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1.
Int J Biol Sci ; 16(3): 529-542, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32015688

RESUMO

Hyperuricemia (HUA) is a metabolic disease characterized by elevated serum uric acid (SUA). Empagliflozin, a kind of sodium-glucose cotransporter 2 inhibitors, has recently emerged as a new antidiabetic agent by facilitating glucose excretion in urine. Moreover, there was evidence of SUA reduction following treatment with empagliflozin in addition to glycaemic control, while the molecular mechanisms remain unknown. To investigate the potential mechanisms, the model of type 2 diabetes (T2DM) with HUA was established by combination of peritoneal injection of potassium oxonate and intragastric administration of hypoxanthine in KK-Ay mice. A series of method such as RT-PCR, western blot, immunochemistry, immunofluorescence were conducted to explore the mechanism. Our results showed that empagliflozin significantly ameliorated the levels of SUA and blood glucose in T2DM mice with HUA. Furthermore, in both kidney and ileum, empagliflozin obviously promoted protein expression of uric acid (UA) transporter ABCG2, p-AMPK, p-AKT and p-CREB. The same trend was observed in human tubular epithelial (HK-2) cells. Additionally, through application of an AMPK inhibitor (Compound C), it was further confirmed empagliflozin exerted its anti-hyperuricemic effects in an AMPK dependent manner. Meanwhile, with the help of ChIP assay and luciferase reporter gene assay, we found that CREB further activated ABCG2 via binding to the promoter of ABCG2 to induce transcription. Taken together, our study demonstrated that empagliflozin treatment played an essential role in attenuating HUA by upregulation of ABCG2 via AMPK/AKT/CREB signaling pathway.

2.
Cryobiology ; 2020 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-32001217

RESUMO

Melatonin is a ubiquitous indoleamine hormone synthesized primarily by the pineal gland. Diverse biological actions of melatonin involve quite complex mechanisms via its membrane receptors. More recently, studies have focused on the role of melatonin in male fertility preservation and male reproductive system. The protective effects of melatonin on immature testicular tissue freshness and activity maintenance and the preservation of sperm and spermatogonial stem cells (SSCs) have attracted considerable attention in recent years. Furthermore, since melatonin has strong antioxidant and anti-apoptotic properties, researchers have examined its potential role in male reproductive system. In this article, recent progress regarding melatonin's effects on male fertility preservation and its potential role is reviewed.

3.
Inflammation ; 2019 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-31802382

RESUMO

Ellipticine, a natural product from Ochrosia elliptica, has been broadly investigated for its anticancer effects. Although inflammation has been clearly identified as a key factor in the onset and progression of cancer, the relationship between ellipticine and inflammation remains unknown. Hence, the aims of the present study were to assess the effects of ellipticine on the inflammatory responses to lipopolysaccharide (LPS)-induced macrophages and to potentially identify the underlying mechanisms involved. Viability testing showed that ellipticine was not significantly toxic to Raw264.7 cells and actually conveyed protective effects to LPS-stimulated Raw264.7 cells and human peripheral blood monocytes by decreasing the secretion of inflammatory factors (TNF-α and IL-6). The results of western blot analysis and electrophoretic mobility shift assays showed that ellipticine markedly suppressed LPS-induced activation of the JNK/AP-1 (c-Fos and c-Jun) signaling pathway, but not ERK/p38/NF-κB pathway (p65 and p50) activation. Furthermore, ellipticine reduced the inflammatory response and mortality in a mouse model of LPS-induced endotoxic shock. Collectively, these data indicate that ellipticine may be a potential therapeutic agent for the treatment of inflammation-associated diseases.

4.
Sci Rep ; 9(1): 14739, 2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-31611570

RESUMO

As a universal quantum character of quantum correlation, the freezing phenomenon is researched by geometry and quantum discord methods, respectively. In this paper, the properties of Rènyi discord is studied for two independent Dimer System coupled to two correlated Fermi-spin environments under the non-Markovian condition. We further demonstrate that the freezing behaviors still exist for Rènyi discord and study the effects of different parameters on this behaviors.

5.
J Orthop Translat ; 18: 59-64, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31508308

RESUMO

Objective: The objective of this study was to investigate the diagnostic discordance of osteoporosis by quantitative computed tomography (QCT) and dual-energy X-ray absorptiometry (DXA) in Chinese elderly men. Methods: A total of 313 males older than 60 years, who underwent both spinal QCT and lumbar spine and hip DXA in our department, were included. The diagnostic criteria established by the World Health Organisation in 1994 were used for DXA to diagnose osteoporosis, and the criteria recommended by the International Society of Clinical Densitometry were used for QCT. The osteoporosis detection rate by the two techniques was calculated, and the difference was compared. The minor discordance was considered present when the different diagnostic classes between the two techniques were adjacent. Major discordance was present when the diagnosis by one technique was osteoporosis and the other was normal. The computed tomography images were reviewed by radiologists to assess whether vertebral fracture, aorta calcification or degeneration was present. Results: In the 313 participants (mean age, 79.6 ± 7.2 years), the osteoporosis detection rate was 10.9% for DXA (lumbar spine and hip) and 45.1% for QCT, a significant difference (p < 0.001). The major discordance, minor discordance and concordance of diagnosis between the two techniques were seen in 8.3%, 50.8% and 40.9%, respectively. QCT detected osteoporosis better than DXA. The causes of this discordance were degeneration of spine, abdominal aorta calcification and vertebral fractures. Conclusion: Our study demonstrated that discordance was common when using QCT and DXA to diagnose osteoporosis and that spinal degeneration, aorta calcification and fracture obscure the bone mineral density measurement of spine by DXA. QCT is a more sensitive method of choice to identify osteoporosis in elderly Chinese men. The translational potential of this article: This study investigated the diagnostic discordance of osteoporosis by quantitative computed tomography (QCT) and dual-energy X-ray absorptiometry (DXA) in Chinese elderly men. The results demonstrated that QCT is a more sensitive method of choice to identify osteoporosis in elderly Chinese men. This work may help clinicians make an appropriate choice of technique for the accurate diagnosis of osteoporosis and identify the patients at high risk of osteoporosis who should be treated early to prevent fractures. This may influence the therapeutic plan and the overall prognosis of patients.

6.
Biosens Bioelectron ; 145: 111700, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31539651

RESUMO

DNA methyltransferase (MTase) and polynucleotide kinase (PNK) are both DNA-dependent enzymes that play important roles in DNA methylation and DNA repair processes, respectively. Dysregulation of their activities is associated with various human diseases. Herein, we present a specific and sensitive biosensing strategy, named terminal deoxynucleotidyl transferase (TdT)-activated nicking enzyme amplification reaction (TdT-NEAR), for their activity detection. As for MTase detection, an enclosed dumbbell-shaped oligonucleotide substrate, whose symmetric stem containing a recognition site of Dam MTase and an incomplete recognition sequence of nicking endonuclease Nt.BbvCI, was used. Typically, the substrate is methylated by Dam MTase and subsequently cleaved by Dpn I. In the presence of TdT and dGTP, poly(guanine, G) sequences are extended from the released 3'-OH ends, achieving the conversion of the incomplete Nt.BbvCI recognition sequence to an intact one. The extension products can then be used to trigger Nt.BbvCI-catalyzed cyclic cleavage of fluorophore/quencher-labelled oligonucleotide probe, giving a significantly enhanced fluorescence output. Such a sensing system can achieve sensitive and specific detection of Dam MTase with a detection limit of 0.002 U/mL. The unique working mechanism endows the sensing system with improved anti-interference capability and thus increased application potential in complex biological samples. Moreover, it was also demonstrated to work well for Dam MTase inhibitor screening and inhibitory activity evaluation, thus holding great potential in disease diagnosis and drug discovery. Using a simpler 3'-phosphorylated linear substrate and the same fluorescent probe, the TdT-NEAR strategy can be easily extended to the activity analysis of PNK, thus revealing wide application potential in bioanalysis.

8.
J Mater Chem B ; 7(39): 5966-5971, 2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31524915

RESUMO

Effective photosensitizers (PSs) are highly desirable in many applications, such as photodynamic therapy and catalytic chemistry. Here, we demonstrated that vesicles of cucurbit[7]uril (Q[7] or CB[7])-anchored polymers enhanced photosensitization in the nucleus. The polyacrylic acid chain spacer triggered Q[7] polymers on the surfaces of the vesicles at a regular distance, thus not only leading to efficient inhibition of the aggregation induced self-quenching of the porphyrin based cationic PS in aqueous solution but also maintaining the PS at high concentration on the nanoscale via stable host-guest interactions. Further experiments indicated that Q[7] polymer based vesicles as a PS loading vehicle had a high penetration depth, entering the nuclei of cancer cells. Therefore, highly enhanced photosensitization and efficient anticancer effects were achieved.

9.
Aging (Albany NY) ; 11(15): 5646-5665, 2019 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-31399552

RESUMO

BACKGROUND: Long noncoding RNAs have been known to be involved in multiple types of malignancies, including invasive breast cancer (IBC). This study aimed to explore the role of long noncoding RNAs in IBC and elucidate the potential molecular mechanisms. METHODS: Using TCGA microarray data analysis, we identified a long noncoding RNA, MIR210HG, highly expressed in IBC. Kaplan-Meier method and the log-rank test were used for survival analysis. The gain-of-function experiments were performed to assess the function of MIR210HG in IBC invasion and migration in both in vitro and in vivo settings. Bioinformatic analysis as well as luciferase reporter assay, rescue experiments and western blot assay revealed the mode of action of MIR210HG. RESULTS: The aberrantly enhanced MiR210HG expression predicted poor prognosis and lower survival rate. Knockdown of MiR210HG suppressed IBC cell invasion and metastasis both in vitro and in vivo. MiR-1226-3p was identified and validated to be the target miRNA of MiR210HG. Furthermore, MiR210HG functions as a competing endogenous RNAs (ceRNA) which sponges miR-1226-3p, therefore upregulates the expression of mucin1 (MUC1-C). CONCLUSIONS: Our study demonstrated that MiR210HG sponges miR-1226-3p to facilitate invasive breast cancer cell invasion and metastasis by regulating mucin-1c and EMT pathway, revealing the oncogenic role of MiR210HG in IBC cells.

10.
Front Pharmacol ; 10: 886, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31447680

RESUMO

Objective: Calcium dobesilate (CaD), an effective drug for the treatment of diabetic microvascular complications, especially diabetic retinopathy, is widely used in the clinic. Interestingly, several studies have indicated that CaD is therapeutic for diabetic kidney disease (DKD). Recently, evidence has indicated that altered vascular endothelial growth factor (VEGF) expression and decreased autophagy are the main pathological mechanisms of proteinuria. Thus, this study was conducted to explore the effect of CaD on restoring autophagy in DKD and the possible signaling pathway between VEGF and autophagy. Methods: Obese mice with spontaneous diabetes (KK-Ay) and high-fat diet- and streptozotocin-induced diabetic mice (HFD/STZ) were used in this study. Biochemical staining, western blotting, and immunohistochemistry were conducted to determine the angioprotective effect of CaD and the underlying mechanism between autophagy and VEGF/VEGFR. Results: Our results showed that CaD was capable of reducing albuminuria and restoring renal histological changes in KK-Ay and HFD/STZ-induced diabetic mice. CaD restored autophagy by decreasing the protein expression of LC3 II, Atg5, and beclin 1 and increasing the expression of P62. Moreover, CaD reduced the activation of the autophagy-related PI3K/AKT/mTOR pathway possibly via decreasing VEGF and downregulating VEGF receptor 2. Conclusion: Overall, CaD, as a novel potential therapeutic drug for DKD, plays a key role in protecting renal function and restoring autophagy by blocking VEGF/VEGFR2 and inhibiting the PI3K/AKT/mTOR signaling pathway.

11.
Zhen Ci Yan Jiu ; 44(7): 543-7, 2019 Jul 25.
Artigo em Chinês | MEDLINE | ID: mdl-31368289

RESUMO

Protein kinase Cε (PKCε) is a transforming oncogene and plays an important role in many cellular processing. In the present paper, we review the development of experimental researches on the acute-chronic pain transformation. Results indicated that prostaglandin E2 (PGE2) / EP1 receptor-Gq-PKCε is an important signaling pathway to modulate chronic pain in peripheral dorsal root ganglion (DRG) neurons, and also plays a role in the later stage of hyperalgesia during transformation from acute to chronic pain. PKCε in DRG neurons induces mechanical and thermal hypersensitivity respectively by over expression of transient receptor potential vanilloid 1 (TRPV1) and TRP ankyrin-1 (TRPA1), further mediating the transformation from acute to chronic pain. Whereas, PGE2-evoked activation of EP1-Gq-PKCε signaling may be the key link in initiating the pain translation process through regulating downstream TRPA1 and TRPV1. Electroacupuncture (EA) has been used to effectively relieving various types of acute and chronic pain for decades, and can significantly inhibit the expression of PKCε and its upstream and downstream molecules. Therefore, it can be inferred that there exists a possibility of EA interventions in interfering the transformation from acute to chronic pain by regulating peripheral PKCε signaling pathway.


Assuntos
Dor Crônica , Eletroacupuntura , Animais , Humanos , Hiperalgesia , Proteína Quinase C-épsilon , Ratos , Ratos Sprague-Dawley , Canais de Cátion TRPV
13.
Chem Commun (Camb) ; 55(53): 7611-7614, 2019 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-31192323

RESUMO

We applied a modified exponential amplification reaction (EXPAR) strategy to design a label-free and "one-pot" biosensor for ultrasensitive detection of polynucleotide kinase (PNK). This method was also successfully applied in the screening of PNK inhibitors and analysis of the endogenous PNK activity at the single-cell level.


Assuntos
Técnicas Biossensoriais , Técnicas de Amplificação de Ácido Nucleico , Polinucleotídeo 5'-Hidroxiquinase/análise , Razão Sinal-Ruído , Células HeLa , Humanos , Polinucleotídeo 5'-Hidroxiquinase/metabolismo , Espectrometria de Fluorescência
14.
Chem Commun (Camb) ; 55(53): 7603-7606, 2019 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-31199419

RESUMO

A biosensor with all the advantages of ultra-high sensitivity, easy operation, straightforward signal output and universal applicability is introduced. The biosensor was demonstrated to work well in the detection of polynucleotide kinase and DAM methyltransferase, thus providing a powerful tool for clinical diagnosis, drug screening and disease therapeutic assay.


Assuntos
Técnicas Biossensoriais , DNA/química , Técnicas de Amplificação de Ácido Nucleico , Polinucleotídeo 5'-Hidroxiquinase/análise , DNA Metiltransferases Sítio Específica (Adenina-Específica)/análise , Temperatura Ambiente , Células HeLa , Humanos , Polinucleotídeo 5'-Hidroxiquinase/genética , Polinucleotídeo 5'-Hidroxiquinase/metabolismo , DNA Metiltransferases Sítio Específica (Adenina-Específica)/genética , DNA Metiltransferases Sítio Específica (Adenina-Específica)/metabolismo , Espectrometria de Fluorescência
15.
Angew Chem Int Ed Engl ; 58(30): 10184-10188, 2019 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-31090998

RESUMO

Although great achievements have been made in the synthesis of giant lanthanide clusters, novel structural models are still scarce. Herein, we report a giant lanthanide cluster Dy76 , constructed from [Dy3 (µ3 -OH)4 ] and [Dy5 (µ4 -O)(µ3 -OH)8 ] building blocks. As the largest known Dy cluster, the structure of Dy76 can be seen as arising from the fusion of two Dy48 clusters; these clusters can be isolated under various synthetic conditions and were characterized by single-crystal X-ray diffraction. This new, fused structural model of the pillar motif has not been found in Ln clusters. Furthermore, the successful conversion of Dy76 back into Dy48 in a retrosynthetic manner supports the proposed fusion formation mechanism of Dy76 . Electrospray ionization mass spectrometry (ESI-MS) analysis suggests that the metal cluster skeleton of Dy76 shows good stability in various solvents. This work not only reveals a new structural type of Ln clusters but also provides insight into the novel fusion assembly process.

16.
Front Biosci (Landmark Ed) ; 24: 1316-1329, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-31136981

RESUMO

Blood-testis barrier (BTB) that is constructed by testicular Sertoli cells (SCs) is essential for spermatogenesis. Krüppel-like factor 6 (Klf6), a nuclear transcription regulator, is reported to be associated with tight junction molecules of BTB between SCs during spermatogenesis; however, the specific regulatory role and mechanism of Klf6 in BTB regulation are still unknown. Here, we primarily confirmed the temporal and spatial expression patterns of Klf6 in mouse testes. Then, Klf6 was silenced in mouse cultured SCs using either Klf6-siRNA or Klf6-shRNA lentivirus. We mainly found that: (i) Klf6 was indispensable for the proliferative activity of mouse SCs; (ii) Klf6 regulated the integrity and permeability of BTB; (iii) Klf6 knockdown led to the significant upregulation of Zo-1, Claudin-11 and Vimentin, and downregulation of Claudin-3. Furthermore, Zo-1 and Claudin-3, participated in the tight junction remolding, were determined as targets of transcription factor Klf6 by luciferase assay. In summary, our findings suggest that Klf6 regulates the BTB assembly and disassembly via mainly targeting Zo-1 and Claudin-3 in mouse SCs.


Assuntos
Barreira Hematotesticular/metabolismo , Fator 6 Semelhante a Kruppel/metabolismo , Células de Sertoli/metabolismo , Testículo/metabolismo , Junções Íntimas/metabolismo , Animais , Células Cultivadas , Claudina-3/genética , Claudina-3/metabolismo , Claudinas/genética , Claudinas/metabolismo , Regulação da Expressão Gênica , Fator 6 Semelhante a Kruppel/genética , Masculino , Camundongos Endogâmicos ICR , Microscopia Eletrônica de Transmissão , Interferência de RNA , Espermatogênese/genética , Testículo/ultraestrutura , Vimentina/genética , Vimentina/metabolismo , Proteína da Zônula de Oclusão-1/genética , Proteína da Zônula de Oclusão-1/metabolismo
17.
Phytother Res ; 33(6): 1706-1716, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30989726

RESUMO

Celastrol could inhibit cancer cell growth in vitro. However, effect(s) of celastrol on gastric cancer is not well studied. Therefore, we investigated the effects of celastrol on human gastric cancer cell line MKN45 and the underlying mechanisms. We found that celastrol inhibited cell proliferation, migration, and invasion and induced cell apoptosis and G2/M cell cycle arrest (p < .05, p < .01, or p < .001). Under celastrol treatment, overexpression of microRNA-21 (miR-21) increased cell viability, migration, and invasion and inhibited cell apoptosis compared with negative control (p < .05, p < .01, or p < .001). In addition, the phosphorylation of PTEN was significantly up-regulated, whereas PI3K, AKT, p65, and IκBα phosphorylation was statistically decreased by celastrol (p < .05 or p < .01) and then further reversed by miR-21 overexpression (p < .05 or p < .01). On the other side, miR-21 silence showed contrary results (p < .05) as relative to miR-21 overexpression. In conclusion, celastrol inhibits proliferation, migration, and invasion and inactivates PTEN/PI3K/AKT and nuclear factor κB signaling pathways in MKN45 cells by down-regulating miR-21.


Assuntos
Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , MicroRNAs/genética , Neoplasias Gástricas/patologia , Triterpenos/farmacologia , Apoptose/efeitos dos fármacos , Apoptose/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Metástase Neoplásica , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Neoplasias Gástricas/genética
18.
Zhongguo Zhong Yao Za Zhi ; 44(5): 875-879, 2019 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-30989843

RESUMO

At present,the function evaluation of health food containing Chinese materia medica is in lack of theoretical support of Chinese medicine,which can't reflect the function characteristics,dose-effect relationship and mechanism of functional food. What' s more,the evaluation technology of health food containing Chinese materia medica is relatively lagging behind and has been abolished now,which seriously restricts the development of health food containing Chinese materia medica industry. The proportion of health food containing Chinese materia medica with enhancing immune function is the highest among approved products,which is up to 30.33%. By collecting,analyzing and digging the current evaluation situation of enhancing immune function of health food containing Chinese materia medica,this paper has shown that there is no difference between health food containing Chinese materia medica evaluation and other functional food evaluation. What's more,there is a lack of characteristics of traditional Chinese medicine(TCM). The technological means including evaluation of immune active substances is under-developed and the immune cell evaluation needs to be refined and improved urgently,restricting the development of health food containing Chinese materia medica industry. Therefore,the evaluation of the enhanced immune function of health food containing Chinese materia medica should be guided by health-preserving theory in TCM,and based on the identification of TCM constitution for its claim of health function. With TCM theory and modern scientific technological means,a new evaluation model for immune function enhancement of health food containing Chinese materia medica is put forward to distinguish it from other functional food and traditional medicines. Formulation of the evaluation technology and technical specifications suitable for health food containing Chinese materia medica can fundamentally ensure the healthy,orderly,fast and sustainable development of health food containing Chinese materia medica industry.


Assuntos
Alimento Funcional , Materia Medica , Medicina Tradicional Chinesa , Humanos , Sistema Imunitário , Projetos de Pesquisa , Tecnologia
19.
ACS Sens ; 4(4): 1090-1096, 2019 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-30945529

RESUMO

Telomerase is a universal biomarker of malignant tumors. Sensitive and reliable analysis for telomerase activity is of vital importance for both early diagnosis and therapy of malignant tumors. Herein, a novel fluorescent strategy was proposed for sensitive and label-free detection of telomerase activity. One highlight of this strategy is that an exponential signal amplification can be triggered by a very short telomerase extension product (TEP). Without adding dATP, the designed telomerase primer can be easily controlled to extend five bases (GGGTT) to give short TEP with definite length. The resulting short TEP can then be constructed as a circular rolling circle amplification (RCA) template and thus initiate a nicking enzyme-mediated exponential RCA, producing G-rich amplification products that can be sensitively probed via specific binding between the fluorescent dye Thioflavin T (ThT) and the nucleic acid G-quadruplexes. Elevated telomerase translocation efficiency, combined with exponential signal amplification and specific probing of RCA products by ThT, endow the sensing platform with extraordinarily high detection sensitivity. The requirement for short TEP increases the possibility to analyze telomerase with low activity. The proposed sensing platform can achieve sensitive telomerase activity detection in individual cells, even with the interference of accumulated normal cells. It was also demonstrated to show excellent capability in screening for the inhibitors of telomerase. Therefore, the proposed sensing platform has great potential for not only clinical diagnosis but also anticancer drug development.

20.
ACS Appl Mater Interfaces ; 11(16): 14684-14692, 2019 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-30942569

RESUMO

Developing a highly efficient carrier for tumor-targeted delivery and site-specific release of anticancer drugs is a good way to overcome the side effects of traditional cancer chemotherapy. Benefiting from the nontoxic and biocompatible characteristics, DNA-based drug carriers have attracted increasing attention. Herein, we reported a novel and readily manipulated strategy to construct spherical DNA nanocarriers. In this strategy, terminal deoxynucleotidyl transferase (TdT)-catalyzed DNA extension reaction is used to prepare a thick DNA layer on a gold nanoparticle (AuNP) surface by extending long poly(C) sequences from DNA primers immobilized on AuNPs. The poly(C) extension products can then hybridize with G-rich oligonucleotides to give CG-rich DNA duplexes (for loading anticancer drug doxorubicin, Dox) and multiple AS1411 aptamers. Via synergic recognition of multiple aptamer units to nucleolin proteins, biomarker of malignant tumors, Dox-loaded DNA carrier can be efficiently internalized in cancer cells and achieve burst release of drugs in acidic organelles because of i-motif formation-induced DNA duplex destruction. An as-prepared pH-responsive drug carrier was demonstrated to be promising for highly efficient delivery of Dox and selective killing of cancer cells in both in vitro and in vivo experiments, thus showing a huge potential in anticancer therapy.


Assuntos
Adutos de DNA , DNA Nucleotidilexotransferase/química , Doxorrubicina , Ouro , Nanopartículas Metálicas , Neoplasias Experimentais/tratamento farmacológico , Animais , Adutos de DNA/química , Adutos de DNA/farmacologia , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacologia , Doxorrubicina/química , Doxorrubicina/farmacologia , Feminino , Ouro/química , Ouro/farmacologia , Células HeLa , Humanos , Concentração de Íons de Hidrogênio , Nanopartículas Metálicas/química , Nanopartículas Metálicas/uso terapêutico , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Células NIH 3T3 , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/patologia , Oligodesoxirribonucleotídeos/química , Oligodesoxirribonucleotídeos/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto
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