Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 64
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
J Am Chem Soc ; 142(5): 2129-2133, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-31955575

RESUMO

Labile heme (LH) is an important signaling molecule in virtually all organisms. However, specifically detecting LH remains an outstanding challenge. Herein, by learning from the bioactivation mechanism of artemisinin, we have developed the first LH-responsive small-molecule fluorescent probe, HNG, based on a 4-amino-1,8-naphthalimide (NG) fluorophore. HNG showed high selectivity for LH without interference from hemin, protein-interacting heme, and zinc protoporphyrin. Using HNG, the changes of LH levels in live cells were imaged, and a positive correlation of LH level with the degree of hemolysis was uncovered in hemolytic mice. Our study not only presents the first molecular probe for specific LH detection but also provides a strategy to construct probes with high specificity through a bioinspired approach.

2.
Neurosurg Rev ; 2020 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-31953781

RESUMO

Atorvastatin therapy in chronic subdural hematoma patients has attracted more and more clinical attention. To evaluate the efficacy of atorvastatin in the treatment of chronic subdural hematoma. A systematic literature search was performed in the PubMed, Embase, and Cochrane Library databases; related controlled trials comparing the efficacy of atorvastatin in the treatment of chronic subdural hematoma published from inception to December 2018 were collected. We used Cochrane risk of bias method to evaluate the quality of the included studies. Meta-analysis was used to analyze the included data by RevMan 5.3 software. Of the 53 retrieved studies, 6 trials were included. Results of meta-analysis showed that compared with chronic subdural hematoma patients without atorvastatin treatment, both in patients who have had surgery and those who have not, atorvastatin were effective in reducing the incidence of recurrence requires surgery (OR = 0.30, 95% CI 0.19-0.48, P < 0.00001). And improve the recovery rate of neurological function of patients (OR = 1.75, 95% CI 1.08-2.83, P = 0.02). This meta-analysis suggests that patients with chronic subdural hematoma can improve their prognosis after receiving atorvastatin. Additionally, the neurological function recovery appears to be improving by atorvastatin.

3.
Nano Lett ; 19(8): 4965-4973, 2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31298859

RESUMO

The biggest challenge of potassium-ion batteries (KIBs) application is to develop high-performance electrode materials to accommodate the potassium ions large size. Herein, by rational design, we carbonize three-dimensional (3D) ordered macroporous ZIF-8 to fabricate 3D interconnected nitrogen-doped hierarchical porous carbon (N-HPC) that shows excellent rate performance (94 mAh g-1 at 10.0 A g-1), unprecedented cycle stability (157 mA g-1 after 12000 cycles at 2.0 A g-1), and superior reversible capacity (292 mAh g-1 at 0.1 A g-1). The 3D hierarchical porous structure diminishes the diffusion distance for both ions/electrons, while N-doping improves the reactivity and electronic conductivity via producing more defects. In addition, the bicontinuous structure possesses a large specific surface area, decreasing the current density, again improving the rate performance. In situ Raman spectra analysis confirms the potassiation and depotassiation in the N-HPC are highly reversible processes. The galvanostatic intermittent titration measurement and first-principles calculations reveal that the interconnected macropores are more beneficial to the diffusion of the K+. This 3D interpenetrating structure demonstrates a superiority for energy storage applications.

4.
Biochem Biophys Res Commun ; 517(2): 272-277, 2019 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-31349969

RESUMO

QT interval prolongation and depolarization of resting membrane potential (RMP) were found in acute myocardial infarction (MI) which is involved in the arrhythmogenic mechanism and raising the risk to initiate torsade de pointes. However, clinical anti-arrhythmic agents that primarily act on QT interval and RMP are not currently available. Our objective was to determine whether Apelin, an endogenous peptide ligand of receptor APJ, affects QT interval and RMP and underlying mechanisms. To test this viewpoint, mice were subjected to MI by ligating the left main coronary artery and Apelin was applied through tail vein at 5 min prior coronary occlusion in tested group. Compared to MI group, pretreatment of Apelin (15 µg/kg) shortened QTc and QT interval induced by MI, significantly elevated RMP and shortened action potential duration (APD) by increased IK1 currents recorded using whole-cell patch technique from cardiomyocytes underwent MI. In cultured neonatal mouse cardiomyocytes, Apelin (1 µmol/L) restored hypoxia-induced Kir2.1 down-regulation, which was abolished by IP3K inhibitor LY-294002. Additionally, Apelin elicited a time-dependent increase in phosphorylation of Akt leading to increase in PI3-kinase activity. These results showed that Apelin enhanced IK1/Kir2.1 currents via IP3K pathway as by rescue ischemia- and hypoxia-induced RMP depolarization and prolongation of QT interval, which may prevent or cure acute ischemic-mediated arrhythmias. This study brings new information to anti-arrhythmic theories and provides a potential target for the clinical management of acute ischemia-related arrhythmias.

5.
Epilepsy Res ; 154: 139-143, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31151073

RESUMO

PURPOSE: Valproic acid (VPA) is frequently used in the treatment of epilepsy. The adverse effects of VPA include hyperammonemia (HA) which is characterized by abnormally elevated blood ammonia level. Carbamoyl-Phosphate Synthase 1 (CPS1) is an enzyme catalyzing the initial step of removing ammonia from blood. Studies have demonstrated that the CPS1 polymorphism rs1047891-A allele carriers were susceptible to VPA-induced HA. However, the evidences remained controversial. In this study, we sought to validate the association between rs1047891 and VPA-induced HA by combining the association results from previous studies together. METHODS: We first conducted a systematic meta-analysis to determine whether rs1047891 was statistically significant. Then, we further evaluated the pleiotropic effects of rs1047891 using published genome-wide association studies (GWAS) and UKBB results. A conditional analysis was conducted to investigate whether the association between rs1047891 and VPA-induced HA was mediated by cardiovascular or renal disease risk factors or vice versa. RESULTS: The allelic, dominant and recessive ORs of rs1047891-A were all significant in our fixed-effect meta-analysis. In GWAS catalog and UKBB data, rs1047891 was associated with basal metabolic rate, adiposity and hematology traits, cardiovascular and renal disease risk factors. We further proved that plasma HDL cholesterol and homocysteine level, in addition to eGFR by serum creatinine, were associated with VPA-induced HA risk independently from rs1047891 polymorphism. CONCLUSION: In conclusion, the SNP rs1047891 was associated with VPA-induce HA among epilepsy patients. Meanwhile, plasma HDL cholesterol and homocysteine level had independent effects from it.

6.
Artigo em Inglês | MEDLINE | ID: mdl-30906280

RESUMO

Fibroblast growth factor 1 (FGF1) is reported to be expressed in the testis. How FGF1 affects stem Leydig cell development remains unclear. Here, we report the effects of FGF1 on rat stem Leydig cell development in an ethane dimethane sulfonate (EDS)-treated model. FGF1 (100 ng/testis) significantly increased serum testosterone level, increased PCNA-positive Leydig cell percentage and Leydig cell number, but down-regulated the expression of Lhcgr, Star, Cyp11a1, Hsd3b1, Cyp17a1, and Hsd11b1 in Leydig cells per se, after its daily intratesticular injection from post-EDS day 14 for 14 days. Primary culture of the seminiferous tubules showed that FGF1 stimulated EdU incorporation to stem Leydig cells but blocked the differentiation into the Leydig cell lineage, possibly via FGFR1-mediated mechanism. In conclusion, FGF1 promotes stem Leydig cell proliferation but blocks its differentiation.

7.
Am J Physiol Lung Cell Mol Physiol ; 316(5): L918-L933, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-30628487

RESUMO

The involvement of several microRNAs (miRs) in the initiation and development of tumors through the suppression of the target gene expression has been highlighted. The aberrant expression of miR-181d-5p and cyclin-dependent kinase inhibitor 3 (CDKN3) in non-small-cell lung cancer (NSCLC) was then screened by microarray analysis. In the present study, we performed a series of in vivo and in vitro experiments for the purpose of investigating their roles in NSCLC and the underlying mechanism. There was a high expression of CDKN3, whereas miR-181d-5p was downregulated in NSCLC. Quantitative RT-PCR, Western blot analysis, and dual-luciferase reporter gene assay further identified that CDKN3 could be negatively regulated by miR-181d-5p. Moreover, the upregulation of miR-181d-5p or silencing of CDKN3 could inactivate the Akt signaling pathway. A549 with the lowest miR-181d-5p and H1975 with the highest CDKN3 among the five NSCLC cell lines (H1299, A549, H1975, NCI-H157, and GLC-82) were adopted for in vitro experiments, in which expression of miR-181d-5p and CDKN3 was altered by transfection of miR-181d-5p mimic/inhibitor or siRNA-targeting CDKN3. Afterwards, cell proliferation, apoptosis, invasion, migration, and angiogenesis, as well as epithelial-mesenchymal transition (EMT), were evaluated, and tumorigenicity was assessed. In addition, an elevation in miR-181d-5p or depletion in CDKN3 led to significant reductions in proliferation, invasion, migration, angiogenesis, EMT, and tumorigenicity of NSCLC cells, coupling with increased cell apoptosis. In conclusion, this study highlights the tumor-suppressive effects of miR-181d-5p on NSCLC via Akt signaling pathway inactivation by suppressing CDKN3, thus providing a promising therapeutic strategy for the treatment of NSCLC.

8.
Cell Rep ; 26(4): 884-892.e4, 2019 01 22.
Artigo em Inglês | MEDLINE | ID: mdl-30673611

RESUMO

DNA variants in the SLC16A11 coding region were identified to be strongly associated with type 2 diabetes (T2DM) in a Mexican population. Previous studies suggested that these variants disrupt SLC16A11 function and therefore proposed to revive SLC16A11 levels or activity to achieve therapeutic benefit. However, with knockout mouse models, here we show that Slc16a11 depletion has no significant metabolic defects. Further studies demonstrate that reconstitution of the mutant, but not the wild-type Slc16a11, in the liver of knockout mice causes more triglyceride accumulation and induction of insulin resistance via upregulation of lipin 1, suggesting gaining of aberrant functions of the mutant protein that affects lipid metabolism. Our findings offer a different explanation to the function of these diabetic variants, challenging the concept of enhancing SLC16A11 function to treat T2DM. The contradictory results by our and previous studies suggest that how the SLC16A11 locus contributes to human metabolism warrants further investigation.

9.
Anal Chem ; 91(4): 2727-2733, 2019 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-30663316

RESUMO

Nanoscale metal-organic frameworks (NMOFs) have been applied for biomedical sensing in recent years. However, it is still a great challenge to construct a highly efficient NMOFs fluorescent probe for sensing in a biological system, with high signal-to-noise ratio, photostability, and deep tissue penetration. Herein, for the first time, we report the two-photon metal-organic framework (TP-MOF) as a sensing platform. The design of TP-MOF is based on NMOFs incorporating a target-responsive two-photon organic moiety through click chemistry. PCN-58, as a model building block, was covalently modified with a small-molecule probe for H2S or Zn2+ as model analytes. TP-MOF probes retain the fluorescence-responsive properties of the TP organic moiety and possess excellent photostability and selectivity, as well as biocompatibility. Benefiting from the near-infrared (∼820 nm) excited two-photon fluorophore, TP-MOF probes serve to sense and image their respective targets in live cells and tissue slices with a penetration of 130 µm. The molecular design presented here bodes well for the extension to other MOFs displaying sensing components for other analytes of interest.

10.
J Neurol Sci ; 397: 174-178, 2019 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-30641247

RESUMO

BACKGROUND: Prasugrel as a second generation P2Y12 adenosine diphosphate receptor antagonist which in the cerebral aneurysms with Endovascular treatment have become more emphasized. OBJECTIVE: To compare the efficacy and safety of prasugrel therapy for intracranial aneurysms with endovascular treatment. METHODS: The databases of PubMed, Embase, Cochrane Library databases and China Biology Medicine disc were retrieved with computers for collecting controlled trials about the comparison in the efficacy and safety of prasugrel and clopidogrel published from inception to September 2018. At the same time, the reference materials of included literature were retrieved manually. After rigorous evaluation on literature quality, the eligible data of the trials was extracted and given a Meta-analysis by applying RevMan5.3 software. RESULTS: Of the 96 studies identified, 7 trials were included. Results of meta-analysis showed that compared with patients receiving clopidogrel treatment, novel platelet P2Y12 receptor inhibitor prasugrel were effective in reducing the incidence of thromboembolic events (OR = 0.19, 95%CI: 0.08-0.45, P = .0001), but did not increase the risk of hemorrhagic complication (OR = 1.00, 95%CI: 0.53-1.89, P = 1.00), and the PRU (OR = 0.19, 95%CI: 0.08-0.45, P = .0001) and Percentage inhibition of platelet (MN = 37.05, 95%CI: 33.37-40.73, P < .00001) were controlled in a better range. CONCLUSION: In antiplatelet therapy after aneurysmal interventional therapy, the second generation of P2Y12 adenosine receptor antagonist prasugrel can significantly reduce the risk of thrombosis without increasing the risk of bleeding.

11.
J Cell Mol Med ; 23(1): 426-438, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30320465

RESUMO

Oncostatin M (OSM) is a pleiotropic cytokine within the interleukin six family of cytokines, which regulate cell growth and differentiation in a wide variety of biological systems. However, its action and underlying mechanisms on stem Leydig cell development are unclear. The objective of the present study was to investigate whether OSM affects the proliferation and differentiation of rat stem Leydig cells. We used a Leydig cell regeneration model in rat testis and a unique seminiferous tubule culture system after ethane dimethane sulfonate (EDS) treatment to assess the ability of OSM in the regulation of proliferation and differentiation of rat stem Leydig cells. Intratesticular injection of OSM (10 and 100 ng/testis) from post-EDS day 14 to 28 blocked the regeneration of Leydig cells by reducing serum testosterone levels without affecting serum luteinizing hormone and follicle-stimulating hormone levels. It also decreased the levels of Leydig cell-specific mRNAs (Lhcgr, Star, Cyp11a1, Hsd3b1, Cyp17a1 and Hsd11b1) and their proteins by the RNA-Seq and Western blotting analysis. OSM had no effect on the proliferative capacity of Leydig cells in vivo. In the seminiferous tubule culture system, OSM (0.1, 1, 10 and 100 ng/mL) inhibited the differentiation of stem Leydig cells by reducing medium testosterone levels and downregulating the expression of Leydig cell-specific genes (Lhcgr, Star, Cyp11a1, Hsd3b1, Cyp17a1 and Hsd11b1) and their proteins. OSM-mediated action was reversed by S3I-201 (a STAT3 antagonist) or filgotinib (a JAK1 inhibitor). These data suggest that OSM is an inhibitory factor of rat stem Leydig cell development.

12.
Pathol Oncol Res ; 25(1): 369-376, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29134462

RESUMO

This study aims to explore the roles of fibroblast activation protein (FAP) and hepatocyte growth factor (HGF) expressions in the angiogenesis and metastasis of gastric cancer (GC). From May 2012 to December 2015, 110 GC patients who received surgical treatment in the First Hospital of Qinhuangdao were selected. The HGF and FAP expressions in 110 cases of GC, 130 cases of normal gastric mucosa and 115 cases of gastric ulcer were detected by streptavidin-perosidase (SP) method. Venous blood HGF level of GC patients was tested by enzyme-linked immunosorbent assay (ELISA). The micro-vessel number of the patients in the three groups were calculated and analyzed. In GC group, positive expression rates of FAP and HGF protein were 61.8% and 67.3% respectively, which were both higher than those in normal gastric mucosa and gastric ulcer groups. The micro-vessel numbers in patients of the normal gastric mucosa and gastric ulcer groups are far less than that in GC group. FAP, HGF and micro-vessel density (MVD) were significantly correlated with infiltration depth, tumor-node-metastasis (TNM) staging, lymph node metastasis (LNM) and distant metastasis. The results of ELISA showed that serum HGF level was related to tumor size, infiltration degree, TNM staging, LNM and distant metastasis. FAP and HGF expressions in GC were positively correlated with MVD, and the expressions of FAP and HGF in GC were in positive correlation. Our study provided evidence that high FAP and HGF expressions may be positively correlated with the angiogenesis and metastasis of GC.


Assuntos
Adenocarcinoma/secundário , Biomarcadores Tumorais/metabolismo , Gelatinases/metabolismo , Fator de Crescimento de Hepatócito/metabolismo , Proteínas de Membrana/metabolismo , Neovascularização Patológica/patologia , Serina Endopeptidases/metabolismo , Neoplasias Gástricas/patologia , Adenocarcinoma/irrigação sanguínea , Adenocarcinoma/metabolismo , Feminino , Seguimentos , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Neovascularização Patológica/metabolismo , Prognóstico , Neoplasias Gástricas/irrigação sanguínea , Neoplasias Gástricas/metabolismo , Taxa de Sobrevida
13.
Int J Ophthalmol ; 11(12): 1916-1921, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30588422

RESUMO

AIM: To recombine the human alpha B-crystallin (αB-crystallin) using gene cloning technology and prokaryotic expression vector and confirm the biological activity of recombinant human αB-crystallin. METHODS: Cloning the human αB-crystallin cDNA according to the nucleotide sequence of the human αB-crystallin, constructing the pET-28/CRYAB prokaryotic expression plasmid by restriction enzyme digestion method, and stably expressing transformed into the Escherichia coli (E. coli) DH5 alpha. The recombinant human αB-crystallin was purified by Q sepharose. By enzyme digestion analysis, Western blotting and sequencing, the recombinant human αB-crystallin was identified and the activity of its molecular protein was detected. RESULTS: Compared with the gene bank (GeneBank), the cloned human sequence of human αB-crystallin cDNA has the same open reading frame. Identification and sequencing of the cloned human αB-crystallin cDNA in prokaryotic expression vector confirmed the full length sequence, and the vector was constructed successfully. The E. coli containing plasmid pET-28/CRYAB induced by isopropyl-ß-D-thiogalactoside successfully expressed the human αB-crystallin. Insulin confirmed that the recombinant human αB-crystallin has a molecular chaperone activity. CONCLUSION: The prokaryotic expression vector pET-28/CRYAB of recombinant human αB-crystallin is successfully constructed, and the recombinant human αB-crystallin with molecular chaperone activity is obtained, which lay a foundation for the research and application of the recombinant human αB-crystallin and its chaperone activity.

14.
Chem Sci ; 9(44): 8402-8408, 2018 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-30542589

RESUMO

The complex environment of living organisms significantly challenges the selectivity of classic small-molecule fluorescent probes for bioimaging. Due to their predesigned topological structure and engineered internal pore surface, covalent organic frameworks (COFs) have the ability to filter out coexisting interference components and help to achieve accurate biosensing. Herein, we propose an effective interference-resistant strategy by creating a COF-based hybrid probe that combines the respective advantages of COFs and small-molecule probes. As a proof of concept, a two-photon fluorescent COF nanoprobe, namely TpASH-NPHS, is developed for targeting hydrogen sulfide (H2S) as a model analyte. TpASH-NPHS exhibits limited cytotoxicity, excellent photostability and long-term bioimaging capability. More importantly, compared with the small-molecule probe, TpASH-NPHS achieves accurate detection without the interference from intracellular enzymes. This allows us to monitor the levels of endogenous H2S in a mouse model of cirrhosis.

15.
Chem Res Toxicol ; 31(12): 1315-1322, 2018 12 17.
Artigo em Inglês | MEDLINE | ID: mdl-30422632

RESUMO

Ziram is a dimethyldithiocarbamate fungicide, which may influence the male reproductive system as a potential endocrine disruptor. We interrogated the disruption of ziram on rat progenitor Leydig cell development. Prepubertal male Sprague-Dawley rats were orally treated with 0, 2, 4, or 8 mg/kg ziram for 2 weeks. We investigated the effects of ziram on serum testosterone levels, Leydig cell number, and Leydig and Sertoli cell gene and protein expression, SIRT1/PGC-1α levels, and phosphorylation of AKT1, ERK1/2, and AMPK in vivo. We also interrogated the effects of ziram on reactive oxidative species (ROS) level, apoptosis rate, and mitochondrial membrane potential of progenitor Leydig cells in vitro. Ziram decreased serum testosterone and follicle-stimulating hormone levels, the down-regulated Leydig cell-specific gene ( Lhcgr, Scarb1, Star, Cyp17a1, and Hsd17b3), and their protein expression. However, ziram stimulated anti-Müllerian hormone production. Ziram lowered SIRT1/PGC-1α and phosphorylated protein levels of AKT1. Ziram induced ROS and apoptosis and lowered the mitochondrial membrane potential of progenitor Leydig cells in vitro. In conclusion, ziram disrupts Leydig cell development during the prepubertal period potentially through the SIRT1/PGC-1α and phosphorylated AKT1 signaling.


Assuntos
Fungicidas Industriais/toxicidade , Puberdade Tardia/etiologia , Transdução de Sinais/efeitos dos fármacos , Testículo/efeitos dos fármacos , Ziram/toxicidade , Animais , Apoptose/efeitos dos fármacos , Enzima de Clivagem da Cadeia Lateral do Colesterol/metabolismo , Regulação para Baixo/efeitos dos fármacos , Fungicidas Industriais/química , Células Intersticiais do Testículo/citologia , Células Intersticiais do Testículo/efeitos dos fármacos , Células Intersticiais do Testículo/metabolismo , Masculino , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Puberdade Tardia/metabolismo , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Sirtuína 1/metabolismo , Testículo/metabolismo , Testosterona/sangue , Ziram/química
16.
BMC Med Genet ; 19(1): 204, 2018 11 26.
Artigo em Inglês | MEDLINE | ID: mdl-30477447

RESUMO

BACKGROUND: Von Hippel-Lindau (VHL) disease is an autosomal dominant inherited cancer syndrome, and VHL is identified as a tumor suppressor gene. The main objective of this study was to identify disease-causing mutations in a Chinese family affected with VHL disease. METHODS: Genomic DNA was extracted from peripheral blood from a Chinese family with VHL. A predicted pathogenic variant was identified by targeted exome capture technology and next-generation sequencing. RESULTS: A novel heterozygous mutation (c.349 T > A, p.W117R) was detected in affected family members. No mutation was detected in unaffected family members or in the 150 normal controls. The mutation segregated with the disease phenotype throughout three generations. Histopathological examination revealed the characteristics of hemangioblastoma. CONCLUSIONS: A novel W117R was detected in the VHL gene that caused retinal hemangioblastomas in affected members of a Chinese family.


Assuntos
Hemangioblastoma/genética , Mutação de Sentido Incorreto , Neoplasias da Retina/genética , Proteína Supressora de Tumor Von Hippel-Lindau/genética , Doença de von Hippel-Lindau/genética , Adulto , Grupo com Ancestrais do Continente Asiático , Criança , Análise Mutacional de DNA , Feminino , Expressão Gênica , Hemangioblastoma/diagnóstico , Hemangioblastoma/etnologia , Hemangioblastoma/patologia , Heterozigoto , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Linhagem , Fenótipo , Retina/metabolismo , Retina/patologia , Neoplasias da Retina/diagnóstico , Neoplasias da Retina/etnologia , Neoplasias da Retina/patologia , Doença de von Hippel-Lindau/diagnóstico , Doença de von Hippel-Lindau/etnologia , Doença de von Hippel-Lindau/patologia
17.
Chem Soc Rev ; 47(18): 7140-7180, 2018 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-30140837

RESUMO

Abnormal enzymatic activities are directly related to the development of cancers. Identifying the location and expression levels of these enzymes in live cancer cells have considerable importance in early-stage cancer diagnoses and monitoring the efficacy of therapies. Small-molecule fluorescent probes have become a powerful tool for the detection and imaging of enzymatic activities in biological systems by virtue of their higher sensitivity, nondestructive fast analysis, and real-time detection abilities. Moreover, due to their structural tailorability, numerous small-molecule enzymatic fluorescent probes have been developed to meet various demands involving real-time tracking and visualizing different enzymes in live cancer cells or in vivo. In this review, we provide an overview of recent advances in small-molecule enzymatic fluorescent probes mainly during the past decade, including the design strategies and applications for various enzymes in live cancer cells. We also highlight the challenges and opportunities in this rapidly developing field of small-molecule fluorescent probes for interventional surgical imaging, as well as cancer diagnosis and therapy.


Assuntos
Enzimas/análise , Corantes Fluorescentes/química , Neoplasias/diagnóstico por imagem , Neoplasias/enzimologia , Imagem Óptica , Bibliotecas de Moléculas Pequenas/química , Enzimas/metabolismo , Humanos , Neoplasias/patologia
18.
Chem Commun (Camb) ; 54(81): 11383-11386, 2018 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-30137105

RESUMO

Open-shell diradicaloids have been intensively investigated recently due to their attractive and unique optical, electronic and magnetic properties. However, open-shell diradicaloids with non-planar conjugated frameworks are less studied, especially helical-shaped π systems. In this work, we synthesized tetraindeno-based singlet biradicals in a helical geometry, bridged by a curved cyclobutenyl o-quinodimethane molecule. Large diradical characters and extremely small singlet-triplet energy gaps, as well as unusual half-field transitions (forbidden ΔMs = 2) were revealed for these 3D diradicals.

19.
Sci Rep ; 8(1): 13037, 2018 08 29.
Artigo em Inglês | MEDLINE | ID: mdl-30158649

RESUMO

Calorie restriction (CR) extends lifespan and elicits numerous effects beneficial to health and metabolism in various model organisms, but the underlying mechanisms are not completely understood. Gut microbiota has been reported to be associated with the beneficial effects of CR; however, it is unknown whether these effects of CR are causally mediated by gut microbiota. In this study, we employed an antibiotic-induced microbiota-depleted mouse model to investigate the functional role of gut microbiota in CR. Depletion of gut microbiota rendered mice resistant to CR-induced loss of body weight, accompanied by the increase in fat mass, the reduction in lean mass and the decline in metabolic rate. Depletion of gut microbiota led to increases in fasting blood glucose and cholesterol levels independent of CR. A few metabolism-modulating hormones including leptin and insulin were altered by CR and/or gut microbiota depletion. In addition, CR altered the composition of gut microbiota with significant increases in major probiotic genera such as Lactobacillus and Bifidobacterium, together with the decrease of Helicobacter. In addition, we performed fecal microbiota transplantation in mice fed with high-fat diet. Mice with transferred microbiota from calorie-restricted mice resisted high fat diet-induced obesity and exhibited metabolic improvement such as alleviated hepatic lipid accumulation. Collectively, these data indicate that CR-induced metabolic improvement especially in body weight reduction is mediated by intestinal microbiota to a certain extent.


Assuntos
Restrição Calórica , Microbioma Gastrointestinal , Perda de Peso , Animais , Metabolismo , Camundongos
20.
Front Pharmacol ; 9: 833, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30147652

RESUMO

Triphenyltin chloride (TPT) is present in a wide range of human foods. TPT could disrupt testis function as a potential endocrine disruptor of Leydig cells. However, the effect of TPT on pubertal Leydig cell development is still unclear. The objective of the current study was to explore whether exposure to TPT affected Leydig cell developmental process and to clarify the underlying mechanisms. Male Sprague-Dawley rats at 35 days of age were randomly divided into four groups and received normal corn oil (control), 0.5, 1, or 2 mg/kg/day TPT for 18 days. Immature Leydig cells isolated from 35-day-old rat testes were treated with TPT (10 and 100 nM) for 24 h in vitro. In vivo exposure to ≥0.5 mg/kg TPT lowered serum testosterone levels and lowered Star mRNA. TPT at 2 mg/kg also lowered Lhcgr, Cyp11a1, Hsd3b1, Hsd17b3 as well as pAKT1/AKT1, pAKT2/AKT2, and pERK1/2/ERK1/2 ratios. In vitro exposure to TPT (100 nM) increased ROS production and induced cell apoptosis rate in rat immature Leydig cells. In conclusion, TPT exposure disrupts Leydig cell development possibly via interfering with the phosphorylation of AKT1, AKT2, and ERK1/2 kinases.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA