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2.
Se Pu ; 41(6): 482-489, 2023 Jun 08.
Artigo em Chinês | MEDLINE | ID: mdl-37259872

RESUMO

Disinfection of drinking water is critical to prevent waterborne diseases. An unexpected consequence of water disinfection is the formation of disinfection by-products by the interaction of disinfectants with organic matter (natural or anthropogenic) and halides, which present significant toxicological effects and carcinogenic risks. As an emerging disinfection by-product, halobenzoquinones (HBQs) have attracted increasing attention owing to their severe toxicity and high detection rates. The credible determination of HBQs is essential for further studies on their occurrence, toxicity, and control measures; however, HBQs are usually detected in drinking water at trace levels. Therefore, accurate and efficient analytical techniques are critical for HBQ determination and quantitation. In this study, a method based on solid phase extraction (SPE) combined with ultra performance liquid chromatography-triple quadrupole mass spectrometry (UPLC-MS/MS) was developed to determine 13 HBQs, including six chlorobenzoquinones, six bromobenzoquinones, and one iodobenzoquinone, in drinking water. One-liter water samples were added with 2.5 mL of formic acid, and 500 mL of each sample was collected for further enrichment. Pretreatment optimization mainly focused on the SPE column, washing solvent, and nitrogen blowing temperature. After extraction using Plexa SPE columns (200 mg/6 mL), the samples were washed with ultrapure water containing 0.25% formic acid combined with 30% methanol aqueous solution containing 0.25% formic acid, eluted with 6 mL of methanol containing 0.25% formic acid, and then nitrogen blown at 30 ℃. The UPLC-MS/MS parameters were optimized by comparing the results of two reversed-phase columns (BEH C18 and HSS T3) and various concentrations of formic acid in the mobile phase, as well as by establishing the best instrumental conditions. The separation of 13 HBQs was performed using an HSS T3 column (100 mm×2.1 mm, 1.8 µm) via gradient elution with a mixture of 0.1% formic acid aqueous solution and methanol as the mobile phase for 16 min. The 13 HBQs were detected using a triple quadrupole mass spectrometer equipped with a negative electrospray ionization source (ESI-) in multiple reaction monitoring (MRM) mode. Matrix-matched calibration curves were used to quantify the HBQs owing to intense matrix inhibitory effects. The results reflected the good linear relationships of the 13 HBQs and yielded correlation coefficients (r) greater than 0.999. The method detection limits (MDLs, S/N=3) were 0.2-10.0 ng/L, while the method quantification limits (MQLs, S/N=10) were 0.6-33.0 ng/L. The recoveries of the 13 HBQs were 56%-88% at three spiked levels (10, 20, 50 ng/L), and the relative standard deviations (RSDs, n=6) were less than or equal to 9.2%. The optimization method was applied to analyze HBQs in five drinking water samples. Four HBQs, namely, 2,6-dichloro-1,4-benzoquinone (2,6-DCBQ), 2,5-dibromo-1,4-benzoquinone (2,5-DBBQ), 2,6-dibromo-1,4-benzoquinone (2,6-DBBQ), and 2,6-dibromo-3,5-dimethyl-1,4-benzoquinone (2,6-DBDMBQ), were detected in the samples with detection rates of 100%, 20%, 80%, and 20%, respectively. The most frequently detected HBQ, 2,6-DCBQ, also exhibited the highest content (15.0-56.2 ng/L). The method showed high sensitivity, stability, accuracy, and efficiency, rendering it suitable for the analysis of 13 HBQs in drinking water. Compared with previous methods that mainly focused on 2,6-DCBQ and 2,6-DBBQ, the developed method achieved higher throughput and enabled the simultaneous analysis of 13 HBQs. The method presented in this study provides an opportunity to explore different types and concentrations of HBQs in drinking water, offers a deeper understanding of the occurrence of HBQs, and facilitates further studies on the health risks and control measures of these compounds.


Assuntos
Água Potável , Cromatografia Líquida , Água Potável/análise , Desinfecção/métodos , Espectrometria de Massas em Tandem , Metanol/análise , Benzoquinonas/análise , Benzoquinonas/química , Extração em Fase Sólida , Cromatografia Líquida de Alta Pressão
3.
Radiat Res ; 197(2): 157-165, 2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-34644380

RESUMO

To investigate the optimal pre- and post-adaptive statistical iterative reconstruction-V (ASiR-V) levels in pediatric abdominal computed tomography (CT) to minimize radiation exposure and maintain image quality using an animal model. A total of 10 standard piglets were selected and scanned to obtain unenhanced and enhanced images under different pre-ASiR-V conditions. The corresponding images were obtained using ASiR-V algorithm at different post-ASiR-V levels. CT value, signal-to-noise ratio (SNR), contrast noise ratio (CNR) of abdominal tissues, subjective image score, and radiation dose of unenhanced and enhanced scans were analyzed. With the increase of pre-ASiR-V level, the radiation dose in piglets gradually decreased (P < 0.05). Within the same group of pre-ASiR-V, the image noise was decreased (P < 0.05) by increasing post-ASiR-V level. There was no statistical difference between SNR and CNR values. In unenhanced CT, the subjective score of the images with the combination of 40% pre- and 60% post-ASiR-V levels had no statistical difference compared to the combination of 0% pre- and 60% post-ASiR-V levels, while the radiation dose decreased by 31.6%. In the enhanced CT, the subjective image score with the 60% pre- and 60% post-ASiR-V combination had no statistical difference compared to the 0% pre- and 60% post-ASiR-V combination, while the radiation dose was reduced by 48.9%. The combined use of pre- and post-ASiR-V maintains image quality at the reduced radiation dose. The optimal level for unenhanced CT is 40% pre-combined with 60% post-ASiR-V, while that for enhanced CT is 60% pre-combined with 60% post-ASiR-V in pediatric abdominal CT.


Assuntos
Doses de Radiação
4.
Bull Entomol Res ; 111(4): 454-463, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33632348

RESUMO

The tobacco cutworm Spodoptera litura (Lepidoptera: Noctuidae) is a polyphagous pest with a highly selective and sensitive chemosensory system involved in complex physiological behaviors such as searching for food sources, feeding, courtship, and oviposition. However, effective management strategies for controlling the insect pest populations under threshold levels are lacking. Therefore, there is an urgent need to formulate eco-friendly pest control strategies based on the disruption of the insect chemosensory system. In this study, we identified 158 putative chemosensory genes based on transcriptomic and genomic data for S. litura, including 45 odorant-binding proteins (OBPs, nine were new), 23 chemosensory proteins (CSPs), 60 odorant receptors (ORs, three were new), and 30 gustatory receptors (GRs, three were new), a number higher than those reported by previous transcriptome studies. Subsequently, we constructed phylogenetic trees based on these genes in moths and analyzed the dynamic expression of various genes in head capsules across larval instars using quantitative real-time polymerase chain reaction. Nine genes-SlitOBP8, SlitOBP9, SlitOBP25, SlitCSP1, SlitCSP7, SlitCSP18, SlitOR34, SlitGR240, and SlitGR242-were highly expressed in the heads of 3- to 5-day-old S. litura larvae. The genes differentially expressed in olfactory organs during larval development might play crucial roles in the chemosensory system of S. litura larvae. Our findings substantially expand the gene inventory for S. litura and present potential target genes for further studies on larval feeding in S. litura.


Assuntos
Genes de Insetos , Proteínas de Insetos/genética , Receptores Odorantes/genética , Spodoptera/genética , Animais , Feminino , Cabeça , Proteínas de Insetos/metabolismo , Larva/metabolismo , Masculino , Receptores Odorantes/metabolismo , Spodoptera/metabolismo , Transcriptoma
5.
Adv Rheumatol ; 61: 36, 2021. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1284979

RESUMO

Abstract Objectives: To investigate the diagnostic performance of single-source dual-energy computed tomography (DECT) based on gemstone spectral imaging technology (including Discovery CT750HD and Revolution CT) in patients with suspected feet/ankles gouty arthritis, and evaluate the urate deposition with a novel semi-quantitative DECT scoring system. Methods: A total of 196 patients were consecutively included. Feet and ankles were evaluated in all patients by single-source DECT scan. The 2015 EULAR/ACR criteria were used as the reference for the diagnosis of gout. The sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) of DECT for the diagnosis of gout in the early (≤1 year), middle (1-3 years), and late (> 3 years) disease durations were calculated. Besides, a novel semi-quantitative DECT scoring system was assessed for the measurement of urate deposition, and the correlation between the scores and the clinical and serological data were also evaluated. Moreover, the influences of artifacts on the diagnostic performance of DECT were also determined. Results: The sensitivity, specificity, and AUC of DECT in 196 patients were 38.10, 96.43%, and 0.673 in the early-stage group; 62.96, 100.00%, and 0.815 in the middle-stage group; and 77.55, 87.50%, and 0.825 in the late-stage group, respectively. The overall diagnostic accuracies in the AUC of DECT (Discovery CT750HD and Revolution CT) in the middle and late stages of gout were higher than that in the early stage of gout. Besides, the monosodium urate crystals were deposited on the first metatarsophalangeal joints and ankles/midfeet. Age, the presence of tophus, bone erosion, and disease duration considerably affected the total urate score. No statistical difference in the positive detection of nail artifact, skin artifact, vascular calcification, and noise artifact was found between the case and control groups. Conclusion: DECT (Discovery CT750HD and Revolution CT) showed promising diagnostic accuracy for the detection of urate crystal deposition in gout but had limited diagnostic sensitivity for short-stage gout. Longer disease duration, the presence of tophus, and bone erosion were associated with the urate crystal score system. The artifacts do not remarkably affect the diagnostic performance of DECT in gout.

6.
J Cell Mol Med ; 24(22): 12994-13009, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32969198

RESUMO

The persistent transactivation of epidermal growth factor receptor (EGFR) causes subsequent activation of the TGF-ß/Smad3 pathway, which is closely associated with fibrosis and cell proliferation in diabetic nephropathy (DN), but the exact mechanism of persistent EGFR transactivation in DN remains unclear. ARAP1, a susceptibility gene for type 2 diabetes, can regulate the endocytosis and ubiquitination of membrane receptors, but the effect of ARAP1 and its natural antisense long non-coding RNA (lncRNA), ARAP1-AS2, on the ubiquitination of EGFR in DN is not clear. In this study, we verified that the expression of ARAP1 and ARAP1-AS2 was significantly up-regulated in high glucose-induced human proximal tubular epithelial cells (HK-2 cells). Moreover, we found that overexpression or knockdown of ARAP1-AS2 could regulate fibrosis and HK-2 cell proliferation through EGFR/TGF-ß/Smad3 signalling. RNA pulldown assays revealed that ARAP1-AS2 directly interacts with ARAP1. Coimmunoprecipitation, dual-immunofluorescence and ubiquitination assays showed that ARAP1 may maintain persistent EGFR activation by reducing EGFR ubiquitination through competing with Cbl for CIN85 binding. Taken together, our results suggest that the lncRNA ARAP1-AS2 may promote high glucose-induced proximal tubular cell injury via persistent EGFR/TGF-ß/Smad3 pathway activation by interacting with ARAP1.


Assuntos
Proteínas de Transporte/metabolismo , Proteínas Ativadoras de GTPase/metabolismo , Túbulos Renais Proximais/metabolismo , RNA Longo não Codificante , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Proliferação de Células , Nefropatias Diabéticas/metabolismo , Receptores ErbB/metabolismo , Glucose , Humanos , Hibridização in Situ Fluorescente , Túbulos Renais Proximais/patologia , Camundongos , Camundongos Endogâmicos C57BL , Microscopia de Fluorescência , Oligonucleotídeos Antissenso/farmacologia , Ligação Proteica , RNA Longo não Codificante/genética , RNA-Seq , Proteína Smad3/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Ubiquitina/metabolismo
7.
J Hazard Mater ; 397: 122777, 2020 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-32388456

RESUMO

Athetis lepigone is one of the most severe polyphagous pests, and it has developed resistance to different chemical insecticides. Insects primarily rely on the olfactory system to recognize various environmental chemicals, including xenobiotics such as insecticides. Here, we expressed two A. lepigone pheromone-binding proteins (AlepPBP2 and AlepPBP3), and observed they had higher binding affinities to phoxim than other insecticides, with Ki was 3.30 ±â€¯0.38 µM and 3.27 ±â€¯0.10 µM, respectively. Molecular dynamics simulation, binding mode analysis, and computational alanine scanning showed that six residues (Phe15, Phe39, Ile55, Leu65, Ile97, and Phe122) of AlepPBP2 and three residues (Phe12, Ile52, and Ile134) of AlepPBP3 maybe as potential residues that can change protein ability to bind an organophosphorus insecticide phoxim. Then, we used site-directed mutagenesis assay to mutate these residues into alanine, respectively. Subsequently, the binding assays displayed that Phe15, Phe39, and Ile97 of AlepPBP2, Phe12 and Ile134 of AlepPBP3 caused a significant decrease of AlepPBPs binding ability to phoxim, suggesting they should play crucial roles in the AlepPBPs/phoxim interactions. Our findings could further advance in using PBPs as unique targets to design and develop precise and environmentally-friendly pest control agents with high insecticidal potential using a computer-aided drug design (CADD) approach.


Assuntos
Inseticidas , Transtornos do Olfato , Animais , Proteínas de Transporte , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismo , Inseticidas/toxicidade , Feromônios
8.
J Agric Food Chem ; 68(22): 6092-6103, 2020 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-32392414

RESUMO

Athetis lepigone is a polyphagous pest found around the world that feeds on maize, wheat, and various other important crops. Although it exhibits a degree of resistance to various chemical insecticides, an effective pest-control method has not yet been developed. The sex pheromone communication system plays an essential role in the mating and reproduction of moths, in which pheromone-binding proteins (PBPs) are crucial genes. In this study, we cloned and purified the protein AlepPBP1 using an E. coli expression system and found it had a higher binding affinity to two sex pheromones of A. lepigone, namely, Z7-12:Ac and Z9-14:Ac (with Ki 0.77 ± 0.10 and 1.10 ± 0.20 µM, respectively), than to other plant volatiles. The binding-mode analysis of protein conformation with equilibrium stabilization was obtained using molecular dynamics (MD) simulation and indicated that hydrophobic interactions involving several nonpolar residues were the main driving force for the binding affinity of AlepPBP1 with sex pheromones. Computational alanine scanning (CAS) was performed to further identify key amino acid residues and validate their binding contributions. Each key residue, including Phe36, Trp37, Val52, and Phe118, was subsequently mutated into alanine using site-directed mutagenesis. Binding assays showed that the efficient binding abilities to Z7-12:Ac (F36A, W37A, and F118A) and Z9-14:Ac (F36A, W37A, V52A, and F118A) were almost lost in the mutated proteins. Our results demonstrated that these key amino acid residues are crucial for determining the binding ability of AlepPBP1 to sex pheromones. These findings provide a basis for the use of AlepPBP1 in the studies as a specific target for the development of novel behavioral antagonists with marked inhibition or mating-disruption abilities using computer-aided drug design (CADD).


Assuntos
Proteínas de Transporte/metabolismo , Proteínas de Insetos/metabolismo , Mariposas/metabolismo , Atrativos Sexuais/metabolismo , Motivos de Aminoácidos , Animais , Proteínas de Transporte/química , Proteínas de Transporte/genética , Feminino , Proteínas de Insetos/química , Proteínas de Insetos/genética , Cinética , Masculino , Simulação de Acoplamento Molecular , Mariposas/química , Mariposas/efeitos dos fármacos , Mariposas/genética , Ligação Proteica , Atrativos Sexuais/química , Atrativos Sexuais/farmacologia
9.
Pestic Biochem Physiol ; 164: 173-182, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32284124

RESUMO

Athetis lepigone (Alep) is a polyphagous pest native to Europe and Asia that has experienced major outbreaks in the summer maize area of China since 2011 and has shown evidence of resistance to some insecticides. Insect olfaction is crucial for recognition of sex pheromones, host plant volatiles and even insecticides, in which two general-odorant binding proteins (GOBPs) play important roles. To elucidate the functions of GOBPs in A. lepigone, we first expressed the two AlepGOBP proteins in the E. coli expression system. Then, the results of fluorescence competitive binding assays demonstrated that the high binding affinity of AlepGOBP2 with sex pheromones [(Z)-7-dodecenyl acetate (Z7-12:Ac), Ki = 0.65 µM; (Z)-9-tetradecenyl acetate (Z9-14:Ac), Ki = 0.83 µM], two maize plant volatiles [Ocimene, Ki = 9.63 µM; (E)-ß-Farnesene, Ki = 4.76 µM] and two insecticides (Chlorpyrifos Ki =5.61 µM; Phoxim, Ki = 4.38 µM). However, AlepGOBP1 could only bind Ocimene (Ki = 13.0 µM) and two insecticides (Chlorpyrifos Ki =4.46 µM; Phoxim, Ki = 3.27 µM). These results clearly suggest that AlepGOBP1 and AlepGOBP2 differentiate among odorants and other ligands. The molecular docking results further revealed different key residues involved in the ligand binding of AlepGOBPs. In summary, this study provides a foundation for exploring the olfactory mechanism of A. lepigone and identified two potential target genes for the development of highly effective insecticides in the future.


Assuntos
Inseticidas , Mariposas , Atrativos Sexuais , Animais , China , Escherichia coli , Proteínas de Insetos , Simulação de Acoplamento Molecular , Odorantes , Feromônios
10.
Front Cell Infect Microbiol ; 10: 581535, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33489931

RESUMO

Background: Pseudomonas aeruginosa (PA) is one of the most common Gram-negative bacteria causing hospital-acquired pulmonary infection, with high drug resistance and mortality. Therefore, it is urgent to introduce new non-antibiotic treatment strategies. Mesenchymal stem cells (MSCs), as important members of the stem cell family, were demonstrated to alleviate pathological damage in acute lung injury. However, the potential mechanism how MSC alleviate acute lung infection caused by PA remains unclear. Objective: The purpose of this study was to investigate the effects of Adipose-derived mesenchymal stem cells (ASCs) on acute pulmonary infections and the possible mechanisms how ASCs reduce pulmonary inflammation induced by PA. Methods: The therapeutic and mechanistic effects of ASCs on PA pulmonary infection were evaluated respectively in a murine model as well as in an in vitro model stimulated by PA and co-cultured with ASCs. Results: 1. ASCs treatment significantly reduced the bacterial load, inflammation of lung tissue and histopathological damage by PA. 2. PA infection mainly activated Nod-like receptor containing a caspase activating and recruitment domain 4 (NLRC4) inflammasome in the lung of mice. ASCs attenuated acute lung infection in mice by inhibiting NLRC4 inflammasome activation. 3. NLRC4-/- mice showed a significant improvement in survival rate and lung bacterial load after PA infection. 4. ASCs mainly increased expression and secretion of STC-1 in response to PA-stimulated NLRC4 inflammasome activation. Conclusions: PA infection attenuated macrophage phagocytosis through activation of NLRC4 inflammasome in macrophages, which eventually led to pulmonary inflammatory damage in mouse; ASCs reduced the activation of NLRC4 inflammasome in macrophages induced by PA infection, thereby increasing the phagocytic ability of macrophages, and ultimately improving lung tissue damage in mouse; ASCs may inhibit NLRC4 inflammasome through the secretion of STC-1.


Assuntos
Inflamassomos , Células-Tronco Mesenquimais , Animais , Proteínas Reguladoras de Apoptose/metabolismo , Proteínas de Ligação ao Cálcio , Inflamassomos/metabolismo , Pulmão/metabolismo , Células-Tronco Mesenquimais/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Pseudomonas aeruginosa/metabolismo
11.
Asian Pac J Cancer Prev ; 18(7): 1769-1772, 2017 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-28749103

RESUMO

Background: Cervical cancer is the most common gynecological malignant disorder worldwide. Activated platelets play a key role in cancer development and progression. Mean platelet volume (MPV) is an early indicator of platelet activation. The aim of the present study was to evaluate MPV levels in patients with cervical cancer. Materials and methods: A total of 181 patients with cervical cancer and 181 controls between January 2015 and June 2015 were included in the study. Patient characteristics and hematologic test data at initial diagnosis were collected and odds ratios (ORs) and 95% confidence intervals (CIs) for risk of cervical cancer were calculated using multivariate logistic regression analyses across MPV quartiles. Results: MPV levels were decreased in patients with cervical cancer compared with control subjects. A significant correlation between MPV and FIGO stage was found. Moreover, after adjusting for other risk factors, the ORs (95%CIs) for cervical cancer according to MPV quartiles were 4.450 (1.975-10.026), 2.505 (1.206-5.202), 0.573 (0.261-1.259), and 1.000, respectively. Conclusions: MPV was found to be independently associated with the presence of cervical cancer. Our results suggest that MPV could be potential diagnostic screening tool.

12.
Oncotarget ; 8(12): 20213-20219, 2017 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-28423627

RESUMO

BACKGROUND: Activated platelets promote tumor cell growth, aberrant angiogenesis, and invasion. However, the value of platelet indices for predicting survival in gastric cancer remains unknown. The goal of this study was to investigate the predictive significance of platelet indices in gastric cancer. RESULT: Reduced platelet distribution width (PDW) was significantly correlated with age, carcinoembryonic antigen, tumor stage, nodule stage, and tumor-nodule-metastases stage. Moreover, decreased PDW correlated with a shorter overall survival in gastric cancer. Multivariate analysis identified PDW as an independent prognostic factor for overall survival (hazard ratio: 0.493, 95% confidence interval: 0.319-0.761, p = 0.001). METHOD: A total of 294 patients with gastric cancer were retrospectively analyzed between January 2009 and December 2009. The association between platelet indices and overall survival were evaluated. The prognostic analysis was carried out with Cox regression model. CONCLUSION: PDW is easily available with routine blood counts. Our data revealed that reduced PDW is unfavorable prognostic factor in gastric cancer. Further studies are warranted.


Assuntos
Plaquetas/patologia , Neoplasias Gástricas/patologia , Idoso , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas/mortalidade
13.
Yao Xue Xue Bao ; 52(1): 86-90, 2017 01.
Artigo em Chinês | MEDLINE | ID: mdl-29911782

RESUMO

The study was designed to explore the effects of HS060098 on activation of peroxisome proliferator-activated receptors (PPARα, γ and δ) and in the down-regulation of hyperlipidemia in golden hamster. Luciferase gene reporters of PPARα, PPARγ and PPARδ were constructed in HepG2 cells and the green fluorescent protein (GFP) was used as an internal reference. Transfected cells were then cultured with various concentrations of HS060098 for 24 h. The peroxisome proliferator-response element luciferase activity was determined by the dual-luciferase reporter gene assay system. To investigate the lipid-lowering effect of HS060098, hyperlipidemic golden hamsters fed by high-diet were administered orally with HS060098 through prophylactic and therapeutic approaches respectively. The levels of blood lipids such as total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) and fat index in hamsters were evaluated. The results showed that HS060098 was a potent activator of PPARδ with a good selectivity and the median effective concentration (EC(50)) is 0.01 µmol·L(-1), while no obvious PPARα and PPARγ activation was observed. In the golden hamster, oral administration of HS060098 (5, 10, 20 mg·kg(-1)·d(-1)) for 2 weeks, led to a significant decrease the concentrations of plasma TC, TG, LDL-C and fat index (P < 0.05 or P < 0.01), whereas the contents of plasma HDL-C were increased significantly (P < 0.05 or P < 0.01). The data suggest that HS060098 is a novel PPARδ agonist with a significant activity in the prevention and therapy of hyperlipemia in golden hamster.


Assuntos
Hiperlipidemias/tratamento farmacológico , Lipídeos/sangue , PPAR delta/agonistas , Animais , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Cricetinae , Células Hep G2 , Humanos , Mesocricetus , PPAR alfa , PPAR gama , Transfecção , Triglicerídeos/sangue
14.
Clin Exp Pharmacol Physiol ; 44(3): 413-420, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-27896845

RESUMO

STAT3 is persistently activated in a wide variety of human tumours, and aberrant STAT3 activity promotes tumour growth, invasion and metastasis. To explore STAT3 down-regulation in human oesophageal cancer cells, cell proliferation, apoptosis and mitochondrial mechanisms were explored in oesophageal carcinoma TE1 cell cultures. We demonstrate for the first time that STAT3 down-regulation by RNAi is sufficient to inhibit oesophageal cancer cell proliferation inducing cell apoptosis. Further, we demonstrate that mitochondrial transmembrane potential is impaired thereby leading to collapsed mitochondrial membrane potential, abnormal mitochondrial membrane depolarization, nuclear DNA fragmentation and cell cycle G2/M arrest under the conditions of STAT3 down-regulation. Thus, our results suggest that STAT3 inhibition is a valid approach to induce oesophageal carcinoma cell mitochondrial-dependent apoptosis in therapeutic strategies against oesophageal cancers.


Assuntos
Apoptose , Neoplasias Esofágicas , Pontos de Checagem da Fase G2 do Ciclo Celular , Pontos de Checagem da Fase M do Ciclo Celular , Potencial da Membrana Mitocondrial/fisiologia , Fator de Transcrição STAT3/antagonistas & inibidores , Apoptose/genética , Linhagem Celular Tumoral , Sobrevivência Celular , Regulação para Baixo , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patologia , Pontos de Checagem da Fase G2 do Ciclo Celular/genética , Humanos , Pontos de Checagem da Fase M do Ciclo Celular/genética , Interferência de RNA , Fator de Transcrição STAT3/genética
15.
Yi Chuan ; 37(8): 731-40, 2015 08.
Artigo em Chinês | MEDLINE | ID: mdl-26353387

RESUMO

Idiopathic basal ganglia calcification (IBGC), also known as Fahr's disease, is an inheritable neurodegenerative syndrome characterized by mineral deposits in the basal ganglia and other brain regions. Patients with IBGC are often accompanied with movement disorders, cognitive impairment as well as psychiatric abnormalities. So far, no therapeutic drug has been developed for the treatment of IBGC. Recently, genetic studies have identified several genes associated with IBGC, including SLC20A2, PDGFRB, PDGFB, ISG15 and XPR1. Loss-of-function mutations in these genes have been associated with disturbance in phosphate homeostasis in brain regions, the dysfunction of blood-brain barrier as well as enhanced IFN-α/ß immunity. In this review, we summarize the latest research progress in the studies on molecular genetics of IBGC, and discuss the molecular mechanisms underlying the pathophysiology of mutations of different genes.


Assuntos
Doenças dos Gânglios da Base/genética , Calcinose/genética , Doenças Neurodegenerativas/genética , Citocinas/genética , Humanos , Mutação , Receptor beta de Fator de Crescimento Derivado de Plaquetas/fisiologia , Receptores Acoplados a Proteínas G/genética , Receptores Virais/genética , Transdução de Sinais , Proteínas Cotransportadoras de Sódio-Fosfato Tipo III/genética , Ubiquitinas/genética , Receptor do Retrovírus Politrópico e Xenotrópico
16.
Acta Pharmacol Sin ; 36(9): 1074-84, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26235743

RESUMO

AIM: To investigate the mechanisms underlying anticancer action of the benzimidazole acridine derivative N-{(1H-benzo[d]imidazol-2-yl)methyl}-2-butylacridin-9-amine(8m) against human colon cancer cells in vitro. METHODS: Human colon cancer cell lines SW480 and HCT116 were incubated in the presence of 8m, and then the cell proliferation and apoptosis were measured. The expression of apoptotic/signaling genes and proteins was detected using RT-PCR and Western blotting. ROS generation and mitochondrial membrane depolarization were visualized with fluorescence microscopy. RESULTS: 8m dose-dependently suppressed the proliferation of SW480 and HCT116 cells with IC50 values of 6.77 and 3.33 µmol/L, respectively. 8m induced apoptosis of HCT116 cells, accompanied by down-regulation of Bcl-2, up-regulation of death receptor-5 (DR5), truncation of Bid, cleavage of PARP, and activation of caspases (including caspase-8 and caspase-9 as well as the downstream caspases-3 and caspase-7). Moreover, 8m selectively activated JNK and p38 without affecting ERK in HCT116 cells. Knockout of JNK1, but not p38, attenuated 8m-induced apoptosis. In addition, 8m induced ROS production and mitochondrial membrane depolarization in HCT116 cells. Pretreatment with the antioxidants N-acetyl cysteine or glutathione attenuated 8m-induced apoptosis and JNK activation in HCT116 cells. CONCLUSION: The new benzimidazole acridine derivative, 8m exerts anticancer activity against human colon cancer cells in vitro by inducing both intrinsic and extrinsic apoptosis pathways via the ROS-JNK1 pathway.


Assuntos
Acridinas/farmacologia , Antineoplásicos/farmacologia , Benzimidazóis/farmacologia , Neoplasias do Colo/tratamento farmacológico , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Acridinas/química , Antineoplásicos/química , Apoptose , Benzimidazóis/química , Caspases/metabolismo , Linhagem Celular Tumoral , Colo/efeitos dos fármacos , Colo/metabolismo , Colo/patologia , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Células HCT116 , Humanos
17.
Huan Jing Ke Xue ; 35(9): 3397-407, 2014 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-25518657

RESUMO

Three-dimensional fluorescence spectroscopy combined with ultraviolet-visible absorption spectra was used to investigate the photobleaching process of dissolved organic matter (DOM) sampled from Fujiang River (FJ), Jialingjiang River (JLJ) and the confluence (FJ-JLJ) under natural solar radiation. The results indicated that obvious photochemical degradation of colored dissolved organic matter (CDOM) concentration [ α(280) ] and all fluorescence peaks intensity (A, C, M and T) occurred under natural solar radiation, and the degradation degree was in order of JLJ > FJ-JLJ > FJ. Photobleaching properties of DOM samples from different locations showed significant differences, which could be partially explained by the sampling sites surroundings including various landuse types, and dilution effect of river confluence. Light-induced bleaching activity of JLJ samples, which was mainly terrestrial input from forest system, was the highest as compared to the lowest activity of FJ samples, which was predominated by urban inputs. Samples from confluence were in the middle. Additionally, the spectrum slope(S) and absorbance ratio (A250/A350) were increased, while the humification index(HIX) was decreased with increasing irradiation time, which can be used as important indicators for photobleaching properties changes during the process. More importantly, the predominantly allochthonous (terrigenous) characteristics of DOM almost showed a tendency of transferring to autochthonous (authigenic) characteristics due to photobleaching. Especially, IT/Ic firstly decreased and then increased significantly in the process. Thus the photodegradation process may exaggerate DOM autochthonous contribution, and further interfere with the assessment of anthropogenic impacted-water quality by using IT/Ic. In addition, mechanisms of light-induced DOM degradation process consistently showed by absorption and fluorescence spectrum parameters suggested the validation of analyzing DOM geochemical characteristics by the two important spectra tools.


Assuntos
Compostos Orgânicos/química , Fotodegradação , Rios/química , Luz Solar , China , Monitoramento Ambiental , Espectrometria de Fluorescência , Qualidade da Água
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