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1.
Talanta ; 269: 125469, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38043337

RESUMO

Telomerase (TE) is a promising diagnostic and prognostic biomarker for many cancers. Quantification of TE activity in living cells is of great significance in biomedical and clinical research. Conventional fluorescence-based sensors for quantification of intracellular TE may suffer from problems of fast photobleaching and auto-fluorescence of some endogenous molecules, and hence are liable to produce false negative or positive results. To address this issue, a fluorescence-SERS dual-signal nano-system for real-time imaging of intracellular TE was designed by functionalizing a bimetallic Au@Ag nanostructure with 4-p-mercaptobenzoic acid (internal standard SERS tag) and a DNA hybrid complex consisted of a telomerase primer strand and its partially complimentary strand modified with Rhodamine 6G. The bimetallic Au@Ag nanostructure serves as an excellent SERS-enhancing and fluorescence-quenching substrate. Intracellular TE will trigger the extension of the primer strand and cause the shedding of Rhodamine 6G-modified complimentary strand from the nano-system through intramolecular DNA strand displacement, resulting in the recovery of the fluorescence of Rhodamine 6G and decrease in its SERS signal. Both the fluorescence of R6G and the ratio between the SERS signals of 4-p-mercaptobenzoic acid and Rhodamine 6G can be used for in situ imaging of intracellular TE. Experimental results showed that the proposed nano-system was featured with low background, excellent cell internalization efficiency, good biocompatibility, high sensitivity, good selectivity, and robustness to false positive results. It can be used to distinguish cancer cells from normal ones, identify different types of cancer cells, as well as perform absolute quantification of intracellular TE, which endows it with great potential in clinical diagnosis, target therapy and prognosis of cancer patients.


Assuntos
Nanoestruturas , Telomerase , Humanos , Fluorescência , Telomerase/metabolismo , DNA
2.
Korean Circ J ; 52(9): 680-696, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36097836

RESUMO

BACKGROUND AND OBJECTIVES: Circular RNAs were known to play vital role in myocardial ischemia reperfusion injury (MIRI), while the role of CircZNF609 in MIRI remains unclear. This study was aimed to investigate the function of CircZNF609 in MIRI. METHODS: Hypoxia/reoxygenation (H/R) model was established to mimic MIRI in vitro. Quantitative polymerase chain reaction was performed to evaluate gene transcripts. Cellular localization of CircZNF609 and miR-214-3p were visualized by fluorescence in situ hybridization. Cell proliferation was determined by CCK-8. TUNEL assay and flow cytometry were applied to detect apoptosis. Lactate dehydrogenase was determined by commercial kit. ROS was detected by DCFH-DA probe. Direct interaction of indicated molecules was determined by RIP and dual luciferase assays. Western blot was used to quantify protein levels. In vivo model was established to further test the function of CircZNF609 in MIRI. RESULTS: CircZNF609 was upregulated in H/R model. Inhibition of CircZNF609 alleviated H/R induced apoptosis, ROS generation, restored cell proliferation in cardiomyocytes and human umbilical vein endothelial cells. Mechanically, CircZNF609 directly sponged miR-214-3p to release PTGS2 expression. Functional rescue experiments showed that miR-214-3p/PTGS2 axis was involved in the function of circZNG609 in H/R model. Furthermore, data in mouse model revealed that knockdown of CircZNF609 significantly reduced the area of myocardial infarction and decreased myocardial cell apoptosis. CONCLUSIONS: CircZNF609 aggravated the progression of MIRI via targeting miR-214-3p/PTGS2 axis, which suggested CircZNF609 might act as a vital modulator in MIRI.

3.
Mol Pain ; 15: 1744806919842464, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30987515

RESUMO

Neuropathic pain is a type of chronic pain induced by either central or peripheral nerve injury. MicroRNAs have been recently linked to many diseases, including neuropathic pain. However, the role of miR-7a in neuropathic pain still remains elusive. Thus, we aim to investigate the effects of miR-7a on neuropathic pain based on the spinal nerve ligation rat model. After establishment of spinal nerve ligation rat models, rats were infected with adeno-associated virus-neurofilament light polypeptide, adeno-associated virus-miR-7a or treated with metformin. The paw withdrawal threshold and paw withdrawal latency were assessed afterward, and the expression of miR-7a and neurofilament light polypeptide as well as their interaction was determined. Subsequently, miR-7a was overexpressed or silenced in dorsal root ganglion cells to investigate the role of miR-7a in neuropathic pain. Furthermore, the regulatory effect of neurofilament light polypeptide on neuropathic pain was detected using plasmid overexpressing neurofilament light polypeptide. Spinal nerve ligation rat model exhibited upregulation of neurofilament light polypeptide but downregulation of miR-7a. In addition, neurofilament light polypeptide accumulation or miR-7a inhibition decreased paw withdrawal threshold and paw withdrawal latency. Then, neurofilament light polypeptide accumulation or miR-7a inhibition was observed to increase the phosphorylation level of signal transducer and activator of transcription. miR-7a was found to directly target neurofilament light polypeptide and downregulate neurofilament light polypeptide. In addition, inhibiting the signal transducer and activator of transcription signaling pathway was also revealed to increase paw withdrawal threshold and paw withdrawal latency. Collectively, our study demonstrated that miR-7a ameliorated neuropathic pain via blocking the signal transducer and activator of transcription signaling pathway by repressing neurofilament light polypeptide. These findings, if taken further, can be of important clinical significance in treating patients with neuropathic pain.


Assuntos
MicroRNAs/metabolismo , Neuralgia/genética , Proteínas de Neurofilamentos/metabolismo , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais , Nervos Espinhais/patologia , Animais , Sequência de Bases , Modelos Animais de Doenças , Regulação para Baixo/genética , Ligadura , Masculino , MicroRNAs/genética , Modelos Biológicos , Proteínas de Neurofilamentos/genética , Ratos Sprague-Dawley , Regulação para Cima/genética
4.
Bioorg Med Chem Lett ; 25(17): 3592-6, 2015 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-26152428

RESUMO

Au, Se and porphyrin are widely used components in the design of anticancer drugs, but their combination has never been referred to. In this work, a Se-modified porphyrin Au(III) complex, [AuTPP-Se]Cl, was designed and synthesized as a potential anticancer agent. This compound exhibits remarkable antiproliferative activity on all the six tested cancer cells. Its potency on HepG2 is even ten times higher than that of CDDP. The synergistic action among Au, Se and porphyrin components was validated. Mechanism study showed that both the induction of mitochondria-dependent apoptosis and the arrest of cell cycle contribute to the anticancer activity of [AuTPP-Se]Cl.


Assuntos
Antineoplásicos/química , Compostos Organoáuricos/química , Porfirinas/química , Compostos de Selênio/química , Antineoplásicos/farmacologia , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Humanos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/patologia , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Compostos Organoáuricos/farmacologia , Porfirinas/farmacologia , Compostos de Selênio/farmacologia
5.
World J Gastroenterol ; 19(32): 5326-33, 2013 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-23983437

RESUMO

AIM: To explore the protective effect and the relevant mechanisms of Fufang Biejia Ruangan Pills (FFBJRGP) on hepatic fibrosis in vivo and in vitro. METHODS: Hepatic fibrosis was induced by carbon tetrachloride composite factors. Adult Wistar rats were randomly divided into four groups: normal control group; hepatic fibrosis model group; FFBJRGP-treated group at a daily dose of 0.55 g/kg; and colchicine-treated group at a daily dose of 0.1 g/kg. The effects of FFBJRGP on liver function, serum levels of hyaluronic acid (HA), type IV collagen (CIV), type III procollagen (PC III), laminin (LN), histopathology, and expression of transforming growth factor (TGF-ß1) and Smad3 in hepatic fibrosis were evaluated in vivo. The effects of FFBJRGP on survival rate, hydroxyproline content and cell cycle distribution were further detected in vitro. RESULTS: Compared with the hepatic fibrosis model group, rats treated with FFBJRGP showed a reduction in hepatic collagen deposition and improvement in hepatic lesions. Compared with those of the model group, the activities of alanine aminotransferase (62.0 ± 23.7 U/L) and aspartate aminotransferase (98.8 ± 40.0 U/L) in the FFBJRGP-treated group were decreased (50.02 ± 3.7 U/L and 57.2 ± 30.0 U/L, respectively, P < 0.01). Compared with those in the model group, the levels of PCIII (35.73 ± 17.90 µg/mL), HA (563.82 ± 335.54 ng/mL), LN (89.57 ± 7.59 ng/mL) and CIV (29.20 ± 6.17 ng/mL) were decreased to 30.18 ± 9.41, 456.18 ± 410.83, 85.46 ± 7.51 and 28.02 ± 9.45 ng/mL, respectively. Reverse-transcriptase polymerase chain reaction and Western blotting also revealed that expression of TGF-ß1 and Smad3 were down-regulated in vivo. Cell proliferation was inhibited, the level of hydroxyproline was decreased compared with the control group (P < 0.01), and the cell cycle was redistributed when exposed to FFBJRGP in vitro. CONCLUSION: FFBJRGP inhibits hepatic fibrosis in vivo and in vitro, which is probably associated with downregulation of fibrogenic signal transduction of the TGF-ß-Smad pathway.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Hepatócitos/efeitos dos fármacos , Cirrose Hepática Experimental/tratamento farmacológico , Fígado/efeitos dos fármacos , Medicina Tradicional Chinesa , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Biomarcadores/sangue , Tetracloreto de Carbono , Ciclo Celular/efeitos dos fármacos , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Colágeno Tipo III/sangue , Colágeno Tipo IV/sangue , Feminino , Hepatócitos/metabolismo , Hepatócitos/patologia , Humanos , Ácido Hialurônico/sangue , Hidroxiprolina/metabolismo , Laminina/sangue , Fígado/metabolismo , Fígado/patologia , Cirrose Hepática Experimental/induzido quimicamente , Cirrose Hepática Experimental/metabolismo , Cirrose Hepática Experimental/patologia , Masculino , Pró-Colágeno/sangue , Ratos , Ratos Wistar , Proteína Smad3/metabolismo , Comprimidos , Fator de Crescimento Transformador beta1/metabolismo
6.
Pain Med ; 13(4): 518-21, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22360763

RESUMO

OBJECTIVE: The objective of this study was to assess outcomes and safety of consecutive neurolytic celiac plexus block (NCPB) technique. DESIGN: Retrospective clinical data analysis. SETTING: The study was conducted in three pain departments and academic medical center. PATIENTS: The subject of this study was 12 patients with terminal visceral (mostly pancreatic) cancer who failed conservative measures. INTERVENTIONS: Twelve celiac plexus alcohol neurolytic procedures were performed for pain control after a positive diagnostic block. MATERIALS AND METHODS: Twelve patients with terminal visceral (mostly pancreatic) cancer who failed conservative measures were managed by consecutive NCPB guided by computed tomography at the pain department of Beijing Xuanwu Hospital between January 2005 and June 2010. The present study evaluated the efficacy of consecutive NCPB technique with regard to pain relief, as well as its adverse effects and complications. RESULTS: The efficacy of consecutive NCPB technique with regard to pain relief was observed by a marked decrease in the visual analog score and in opioid consumption, with preprocedural mean values dropping from (8.7±1.0) and (155±56)mg/day of morphine to (1.8±1.1) and (0)mg/day at the first postprocedural visit, respectively. These results persisted during the 6-month follow-up period or until death. Minor adverse effects (moderate diarrhea and mild hypotension) were frequent (N=3, and N=4, respectively), and severe complications occurred in one patient with a transient paraparesis (N=1). No procedure-related mortality was observed. CONCLUSIONS: The consecutive NCPB technique can provide analgesia and the alleviation of the secondary undesirable effects of analgesic drugs resulting from the decrease of morphine consumption in patients with upper abdominal malignancies. In the subject group, the reliability of its analgesic effect is high, with lower rate of severe complications.


Assuntos
Plexo Celíaco/efeitos dos fármacos , Etanol/uso terapêutico , Bloqueio Nervoso/métodos , Neurotoxinas/uso terapêutico , Dor Intratável/terapia , Neoplasias Pancreáticas/complicações , Idoso , Anestésicos Locais/administração & dosagem , Plexo Celíaco/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neurotoxinas/administração & dosagem , Dor Intratável/etiologia , Dor Intratável/fisiopatologia , Estudos Retrospectivos , Resultado do Tratamento
7.
World J Gastroenterol ; 16(12): 1458-64, 2010 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-20333785

RESUMO

AIM: To explore the anti-fibrotic effect of Haobie Yangyin Ruanjian decoction (HYRD) on CCl(4)-induced hepatic fibrosis in rats and its modulation on the transforming growth factor (TGF) beta-Smad signaling pathway. METHODS: Fifty-six healthy Wistar rats were randomly divided into five groups: normal control group (n = 6), CCl(4)-induced hepatic fibrosis group (n = 14) and three treatment groups (the treated rats received HYRD via oral administration at daily dosages of 8.2, 2.5 and 0.82 g/kg, respectively) of HYRD (n = 12, respectively). Experimental hepatic fibrosis was induced by subcutaneous injection of carbon tetrachloride solution (CCl(4) dissolved in peanut oil, 4:6, V/V) with 0.5 mL/100 g body weight for the first time, and then 0.3 mL/100 g body weight twice a week for 8 wk. In the former 2 wk, rats were raised by feedstuff I (80% corn meal, 20% lard, 0.5% cholesterol). After 2 wk, they were raised by feedstuff II (corn meal and 0.5% cholesterol). Except for the control group, 30% alcohol solution was given orally to each rat every other day from the beginning, 1 mL for each rat. Liver function parameters and hepatic hydroxyproline content were detected by chromatometry. Serum levels of hyaluronic acid (HA), type IV collagen (CIV), type III precollagen (PCIII) and laminin (LN) were assayed with radioimmunoassay. Deposition of collagen was observed with hematoxylin-eosin staining and collagen staining. Gene expression of TGFbeta1 and Smad3 were detected with real-time reverse transcriptase-polymerase chain reaction and Western blotting, respectively. RESULTS: The serum levels of alanine transaminase and aspartate transaminase were increased in the model group compared with the control group (P < 0.01), and they were decreased in the three treatment groups compared with the model group. The serum levels of total protein and albumin were decreased in the model group and increased in the three treatment groups. The hepatic hydroxyproline content and serum levels of PCIII, HA, LN and CIV were markedly increased in the model group compared with the control group, and decreased in the treatment groups. The gene expression of TGFbeta1 and Smad3 was enhanced in the model group compared with the control group, and HYRD could down regulate their expression. CONCLUSION: HYRD can inhibit hepatic fibrosis induced by CCl(4) in rats, which is probably associated with its down-regulation on fibrogenic signal transduction of TGFbeta-Smad pathway.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Cirrose Hepática/prevenção & controle , Fígado/efeitos dos fármacos , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Biomarcadores/sangue , Western Blotting , Tetracloreto de Carbono , Colágeno Tipo III/sangue , Colágeno Tipo IV/sangue , Modelos Animais de Doenças , Feminino , Ácido Hialurônico/sangue , Hidroxiprolina/metabolismo , Laminina/sangue , Fígado/metabolismo , Fígado/patologia , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/genética , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , Masculino , RNA Mensageiro/metabolismo , Radioimunoensaio , Ratos , Ratos Wistar , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais/efeitos dos fármacos , Proteína Smad3/genética , Fator de Crescimento Transformador beta1/genética
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