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1.
Sci Rep ; 10(1): 3094, 2020 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-32080227

RESUMO

Involvement of long non-coding RNAs (lncRNAs) in the regulation of gene expression in cis has been well studied in eukaryotes but relatively little is known whether and how lncRNAs affect gene expression in tans. In Arabidopsis thaliana, COLDAIR, a previously reported lncRNA, is produced from the first intron of FLOWERING LOCUS C (FLC), which encodes a repressor of flowering time. Our results indicated that the exogenously overexpressed COLDAIR enhances the expression of FLC in trans, resulting in a late-flowering phenotype. In 35S-COLDAIR lines, the enhanced expression of FLC is correlated with the down-regulation of the repressive histone mark H3K27me3 and with the up-regulation of the active histone mark H3K4me3 at the FLC chromatin. Furthermore, we demonstrated that overexpression of intronic lncRNAs from several other H3K27me3-enriched MADS-box genes also activates the expression of their host genes. This study suggests that the involvement of overexpressed intronic lncRNAs in gene activation may be conserved in H3K27me3-enriched genes in eukaryotes.

2.
Biochem Biophys Res Commun ; 524(1): 77-82, 2020 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-31980179

RESUMO

OBJECTIVES: Protein arginine methyltransferase 2 (PRMT2) is closely related to the occurrence and development of atherosclerosis. However, its underlying mechanisms remain to be elucidated. The purpose of this study is to observe the effect of overexpression of PRMT2 on the formation of foam cells and to explore its possible mechanism in RAW 264.7 macrophage. METHODS: Lentivirus vector of overexpression PRMT2 (LV-PRMT2) was constructed. LV-PRMT2 and lentivirus vector GV492 were transfected into RAW 264.7 macrophages, positive clone cells were screened by treatment with 4.0 µg/mL puromycin for 4 weeks. The macrophages were treated with ox-LDL (50 µg/mL) for 48 h to induce foaming. The lipid accumulation of macrophages was observed by oil red O staining. The levels of cellular total cholesterol (TC), free cholesterol (FC) and cholesteryl ester (CE) were measured by high performance liquid chromatography (HPLC) assays. The cholesterol efflux of macrophages was tested by the [3H] labeled cholesterol. The expressions of ATP binding cassette transporter A1 (ABCA1), ATP binding cassette transporter G1 (ABCG1), CD36 and scavenger receptor A1 (SR-A1) in macrophages were measured by Western Blot. RESULTS: The results showed that LV-PRMT2 and lentivirus vector has been successfully transfected into RAW 264.7 macrophage. Compared with the Vector group, the mRNA and protein expressions of PRMT2 were significantly up-regulated (P < 0.05). Compared with Control group, the expression of PRMT2 was significantly down-regulated in ox-LDL group (P < 0.05). A large number of red lipid droplets appeared in the cells in Vector group. Compared with Vector group, lipid droplets, the levels of TC, FC and CE and CE/TC, cholesterol efflux rate and expression of ABCA1 in RAW 264.7 macrophage was significantly decreased in LV-PRMT2 group (all P < 0.05). There was no significant difference about the expressions of ABCG1, CD36 and SR-A1 between LV-PRMT2 group and Vector group (all P > 0.05). CONCLUSIONS: Overexpression of PRMT2 inhibits the formation of foam cell induced by ox-LDL in RAW 264.7 macrophage, and the mechanism may be related to the increase of ABCA1 expression and ABCA1 mediated cholesterol efflux.

3.
Transplant Proc ; 52(1): 54-60, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31901324

RESUMO

BACKGROUND: Kidneys at higher risk for allograft failure are defined by the Kidney Donor Profile Index (KDPI) > 85% in the current kidney allocation system (KAS), replacing the historical concept of expanded criteria donor (ECD) kidneys in the previous KAS. Discrepancies exist in the classification of "high-risk kidneys" between the 2 KAS. In the current KAS, only recipients of KDPI > 85% kidneys are counseled about the high risk of allograft failure and are required to sign a consent. In this study, we evaluated the outcomes and allocation of kidneys with discordant classification. METHODS: Using the Scientific Registry of Transplant Recipients, kidneys transplanted between 01/2002 and 09/2016 were classified according to the old (standard criteria donor [SCD]/ECD) and current (KDPI) KAS. We then grouped them as concordant (KDPI ≤ 85% + SCD or KDPI > 85% + ECD) and discordant (KDPI ≤ 85% + ECD or KDPI > 85% + SCD) kidneys. RESULTS: Approximately 11% of transplanted kidneys were discordant in classification. Among kidneys with KDPI ≤ 85%, ECD status conferred a 64% (95% CI: 56%-73%) higher risk of allograft failure compared to SCD status. However, SCD/ECD status was not associated with differential outcomes in KDPI > 85% kidneys. These ECD kidneys have KDPIs > 50% and have been transplanted across all estimated post-transplant survival (EPTS) deciles. CONCLUSION: Adequate counseling about the risk and benefit of accepting ECD kidneys with KDPI ≤ 85% versus waiting on dialysis should be explored with the patients, especially those with lower EPTS.

4.
Pest Manag Sci ; 76(3): 1071-1077, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31515949

RESUMO

BACKGROUND: Discovery of novel insecticides and targets has received global attention in recent years. Ten genes coding for enzymes involved in the juvenile hormone biosynthetic pathway of Manduca sexta were studied as potential insecticide targets. RESULTS: We determined the expression of genes encoding some critical enzymes in the JH biosynthetic pathway. Farnesol dehydrogenase (FOLD), Juvenile hormone acid O-methyltransferase (JHAMT) and Juvenile hormone epoxidase (CYP15C1) were selected as the candidate targets based on gene expression results. RNAi silencing and enzyme inhibitor tests were performed to validate whether these candidate genes could be the potential insecticide targets. The down-regulation of FOLD, JHAMT and CYP15C1 resulted in a 68%, 82% and 79% reduction in the rates of JH biosynthesis in vitro, respectively. In addition, RNA interference and inhibitor studies of these enzymes following oral administration demonstrated the potential application in pest management, with respect to high mortality and effects on growth. CONCLUSION: Based on our study, FOLD, JHAMT and CYP15C1 could be potential targets for pest control as a consequence of their important roles in insect development. © 2019 Society of Chemical Industry.

5.
Psychiatr Q ; 90(3): 471-480, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31079346

RESUMO

Cognitive deficits are a core feature of major depressive disorder (MDD). However, there are no previous studies that directly compare cognitive performance between first-episode drug-naive depressive patients (FDDP) and medicated depressive patients (MDP). Therefore, the aim of this study was to investigate whether there were the differences in cognitive functions between FDDP and MDP. Sixty-two FDDP, 111 MDP and 90 healthy controls were enrolled in a Chinese population. Cognitive functions were assessed using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). There were the differences in the RBANS total score (F = 26.55, p < 0.001), subscales of immediate memory (F = 3.95, p = 0.02), language (F = 54.11, p < 0.001) and delayed memory (F = 11.19, p = 0.001) among the three groups after controlling for gender, education, smoking and body mass index (BMI). These differences in the RBANS total score, subscales of language and delayed memory passed the Bonferroni corrections (all, p < 0.05). Compared to healthy controls, FDDP and MDP had poorer cognitive performance including the RBANS total score, and subscales of language and delayed memory (all, p < 0.05) after controlling for the variables. FDDP experienced greater language deficits than MDP (p < 0.05) after controlling for the variables. Education was correlated with the language score in FDDP (r = 0.61, p < 0.001). Multivariate regression analysis indicated that education was an independent contributor to the language score in FDDP (ß = 3.11, t = 5.48, p < 0.001). Our findings indicated that FDDP had poorer language performance than MDP. Moreover, education could influence the language performance in FDDP.

6.
Environ Toxicol Pharmacol ; 68: 13-18, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30852303

RESUMO

Alternate forms of drug crystals display different physicochemical properties. These include stability, dissolution rate, bioavailability and solubility, which can affect pharmacokinetics and pharmacodynamics. It is therefore important to compare the crystal forms of cedrol to obtain optimal anti-inflammatory and analgesic effects. This study, for the first time, obtained and reports three novel forms (I-III) of cedrol polymorphs. The three forms of cedrol were recrystallized from seven organic solvents by slow cooling or volatilization and identified by thermal analysis, fourier transform infrared spectroscopy, scanning electron microscopy and powder X-ray diffraction analysis. Form I originated from acetone and cyclohexane. Form II was obtained from ethanol, ethyl acetate, acetonitrile and n-hexane. Form III was recrystallized from methanol. The anti-inflammatory and analgesic activities of the three crystalline forms were evaluated by acetic acid induced writhing in mice, the hot plate method, carrageenan induced mouse paw edema models, Xylene-induced mouse ear edema models and cotton pellet-induced mouse granuloma models. Experimental results revealed that the highest performance was achieved from Form I. These findings are of great significance during the early research study of cedrol polymorphs.


Assuntos
Analgésicos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Edema/tratamento farmacológico , Granuloma/tratamento farmacológico , Dor/tratamento farmacológico , Terpenos/uso terapêutico , Ácido Acético , Animais , Carragenina , Fibra de Algodão , Edema/induzido quimicamente , Feminino , Temperatura Alta , Camundongos , Dor/induzido quimicamente , Xilenos
7.
Mediators Inflamm ; 2019: 5160694, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30718973

RESUMO

Background: Acute exacerbation of IPF (AE-IPF) is associated with high mortality. We studied changes in pathogen involvement during AE-IPF and explored a possible role of infection in AE-IPF. Objectives: Our purpose is to investigate the role of infection in AE-IPF. Methods: Overall, we recruited 170 IPF patients (48 AE-IPF, 122 stable) and 70 controls at Shanghai Pulmonary Hospital. Specific IgM against microbial pathogens and pathogens in sputum were assessed. RNA sequences of pathogens in nasopharyngeal swab of IPF patients were detected by PathChip. A panel of serum parameters reflecting immune function were assessed. Results: Antiviral/bacterial IgM was higher in IPF vs. controls and in AE-IPF vs. stable IPF. Thirty-eight different bacterial strains were detected in IPF patient sputum. Bacteria-positive results were found in 9/48 (18.8%) of AE-IPF and in 26/122 (21.3%) stable IPF. Fifty-seven different viruses were detected in nasopharyngeal swabs of IPF patients. Virus-positive nasopharyngeal swabs were found in 18/30 (60%) of tested AE-IPF and in 13/30 (43.3%) of stable IPF. AE-IPF showed increased inflammatory cytokines (IL-6, IFN-γ, MIG, IL-17, and IL-9) vs. stable IPF and controls. Mortality of AE-IPF in one year (39.5%) was higher compared to stable IPF (28.7%).Conclusions. IPF patients had different colonization with pathogens in sputum and nasopharyngeal swabs; they also displayed abnormally activated immune response, which was exacerbated during AE-IPF.


Assuntos
Fibrose Pulmonar Idiopática/sangue , Fibrose Pulmonar Idiopática/complicações , /complicações , Idoso , China , Citocinas/sangue , Feminino , Humanos , Imunoglobulina M/imunologia , Imunossupressão , Inflamação , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , RNA Viral/isolamento & purificação , Análise de Sequência de RNA , Escarro/microbiologia , Escarro/virologia
8.
J Cell Mol Med ; 23(2): 908-919, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30378252

RESUMO

BACKGROUND: Patients with idiopathic pulmonary fibrosis (IPF) often experience acute exacerbation (AE) after an episode of common cold. AIMS: To establish a mouse model of virus infection-induced AE-IPF and investigate the mechanism underlying the AE-IPF. METHODS: Herpes simplex virus 1 (HSV1) was inoculated intranasally to wild-type (WT) and IL-17A gene knockout (IL-17A-/- ) mice 21 days after intratracheal administration of bleomycin (BLM). RESULTS: HSV1 infection caused acute exacerbation in mice with BLM-induced fibrosis. Compared with the BLM+Saline mice, the mice with BLM+HSV1 showed significantly higher acute lung injury (ALI) score (P < 0.0001), lower survival rate (100% vs 21.4%, P < 0.0001), poorer lung function and higher inflammatory response representing by increased total inflammatory cells in bronchoalveolar lavage fluid (BALF) (P = 0.0323), increased proportion of Th17 cells in peripheral blood (P = 0.0004) and higher inflammatory factors in BALF. In addition, HSV1 infection increased the expression of endoplasmic reticulum stress (ERS)-related proteins in mice with BLM-induced fibrosis. The inhibition of ERS by tauroursodeoxycholic acid (TUDCA, an ERS inhibitor) significantly reduced the IL-17A levels in BALF (P = 0.0140) and TH17 cells in the peripheral blood (P = 0.0084) of mice with BLM+HSV1, suggesting that suppression of ERS may reduce TH17 response in mice with AE-IPF. Compared with WT mice with BLM+HSV1, IL-17A-/- mice with BLM+HSV1 had lower ALI score (P = 0.0119), higher survival rate (78.6% vs 21.4%, P = 0.004), improved lung function, and milder inflammatory response. CONCLUSIONS: HSV1 infection in addition to BLM-induced IPF can successfully establish AE-IPF in mice. IL-17A and ERS promote lung inflammation in AE-IPF development.

9.
Am J Physiol Cell Physiol ; 316(6): C782-C791, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-30540496

RESUMO

Cell permeability and epithelial-mesenchymal transition (EMT) were found to be enhanced in diabetic retinopathy, and the aim of this study was to investigate the underlying mechanism. ARPE-19 cell line or primary retinal pigment epithelial (RPE) cells were cultured under high or normal glucose conditions. Specific shRNAs were employed to knock down ADP-ribosylation factor 6 (ARF6), GEP100, or VEGF receptor 2 (VEGFR2) in ARPE-19 or primary RPE cells. Cell migration ability was measured using Transwell assay. Western blotting was used to measure indicated protein levels. RPE cells treated with high glucose showed increased cell migration, paracellular permeability, EMT, and expression of VEGF. Knockdown of VEGFR2 inhibited the high-glucose-induced effects on RPE cells via inactivation of ARF6 and MAPK pathways. Knockdown ARF6 or GEP100 led to inhibition of high-glucose-induced effects via inactivation of VEGFR2 pathway. Knockdown of ARF6, but not GEP100, decreased high-glucose-induced internalization of VEGFR2. High-glucose enhances EMT and cell permeability of RPE cells through activation of VEGFR2 and ARF6/GEP100 pathways, which form a positive feedback loop to maximize the activation of VEGF/VEGFR2 signaling.


Assuntos
Fatores de Ribosilação do ADP/metabolismo , Transição Epitelial-Mesenquimal/fisiologia , Glucose/administração & dosagem , Fatores de Troca do Nucleotídeo Guanina/metabolismo , Epitélio Pigmentado da Retina/metabolismo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Animais , Permeabilidade da Membrana Celular/efeitos dos fármacos , Permeabilidade da Membrana Celular/fisiologia , Células Cultivadas , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Glucose/toxicidade , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Epitélio Pigmentado da Retina/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia
10.
Hua Xi Kou Qiang Yi Xue Za Zhi ; 36(5): 475-481, 2018 Oct 01.
Artigo em Chinês | MEDLINE | ID: mdl-30465338

RESUMO

OBJECTIVE: Soluble triggering receptors expressed by myeloid cells-1 (sTREM-1) and inflammatory cytokine tumor necrosis factor-α (TNF-α) in macrophage cells were stimulated by Porphyromonas gingivalis-lipopolysaccharide (Pg-LPS) to investigate the expression of triggering receptors expressed by myeloid cells-1 (TREM-1) and further explore the correlation between TREM-1 and the pathogenesis of periodontitis. METHODS: THP-1 cells (a human monocytic cell line derived from an acute monocytic leukemia patient) were induced to differentiate THP-1 macrophages by phorbol-12-myristate-13-acetate and were injected with 0 (blank control), 0.5, or 1.0 µg·mL⁻¹ Pg-LPS. The THP-1 cells were then grouped in accordance with incubation time, and each group was incubated for 4, 6, 12, or 24 h. The expression of the TREM-1 mRNA in macrophages was detected by real-time quantitative polymerase chain reaction, while the expression of TREM-1 protein was detected by Western blot; the site where TREM-1 protein expression was observed in macrophages was detected by immunofluorescence staining, and the expression of soluble sTREM-1 and TNF-α in cell culture medium was detected by enzyme-linked immunosorbent assay. RESULTS: Compared with the blank control group, the expression of TREM-1 mRNA, TREM-1 protein, and sTREM-1 in Pg-LPS-stimulated macrophages was significantly upregulated (P<0.05). The expression of TREM-1 mRNA, TREM-1 protein, and sTREM-1 in the supernatant of cell culture was higher in the 1.0 µg·mL⁻¹ Pg-LPS group than in the 0.5 µg·mL⁻¹ group; this expression was statistically significant since the 6, 4, and 4 h time point (P<0.05). Cell immunofluorescence staining showed that TREM-1 protein was positive when the THP-1 macrophages was stimulated by Pg-LPS (1.0 µg·mL⁻¹) for 24 h, and the staining sites of TREM-1 were mainly located in the cell membrane of the macrophages (P<0.05). The expression level of TNF-α increased in groups stimulated by Pg-LPS, and the expression level of TNF-α was significantly higher in 1.0 µg·mL⁻¹ Pg-LPS stimulated groups than in 0.5 µg·mL⁻¹ Pg-LPS-stimulated groups since the 6 h time point (P<0.05). The expressions of TREM-1 mRNA, TREM-1 protein, and sTREM-1 in 0.5 µg·mL⁻¹ Pg-LPS-stimulated macrophages were positively correlated with one another (r=1, P<0.05), but no statistically significant correlation was found in the expression of TNF-α. The positive correlation between sTREM-1 and TNF-α expressions was detected when macrophages were stimulated by 1.0 µg·mL⁻¹ Pg-LPS (r=1, P<0.05). CONCLUSIONS: The expression of TREM-1 mRNA, TREM-1 protein, and sTREM-1 in the culture supernatant in Pg-LPS-stimulated macrophages was significantly upregulated on the basis of the concentration of Pg-LPS; moreover, their upregulation was positively correlated with one another. The expression of TNF-α in the supernatant of cell culture was also upregulated and was positively correlated with the expression of sTREM-1 at the group of high Pg-LPS concentration (1.0 µg·mL⁻¹). Results reveal that TREM-1, which has been realized as a proinflammatory receptor protein, can promote the development of periodontitis by regulating the expression of TNF-α in macrophages.


Assuntos
Lipopolissacarídeos , Periodontite , Porphyromonas gingivalis , Receptor Gatilho 1 Expresso em Células Mieloides , Fator de Necrose Tumoral alfa , Adulto , Humanos , Macrófagos/metabolismo , Células Mieloides , Periodontite/metabolismo , Periodontite/microbiologia , Porphyromonas gingivalis/patogenicidade , Receptor Gatilho 1 Expresso em Células Mieloides/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
11.
J Food Sci ; 83(11): 2819-2826, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30325500

RESUMO

Nano-titanium dioxide (TiO2 ) was modified with the surfactant sodium laurate (SL) via ultrasonic microwave-assisted technology to improve the dispersion of TiO2 in polymer matrices. As revealed by Fourier transform infrared spectroscopy, X-ray diffraction, and scanning electron microscopy analyses, SL was well adsorbed onto the TiO2 surface through chemical bonding, resulting in SL-modified TiO2 (TiO2 -SLx). The hydrophobicity and dispersibility of TiO2 -SLx increased significantly compared to unmodified nano-TiO2 . With an increase in the SL concentration from 5% to 15%, the agglomeration of TiO2 -SLx particles decreased considerably, while the particles were more uniform. TiO2 -SLx nanoparticles (3 wt%) were then incorporated into acetylated distarch phosphate/chitosan (ADPS/CS) blended matrices to reinforce the biopolymers. Relative to unmodified TiO2 , TiO2 -SLx exhibited a better dispersion capability. Furthermore, as the SL concentration increased, the tensile strength (TS) of the composite films increased, while the elongation at break (E), water vapor permeability (WVP), and solubility all decreased. The composite film containing TiO2 -SL15 (TiO2 modified with 15% SL; ADPS/CS-TiO2 -SL15 film) displayed the highest TS (31.50 MPa), which was 33.70% higher than that of the pure ADPS/CS film, whereas the ADPS/CS-TiO2 -SL25 film exhibited the lowest E. Further, the ADPS/CS-TiO2 -SL15 film displayed the lowest WVP (0.90 × 10-12 g·cm-1 ·s-1 ·Pa-1 ) and solubility (22.91%), which decreased by 30.23% and 26.03% compared to that of the pure ADPS/CS film, respectively. Therefore, SL modification and the use of ultrasonic microwave-assisted technology are promising for the preparation of nanofillers for biopolymer reinforcement. PRACTICAL APPLICATION: Nano-titanium dioxide (TiO2 ) nanoparticles were modified using the anionic surfactant sodium laurate via ultrasonic-microwave assisted technology, to improve the dispersion of the TiO2 nanoparticles in polymer matrices. Modified TiO2 nanoparticles were incorporated into acetylated di-starch phosphate/Chitosan blend films, causing the tensile strength of the composite film to increase and the water solubility and water vapor permeability of the composite film to decrease, making the films suitable for packaging applications.


Assuntos
Quitosana/química , Ácidos Láuricos/química , Nanopartículas/química , Fosfatos/química , Amido/química , Titânio/química , Interações Hidrofóbicas e Hidrofílicas , Microscopia Eletrônica de Varredura , Permeabilidade , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier , Resistência à Tração , Difração de Raios X
12.
Molecules ; 23(4)2018 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-29614008

RESUMO

Insect G protein coupled receptors (GPCRs) have important roles in modulating biology, physiology and behavior. They have been identified as candidate targets for next-generation insecticides, yet these targets have been relatively poorly exploited for insect control. In this study, we present a pipeline of novel Manduca sexta allatotropin (Manse-AT) antagonist discovery with homology modeling, docking, molecular dynamics simulation and structure-activity relationship. A series of truncated and alanine-replacement analogs of Manse-AT were assayed for the stimulation of juvenile hormone biosynthesis. The minimum sequence required to retain potent biological activity is the C-terminal amidated octapeptide Manse-AT (6-13). We identified three residues essential for bioactivity (Thr4, Arg6 and Phe8) by assaying alanine-replacement analogs of Manse-AT (6-13). Alanine replacement of other residues resulted in reduced potency but bioactivity was retained. The 3D structure of the receptor (Manse-ATR) was built and the binding pocket was identified. The binding affinities of all the analogs were estimated by calculating the free energy of binding. The calculated binding affinities corresponded to the biological activities of the analogs, which supporting our localization of the binding pocket. Then, based on the docking and molecular dynamics studies of Manse-AT (10-13), we described it can act as a potent Manse-AT antagonist. The antagonistic effect on JH biosynthesis of Manse-AT (10-13) validated our hypothesis. The IC50 value of antagonist Manse-AT (10-13) is 0.9 nM. The structure-activity relationship of antagonist Manse-AT (10-13) was also studied for the further purpose of investigating theoretically the structure factors influencing activity. These data will be useful for the design of new Manse-AT agonist and antagonist as potential pest control agents.


Assuntos
Hormônios de Inseto/antagonistas & inibidores , Hormônios de Inseto/metabolismo , Manduca/metabolismo , Neuropeptídeos/antagonistas & inibidores , Neuropeptídeos/metabolismo , Animais , Hormônios de Inseto/química , Inseticidas/química , Neuropeptídeos/química , Receptores Acoplados a Proteínas-G/antagonistas & inibidores , Receptores Acoplados a Proteínas-G/química , Receptores Acoplados a Proteínas-G/metabolismo , Relação Estrutura-Atividade
13.
J Agric Food Chem ; 66(14): 3644-3650, 2018 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-29566485

RESUMO

FGLamide allatostatins (ASTs) are regarded as possible insecticide candidates, although their lack of in vivo effects, rapid degradation, poor water solubility, and high production costs preclude their practical use in pest control. In contrast to previous research, the C-terminal tripeptide (FGLa) was selected as the lead compound in this study. Five nonpeptide AST analogues (2-amino-1-[3-oxo-3-(substituted-anilino)propyl]pyridinium nitrate derivatives) were designed on the basis of the structure-activity relationship and docking results of FGLa. All of the nonpeptide analogues (S1-S5) were more potent against juvenile-hormone (JH) biosynthesis than the lead compound. They significantly inhibited the biosynthesis of JH in vivo following injection. A pest-control application demonstrated that S1 and S3 have larvicidal effects following oral administration (the IC50 values were 0.020 and 0.0016 mg/g, respectively). The good oral toxicities and excellent water solubilities of S1 and S3 suggest that they have considerable potential as insecticides for pest management.


Assuntos
Corpora Allata/efeitos dos fármacos , Inseticidas/química , Inseticidas/farmacologia , Neuropeptídeos/química , Neuropeptídeos/farmacologia , Animais , Corpora Allata/metabolismo , Hormônios Juvenis/biossíntese , Controle de Pragas , Relação Estrutura-Atividade
14.
Psychol Med ; 48(15): 2508-2514, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29415791

RESUMO

BACKGROUND: The pathophysiology of cognitive impairment in patients with the major depressive disorder (MDD) may involve neuroinflammation mediated by cytokines. OBJECTIVE: The aim of this study was to examine the serum interleukin-6 (IL-6) levels, sustained attention, and their association in patients with MDD. METHODS: Thirty patients with MDD and 30 healthy controls were enrolled in this case-control study. Sustained attention was measured using the Rapid Visual Information Processing (RVP) task in the Cambridge Neuropsychological Tests Automated Battery. The serum IL-6 levels of all subjects were assessed by sandwich enzyme-linked immunosorbent assays. RESULTS: There were significant differences in the log10RVP total hits, log10RVP total misses, and log10RVP mean latency between patients with MDD and healthy controls (F = 6.04, p = 0.017; F = 19.77, p < 0.0001; F = 14.42, p < 0.0001, respectively). The serum levels of Log10IL-6 were significantly higher in patients with MDD than in healthy controls (F = 192.27, p < 0.0001). The log10IL-6 levels were also positively correlated with the log10RVP mean latency in patients with MDD (r = 0.45, p = 0.013). A further stepwise multivariate regression analysis indicated that the log10IL-6 levels were significantly associated with the log10RVP mean latency in patients with MDD (ß = 0.31, t = 2.41, p = 0.025). CONCLUSIONS: Our data suggested that increased IL-6 levels were associated with the psychopathology of MDD, and that abnormal IL-6 levels were implicated in the impairment of sustained attention in patients with MDD.


Assuntos
Atenção/fisiologia , Disfunção Cognitiva , Transtorno Depressivo Maior , Interleucina-6/sangue , Adulto , Disfunção Cognitiva/sangue , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/fisiopatologia , Transtorno Depressivo Maior/sangue , Transtorno Depressivo Maior/complicações , Transtorno Depressivo Maior/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
15.
Respir Res ; 19(1): 21, 2018 01 26.
Artigo em Inglês | MEDLINE | ID: mdl-29373969

RESUMO

BACKGROUND: Abnormal apoptosis of lung endothelial cells has been observed in emphysematous lung tissue and has been suggested to be an important upstream event in the pathogenesis of chronic obstructive pulmonary disease (COPD). Studies have shown that microRNAs (miRNAs) contribute to the pathogenesis of pulmonary diseases by regulating cell apoptosis. The present study was designed to investigate the expression of microRNA-34a (miR-34a) in human pulmonary microvascular endothelial cells (HPMECs) exposed to cigarette smoke extract (CSE), and the potential regulatory role of miR-34a in endothelial cell apoptosis. RESULTS: Our results showed that the expression of miR-34a was significantly increased in CSE-treated HPMECs, and inhibiting miR-34a attenuated CSE-induced HPMEC apoptosis. Furthermore, expression of Notch-1, a receptor protein in the Notch signalling pathway, was decreased and was inversely correlated with miR-34a expression in HPMECs treated with CSE. Computational miRNA target prediction confirmed that Notch-1 is a target of miR-34a. Luciferase reporter assay further confirmed the direct interaction between miR-34a and the 3'-untranslated region (UTR) of Notch-1. Restoration of Notch-1 pathway was able to partially block the effect of miR-34a on HPMEC apoptosis. These results indicate that Notch-1 is a critical downstream target of miR-34a in regulating the CSE-induced HPMEC apoptosis. CONCLUSIONS: Our results suggest that miR-34a plays a key role in CSE-induced endothelial cell apoptosis by directly regulating its target gene Notch-1 in endothelial cells.


Assuntos
Apoptose/fisiologia , MicroRNAs/biossíntese , Microvasos/metabolismo , Receptor Notch1/biossíntese , Mucosa Respiratória/metabolismo , Poluição por Fumaça de Tabaco/efeitos adversos , Apoptose/efeitos dos fármacos , Linhagem Celular , Fumar Cigarros/efeitos adversos , Humanos , Microvasos/efeitos dos fármacos , Receptor Notch1/antagonistas & inibidores , Mucosa Respiratória/efeitos dos fármacos , Mucosa Respiratória/patologia
16.
J Chromatogr A ; 1538: 67-74, 2018 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-29361282

RESUMO

A method for rapid quantitation of insect juvenile hormones (JH) and intermediates in the biosynthetic pathway, both in vitro and in vivo (hemolymph and whole body), has been developed using GC-MS/MS. This method is as simple as the radiochemical assay (RCA), the most commonly used method for measurement of JH biosynthesis in vitro, without need for further purification and derivatization, or radioactive precursors or ligands. It shows high sensitivity, accuracy and reproducibility. Linear responses were obtained the range of 1-800 ng/mL (approximately 4-3000 nM). Recovery efficiencies for farnesol, farnesal, methyl farnesoate and JH III were approximately 100% in vitro and over 90% in vivo, with excellent reproducibility at three different spike levels. Titer of JH III in the hemolymph was relatively low at day 0 (adult female emergence) (79.68 ±â€¯5.03 ng/mL) but increased to a maximum of 1717 ng/mL five days later. In whole body, JH III quantity reached a maximum on day 4 (845.5 ±â€¯87.9 ng/g) and day 5 (679.7 ±â€¯164.6 ng/g) and declined rapidly thereafter. It is in agreement with the hemolymph titer changes and biosynthetic rate of JH in vitro. Comparison with the results of inhibition of JH biosynthesis by two known inhibitors (allatostatin (AST) mimic H17 and pitavastatin) using RCA and GC-MS/MS, showed that there was little difference between the two methods In contrast to other methods, the present method with GC-MS/MS can be used to elucidate the mechanism of inhibition by inhibitors of JH biosynthesis without any derivatization and purification. This method is applicable to screening of JH inhibitors and the study of inhibitory mechanisms with high sensitivity and accurate quantification. It may also be useful for the determination of JH titer in other Arthropods.


Assuntos
Vias Biossintéticas/fisiologia , Técnicas de Química Analítica/métodos , Baratas/química , Entomologia/métodos , Cromatografia Gasosa-Espectrometria de Massas , Hormônios Juvenis/análise , Animais , Técnicas de Química Analítica/instrumentação , Baratas/crescimento & desenvolvimento , Farneseno Álcool/análogos & derivados , Farneseno Álcool/análise , Farneseno Álcool/isolamento & purificação , Ácidos Graxos Insaturados/análise , Ácidos Graxos Insaturados/isolamento & purificação , Hemolinfa/química , Hormônios Juvenis/química , Reprodutibilidade dos Testes , Sesquiterpenos/análise , Sesquiterpenos/isolamento & purificação
17.
Clin Nutr ; 37(2): 516-521, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-28040302

RESUMO

BACKGROUND: The most typical chronic liver disease in children and adolescents is non-alcoholic fatty liver disease (NAFLD). The dietary addition of ω-3 polyunsaturated fatty acids (PUFAs) provides a promising therapy for children with NAFLD due to its convenience and safety; however, several studies suggested contradictory results for PUFA supplementation in children. Hence, we performed a systematic review and meta-analysis to evaluate the effectiveness of PUFA supplementation in children with NAFLD. METHODS: Published randomized controlled trials (RCTs) that evaluated the effectiveness of the dietary addition of PUFA in children with NAFLD were considered. The primary result was the alteration in hepatic steatosis grade on ultrasound after treatment. The secondary outcomes included alanine aminotransferase (ALT), aspartate aminotransferase (AST), C-reactive protein (CRP) and components of metabolic syndrome. Predefined sensitivity analysis was also performed to explore possible explanations for heterogeneity in the evaluations. RESULTS: In total, 4 studies with 263 subjects were identified. PUFA supplementation was associated with significantly improved hepatic steatosis grade on ultrasound (risk difference: 25%, 95% CI: 12-38%), without heterogeneity (P = 0.27, I2 = 24%). Sensitivity analysis confirmed the robustness of our findings. PUFA supplementation could decrease AST levels after 6 months, but could only reduce ALT levels after 12 months. PUFA did not have a significant effect on most components of metabolic syndrome and the CRP level. CONCLUSION: ω-3 PUFA supplementation can improve liver steatosis and liver functions, and it is a potential food supplementation to treat NAFLD in children.


Assuntos
Ácidos Graxos Ômega-3/uso terapêutico , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Adolescente , Criança , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
18.
Oncol Rep ; 39(1): 331-337, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29192321

RESUMO

This study investigated how miR­106b­5p/PTEN signaling affects the cell cycle of malignant melanoma (MM) cells. miR­106b­5p mRNA was identified with qRT­PCR. Through transient transfection, miR­106b­5p or PTEN was upregulated and downregulated in MM cells. With such transfected cells, MTT assay, colony formation assay and flow cytometry were carried out to investigate the role of miR­106b­5p in cell cycle progression after the transfected cells were treated with reverse-regulation of miR­106b­5p or PTEN. Western blot analysis was used to quantify all proteins, and a luciferase reporter assay was carried out to validate miR­106b­5p targeting PTEN. miR­106b­5p mRNA was overexpressed in MM tissues and cell lines. MM cells with upregulated miR­106b­5p presented faster growth and shorter cell cycles, while those with knockdown of miR­106b­5p presented the opposite trend. PTEN was subject to post­transcriptional regulation of miR­106b­5p. Based on such a finding, further exploration was carried out to investigate the interaction between cyclin D1 and P27Kip1, with the finding that miR­106b­5p can stimulate cyclin D1 and suppress P27Kip1 via the Akt/ERK pathway. The results of this study suggest that miR­106b­5p may be a promoter in MM progression, possibly by targeting PTEN and thus regulating the downstream cell­cycle-related proteins and Akt/ERK pathway.


Assuntos
Melanoma/genética , MicroRNAs/genética , PTEN Fosfo-Hidrolase/genética , Regulação para Cima , Regiões 5' não Traduzidas , Ciclo Celular , Linhagem Celular Tumoral , Proliferação de Células , Progressão da Doença , Regulação Neoplásica da Expressão Gênica , Humanos , Sistema de Sinalização das MAP Quinases
19.
Drug Deliv ; 24(1): 1770-1781, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29160134

RESUMO

The advent of nanomedicine requires novel delivery vehicles to actively target their site of action. Here, we demonstrate the development of lung-targeting drug-loaded liposomes and their efficacy, specificity and safety. Our study focuses on glucocorticoids methylprednisolone (MPS), a commonly used drug to treat lung injuries. The steroidal molecule was loaded into functionalized nano-sterically stabilized unilamellar liposomes (NSSLs). Targeting functionality was performed through conjugation of surfactant protein A (SPANb) nanobodies to form MPS-NSSLs-SPANb. MPS-NSSLs-SPANb exhibited good size distribution, morphology, and encapsulation efficiency. Animal experiments demonstrated the high specificity of MPS-NSSLs-SPANb to the lung. Treatment with MPS-NSSLs-SPANb reduced the levels of TNF-α, IL-8, and TGF-ß1 in rat bronchoalveolar lavage fluid and the expression of NK-κB in the lung tissues, thereby alleviating lung injuries and increasing rat survival. The nanobody functionalized nanoparticles demonstrate superior performance to treat lung injury when compared to that of antibody functionalized systems.


Assuntos
Lesão Pulmonar Aguda/tratamento farmacológico , Lipossomos/química , Metilprednisolona/química , Metilprednisolona/farmacologia , Nanopartículas/química , Proteína A Associada a Surfactante Pulmonar/química , Animais , Líquido da Lavagem Broncoalveolar/química , Sistemas de Liberação de Medicamentos/métodos , Glucocorticoides/química , Glucocorticoides/farmacologia , Interleucina-8/metabolismo , Pulmão/efeitos dos fármacos , Masculino , Surfactantes Pulmonares/química , Surfactantes Pulmonares/farmacologia , Ratos , Ratos Sprague-Dawley , Fator de Crescimento Transformador beta1/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
20.
Sci Rep ; 7(1): 12358, 2017 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-28955041

RESUMO

A correction to this article has been published and is linked from the HTML version of this paper. The error has been fixed in the paper.

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