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1.
Chem Commun (Camb) ; 2020 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-32986052

RESUMO

Herein, a highly regioselective propargylic benzylation with propargylic carbonates and benzyl 1,4-dihydropyridine derivatives was developed via a photoredox/palladium dual-catalyzed process, which represents a novel catalytic model for non-terminal propargylic functionalization. The reaction showed excellent regioselectivity and functional group compatibility. A radical coupling mechanism between the propargylic radical and benzyl radical was proposed.

2.
Biol Trace Elem Res ; 2020 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-32770328

RESUMO

The role of elements in physiological and pathological metabolic processes remains an unmet challenge in biomedical research and clinical applications. Herein, a visual elemental imaging of tumor tissue platform of a laser-induced breakdown spectroscopy (LIBS) was developed to initially understand anti-tumor mechanisms. The relative enrichment degree and heterogeneous spatial distributions of four elements (calcium, sodium, copper, and magnesium) of tumor tissue from different treated could be easy to visualize. In particular, significant differences in the distribution of elements were observed in tumor tissue from drug-loading complex (hydrogel/DOX) treatment group. Correspondingly, the analysis of histopathological morphology showed that the morphology and density of tumor tissue in hydrogel/DOX treatment group changed obviously by using hematoxylin and eosin (H&E) staining assay, meanwhile cleaved caspase-3 (caspase-3) and tumor necrosis factor (TNF-α) were expressed at high levels tumors tissue in hydrogel/DOX treatment group by using immunohistochemical (IHC) staining. These results would endow different biological elements with incredible potential to study the mechanisms of anti-tumor, which opens new direction and perspectives for the multi-elemental mapping of biological tissues, especially in clinic application. The integrated platform of DNA nanohydrogel drug carrier-based anti-tumor treatment combined with LIBS elemental imaging, via tail intravenous injection of saline, hydrogel, DOX, and hydrogel/DOX in breast cancer xenograft tumor mice. (A) The workflow is outlined starting from nanohydrogel drug carrier-based anti-tumor treatment. (B) Schematic diagram of LIBS imaging platform.

3.
Fish Shellfish Immunol ; 106: 190-196, 2020 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-32755683

RESUMO

Infectious spleen and kidney necrosis virus (ISKNV) cause a high mortality disease which brings substantial economic losses to the mandarin fish culture industry in China. This study was aimed at optimizing the efficacy of a SWCNTs-based immersion subunit vaccine (SWCNTs-M-MCP) which as a promising vaccine against ISKNV. Mandarin fish were vaccinated by immersion, then we designed an orthogonal experiment to optimize different parameters affecting vaccination such as immune duration of bath immunization, immune dose, and fish density when immunized. Our results showed that the highest relative percent survival (86.7%) was found in the group 6 with 8 h of immune duration, 20 mg/L of immune dose, and 8 fish per liter of fish density. And other immune responses (serum antibody production, enzyme activities, and immune-related genes expression) also demonstrated similar results. In addition, the expression of IRF-I in group 6 (8 h, 20 mg/L, 8 fish per liter) was significant extents, and about 16-folds increases were obtained than the control group at 21 d post-vaccination. And the highest specific antibody response was significantly increased (more than 4-folds) than control group which was found in group 6. The optimum immune duration, immune dose, and fish density of SWCNTs-M-MCP were 8 h, 20 mg/L, 8 fish per liter, respectively. Importantly, our results also showed that immune duration had the greatest effect on the immune response of our vaccine, followed by immune dose. The study reported herein provides a helpful reference for the effective use of vaccine in fish farming industry.

4.
J Org Chem ; 2020 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-32614579

RESUMO

A palladium-catalyzed, photochemical tandem cyclization/dicarbofunctionalization of unactivated alkyl halides containing an alkene moiety offers an appealing route to produce five- or six-membered rings in a redox-neutral fashion. Multisubstituted carbo- and heterocyclic compounds were prepared through the formation of new C-B or C-O bonds, which provides a convenient synthetic route for further transformations. This protocol is characterized by the reaction of alkene regio- and stereoselectivities, good functional group compatibility, wide substrate scope, and mild reaction conditions.

5.
Org Biomol Chem ; 2020 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-32483581

RESUMO

Palladium catalyzed visible-light-mediated borylation of inactivated aryl and alkyl halides is reported; the method provided high yields and excellent functional group compatibility. Furthermore, arylsilicates were synthesized selectively using dimethylphenylsilyl boronic ester via changing the reaction conditions. Finally, the possible reaction mechanism is determined through fluorescence quenching and turn on/off experiments.

6.
Biomed Mater Eng ; 31(3): 143-155, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32474462

RESUMO

BACKGROUND: Snoring source analysis is essential for an appropriate surgical decision for both simple snorers and obstructive sleep apnea/hypopnea syndrome (OSAHS) patients. OBJECTIVE: As snoring sounds carry significant information about tissue vibrations within the upper airway, a new feature entitled compressed histogram of oriented gradients (CHOG) is proposed to recognize vibration patterns of the snoring source acoustically by compressing histogram of oriented gradients (HOG) descriptors via the multilinear principal component analysis (MPCA) algorithm. METHODS: Each vibration pattern corresponds to a sole or combinatorial vibration among the four upper airway soft tissues of soft palate, lateral pharyngeal wall, tongue base, and epiglottis. 1037 snoring events from noncontact sound recordings of 76 simple snorers or OSAHS patients during drug-induced sleep endoscopy (DISE) were evaluated. RESULTS: With a support vector machine (SVM) as the classifier, the proposed CHOG achieved a recognition accuracy of 89.8% for the seven observable vibration patterns of the snoring source categorized in our most recent work. CONCLUSION: The CHOG outperforms other single features widely used for acoustic analysis of sole vibration site.

7.
Fish Shellfish Immunol ; 104: 262-268, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32534229

RESUMO

Spring viremia of carp virus (SVCV) causes devastating disease in aquaculture, resulting in significant economic impact. To develop an effective means against SVCV infection, a Lactococcus lactis (L.lactis) based subunit vaccine (pNZ-UGA) was developed based on surface displaying of SVCV glycoprotein using anchoring motif of the cA (C terminus of the peptidoglyvsn-binding) domains of AcmA, a major autolysin from L.lactis. The surface expression of SVCV glycoprotein was verified by indirect immunofluorescence assay. The efficacy of the constructed vaccine was further evaluated in common carp. The results showed that the higher levels of specific IgM could be detected in fish vaccinated with pNZ-UGA, compared with that in PBS and L.lactis groups. Immune-related genes including TNF-α, IL-6b, IL-1ß, Cxcr 1, Cxca, IFNg2b, I-IFN, and IgM expression in pNZ-UGA group were strongly up-regulated, revealing that robust innate immune response was induced. Notably, the lowest cumulative mortality (13.46%) was observed in fish vaccinated with pNZ-UGA vaccine after SVCV challenge, whereas the cumulative mortality were 100.00% and 92.31% in PBS and L.lactis groups, respectively. This study suggests the potential use of the recombinant L.lactis with surface displaying antigen proteins as effective vaccines against SVCV and other fish virus infection.

8.
Aquat Toxicol ; 225: 105550, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32593114

RESUMO

Plant diversity has important functions in ecosystem productivity overyielding and community stability. Little is known about the mechanism causing productivity overyielding and stability under harsh conditions. This study investigated the photosynthetic response and subcellular distribution of uni- and co-cultured duckweeds (Lemna aequinoctialis and Spirodela polyrhiza) under excess copper (1.0 mg/L) and low temperature (5 °C) conditions. The results showed that the growth of uni-cultured L. aequinoctialis was not different from that of uni-cultured S. polyrhiza across copper treatments at control temperature (25 °C). The growth rate of L. aequinoctialis increased by 55.5 % under excess copper concentration when it coexisted with S. polyrhiza, compared with uni-culture. Subcellular distributions of copper were predominantly distributed in cell walls. S. polyrhiza accumulated more copper in cell walls than L. aequinoctialis under uni-cultured condintion at excess copper concentration. Co-cultured S. polyrhiza increased copper accumulation in cell walls of co-cultured L. aequinoctialis to decrease toxicity at excess copper concentration, compared with L. aequinoctialis. Low temperature increased copper toxicity, with duckweeds having lower growth rate and photosynthetic activities (Fv/Fm). The L. aequinoctialis growth rate in co-culture was higher than in uni-culture under excess copper concentration and low temperature conditions, indicating that S. polyrhiza decreased the copper toxicity for L. aequinoctialis. The photosynthetic activity (Fv/Fm) of co-cultured L. aequinoctialis was higher than that of uni-cultured L. aequinoctialis exposed to excess copper concentration at low temperature. The community that formed by co-culturing S. polyrhiza and L. aequinoctialis produced more biomass by avoiding the toxicity of excess copper through heavy metal compartmentalization and photosynthetic activities.


Assuntos
Resposta ao Choque Frio/fisiologia , Metais Pesados/metabolismo , Poluentes Químicos da Água/toxicidade , Araceae/crescimento & desenvolvimento , Araceae/fisiologia , Biomassa , Cobre/toxicidade , Ecossistema , Metais Pesados/toxicidade , Fotossíntese
9.
Science ; 368(6493): 874-877, 2020 05 22.
Artigo em Inglês | MEDLINE | ID: mdl-32439790

RESUMO

Precise fabrication of semiconducting carbon nanotubes (CNTs) into densely aligned evenly spaced arrays is required for ultrascaled technology nodes. We report the precise scaling of inter-CNT pitch using a supramolecular assembly method called spatially hindered integration of nanotube electronics. Specifically, by using DNA brick crystal-based nanotrenches to align DNA-wrapped CNTs through DNA hybridization, we constructed parallel CNT arrays with a uniform pitch as small as 10.4 nanometers, at an angular deviation <2° and an assembly yield >95%.

10.
Carbohydr Polym ; 238: 116073, 2020 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-32299562

RESUMO

Off-target drug delivery, together with multidrug resistance (MDR), are two keys obstacles that account for the disappointing outcome in clinical chemotherapy of cancer. To solve these dilemmas, Herein, we constructed cancer cell membrane (CCM) modified silica (CS) nanoparticles (CCM/CS) to co-deliver Ca2+ channel siRNA with doxorubicin (DOX) to construct a platform (CCM/CS/R-D) for the efficient therapy of cervical cancer. It was demonstrated that the optimal CCM/CS/R-D was spherical nanoparticles with size at 122.39 ±â€¯4.69 nm and the surface charge of -27.76 ±â€¯3.12 mV. In addition, the CCM/CS/R-D showed acid responsive drug release while high stability under physiological conditions with negligible hemolysis. The CCM/CS/R-D showed CCM mediated cellular uptake and efficient endosomal escape as well as siRNA transfection potential (comparable to that of PEI 25 K) on MDR cervical cancer cells (HeLa/DOX). Most importantly, the MDR of cancer cells was conquered through modulation of T-type Ca2+ (Cav) channels. It was observed that the Cav channel siRNA could negatively regulate the level of cytosolic Ca2+ concentration which triggered G0/G1 phase cell cycle arrest and elevated intracellular drug retention in HeLa/DOX cells without significantly affect the expression of P-glycolprotein (P-gp). The in vitro and in vivo experiments revealed that CCM/CS/R-D exerted greatly enhanced tumor targetability and therapeutic effect on HeLa/DOX, which was superior than CS/R-D or mono delivery system (CCM/CS/R or CCM/CS/D).

11.
Curr Med Sci ; 40(2): 313-319, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32337691

RESUMO

Ventricular septum defects (VSDs) are common types of congenital heart diseases caused by developmental defect; they contribute to 25%-30% of all adult congenital heart diseases. The peroxisome proliferator-activated receptor gamma (PPAR-γ) is widely expressed in mammalian tissues and in the immune system, regulating cell differentiation and immune and inflammatory responses. The PPAR-γ gene has recently been found crucial for heart development, but the mechanism of action is not clear. This study aims to investigate the effects of the PPAR-γ gene in the myocardium on the development of ventricular septation. In this study, we applied Cre-loxP recombination enzyme (CRE) technology to downregulate the expression of the PPAR-γ gene in different cardiac tissues, RT-PCR to examine the expression of the c-fos and TGF-ß1 genes, and histology staining to check the defect of embryonic heart at embryonic day 14.5 (E14.5). We found that the downregulation of the PPAR-γ gene resulted in a ventricular membranous septation defect of the embryonic heart at E14.5. Furthermore, only conversion of a Tnt:Cre, but not Mef2c:Cre, Tie2:Cre, or Wnt:Cre PPAR-γ floxed allele to a null allele resulted in VSD. PPAR-γTnt-Cre/+ embryos showed increases in atrioventricular (AV)-cushion cells and the expression of c-fos gene but no change in the expression of TGF-ß1 at E10.5. Our study demonstrates PPAR-γ in the myocardium is required for ventricular septation through regulation of AV-cushion cell proliferation by a Tnt/c-fos signal.

12.
Clin Exp Med ; 20(3): 373-380, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32206927

RESUMO

Follicular help T cells (Tfh) play an important role in the activation and differentiation of B cells, while follicular regulatory T cells (Tfr) control Tfh and resulting humoral immune responses. Accumulating evidence has demonstrated that the dysregulation of Tfr contributed to the pathogenesis of infectious diseases. However, the role of Tfr in Epstein-Barr virus (EBV) infection remains lacking. Fifty-five EBV-infected infectious mononucleosis (IM) patients and 21 healthy individuals (HIs) were recruited in the study. We investigated the number of Tfr (FoxP3+CXCR5+PD-1+CD4+) and Tfh (FoxP3-CXCR5+PD-1+CD4+) of peripheral blood in IM patients at diagnosis (D0) and day 15 after diagnosis (D15) via multicolor flow cytometry. Results revealed that circulating Tfh (cTfh) and Tfr (cTfr) of IM at D0 were both increased compared to HIs, and cTfr began to decline and return to normal at D15, while cTfh was still higher than those of HIs. More interestingly, the cTfr/cTfh ratio of IM at D0 and D15 was lower than that of HIs, suggesting that the balance between cTfh and cTfr was disturbed during primary EBV infection. Correlation analysis showed a positive correlation between cTfr with CD19+IgD+CD27- naive B cells, CD19+IgD-CD27hi plasmablasts or CD19+CD24hiCD27hi B cells. Moreover, both cTfr and the cTfr/cTfh ratio of IM at D0 were negatively correlated with EBV DNA virus load. These results indicate that an imbalance of cTfr and cTfh cells may be involved in the immunopathogenesis of EBV-infected IM patients and may provide novel strategies for controlling EBV-related disease.

13.
Fish Shellfish Immunol ; 100: 317-323, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32173450

RESUMO

Largemouth bass ulcerative syndrome virus (LBUSV) is an important virus induce the mortality of largemouth bass (Micropterus Salmoides). In this study, we reported a single-walled carbon nanotubes (SWCNTs) containing LBUSV major capsid protein (MCP) subunit vaccine (SWCNTs-MCP) which was evaluated for its protective effect on largemouth bass by immersion immunization. We found an elevation in serum antibody levels, enzyme activities, complement C3 content and immune-related genes (IgM, TGF-ß, IL-1ß, IL-8, TNF-α and CD4) expression, in the SWCNTs-MCP immunized groups compared with the pure MCP group. The survival rates for control group, pure MCP protein groups (40 mg L-1) and four SWCNTs-MCP groups (5 mg L-1, 10 mg L-1, 20 mg L-1 and 40 mg L-1) were 0%, 27.78%, 30.56%, 50.00%, 66.67% and 80.56%, respectively. The results suggests that with the assistance of SWCNTs, the immune protection of the SWCNTs-MCP group (40 mg L-1) increased up 52.78%-80.1% compared with pure MCP group (40 mg L-1). Our results demonstrate that the single-walled carbon nanotube subunit vaccine can be used as a new immunization method against LBUSV showing protection following challenge with LBUSV. Taken together, our results demonstrate that the single-walled carbon nanotube subunit vaccine can be used as a new method against LBUSV and have a high immune protection during the largemouth bass farm.

14.
Fish Shellfish Immunol ; 99: 548-554, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32109609

RESUMO

Micropterus Salmoides rhabdovirus (MSRV), as a common aquatic animal virus, can cause lethal and epidemic diseases in the cultivation of largemouth bass. In this study, we reported a kind of immersion single-walled carbon nanotubes-loaded subunit vaccine which composited by glycoprotein (G) of MSRV, and evaluated its protective effect on largemouth bass. The results showed that a stronger immune response including serum antibody levels, enzyme activities (superoxide dismutase, acid phosphatase, alkaline phosphatase and total antioxidant capacity), complement C3 content and immune-related genes (IgM, TGF-ß, IL-1ß, IL-8, TNF-α, CD4) expression can be induced obviously with single-walled carbon nanotubes-glycoprotein (SWCNTs-G) groups compared with G groups when largemouth bass were vaccinated. After bath immunization with G or SWCNTs-G for 28 days, fish were challenged with a lethal dose of MSRV. The survival rates for control group (PBS), SWCNTs group (40 mg L-1), pure G protein groups (40 mg L-1) and three SWCNTs-G groups (5 mg L-1, 10 mg L-1 and 40 mg L-1) were 0%, 0%, 39.5%, 36.7%, 43.6%and 70.1%, respectively. Importantly, with the assistance of SWCNTs, the immune protective rate of the SWCNTs-G group (40 mg L-1) increased by approximately 30.6%. This study suggested that SWCNTs-G is a promising immersion subunit vaccine candidate against the death caused by MSRV.

15.
J Am Chem Soc ; 142(7): 3311-3315, 2020 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-32011869

RESUMO

DNA nanostructures (DNs) have garnered a large amount of interest as a potential therapeutic modality. However, DNs are prone to nuclease-mediated degradation and are unstable in low Mg2+ conditions; this greatly limits their utility in physiological settings. Previously, PEGylated oligolysines were found to protect DNs against low-salt denaturation and to increase nuclease resistance by up to ∼400-fold. Here we demonstrate that glutaraldehyde cross-linking of PEGylated oligolysine-coated DNs extends survival by up to another ∼250-fold to >48 h during incubation with 2600 times the physiological concentration of DNase I. DNA origami with cross-linked oligolysine coats are non-toxic and are internalized into cells more readily than non-cross-linked origami. Our strategy provides an off-the-shelf and generalizable method for protecting DNs in vivo.

16.
J Glob Antimicrob Resist ; 20: 339-341, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32061813

RESUMO

OBJECTIVES: The resistance rate of Klebsiella pneumoniae to commonly used antibiotics has been increasing rapidly, causing serious concern among clinicians and microbiologists. Resistance to carbapenems in K. pneumoniae is increasing dramatically in Chinese hospitals. Here we report the genome sequence of an NDM-1 and KPC-2 co-producing K. pneumoniae (CRKP380) isolated from a bloodstream infection in Hangzhou, China. METHODS: The whole genome sequence of strain CRKP380 was determined using an Illumina NovaSeq 6000 platform. Antimicrobial resistance genes (ARGs) were identified using the BacWGSTdb server. The phylogenetic relationship between strain CRKP380 and other K. pneumoniae strains isolated from Hangzhou currently deposited in the NCBI GenBank database was analysed using a core genome-based single nucleotide polymorphism strategy. RESULTS: Klebsiella pneumoniae CRKP380 was resistant to all antibiotics tested except tigecycline and colistin. The genome sequence of K. pneumoniae CRKP380 consisted of 75 contigs comprising 5 590 460 bp. According to the Pasteur multilocus sequence typing (MLST) scheme, CRKP380 belongs to ST11. Eight ARGs were identified in CRKP380, including two carbapenemase genes (blaKPC-2 and blaNDM-1). Ten phylogenetically-related K. pneumoniae strains from Hangzhou were identified with identical ARGs and the same capsular serotype KL105, but none of these strains carried the blaNDM gene. CONCLUSION: Here we report the genome sequence of a K. pneumoniae ST11 clinical strain co-carrying blaNDM-1 and blaKPC-2 from Hangzhou, China. The genome sequence of CRKP380 can be used as a reference sequence for future comparative genomic analysis, including the acquisition and mobilisation of carbapenem resistance genes.

17.
Gynecol Oncol ; 157(2): 429-436, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32067814

RESUMO

OBJECTIVE: To compare 3-year overall survival (OS) and disease-free survival (DFS) rates of robot-assisted radical hysterectomy (RRH) and abdominal radical hysterectomy (ARH) for cervical cancer. METHODS: We retrospectively compared the oncological outcomes of 10,314 cervical cancer patients who received RRH (n = 1048) or ARH (n = 9266) and whose stages were IA1 with lymphovascular space invasion (LVSI)-IIA2. Kaplan-Meier survival analysis and log-rank tests were used to compare the 3-year OS and DFS rates between the RRH and ARH groups. Cox proportional hazards model and propensity score matching was used to estimate the surgical approach-specific survival. RESULTS: RRH and ARH showed similar 3-year OS and DFS rates (93.5% vs. 94.1%, p = 0.486; 90.0% vs. 90.4%, p = 0.302). RRH was not associated with a lower 3-year OS rate by the multivariable analysis (HR 1.23, 95% CI 0.89-1.70, p = 0.206), but it was associated with a lower 3-year DFS rate (HR 1.20, 95% CI 1.09-1.52, p = 0.035). After propensity score matching, patients who underwent RRH had decreased 3-year OS and DFS rates compared to those who underwent ARH (94.4% vs. 97.8%, p = 0.002; 91.1% vs. 95.4%, p = 0.001), and RRH was associated with lower 3-year OS and DFS rates. Among patients with stage IB1 and tumor size <2 cm, RRH was not associated with decreased 3-year OS and DFS rates (HR1.688, 95% CI 0.423-6.734, p = 0.458; HR1.267, 95%CI 0.518-3.098, p = 0.604). CONCLUSIONS: Overall, RRH was associated with worse 3-year oncological outcomes than ARH in patients with FIGO stage IA1 with LVSI- IIA2 cervical cancer. However, RRH showed similar 3-year oncological outcomes with ARH among those with stage IB1 and tumor size <2 cm.

18.
Fish Shellfish Immunol ; 97: 432-439, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31883470

RESUMO

As a high mortality disease, Infectious spleen and kidney necrosis virus (ISKNV) can cause massive economic damage on mandarin fish farming industry in China, which seriously hindered the development of mandarin fish farming industry. In this research, SWCNTs (single-walled carbon nanotubes) as a candidate for DNA vaccine carrier was vaccinated by immersion (1, 2, 5, 10, 20 mg/L) in juvenile mandarin fish. In muscle, spleen and kidney tissues, the results showed that transcription and expression of MCP gene can be detected in pcDNA-MCP and SWCNTs-pcDNA-MCP groups after bath immunization. The immune response (immune-related genes expression, serum antibody production, enzyme activities and C3 content) was significantly enhanced in fish which vaccinated with SWCNTs-pcDNA-MCP in comparison with those vaccinated with pcDNA-MCP alone. After 14 d challenge, the RPS (relative percentage survival) can be enhanced which using SWCNTs as a carrier in SWCNTs-pcDNA-MCP (82.4%) group at 20 mg/L (the highest vaccine dose) than the naked pcDNA-MCP (54.2%) group. This study reveals that functionalized SWCNTs could be a promising immersion DNA vaccine carrier in aquaculture.

19.
ACS Appl Mater Interfaces ; 11(50): 46479-46489, 2019 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-31747745

RESUMO

DNA nanostructure-based drug delivery system (DDS) has become an advanced therapeutic strategy for cancer because of its unsurpassed editability, intrinsic biodegradability, and tunable multifunctionality. An intelligent DNA nanosystem integrating targeting, immunostimulation, and chemotherapy was constructed based on unmethylated cytosine-phosphate-guanine oligonucleotides (CpG ODNs) DNA nanohydrogels (CpG-MUC1-hydrogel). By facile one-step self-assembly, the cross-shaped DNAs (C-DNAs) assembled from pH-responsive I-motif sequences and targeted MUC1 aptamer-immunoadjuvant CpG-fused sequences (CpG-MUC1) were integrated into DNA nanohydrogels with controllable size by the hybridization of DNA linkers. Subsequently, DOX was successively intercalated into the base pairs of CpG-MUC1-hydrogel, resulting in CpG-MUC1-hydrogel/Dox that would disassemble and release DOX and CpGs at acidic conditions. After MUC1-mediated internalization, CpG-MUC1-hydrogel/Dox dissociated in the endo/lysosomes and induced favorable apoptosis of tumor cells. Afterward, liberated CpGs triggered vast cytokine secretion from immune cells which elicited potent immune response against malignancy. Notably, CpG-MUC1-hydrogel induced an apoptosis effect on MCF-7 cells via significantly increasing the Bax/Bcl2 ratios and a higher level of tumor necrosis factor (TNF-α) on RAW264.7 cells than naked CpGs. Our results demonstrated that self-assembled CpG-MUC1-hydrogel represented an attractive DDS for precise delivery, potent immunostimulating activity, and considerable combination efficiency with few adverse effects, which is expected to make breakthroughs in clinical translation.


Assuntos
Apoptose/efeitos dos fármacos , DNA/farmacologia , Sistemas de Liberação de Medicamentos , Hidrogéis/farmacologia , Neoplasias/tratamento farmacológico , Animais , Aptâmeros de Nucleotídeos/química , Aptâmeros de Nucleotídeos/farmacologia , DNA/química , Doxorrubicina/química , Doxorrubicina/farmacologia , Liberação Controlada de Fármacos/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Hidrogéis/química , Concentração de Íons de Hidrogênio , Células MCF-7 , Camundongos , Mucina-1/química , Mucina-1/genética , Mucina-1/farmacologia , Nanoestruturas/química , Neoplasias/genética , Neoplasias/patologia , Oligodesoxirribonucleotídeos/química , Oligodesoxirribonucleotídeos/farmacologia , Proteínas Proto-Oncogênicas c-bcl-2/genética , Células RAW 264.7 , Fator de Necrose Tumoral alfa/genética , Proteína X Associada a bcl-2/genética
20.
Mol Ther Nucleic Acids ; 18: 24-33, 2019 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-31479922

RESUMO

The aim of this study is to explore the roles of circular RNA (circRNA) Cdr1as on cisplatin resistance in ovarian cancer and explore the underlying mechanisms. We investigated the expression of circRNAs in five paired cisplatin-sensitive and cisplatin-resistant tissues of ovarian cancer by microarray analysis. The quantitative real-time PCR analysis was to investigate the expression pattern of Cdr1as in cisplatin-resistant ovarian cancer patient tissues and cell lines. Then, the effects of Cdr1as on cisplatin resistance, cell proliferation, and apoptosis were assessed in ovarian cancer cells. In this study, Cdr1as was observed to be downregulated in cisplatin-resistant patient tissues and cell lines. Overexpression of Cdr1as inhibited cell proliferation and promoted the cisplatin-induced cell apoptosis in ovarian cancer cells. Then we demonstrated that repressed Cdr1as promoted the miR-1270 expression, and miR-1270 could bind to the predicted binding site of Cdr1as. Furthermore, we found that miR-1270 displayed its role via modulating the Suppressor of Cancer Cell Invasion (SCAI) expression. Importantly, we demonstrated that Cdr1as was downregulated in serum exosomes from cisplatin-resistant patients. In summary, our study demonstrated that Cdr1as sensitizes ovarian cancer to cisplatin by regulating the miR-1270/SCAI signaling pathway.

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