for stroke treatment.


Assuntos
Fibrinolíticos/toxicidade , Receptores de N-Metil-D-Aspartato/metabolismo , Acidente Vascular Cerebral/metabolismo , Sequência de Aminoácidos , Animais , Domínio Catalítico , Células Cultivadas , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Camundongos , Modelos Moleculares , Dados de Sequência Molecular , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Ativadores de Plasminogênio/metabolismo , Ligação Proteica , Estrutura Quaternária de Proteína , Receptores de N-Metil-D-Aspartato/química , Receptores de N-Metil-D-Aspartato/genética , Transdução de Sinais , Técnicas de Cultura de Tecidos , Ativador de Plasminogênio Tecidual/química , Ativador de Plasminogênio Tecidual/metabolismo
19.
Zootaxa ; 4341(2): 279-282, 2017 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-29245692

RESUMO

Coeliccia bhriulieci sp. nov. (holotype male from Tay Giang district, Quang Nam province, central Vietnam, deposited in the Zoological collection of the Southern Institute of Ecology, Vietnam Academy of Science and Technology, Ho Chi Minh City, Vietnam) is described based on male specimens. The new species is easily distinguished from other Coeliccia species in the Southeast Asian region by the combination of its blue abdominal tip, black anal appendages and structure of genital ligula with two long flagella extending from lateral corners of apical segment.


Assuntos
Odonatos , Animais , Ecologia , Masculino , Vietnã
20.
Oncol Lett ; 13(4): 2097-2104, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28454367

RESUMO

Matrix metalloproteinases (MMPs), a family of endopeptidases also known as gelatinases, have been reported to affect the acquisition of the cell proliferative, cell invasive and metastatic phenotype of several types of cancer. In particular, the gelatinases MMP-2 and -9 have been revealed to facilitate tumor growth and invasion in patients with colorectal cancer (CRC). However, it is not known whether the gelatinase activity of MMP-2 and -9 is also elevated in Vietnamese patients with CRC. The activity of MMP-2 and -9 in the tissue samples of 103 patients with CRC was evaluated by gelatin zymography and quantified using ImageJ. The association between the level of activity of MMP-2 and -9 and various clinicopathological factors was analyzed, and Chisio BioPAX Editor software was used to visualize the biological pathways regulating the activity of the MMPs. The present study noticed significantly increased activity of active MMP-2 and MMP-9 in tumor tissues (P<0.01), and significantly decreased levels of pro-form MMP-2 and MMP-9 in tumor tissues (P<0.01), compared with that in adjacent tissues in patients with CRC. A correlation between the normalized different activity of MMP-2 and -9 and various clinicopathological features was observed. Furthermore, bioinformatics analysis indicated that the alteration in the activity of MMP-2 and MMP-9 may have been controlled by biological pathways involving the tissue inhibitors of metalloprotease-2 and -1. These findings indicate that the activity of the gelatinases MMP-2 and -9 affects the tumor progression and metastasis of patients with CRC, providing a potential novel approach for determining the prognosis of CRC.

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