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1.
Artigo em Inglês | MEDLINE | ID: mdl-31476762

RESUMO

Addiction is a chronic relapsing disorder, and during recovery many people experience several relapse events as they attempt to voluntarily abstain from drug. New preclinical relapse models have emerged that capture this common human experience, and mounting evidence indicates that resumption of drug seeking after voluntary abstinence recruits neural circuits distinct from those recruited during reinstatement after experimenter-imposed abstinence or abstinence due to extinction training. Ventral pallidum (VP), a key limbic node involved in drug seeking, has well-established roles in conventional reinstatement models tested following extinction training, but it is unclear whether this region also participates in more translationally relevant models of relapse. Here we show that chemogenetic inhibition of VP neurons decreased cocaine-, context-, and cue-induced relapse tested after voluntary, punishment-induced abstinence. This effect was strongest in the most compulsive, punishment-resistant rats, and reinstatement was associated with neural activity in anatomically defined VP subregions. VP inhibition also attenuated the propensity of rats to display "abortive lever pressing," a species-typical risk assessment behavior seen here during punished drug taking, likely resulting from concurrent approach and avoidance motivations. These results indicate that VP, unlike other connected limbic brain regions, is essential for resumption of drug seeking after voluntary abstinence. Since VP inhibition effects were strongest in the most compulsively cocaine-seeking individuals, this may also indicate that VP plays a particularly important role in the most pathological, addiction-like behavior, making it an attractive target for future therapeutic interventions.

3.
ACS Appl Mater Interfaces ; 11(29): 26235-26242, 2019 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-31245998

RESUMO

Two-dimensional (2D) hybrid nanosheets made of electrochemically active materials and graphene, featuring fast reaction kinetics and excellent structural stability, are appealing as electrodes for supercapacitors. Herein, we report a general polyethyleneimine (PEI)-mediated fabrication of the 2D cobalt sulfide/graphene hybrid nanosheets via a facile hydrothermal strategy. Detailed analysis reveals that the uniform cobalt sulfide (CoS) nanoparticles are well-anchored on the 2D graphene surface. Thereinto, the nitrogen species originating from the PEI molecules as bridging sites are helpful in enhancing the coupling effect between the graphene and CoS species, which endows the hybrid nanosheets with high electroactivity and excellent structural stability. The as-obtained hybrid nanosheets with typical pseudocapacitive features demonstrate a high specific capacitance (320 F g-1@1 A g-1) and a superior electrochemical stability with the initial capacitance of 86.5% after 20 000 cycles as electrodes for supercapacitors. The assembled asymmetric supercapacitors by combining activated carbon electrodes further show a high charge storage of 28.8 Wh kg-1 with an output power of 130 W kg-1. More importantly, the similar strategy can be easily extended to fabricate other 2D hybrid nanosheets with extraordinary electrochemical performance with the maximum charge storage of 815 F g-1 and energy density of 44. 6 Wh kg-1. The present work, which achieves the general fabrication of 2D hybrid nanosheets with tuned compositions, may provide a new opportunity for the development of supercapacitors.

4.
Int J Biol Macromol ; 136: 1106-1111, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31252005

RESUMO

The sterilization process, due to its immense energy consumption, high facilities investment, and loss of raw materials by caramelization, during industrial production has drawn much attention. In this study, a methanol-resistant mutant strain, Chaetomium globosum ALE20, was obtained following 20 cycles of adaptive laboratory evolution process. The titer of anticancer polysaccharide (GCP-M) from C. globosum ALE20 reached 9.2 g/L with glycerol as sole carbon source using non-sterilized and fed-batch fermentation strategy. This titer represents a 200% increase compared with the 3.3 g/L attained with batch fermentation. The GCP-M monosaccharide was comprised of galactose, glucose, mannose and glucuronic acid, in a molar ratio of 3.83:66.37:3.26:1.95, respectively, and its weight-average molecular weight and polydispersity were 3.796 × 104 Da and 1.060, respectively. This work presents an ideal alternative and safer fermentation process without sterilization, and a useful approach for enhancing industrial production.

5.
Mol Pharm ; 16(7): 3024-3039, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31095909

RESUMO

The USFDA-approved immunosuppressive drug rapamycin (Rapa), despite its potency, is limited by poor bioavailability and a narrow therapeutic index. In this study, we sought to improve bioavailability of Rapa with subcutaneous (SC) administration and to test its therapeutic feasibility and practicality in a murine model of Sjögren's syndrome (SS), a systemic autoimmune disease with no approved therapies. To improve its therapeutic index, we formulated Rapa with a carrier termed FAF, a fusion of the human cytosolic FK506-binding protein 12 (FKBP12) and an elastin-like polypeptide (ELP). The resulting 97 kDa FAF (i) has minimal burst release, (ii) is "humanized", (iii) is biodegradable, (iv) solubilizes two Rapa per FAF, and (v) avoids organic solvents or amphiphilic carriers. Demonstrating high stability, FAF remained soluble and monodisperse with a hydrodynamic radius of 8 nm at physiological temperature. A complete pharmacokinetic (PK) analysis of FAF revealed that the bioavailability of SC FAF was 60%, with significantly higher blood concentration during the elimination phase compared to IV FAF. The plasma concentration of Rapa delivered by FAF was 8-fold higher with a significantly increased plasma-to-whole blood ratio relative to free Rapa, 24 h after injection. To evaluate therapeutic effects, FAF-Rapa was administered SC every other day for 2 weeks to male non-obese diabetic (NOD) mice, which develop an SS-like autoimmune-mediated lacrimal gland (LG) inflammation and other characteristic features of SS. Both FAF-Rapa and free Rapa exhibited immunomodulatory effects by significantly suppressing lymphocytic infiltration, gene expression of IFN-γ, MHC II, type I collagen and IL-12a, and cathepsin S (CTSS) activity in LG compared to controls. Serum chemistry and histopathological analyses in major organs revealed no apparent toxicity of FAF-Rapa. Given its improved PK and equipotent therapeutic efficacy compared to free Rapa, FAF-Rapa is of further interest for systemic treatments for autoimmune diseases like SS.

6.
Anal Chem ; 91(12): 7911-7919, 2019 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-31137927

RESUMO

Besides high portability, high analytical performances are also crucial concerns for a miniature mass spectrometer to meet the demands in in situ analysis. As a continuous effort in improving analytical performances of the miniature mass spectrometer with continuous atmospheric pressure interface, a hybrid ion funnel was developed and coupled into the system in this study. The hybrid ion funnel consisted of a rectangular ion funnel region and a planar quadrupole field region, which were fabricated by the printed circuit board technology. After systematic optimization, a limit of detection of 1 ng/mL was obtained, which was improved by 10 folds relative to that of 10 ng/mL previously reported for the miniature mass spectrometer. Besides improved ion transmission efficiency, this hybrid ion funnel was also capable of filtering ions according to their mobilities, thus improving the system selectivity. This capability was demonstrated by separation and selective transmission of protein ions at different charge states, reserpine in PEG background and isobaric peptide ions. Resolution of this system was also tested by analyzing isotopic peaks of reserpine. The ppb-level detection sensitivity and isotope resolving capability achieved in this work would greatly expand the application range of miniature mass spectrometers.

7.
Biosens Bioelectron ; 137: 255-262, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31121462

RESUMO

A suspended carbon nanotube (SCNT)-based field effective transistor (SCNT-FET), which was fabricated by utilizing the surface tension of liquid silver to suspend a CNT between two Pd electrodes, was proposed for the detection of DNA hybridization. Benefits from the separation between the CNT and the substrates could be observed; namely, the conductivity of a SCNT-FET was much higher (two orders of magnitude) than that of a FET based on an unsuspended CNT and about 50% sensing surface of CNT was freed from substrate. The Slater-Koster tight-binding method was adopted for geometry optimization and transport property calculation of the SCNT bound with DNA. The result showed that the conductance (G = 1/R) of the SCNT decreased in order with the binding of single-stranded DNA (SSDNA, probe DNA) and double-stranded DNA (DSDNA) and that the ability of DSDNA to weaken the conductivity of the SCNT was several times higher than that of SSDNA. SEM and Raman spectroscopy were used to demonstrate that DNA could be bound successfully onto the SCNT using a 1-pyrenebutanoic acid succinimidyl ester (PBASE) as a linkage. Ultra-high sensitivity detection of DNA [with a limit of detection (LOD) as low as 10 aM] was obtained using such an SCNT-FET, which showed a lower value than that of a previously reported FET DNA biosensor whose sensing materials were in direct contact with the substrate.

8.
Molecules ; 24(10)2019 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-31109085

RESUMO

Apart from non-enzymatic browning, polyphenol oxidase (PPO) also plays a role in the browning reaction of orange (Citrus sinensis Osbeck) juice, and needs to be inactivated during the processing. In this study, the protein with high PPO activity was purified from orange (Citrus sinensis Osbeck) and inactivated by ultrasonic processing. Fluorescence spectroscopy, circular dichroism (CD) and Dynamic light scattering (DLS) were used to investigate the ultrasonic effect on PPO activity and structural changes on purified PPO. DLS analysis illustrated that ultrasonic processing leads to initial dissociation and final aggregation of the protein. Fluorescence spectroscopy analysis showed the decrease in fluorescence intensity leading to the exposure of Trp residues to the polar environment, thereby causing the disruption of the tertiary structure after ultrasonic processing. Loss of α-helix conformation leading to the reorganization of secondary structure was triggered after the ultrasonic processing, according to CD analysis. Ultrasonic processing could induce aggregation and modification in the tertiary and secondary structure of a protein containing high PPO activity in orange (Citrus sinensis Osbeck), thereby causing inactivation of the enzyme.

9.
J Cell Physiol ; 234(12): 21662-21669, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31106425

RESUMO

Abnormal wound healing is likely to induce the formation of hypertrophic scars and keloids, which leads to dysfunction, deformity, and mental problem in the patients. Despite the advances in prevention and management of hypertrophic scar and keloids, the mechanism underlying scar and keloid formation has not been fully elucidated. Recent insights into the role of the epithelial-mesenchymal transition (EMT) in development, wound healing, stem cell regulation, fibrosis, and tumorigenesis have increased our understanding of the pathophysiology of hypertrophic scarring and keloids and suggested new therapeutic targets. This review summarizes recent progress in the elucidation of the role of EMT in physiologic wound healing and pathologic scar formation. This knowledge will facilitate an understanding of EMT roles in scar formation and shed new light on the modulation and potential treatment of hypertrophic scars and keloids.

10.
Nanoscale ; 11(21): 10198-10202, 2019 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-31112201

RESUMO

Hydrogen-storage materials are important carriers for a viable hydrogen economy. Despite palladium being the most studied storage material, the hydrogen-storage mechanism of Pd remains ambiguous owing to the lack of atomic-scale evidence of the diffusion and storage of H atoms in its lattice. In the study reported here, this classical process was investigated on the atomic scale using an in situ transmission electron microscope equipped with an atmospheric-pressure sample holder. The expansion of the Pd interplanar spacings was found to comprise three distinct stages during the diffusion of H atoms. Moreover, the expansion in d-spacing of Pd{111} was markedly different from that of Pd{220}. First-principles calculations indicate that H atoms mainly occupy the centers of the tetrahedral cages in the Pd unit cells during the diffusion stage, and they eventually occupy the octahedral cage centers in the equilibrium state. Moreover, H atoms were detected in substantially high densities in defects such as stacking faults and twin boundaries. These observations on the preferred hydrogen-storage domains can help clarify the hydrogen-storage mechanism and offer guidelines on the future design of higher-capacity hydrogen-storage materials.

11.
Artigo em Inglês | MEDLINE | ID: mdl-31135353

RESUMO

Recently, many reconstruction methods have been developed to improve the lateral resolution of acoustic-resolution photoacoustic microscopy (ARPAM) in out-of-focus regions. Though these methods enhance image resolution to some extent, they require advanced computational hardware and large computational time, especially for three-dimensional cases. However, some methods do not consider the finite size of a transducer, while others employ numerical discretization to build a focused transducer model which is less efficient and accurate. To overcome these problems, we propose a three-dimensional ARPAM imaging reconstruction method with high precision, high efficiency, and low memory cost. It inherits the framework of model-based reconstructions and incorporates the forward acoustic model in hybrid-domain. This hybrid-domain acoustic model promotes an analytical solution to establish a focused transducer model. Furthermore, the non-uniform fast Fourier transform (NUFFT) and deconvolution methods are introduced to reduce the required computational time and memory volume for three-dimensional reconstructions. According to the experiment results reconstructed by the proposed method, the lateral resolution of an ARPAM image recorded by a 20MHz focused transducer (NA 0.393) can reach 88.39µm. This resolution exceeds the diffraction limitation of the focused transducer (137.8µm). When reconstructing a three-dimensional image with 200× 200× 150 pixels, the proposed method takes only 8.15 seconds using a laptop loaded with Intel(R) Core (TM) i7-8550U CPU @ 1.8GHz and 1.06GB memory.

12.
Chemistry ; 25(32): 7618-7622, 2019 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-31001885

RESUMO

The synthesis of antiaromatic NiII -norcorroles having primary, secondary, and tertiary alkyl groups at the reactive meso-positions was attempted. Reductive coupling of a NiII -dipyrrin precursor provided NiII -meso-dihexylnorcorrole, which underwent substantial degradation on silica gel. Introduction of tert-butyl groups was unsuccessful due to the difficult preparation of the corresponding dipyrrin precursor. Meanwhile, NiII -norcorroles with isopropyl and cyclohexyl groups were isolated as stable molecules under ambient conditions. Furthermore, we found that oxidation of NiII -meso-dialkylnorcorroles with hydrogen peroxide in the presence of sodium carbonate gave NiII -5-oxaporphyrins(2.0.1.0). In contrast, oxidation of NiII -meso-dimesitylnorcorrole under the same reaction conditions gave 10-oxaporphyrin(1.1.1.0). The contrasting reactivity can be attributed to the steric congestion around the meso-positions.

13.
Int J Biochem Cell Biol ; 112: 8-17, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31026505

RESUMO

BACKGROUND: With the development of next-generation sequencing (NGS), thousands of circular RNAs (circRNAs) have been found. Many circRNAs have been verified to play vital roles in carcinogenesis. However, whether circRNAs engage in the development and progression of ovarian cancer remains to be clarified. METHODS: We analyzed circRNA expression profiling in epithelial ovarian cancer (EOC) and normal ovarian tissues (NOT) using NGS and validated six randomly selected circRNAs via quantitative real-time-PCR (qRT-PCR), reverse-transcription PCR (RT-PCR) and Sanger sequencing after RNase treatment. CircHIPK3, the most abundant circRNA in our sequencing data, was further knocked down by siRNA. The circHIPK3 function in proliferation, invasion, migration and apoptosis of ovarian cancer cells and normal ovarian epithelial cells was analyzed via cell counting-kit 8 (CCK8), wound healing, transwell and flow cytometry analyses after circHIPK3 was efficiently silenced. RESULTS: Altogether, we found 7333 circRNAs, of which 4505 (61.43%) were newly identified, 2431 were significantly upregulated and 3120 were remarkably downregulated. Six randomly selected differentially expressed circRNAs were examined in 18 EOC and 18 NOT. Furthermore, the results of RT-PCR and Sanger sequencing after RNase treatment confirmed head-to-tail back-splicing. Silencing of circHIPK3 promoted proliferation, migration, and invasion and inhibited apoptosis of ovarian cancer cells (A2780 and SKOV3) and normal ovarian epithelial cells (IOSE80). Additionally, the circHIPK3-miRNA-mRNA axis was predicted as the possible mechanism using bioinformatic approaches. CONCLUSIONS: We identified the circRNA expression profile in ovarian cancer tissues and further verified the existence and expression of six randomly selected differentially expressed circRNAs. Besides, we also found that circHIPK3 is an important regulator of ovarian cancer progression.

14.
AIDS ; 33(9): 1431-1439, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-30889014

RESUMO

OBJECTIVE: The current study aimed to understand epidemiological feature and critical factors associated with pathogenesis of circulating recombinant form (CRF) 01_AE strains in Northeast China. DESIGN: Compared analysis was made between CRF01_AE and non-CRF01_AE samples to understand the pathogenicity features of CRF01_AE. Further analyses between CRF01_AE samples with high or low CD4 cell counts and between samples with different coreceptor usages were done to explore the possible factors correlating to the pathogenesis of CRF01_AE viruses. METHODS: The genotypes of newly identified strains were determined by phylogenetic analyses using Mega 6.06. Coreceptor usage was predicted by Geno2Pheno algorithm. Potential N-linked glycosylation site (PNGS) number was calculated using the online N-glycosite software. The properties of amino acid sequences were analyzed by the online ProtParam tool. RESULTS: CRF01_AE become the main HIV-1 genotype since 2010. Compared with non-CRF01_AE group, the CRF01_AE group showed a higher proportion of samples with CD4 cell count less than 200 cells/µl. Shorter amino acid length, fewer PNGSs and the presence of a basic motif R/KNXT or NR/KT in V4 correlated to a lower CD4 cell count, and existence or coexistence of Thr12, Arg13, Val21 and Lys33, presence of more than 4 of net charges and lack of the PNGS within V3 favored to the X4/R5X4 coreceptor usage of CRF01_AE viruses. CONCLUSION: CRF01_AE has dominated HIV-1 genotype in Northeast China. Infection with CRF01_AE exhibited a fast disease progression, which may be associated with specific amino acid residues and PNGSs in V3 and V4 regions as well as amino acid length of V4 region.

15.
PLoS One ; 14(3): e0213096, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30845246

RESUMO

RATIONALE: We propose renin angiotensin system (RAS) peptides are critical in wound reparative processes such as in acute respiratory distress syndrome (ARDS). Their role in predicting clinical outcomes in ARDS has been unexplored; thus, we used a targeted metabolomics approach to investigate them as potential predictors of outcomes. METHODS: Thirty-nine ARDS patients were enrolled within 24 hours of ARDS diagnosis. Plasma RAS peptide levels were quantified at study entry and 24, 48 and 72 hours using a liquid chromatography-mass spectrometry based metabolomics assay. RAS peptide concentrations were compared between survivors and non-survivors, and were correlated with clinical and pulmonary measures. MEASUREMENTS AND MAIN RESULTS: Angiotensin I (Ang-I or A(1-10)) levels were significantly higher in non-survivors at study entry and 72 hours. ARDS survival was associated with lower A(1-10) concentration (OR 0.36, 95% CI 0.18-0.72, p = 0.004) but higher A(1-9) concentration (OR 2.24, 95% CI 1.15-4.39, p = 0.018), a biologically active metabolite of A(1-10) and an agonist of angiotensin II receptor type 2. Survivors had significantly higher median A(1-9)/A(1-10) and A(1-7)/A(1-10) ratios than the non-survivors (p = 0.001). Increased A(1-9)/A(1-10) ratio suggests that angiotensin converting enzyme II (ACE2) activity is higher in patients who survived their ARDS insult while an increase in A(1-7)/A(1-10) ratio suggests that ACE activity is also higher in survivors. CONCLUSION: A(1-10) accumulation and reduced A(1-9) concentration in the non-survivor group suggest that ACE2 activities may be reduced in patients succumbing to ARDS. Plasma levels of both A(1-10) and A(1-9) and their ratio may serve as useful biomarkers for prognosis in ARDS patients.

16.
Sensors (Basel) ; 19(5)2019 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-30866459

RESUMO

Diabetic patients need long-term and frequent glucose monitoring to assist in insulin intake. The current finger-prick devices are painful and costly, which places noninvasive glucose sensors in high demand. In this review paper, we list several advanced electromagnetic (EM)-wave-based technologies for noninvasive glucose measurement, including infrared (IR) spectroscopy, photoacoustic (PA) spectroscopy, Raman spectroscopy, fluorescence, optical coherence tomography (OCT), Terahertz (THz) spectroscopy, and microwave sensing. The development of each method is discussed regarding the fundamental principle, system setup, and experimental results. Despite the promising achievements that have been previously reported, no established product has obtained FDA approval or survived a marketing test. The limitations of, and prospects for, these techniques are presented at the end of this review.


Assuntos
Técnicas Biossensoriais/métodos , Glicemia/análise , Radiação Eletromagnética , Automonitorização da Glicemia , Humanos , Análise Espectral Raman
17.
EMBO Rep ; 20(4)2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30872316

RESUMO

Cyclic dinucleotides (CDNs) are important second messenger molecules in prokaryotes and eukaryotes. Within host cells, cytosolic CDNs are detected by STING and alert the host by activating innate immunity characterized by type I interferon (IFN) responses. Extracellular bacteria and dying cells can release CDNs, but sensing of extracellular CDNs (eCDNs) by mammalian cells remains elusive. Here, we report that endocytosis facilitates internalization of eCDNs. The DNA sensor cGAS facilitates sensing of endocytosed CDNs, their perinuclear accumulation, and subsequent STING-dependent release of type I IFN Internalized CDNs bind cGAS directly, leading to its dimerization, and the formation of a cGAS/STING complex, which may activate downstream signaling. Thus, eCDNs comprise microbe- and danger-associated molecular patterns that contribute to host-microbe crosstalk during health and disease.

18.
J Virol ; 93(10)2019 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-30842333

RESUMO

Combination anti-retroviral drug therapy (ART) potently suppresses HIV-1 replication but does not result in virus eradication or a cure. A major contributing factor is the long-term persistence of a reservoir of latently infected cells. To study this reservoir, we established a humanized mouse model of HIV-1 infection and ART suppression based on an oral ART regimen. Similar to humans, HIV-1 levels in the blood of ART-treated animals were frequently suppressed below the limits of detection. However, the limited timeframe of the mouse model and the small volume of available samples makes it a challenging model with which to achieve full viral suppression and to investigate the latent reservoir. We therefore used an ex vivo latency reactivation assay that allows a semiquantitative measure of the latent reservoir that establishes in individual animals, regardless of whether they are treated with ART. Using this assay, we found that latently infected human CD4 T cells can be readily detected in mouse lymphoid tissues and that latent HIV-1 was enriched in populations expressing markers of T cell exhaustion, PD-1 and TIGIT. In addition, we were able to use the ex vivo latency reactivation assay to demonstrate that HIV-specific TALENs can reduce the fraction of reactivatable virus in the latently infected cell population that establishes in vivo, supporting the use of targeted nuclease-based approaches for an HIV-1 cure.IMPORTANCE HIV-1 can establish latent infections that are not cleared by current antiretroviral drugs or the body's immune responses and therefore represent a major barrier to curing HIV-infected individuals. However, the lack of expression of viral antigens on latently infected cells makes them difficult to identify or study. Here, we describe a humanized mouse model that can be used to detect latent but reactivatable HIV-1 in both untreated mice and those on ART and therefore provides a simple system with which to study the latent HIV-1 reservoir and the impact of interventions aimed at reducing it.

19.
Drug Deliv ; 26(1): 199-207, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30835586

RESUMO

The multidrug resistance in tumor (MDR) is a major barrier to efficient cancer therapy. Modern pharmacological studies have proven that tetrandrine (TET) has great potential in reversing MDR. However, it has a series of medication problems in clinic such as poor water solubility, low oral bioavailability and short half-life in vivo. Aiming at the above problems, red blood cell membrane-camouflaged TET-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (RPTNs) had been developed. The RPTNs had spherical shell-core double layer structure with average particle size of 164.1 ± 1.65 nm and encapsulation efficiency of 84.1% ± 0.41%. Compared with TET-PLGA nanoparticles (PTNs), the RPTNs reduced RAW 264.7 macrophages' swallowing by 32% due to its retention of natural membrane proteins. The cumulative drug release of RPTNs was 81.88% within 120 h. And pharmacokinetic study showed that the blood half-life of RPTNs was 19.38 h, which was 2.95 times of free drug. When RPTNs of 2 µg/mL TET were administered in combination with adriamycin (ADR), significant MDR reversal effect was observed in drug-resistant cells MCF-7/ADR. In a word, the RPTNs hold potential to improve its efficacy and broaden its clinical application.


Assuntos
Benzilisoquinolinas/síntese química , Membrana Celular/efeitos dos fármacos , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Eritrócitos/efeitos dos fármacos , Nanopartículas/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/síntese química , Animais , Benzilisoquinolinas/administração & dosagem , Benzilisoquinolinas/metabolismo , Membrana Celular/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Relação Dose-Resposta a Droga , Resistência a Múltiplos Medicamentos/fisiologia , Eritrócitos/metabolismo , Células HEK293 , Humanos , Células MCF-7 , Camundongos , Nanopartículas/administração & dosagem , Nanopartículas/metabolismo , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/administração & dosagem , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/metabolismo , Células RAW 264.7
20.
Cancer Biother Radiopharm ; 34(5): 316-324, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30892073

RESUMO

Objective: The aim was to investigate the lncRNA KB-1471A8.2 function in ovarian cancer progression and paclitaxel resistance. Methods: The expression and distribution of KB-1471A8.2 was detected by qRT-PCR. The cell proliferation, apoptosis, invasion, migration and chemoresistance were analyzed by CCK8 assay, flow cytometry and transwell assay. The expression of DEPTOR, whose sequence is reverse overlapped with KB-1471A8.2 was analyzed by qRT-PCR, western blot and immunofluorescence. The cell cycle and the cell cycle related gene expression were analyzed by flow cytometry and qRT-PCR, respectively. Results: KB-1471A8.2 was significantly downregulated in both ovarian cancer tissues and chemoresistant ovarian cancer cells. Overexpression of KB-1471A8.2 significantly inhibited the proliferation, invasion, migration, and paclitaxel resistance, and increased the apoptosis of ovarian cancer cells. KB-1471A8.2 was mainly distributed in the nucleus of ovarian cancer cells. KB-1471A8.2 overexpression significantly decreased the S phase cell ratio, increased the G0/G1 phase cell ratio, but not affected the expression and distribution of DEPTOR. However, cyclin-dependent kinase 4 (CDK4), which is an important regulator of G1/S transition, was significantly decreased in KB-1471A8.2-overexpressed ovarian cancer cells. Conclusion: KB-1471A8.2 could significantly inhibit the development and paclitaxel resistance of ovarian cancer cells, at least partly, by suppressing CDK4 expression.

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